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[ "Photovoltaic cells where light is converted into electric power to be fed to external loads, which are electrically connected to the photovoltaic cells, have been prevailing in a wide range of applications such as consumer electronics, industrial electronics, and space exploration. ", "In consumer electronics, photovoltaic cells that consist of materials such as amorphous silicon are used for a variety of inexpensive and low power applications. ", "Typical conversion efficiency, i.e. the solar cell conversion efficiency, of amorphous silicon based photovoltaic cells is in the range of ˜10% [Yamamoto K, Yoshimi M, Suzuki T, Tawada Y, Okamoto T, Nakajima A. Thin film poly-Si solar cell on glass substrate fabricated at low temperature. ", "Presented at MRS Spring Meeting, San Francisco, April 1998.]. ", "Although the fabrication processes of amorphous silicon based photovoltaic cells are rather simple and inexpensive, one notable downside of this type of cell is its vulnerability to defect-induced degradation that decreases its conversion efficiency.", "\nIn contrast, for more demanding applications such as residential and industrial solar power generation systems, either poly-crystalline or single-crystalline silicon is typically used because there are more stringent requirements of better reliability and higher efficiency than those in consumer electronics. ", "Photovoltaic cells consisting of poly-crystalline and single-crystalline silicon generally offer conversion efficiencies in the range of ˜20% and ˜25% [Zhao J, Wang A, Green M, Ferrazza F. Novel 19.8% efficient ‘honeycomb’ textured multicrystalline and 24.4% monocrystalline silicon solar cell. ", "Applied Physics Letters 1998; 73: 1991-1993.] ", "respectively. ", "As many concerns associated with a steep increase in the amount of the worldwide energy consumption are raised, further development in industrial solar power generation systems has been recognized as a main focus for an alternative energy source. ", "However, due to the high cost ($3 to $5/Watt) of today's Si-based solar cell, it is not yet widely accepted as an alternative energy source solution.", "\nGroup II-VI compound semiconductors, for example CdTe and CdS, have been considered for the purpose of creating industrial solar power generation systems, manufactured at a lower cost and maintaining a moderate conversion efficiency. ", "This approach resulted in a comparable conversion efficiency of ˜17% [Wu X, Keane J C, Dhere R G, DeHart C, Duda A, Gessert T A, Asher S, Levi D H, Sheldon P. 16.5%-efficient CdS/CdTe polycrystalline thin-film solar cell. ", "Proceedings of the 17th European Photovoltaic Solar Energy Conference, Munich, 22-26 Oct. 2001; 995-1000.]. ", "This conversion efficiency is comparable to those for the single crystalline silicon photovoltaic devises; however, the toxic nature of these materials is of great concern for environment.", "\nGroup I-III-VI compound semiconductors, such as CuInGaSe2, have also been extensively investigated for industrial solar power generation systems. ", "This material can potentially be synthesized at a much lower cost than its counterpart, single crystalline silicon. ", "However, a conversion efficiency of ˜19%, is comparable to that of single crystalline silicon based cells and can be obtained, thus far, only by combining with the group II-VI compound semiconductor cells [Contreras M A, Egaas B, Ramanathan K, Hiltner J, Swartzlander A, Hasoon F, Noufi R. Progress toward 20% efficiency in Cu(In,Ga)Se polycrystalline thin-film solar cell. ", "Progress in Photovoltaics: Research and Applications 1999; 7: 311-316.], ", "which again raises issues associated with the toxic nature of these materials.", "\nPhotovoltaic cells designed for several exclusive applications, where the main focus is high conversion efficiency, generally consist of group III-V semiconductors, including GaInP and GaAs. ", "In general, synthesis processes of single crystalline group III-V are very costly because of substantial complications involved in epitaxial growth of group III-V single crystalline compound semiconductors. ", "Typical conversion efficiencies of group III-V compound semiconductor based photovoltaic cells, as these types of photovoltaic cells are intended to be, can be as high as ˜34% when combined with germanium substrates, another very expensive material [King R R, Fetzer C M, Colter P C, Edmondson K M, Law D C, Stavrides A P, Yoon H, Kinsey C S, Cotal H L, Ermer J H, Sherif R A, Karam N H. Lattice-matched and metamorphic CaInP/GaInAs/Ge concentrator solar cells. ", "Proceedings of the World Conference on Photovoltaic Energy Conversion (WCPEC-3), Osaka, May 2003; to be published.], ", "usually more than 10 times as expensive as the conventional Si-solar cell.", "\nAll photovoltaic cells in the prior art described above, regardless of what materials the cell is made from, essentially fall into one specific type of structure, which usually limits its power generation capability. ", "Usually a flat pn-junction structure is used in conventional solar cells (FIG. ", "1A). ", "Shown in FIG. ", "1A is a photovoltaic cell comprising a thick p-type semiconductor layer 101 and a thin n-type semiconductor layer 102 formed on an electrically conductive substrate 100. ", "A pn-junction 103 is formed at the interface between the p-type semiconductor layer 101 and the n-type semiconductor layer 102. ", "Incident light 104 entering the cell generates electron-hole pairs after being absorbed by the p- and also n-type semiconductor layers 101 and 102. ", "The incident light 104 generates electrons 105e and holes 105h in the region near the pn-junction 103 and also electrons 106e and holes 106h in the region far from the pn-junction 103. ", "The photogenerated electrons 105e and 106e (and holes) (hereafter considering only electronics, i.e. minority carriers in p-type semiconductors, although the same explanation is applicable for holes, minority carriers in n-type semiconductors) diffusing toward the pn-junction 103 and entering the pn-junction 103 contribute to photovoltaic effect. ", "The two key factors that substantially impact the conversion efficiency of this type of photovoltaic cell are photo carrier generation efficiency (PCGE) and photo carrier collection efficiency (PCCE).", "\nThe PCGE is the percentage of photons entering a cell which contribute to the generation of photo carriers, which needs to be, ideally, 100%. ", "On the other hand, the PCCE is the percentage of photogenerated electrons 105e and 106e that reach the pn-junction 103 and contribute to the generation of photocurrent. ", "For a monochromatic light, a PCGE of ˜100% can be achieved by simply making the p-type layer 101 thicker; however, electrons 106e generated at the region far away from the pn-junction 103 cannot be collected efficiently due to many adverse recombination processes that prevent photogenerated carriers from diffusing into the pn-junction 103. ", "Thus, the basic structure of current photovoltaic cells has its own limitation on increasing the conversion efficiency.", "\nFIG. ", "1B shows typical monochromatic light intensity behavior 108 inside the semiconductor. ", "As illustrated in FIG. ", "1B, the light intensity behavior 108 inside the bulk semiconductor is exponential. ", "The light intensity p at certain depth x can be expressed as p(x)=Poexp(−αx), where Po is the peak intensity at the surface and α is the absorption co-efficient of the semiconductor in which light is entering. ", "Carriers (not shown here) generated due to light flux 112 absorbed by the pn-junction 103 is only drifted by the junction field and can be collected efficiently, whereas, carriers 106e and 106h generated due to absorption of light-flux 110 by semiconductor region 101 are diffused in all directions. ", "Only those carriers 105e and 105h which are generated closer (a distance equal to or less than the diffusion-length of the semiconductor) to the pn-junction 103 can be collected. ", "Those carriers 106e and 106h which are generated far away (a distance longer than the diffusion-length of the semiconductor) from the pn-junction 103 are recombined and lost. ", "The light flux 112 is usually lost either by leaving out or being absorbed by the substrate.", "\nBoth PCGE and PCCE are largely dependent on the material and structure of the photovoltaic cells. ", "Today's photovoltaic cells are structured in such a way that (a) wide ranges of the solar spectrum cannot be absorbed due to material limitations, and (b) PCCE is low due to its inherent structure. ", "For example, the typical conversion efficiency of today's crystal-Si based solar cell is ˜18%. ", "Wavelengths of the solar spectrum spread from <0.1 μm to 3.5 μm, but Si can only absorb ˜0.4 μm to 0.9 μm of light. ", "˜50% of light belonging to the solar spectrum cannot be absorbed by Si, due to its inherent material properties. ", "The remaining 32% is lost due to (i) recombination of photogenerated carriers and (ii) loss of light, which is represented by 112 in FIG. ", "1B; these two factors are structure dependent. ", "If we could reduce these two factors, ˜50% conversion efficiency could be achieved, even in a Si-based solar cell. ", "If we could capture different wavelengths of light belonging to the solar spectrum by utilizing different alloyed materials, we could increase the conversion efficiency ideally to 100%. ", "Furthermore, if the solar cell detection capability could be extended to the infrared-spectrum, then the solar cell could produce electrical energy not only during the day (while sun is present), but also at night (hereafter defined by when the sun is not out). ", "Additionally, today's solar cell material is not highly radiation-tolerant. ", "Specifically, in space applications, photovoltaic cells should be highly radiation tolerant and have structure and material systems which can generate high-power per unit area.", "\nFor both commercial and space applications, therefore, it would be desirable to have photovoltaic cell structures where both the PCGE and the PCCE can be increased simultaneously by having a photo absorption region which is thick enough to capture all the photons entering the cell and a pn-junction which is located as close to the photo absorption region as possible. ", "It would be further desirable to have, while maintaining ideal PCGE and PCCE, materials which have photo responses at different spectrums in order to efficiently cover a wide spectrum of light that enters a photovoltaic cell. ", "It would be further desirable to have a large junction area within a given volume of a photovoltaic cell so that generated electric power that is proportional to the junction area can be maximized. ", "It would be further desirable to have solar cells which could generate electric power in both day and night.", "\nIn today's solar cell, high-cost is also a main factor, in addition to the issue of low conversion efficiency. ", "It is found that more than 93% of solar cells are silicon (Si) based, meaning a silicon (Si) wafer is the base material, and the rest are thin-film based solar cells. ", "In manufacturing Si-based solar cells, more than 85% of the cost comes from the Si wafer cost, the remaining comes from other processing costs. ", "It is highly desirable to reduce the wafer cost and at the same time increase the conversion efficiency." ]

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[ "Minocycline and oral pigmentation.", "\nMinocycline is a semisynthetic tetracycline used in the treatment of inflammatory acne because of its broad spectrum of activity, less common development of resistant organisms, and its anti-inflammatory effects. ", "A number of adverse reactions are reported, including skin and oral pigmentation. ", "This paper details the pharmacology of minocycline and describes the pigmentation and likely mechanisms active in both hard and soft tissues. ", "Oral pigmentation usually involves the hard tissues only and presents typically as a discrete band occupying the central zone of the alveolar mucosa and palate. ", "As with other sites, it may persist following withdrawal of the drug. ", "Early recognition by the dental practitioner may allow an alternative form of therapy to be sought, minimizing the likelihood of a long-term aesthetic problem." ]

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[ "Anglo concertina\n\nThe Anglo or Anglo-German concertina is a member of the concertina family of free-reed instruments.", "\n\nHistory\nThe Anglo originated as a hybrid between the English and German concertinas. ", "The button layouts are generally the same as the original 20-button German concertinas designed by Carl Friedrich Uhlig in 1834. ", "Within a few years of that date, the German concertina was a popular import in England, Ireland, and North America, due to its ease of use and relatively low price. ", "English manufacturers responded to this popularity by offering their own versions using traditional English methods: concertina reeds instead of long-plate reeds, independent pivots for each button, and hexagon-shaped ends. ", "\n\nInitially the term Anglo-German only applied to concertinas of this type built in England, but as German manufacturers adopted some of these techniques, the term came to apply to all concertinas that used Uhlig's 20-button system. ", "Use of the \"German\" part of the title Anglo-German ceased in the UK during World War I.\n\nPlay\nThe heart of the Anglo system consists of two 10-button rows, each of which produces a diatonic major scale in a pattern devised around 1826 by Bohemian designer Joseph Richter for use in a harmonica (Richter tuning). ", "Five buttons of each row are on each side. ", "The two rows are musically a fifth apart. ", "For example, if the row closest to the player's wrist is in the key of G, the next outer row is in the key of C below. ", "An advantage of the Richter tuning is that pressing three adjacent notes in one row produces a major triad. ", "Also, because the travel direction inverts as you progress up the scale, at the point where the scale crosses from one side of the concertina to the other octaves can be played in the home keys. ", "\n\nA third row of extra notes was eventually added, loosely derived from the C scale. ", "These added accidentals and notes that already existed in the diatonic rows, but in opposite bisonoric orientation, to make additional chords possible and certain melodic passages easier. ", "At this point the instrument was chromatic over two octaves, but not every chord or other note combination was available in either push or draw. ", "There is little variation between makers and models in the layout of the notes in the core diatonic rows, but somewhat more variation in the number and layout of the 'helper' notes. ", "The two most common layouts of this 30-button variety are the Jeffries and Lachenal systems. ", "Layouts with 36, 38 and 40 buttons are not uncommon, and a few anglos have as many as 55 keys (such as the one John Spiers plays). ", "Instruments in the key of C/G are most typical. ", "Other key combinations are also available—G/D and B/F being the most common alternatives. ", "B/F and A/E were popular with the Salvation Army. ", "\n\nThe Anglo concertina is typically held by placing the hands through a leather strap, with the thumbs outside the strap and the palms resting on wooden bars. ", "This arrangement leaves four fingers of each hand free for playing, and the thumbs free to operate an air valve (for expanding or contracting the bellows without sounding a note) or a drone. ", "Anglo concertinas are often associated with the music of Ireland, though they are also used in other musical contexts, particularly in music for the English Morris dance and Boeremusiek. ", "Famous English players of the Anglo include Scan Tester, John Spiers, William Kimber, and John Kirkpatrick.", "\n\nProducers\nGeorge Jones is often credited as the first English chromatic Anglo concertina maker. ", "British firms active in the late 19th and early 20th centuries include those founded by Charles Wheatstone, Charles Jeffries (who built primarily Anglo-style concertinas), Louis Lachenal (who built concertinas in both English and Anglo styles and was the most prolific manufacturer of the period), and John Crabb.", "\n\nReferences\n\n Worral, Dan (2007). ", "A Brief History of the Anglo Concertina in the United States. ", "Concertina.com\n Eydmann, Stuart (2005). ", "The Life and Times of the Concertina: the adoption and usage of a novel musical instrument with particular reference to Scotland. ", "Chapter 6: The Anglo-German Concertina: Product Diversification in an Expanding Market. ", "Concertina.com\n\nCategory:Concertina\nCategory:Irish musical instruments\nCategory:English musical instruments\nCategory:South African musical instruments" ]

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[ "Construction of chimeric arteriviruses reveals that the ectodomain of the major glycoprotein is not the main determinant of equine arteritis virus tropism in cell culture.", "\nThe recent development of arterivirus full-length cDNA clones makes possible the construction of chimeric arteriviruses for fundamental and applied studies. ", "Using an equine arteritis virus (EAV) infectious cDNA clone, we have engineered chimeras in which the ectodomains of the two major envelope proteins, the glycoprotein GP(5) and the membrane protein M, were replaced by sequences from envelope proteins of related and unrelated RNA viruses. ", "Using immunofluorescence microscopy, we monitored the transport of the hybrid GP(5) and M proteins to the Golgi complex, which depends on their heterodimerization and is a prerequisite for virus assembly. ", "The only viable chimeras were those containing the GP(5) ectodomain from the porcine (PRRSV) or mouse (LDV) arteriviruses, which are both considerably smaller than the corresponding sequence of EAV. ", "Although the two viable GP(5) chimeras were attenuated, they were still able to infect baby hamster kidney (BHK-21) and rabbit kidney (RK-13) cells. ", "These cells can be infected by EAV, but not by either PRRSV or LDV. ", "This implies that the ectodomain of the major glycoprotein GP(5), which has been postulated to be involved in receptor recognition, is not the main determinant of EAV tropism in cell culture." ]

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[ "Tuesday, 31 October 2017\n\nIt’s the Halloweenth Day of Halloween!", "\n\nWHOA\n\nOn this, the Halloweenth Day of Halloween, please partake and enjoy some delights to watch and listen to, courtesy of some awexome peoples. ", "Try not to get so scared that you might die of scares and fears that you might die.", "\n\nGreatest American homestar:\n\nHere is pupped Homestar singing a Halloween-ish version of the best TV show theme song of ALL TIME!", "\n\nOpen Mike Eagle and Video Dave in #DeadAss Episode 8: Halloween Special\n\nOpen Mike Eagle (and more importantly, VIDEO DAVE) are still on an independent rap tour (or they were when this episode was made). ", "In this very scary episode, Video Dave makes them some pizzas with a special ingredient and then go to a mall and whoops craziness!", "\n\nOh, also Mike released a brand-new, exclusive Halloween-ish song that might not be here if you’re reading this anytime in the future:\n\nThe Crazy Boy Floyds: 8-Bit Halloween\n\nHere is perhaps the greatest Halloween EP ever released, four songs of scares and fears that you might die!" ]

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[ "Targeting peroxisome proliferator-activated receptor gamma for generation of antidiabetic drug.", "\nThe incidence of Diabetes Mellitus (DM) has increased to alarming levels not only in developed countries but also in developing and underdeveloped countries. ", "Scientific data have made it clear by now that patients with DM are predisposed to many other diseases. ", "One of the worst associations of DM is with obesity and the number of DM patients with obesity is increasing at a very fast pace due to dramatic change in life style around the world in last few decades. ", "This necessitates the discovery of new drugs to treat increasing numbers of people with both DM and obesity. ", "Peroxisome Proliferator activated receptor gamma (PPARγ) is a well known target for DM and thiazolidiniones (TZDs; a common class of antidiabetic drug) which includes rosiglitazone and pioglitazone act through PPARγ. ", "Recent studies have demonstrated that PPARγ apart from being important in glucose utilization also plays a critical role in lipid metabolism and energy homeostasis affecting long-term metabolic status. ", "The possibility of selective modulation of PPARγ has opened up a whole new avenue of research and has the potential of producing some drug which can simultaneously fight both DM and obesity, without the side-effects of the currently available PPARγ modulators. ", "Here, we discuss various aspects of selective modulation of PPARγ action." ]

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[ "True lovers of games crave the best gaming experience. ", "Prepare to be indulged by the GIGABYTE R7 360 Ultra Durable 2 OC graphics card offering performance that will amaze you with astonishing detail that will pull you directly into the action. ", "Know the difference between a good and a top graphics card and you'll never look back." ]

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[ "In situ solution state characterization of MOF-immobilized transition metal complexes by infrared spectroscopy.", "\nTransition metal catalysts immobilized on the surface of MOFs, are being utilized for an ever increasing number of reactions ranging from couplings to olefin oligomerization. ", "While these reactions are usually performed in solution, unlike their homo-geneous counterparts, the insolubility of the MOF systems makes it difficult to obtain detailed mechanistic information by in situ spectroscopic analysis in solution. ", "In this report, we present a synthetic method to solubilize these systems by grafting oligomers on the surface of the MOF particles, making it possible to characterize these species by transmission IR spectros-copy. ", "The fundamental photochemistry of these catalysts was also studied and compared to that of their homogeneous counterparts. ", "This work establishes a proof of principle for in solution monitoring of heterogeneous catalysts." ]

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[ "Treatment of severe cases of pandemic (H1N1) 2009 influenza: review of antivirals and adjuvant therapy.", "\nThree worldwide influenza pandemics were reported in the 20th century: in 1918, 1957 and 1968. ", "All three pandemics were caused by different sub-types of Influenza A viruses: H1N1, H2N2 and H3N2 respectively. ", "In early March 2009, the first cases of influenza -like illness (ILI) were reported from Mexico. ", "This strain was identified as influenza A/ H1N1 strain. ", "Pandemic (H1N1) 2009 influenza most commonly causes a self-limited illness, however, significant morbidity and mortality were reported in the young, the obese and in pregnant women. ", "The drugs of choice for treatment and prophylaxis of pandemic (H1N1) 2009 influenza are the neuraminidase inhibitors, Oseltamivir and Zanamivir. ", "While a few cases of Oseltamivir-resistance are reported, these isolates still retained their susceptibility to the inhaled Neuraminidase inhibitor, Zanamivir. ", "Pandemic (H1N1) 2009 influenza virus is routinely resistant to the adamantanes: Amantadine and Rimantadine. ", "These agents should not be used for the treatment or prophylaxis of pandemic (H1N1) 2009 influenza. ", "The FDA recently approved the emergency use of Peramivir, an intravenous neuraminidase inhibitor, for the treatment of patients with severe influenza. ", "We discuss the use of available antivirals, as well as the effectiveness of adjunctive therapies with immunomodulatory and anti-inflammatory agents, such as immunoglobulins and statins, for the treatment and management of patients with severe H1N1 influenza. ", "This review summarizes the recent patents for the use of antivirals in treatment of severe influenza." ]

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[ "Categories\n\nMeta\n\nSo it has been around 9 months where I literally ceased to update my blog. ", "But hey, I’ve finally managed some free time and here I am, back to writing. ", "Though I wish I could keep this habit for a longer period of time, but then there is a word famous amongst all the IIMs i.e “rigor”. ", "The academic rigor here is just beyond explanation. ", "Yes it could be a culture which was inherited from our mentor institute i.e IIM Lucknow. ", "But then after it stopped mentoring, I believe IIM Kashipur was able to get the balance between the academic rigor and extra-curricular activities.", "\n\nSo, I landed up here on the 29th of June and realised that there was an induction programme going on. ", "So the importance of induction is actually to make us get used to the daily routine we will have to go through in these entire two years. ", "We learnt a lot about clubs, committees and other such student bodies. ", "Apart from that, we learnt the most important thing in MBA (technically PGDM but yeah), i.e Deadlines. ", "Deadlines are meant to keep us on our toes all the time. ", "Finally our induction got over, and we were inducted into the IIM Kashipur family. ", "Here, the familiarity and bonding between the students is so much that all of us know each other by our full names. ", "The entire batch of 200+ students know each other in person very well. ", "The only differentiation could be of the individual’s best friend circle. ", "Apart from that everyone is very much helpful and surviving here is not too tough if you have such people around you.", "\n\nSo, in the initial days it was tough for me. ", "Back during my engineering days I was able to meet my mom on every weekend. ", "Now, it was a totally different scenario for me. ", "Hence initially I had to face a lot of problems in living totally away from parents. ", "But then, the academics kept me busy throughout the entire period of three months. ", "A lot of events happened, like the Coalescence (Annual Business Summit), Kacofonia (Inter-Section wars), Teacher’s day and a lot more.", "\n\nAlso, during these three months, I was finally able to manage some time, and visit the beautiful city of lake, the city of Nainital twice. ", "That too, I was lucky enough to spend my Diwali in Nainital. ", "The views were absolutely mesmerising and I think my iPad might not have done justice to the views which could have been seen from the naked eye. ", "If you want to experience it, I would suggest you to actually visit Nainital during Diwali and experience the same. ", "I am sharing a few glimpses of the view which I was lucky enough to see in person.", "\n\nAnd finally, there was the end term examinations. ", "The end term examinations clashed entirely with the Durga Pujo, and that was a total turn-off for me. ", "But yes, I had taken a calculated risk of catching the Durga Pujo on the last day. ", "The risk was, that I had to leave my exam mid-way to reach home by midnight. ", "And yes, I pulled off the stunt totally in time i.e just before the final call, I was able to reach the Delhi Airport and board the night flight. ", "Finally I was able to reach home and then I was able to catch up with the Durga Puja in Mumbai.", "\n\nSo after a small vacation of a week, I got myself mentally charged. ", "Though my parents were of the opinion that I could have waited for a few more days but then I was bound to return back within a week due to the next term registration processes happening in the college. ", "So, after I came back, finally during Agnitraya, the college Cultural and Management festival of IIM Kashipur, I got spare time to write this experience. ", "I believe I’ll be able to write again in the next three months or so. ", "See you all back again in the next three months.", "\n\nP.S The above picture explains the first three months of my life, a journey into the depth of IIM Kashipur.", "\n\n1. ", "A scenario where Reddit India had tweeted about Flipkart that an Amazon carton was found in a Flipkart office and Flipkart replied to RedditIndia that it had recycled the box into a dustbin. ", "As an Amazon representative how will you reply using a tweet below 100 words and a hashtag.", "\n\nWriting Ability Test : 2 Topics were given to us and we had to write it for about 20 minutes. ", "There was no breakup for specific sections. ", "The first image was of a lady serving food to her daughters and her husband is what I perceived from the picture. ", "You could relate it to the picture below.", "\n\nWe had to think on it for 1 minute, and write down the answers of the questions in the next 4 minutes. ", "And the other topic for the WAT was demonetisation which we had to write 250+ words in 20 minutes.", "\n\nGE (or rather I should say GD disguised as GE) : We had a 12 member group and there were 2 panelists. ", "The topic given to us was, “Should MP / MLAs have basic educational qualifications?”", "\n\nI would say it turned out more into a fish-market than a proper GD with everyone putting in their efforts so as to keep their point in front of the panelists. ", "There was 0 to less co-ordination among the team members and everyone tried to shout as much as possible. ", "As if one shouts, they think that they will be applauded by the panel even if making irrelevant statements *slow-claps*.", "\n\nPersonal Interview : General questions about myself. ", "Why the switch from IT to MBA? ", "What are the technical aspects of a business? ", "Why do you think an MBA will help you in the long run? ", "What do you know about international business? ", "What do you think about demonetisation? ", "Why SIIB Pune?", "\n\nSo it has been three- four months where I haven’t posted a single blog post yet. ", "I might have got time, but I probably utilised the time for some other purposes. ", "Though in these three four months, I did realise that I wasn’t really a perfect fit for the city of Calcutta. ", "But, I did grow a liking for this city in these past few months. ", "I came back home, Mumbai, in the month of August. ", "My final semesters had just ended and I didn’t probably have the time to even attend my college farewell. ", "Not that I was eager to attend it, but I had to wish goodbye to a few friends, which I didn’t.", "\n\nI had attended a rural festival, which I will be sharing with you of course! ", "As a narrator I might face difficulties in explaining how vibrant and glorious the rural areas of West Bengal are, but I would definitely try my best in explaining. ", "Amidst the race to be the best, I find myself lost somewhere in this crowd. ", "I do feel at times, why am I even a part of this rat-race? ", "But, to survive in this world, one has to have a decent amount of qualification and the ability to survive using that qualification. ", "Charles Darwin, you’ve nailed it since 1854!", "\n\nNot only that, it has been already 6+ months that I faced a failure, and it literally took me 3 months to get over it. ", "But now, it seems as a stepping stone as days pass by. ", "People tend to give up after facing setbacks, but to be honest, even if I try I cannot be one of them. ", "I know someday, I will have my share of success and I will shine someday.", "\n\nSo let’s come back to the main topic: The fine line between aspirations and dreams. ", "Aspiration is something, like (of course, don’t go into the medicinal meaning) you aspire to be in one of the top-most B-Schools of the country. ", "But you dream to be rich. ", "Lets explain this mathematically. ", "Aspiration is a function of dream. ", "Say aspiration is x, then dream is f(x). ", "You can prove me wrong as well, but this is my perception towards aspiration.", "\n\nThese few months have been a bit hectic. ", "Life played many games with me, and in retaliation, I too accepted a few challenges and lost some of them. ", "But, in the end, I learnt that I needed to believe in myself. ", "I needed to learn more, concentrate more, and set realistic goals and aspirations instead of jumping to dreams. ", "So, you can consider it as a note which I wrote to myself, or as a narration from me to you, the reader.", "\n\nAh, long time no posts on the blog. ", "It must be surprising to all of you whether I quit blogging or not. ", "Of course I wouldn’t. ", "But I was a little busy giving exams and finally I got some free time to write about a small trip which I took a few days ago.", "\n\nI spent four years of my life in a remote place called Kolaghat situated in Purba Medinipur district. ", "It serves as a border for the two districts of Howrah and Purba Medinipur. ", "It falls en route from Kolkata to Kharagpur. ", "But I had the realisation in my final year that I should be travelling. ", "After all, trips taken in the final year remain memorable to the students. ", "Not that my college life was beautifully amazing, but it was considerably peaceful in the remote area of Kolaghat. ", "Mostly surrounded by natural beauty and of course, some rare birds.", "\n\nSo one fine day, we were sitting on the terrace and discussing pre-independence Bengali Literature. ", "The first name came to our mind was Sarat Chandra Chattopadhyay. ", "As explained by Wikipedia, Sarat Chandra Chattopadhyay was a great Bengali novelist and he is the most plagiarised Bengali author till date. ", "Suddenly, a friend suggested, why not visit his house because we are so nearby to his place. ", "And so, we left one fine afternoon, in search of Sarat Chandra Chattopadhyay’s house.", "\n\nThe friend knew half the route but the remaining half he forgot. ", "Why? ", "Because he was a child when he had visited Sarat Chandra’s house. ", "So according to his directions, we got down on Deulti Station which was the starting point to Sarat Chandra’s house.", "\n\nThe direction towards Sarat Chandra’s house at Samtaber\n\nAfter getting down, we headed towards the main road i.e NH6. ", "Now came the searching part. ", "We asked the locals about the location of Sarat Chandra’s house. ", "They guided us to a nearby auto stand from where we had to catch an auto to his house. ", "So we went to the auto stand, and found out that we were in the right direction. ", "The auto guys charged 100 rupees for a round trip to the auto stand from Sarat Chandra’s place. ", "We didn’t negotiate else it could have come down to 80 rupees. ", "Nevertheless, we left from the auto stand and got down at Sarat Chandra’s house.", "\n\nThe entrance to Sarat Chandra’s house\n\nThen we entered his house. ", "Trust me, the peace and serenity is rarely to be found elsewhere. ", "I know the picture is hazy but I was awestruck in the beauty of the place. ", "The place is mesmerising and simple.", "\n\nThe caretaker, Mr Dulal Manna was an old man, in his 70s. ", "He started us to explain, by suggesting us to go to the first floor and check out the scenery from the place.", "\n\nThe river used to flow in front of the house, during Sarat Chandra’s younger days\n\nWe went on the first floor. ", "The beauty is simply incomparable. ", "The rooms were locked but the caretaker would have opened them on our request. ", "We did not ask the caretaker to open them for us. ", "Then we got down and then the caretaker showed us the place where Sarat Chandra used to sit, and write his novels, and some other places in the home where Netaji Subhash Chandra Bose had come to visit him. ", "The home was beautifully maintained by the old caretaker and he devoted his life in maintaining the house.", "\n\nSarat Chandra’s writing desk\n\nHe stayed in the house for the past 40 years maintaining it. ", "The house has been well maintained and preserved. ", "The house gained Heritage of National Status since the year 2007 and the Government has been trying to maintain the house by helping the caretaker.", "\n\nThe backyard\n\nThen we bid goodbye to the caretaker and due to his photo shy nature we couldn’t click a picture with him.", "\n\nA day well spent, at Sarat Chandra Chattopadhyay’s house. ", "I must say it was a beautiful and serene experience. ", "If you are travelling to Digha, please do spare some time and visit this National Heritage site. ", "Thank me later.", "\n\nMost of us find inspiration around us, in the form of good samaritans. ", "And, everyone has that specific set of people who give us inspiration. ", "Inspiration to do good, and help the mankind in the slightest way possible. ", "Yet, a handful of us, have the guts to create examples which we could narrate in our daily lives.", "\n\nI also had my own set of people who give me inspiration, not only on occasional basis but also on a daily basis. ", "But Siddesh Manjunath, this 10 year old boy, did something, which was enough for me to get inspired for the whole year. ", "I’ll explain in the upcoming paragraph, how did this boy inspire me!", "\n\nSo, this boy, Siddesh Manjunath, worked with his father at a tea shop in Avaregere village in Davangere district, Karnataka. ", "He had studied upto class 5 and then due to certain unfavourable circumstances, he joined his father so that he could add to the household income. ", "And, on his way, from his house to his father’s tea shop, there is a railway track which has to be crossed in order to reach his father’s tea shop.", "\n\nOn the 17th of November, like any other day, he was going to his father’s tea stall to help him. ", "But when he went near the tracks to cross them, he saw that there was a big gap in the railway tracks. ", "He ran furiously towards his dad’s shop and gathered some villagers who, on inspection realized that the gap was serious and there can be serious consequences if not paid attention.", "\n\nAmidst the chaos, Siddesh heard the honking of a train coming from the opposite side. ", "Without giving any second thought, he rushed towards the train with his red T-Shirt waving in the air. ", "At a distance, luckily the driver spotted the red T-shirt and stopped the train immediately. ", "A mishap was averted. ", "And the lives of 800 people were saved that day.", "\n\nThough, if it were not for this little 10 year old boy, there would have been a big accident which would have culminated into loss of lives. ", "Also, if it were not for his courage, the train would not have stopped, and the accident could not have been avoided.", "\n\nObviously, if a 10 year old boy, can save lives of 800+ people, I’m sure, that we, as individuals who have access to our basic necessities can do far more than this little boy has done. ", "Since I read the incident, I felt inspired. ", "And not to mention, this was the best inspiration I could ever get, from someone.", "\n\nI was in the 6th grade during that time. ", "I still remember, on the 26th of July, we had a half day. ", "Our school had instructed our parents to take us along with them. ", "My dad had came to pick me up from the school. ", "I was happy then, unknown to the situation happening in Mumbai. ", "I came back home, only to see dad getting ready for office. ", "Till the time, I could understand and tell dad not to leave the home due to the torrential rainy conditions in Mumbai, my dad had already left for office.", "\n\nWhenever I hear of floods, the very first thing comes to my mind is 2005 Mumbai floods. ", "That was a very devastating phase for the whole of Maharashtra. ", "The casualties were over 1000 along with a lot of cattle killed during the floods. ", "Trains came to a standstill and the skies were totally dark.", "\n\nThen, in recent days, I noticed that there was a very similar situation in Chennai. ", "Universities and apartments were filled with water. ", "People were in chaos. ", "Lack of food and water made situations more worse. ", "Here I’d like to share an anecdote about a person I met on my return flight to Kolkata.", "\n\nSo, the person is a Neuro-surgeon in Singapore and his family was based in Chennai. ", "After a few greetings and exchanges, I came to know that he was going to Kolkata to attend a conference. ", "And from there he’ll be travelling to Chennai to visit his family. ", "After a few talks, I realized that this person had paid 4X the fare to Chennai for a ticket to Coimbatore. ", "Why? ", "Because most of the private airlines were charging excessively for the airports which were nearby to Chennai. ", "He told me that his family was fine, because they were living on the fourth floor. ", "But the ground floor was totally inundated with water. ", "Water was about to reach the first floor as well, but luckily it didn’t.", "\n\nI could see that he wasn’t complaining. ", "Rather he was happy that his family was safe and sound. ", "He just wanted to go home back, to be with his family members.", "\n\nI’d like to raise only one question to my readers. ", "Couldn’t be the flood averted? ", "Weren’t the measures enough to avoid the grave conditions we are seeing today? ", "Is it not possible to avoid the calamities?" ]

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[ "Generations of Russians — even the young — are aware of Raj Kapoor and his cinema and regard him as Bollywood’s numero uno\n\nRanbir Kapoor might be setting hearts aflutter back home in India, but Russia still has just one rockstar Kapoor — and that’s his grandfather.", "\n\nMore than 29 years after his death, Showman Raj Kapoor continues to rule Russia as the king of the Indian film industry.", "\n\nGenerations of Russians — even the young — are aware of Raj Kapoor and his cinema and regard him as Bollywood’s numero uno hero despite the new crop of Indian actors who have made a global mark.", "\n\n“Raj Kapoor for sure still holds the title of the Indian film industry’s king here in Russia. ", "He is the number one association we have when we talk about Indian cinema,” said 25-year old Annie Vo.", "\n\nMoscow-born Ms. Vo, of Vietnamese origin, stressed he was her “favourite” because of the true to life characters he played. “", "His characters are very down to earth, true to life and genuine. ", "Anybody can connect to his films, cutting across age, race, education and social status,” she told PTI.", "\n\nThe creative director at Bardelhi restaurant, which serves Indian food and frequently screens Hindi films at its special movie nights, said she had heard of Ranbir and seen Barfi!, ", "but it is Raj Kapoor’s legacy that lingers.", "\n\n“Call me conservative, but I relate more to Raj’s era of actors and their level of class,” she said.", "\n\nThe Fourth International Film Festival Moscow at which India was represented by Producer-actor, Raj Kapoor. ", "Photo taken on arrival of Raj Kapoor at Moscow Airport shows Soviet film actress Clara Luchko welcoming the Indian film star. ", "| Photo Credit: PIB\n\nRaj Kapoor, who passed away aged 63 in June 1988, acted in a series of classics such as Shree 420 and Awara and is still widely known as “the greatest showman of Indian cinema”.", "\n\nMany in Moscow stressed it was his cinema that introduced Russians to Indian films, which was why he continued to wield such magic.", "\n\nNozima Karimova, a PR firm employee, recalled the reception the actor was accorded at the Tashkent film festival. “", "People spoke of his visit like he was higher than any head of state or any celebrity in the world,” she said.", "\n\nMs. Karimova said she knew the Kapoor family was a part of the Indian film world, but was “not certain” about his grandchildren. “", "For, even today, I watch retro movies of Indian cinema,” she said. ", "Ms. Karimova said she often watched Indian films on Russian Zee TV, aired on many cable networks here dubbed in Russian or with subtitles.", "\n\nMs. Vo added that apart from Kapoor, people liked Mithun Chakraborty, Shah Rukh Khan, Aishwarya Rai and Priyanka Chopra.", "\n\nRaj Kapoor (second from left) talking to Mr. S. Bondarchuk, Soviet film producer (extreme left), I. Skobtseva, Soviet Film actress, Mr. G. Aleksandrov, Soviet film-producer (extreme right). ", "| Photo Credit: PIB\n\nDilmurad, a taxi driver in his 50s, said Barood, a 1976 film featuring Rishi Kapoor, and the 1969 Rajesh Khanna-starrer Aradhana were among his favourites. “", "I went to see Aradhana one morning. ", "I liked it so much that I watched it three times the same day,” he said.", "\n\nSome of the newer releases have their share of viewers, too. ", "Ivan Parfenov, a sports media executive, said he was not a fan of Indian cinema, but was “greatly impressed” by the Rajinikanth-starrer, Robot.", "\n\n“One evening after a few drinks, a few friends and I were at home watching funny videos on YouTube, when a friend put on a clip from Robot. ", "After watching it for 30 seconds I exclaimed that we had to download and watch it,” he said.", "\n\nLeonid Parfenov, creator of a TV and book series called Namedni, year-by-year accounts of important developments in culture and everyday lives in Russia, mentions the role of Raj Kapoor in an article on the popularity of Indian cinema.", "\n\n“It all began with Raj Kapoor, the lead actor in Awara and his songs... The rules of the genre never change: immense love, sweet-sounding songs cause charm and tears,” he wrote in a 1976 chapter titled Seeta and Geeta\n\nTalking about the reason Indian films were popular in Russia, Mr. Parfenov said, “I often saw women on their way from a film in tears and smiling and saying things like ‘Now this is a film about life’.”" ]

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"start": 3851 }, { "analysis_explanation": null, "end": 3988, "entity_type": "DATE_TIME", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 3984 }, { "analysis_explanation": null, "end": 4009, "entity_type": "PERSON", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 4004 }, { "analysis_explanation": null, "end": 4028, "entity_type": "PERSON", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 4014 }, { "analysis_explanation": null, "end": 4052, "entity_type": "NRP", "recognition_metadata": { "recognizer_identifier": "SpacyRecognizer_140094861343280", "recognizer_name": "SpacyRecognizer" }, "score": 0.85, "start": 4046 }, { "analysis_explanation": null, "end": 4081, "entity_type": "LOCATION", 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[ "Which is the closest to -1? ", " (a) j (b) -0.1 (c) -5\nb\nLet i be 0 + 3/(6/4). ", "Let k be 1 - i - 9/6. ", "Which is the closest to 1? ", " (a) k (b) -4 (c) 4\nc\nLet j = -0.1 - 0.1. ", "Let k = 2/103 - -188/927. ", "Suppose -2*g = 3*g. ", "What is the nearest to g in k, -1/3, j?", "\nj\nLet v = -9.5 - -9.4. ", "Which is the nearest to v? ", " (a) 0.1 (b) -0.9 (c) 2/9\na\nSuppose 0 = 4*j - 2*n - 14, j - 11 - 15 = 5*n. ", "Let g be (j + 0)*(0 - 2). ", "Let f = -30.2 + 31.2. ", "What is the closest to f in 0, -1, g?", "\n0\nLet o = 69 + -68.7. ", "What is the nearest to -2/41 in 3/2, -0.4, o?", "\no\nLet l = 6 + -10. ", "Let r(g) = g**3 + 6*g**2 + 4*g - 1. ", "Let t be r(-5). ", "Let d = t + l. Which is the nearest to d? ", " (a) -2 (b) -3 (c) -2/5\nc\nLet m = -0.14 + -3.26. ", "Let h = m + 3. ", "Let t be (6/15)/(14/10). ", "Which is the closest to -0.1? ", " (a) h (b) t (c) -2\na\nLet t(f) = -f + 4. ", "Let y be t(4). ", "Let x = 104.4 + -104. ", "What is the nearest to 0.1 in y, -2, x?", "\ny\nLet n = -2.1 - -2.1. ", "Let h = 0.1 + n. What is the nearest to h in 5/2, -2/15, -5?", "\n-2/15\nLet a be ((-1)/(-3))/((-1)/(-2)). ", "Suppose -4*x + 9 = -2*x - 3*d, 0 = 3*d + 15. ", "What is the nearest to 1/3 in 4/3, a, x?", "\na\nLet z = 6/29 + -56/551. ", "Let s = 3 - 3. ", "Let i = 3 + s. Which is the closest to 1/3? ", " (a) z (b) i (c) -2\na\nLet t = -1 + 2. ", "Which is the closest to t? ", " (a) 0.1 (b) 0.5 (c) -4\nb\nLet z be 1/(-12) - (-4)/(-16). ", "Let g = -0.4 + -4.6. ", "What is the nearest to z in -4, g, 0.1?", "\n0.1\nLet i = 424 - 424.2. ", "Let f = -89/4 - -793/36. ", "Let o = 1 - -2. ", "Which is the nearest to 1? ", " (a) f (b) o (c) i\nc\nLet i = -2 + -2. ", "Let n = i + 3. ", "Let x = 0.4 + -0.3. ", "Which is the closest to -1? ", " (a) x (b) 5/6 (c) n\nc\nLet l = 88/65 - 6/5. ", "Which is the nearest to 0? ", " (a) -0.1 (b) l (c) -1/3\na\nLet h = 37 + -39. ", "Which is the closest to 3/7? ", " (a) 0.3 (b) h (c) 10\na\nLet o = 0 + -0.3. ", "Let k = 1.7 + -2. ", "Let w = k - o. Which is the closest to w? ", " (a) 4 (b) -3 (c) 5\nb\nLet y = -3 - -3.4. ", "What is the closest to -1 in 4/7, y, 1/5?", "\n1/5\nLet q be (3/(-6))/(-1 + 33/30). ", "Let d = 0.4 + -0.4. ", "Which is the nearest to d? ", " (a) -0.2 (b) q (c) -4\na\nSuppose 0 = 2*a - 4*a + 2. ", "Let k(v) = -6*v - 1. ", "Let b = 4 + -5. ", "Let c be k(b). ", "What is the closest to a in -1, c, -2/13?", "\n-2/13\nLet n = 6 + -5.7. ", "Let u be 2/(-6) - (-10)/(-6). ", "Let l = 0 - 0.1. ", "Which is the nearest to l? ", " (a) -5 (b) u (c) n\nc\nLet i(d) = d**3 + 9*d**2 + 10*d + 12. ", "Let a be i(-8). ", "What is the nearest to 2 in 2, -0.5, a?", "\n2\nLet s = 4 - 4.4. ", "Let h(q) = -q**2 + 3*q - 3. ", "Let r be h(2). ", "Let f = 1468/15 - 98. ", "Which is the nearest to -1/2? ", " (a) r (b) f (c) s\nc\nLet f = -58 + 524/9. ", "Which is the nearest to -1? ", " (a) 5 (b) f (c) -5\nb\nSuppose 0 - 36 = -4*l. ", "Let f = 4 - l. Let t be (-8)/(-6)*15/50. ", "What is the closest to t in f, -0.2, -4?", "\n-0.2\nLet a = -1.1 - -0.1. ", "Let h = a - -6. ", "Suppose -4*y - 2*f + 8 = 0, 4*y + f = -3*f + 16. ", "What is the closest to y in h, -0.5, -1/3?", "\n-1/3\nLet q = -0.67 + 0.07. ", "Which is the nearest to q? ", " (a) 1/4 (b) -2 (c) -2/9\nc\nLet t = 4.4 - 0.4. ", "Which is the closest to 1/4? ", " (a) -2 (b) 5 (c) t\na\nLet t = 0.43 - 0.03. ", "Which is the nearest to 1? ", " (a) 4 (b) t (c) 3\nb\nLet d = 3 + -4. ", "Let a = 4 + -3.6. ", "Let k = a + -0.2. ", "What is the nearest to -0.1 in d, 1/2, k?", "\nk\nLet p(n) = n**2 + n + 3. ", "Let q be p(0). ", "Let x = 5.4 - 0.4. ", "Let r = 213/4 + -53. ", "What is the nearest to r in q, x, 1/2?", "\n1/2\nLet p = 0 - 0. ", "What is the closest to p in 4/5, -5/4, 2?", "\n4/5\nLet x(f) = 4*f - 4. ", "Let b(u) = 4*u**2 - 1. ", "Let n be b(1). ", "Let h be x(n). ", "Let d be h/(-4) + (-10)/(-3). ", "What is the closest to -2/5 in 1, 2, d?", "\n1\nLet j = 1.04 - -0.16. ", "Let q = 1.5 - j. What is the closest to q in -4, 0.4, -3?", "\n0.4\nLet i be (-1)/3 - 14874/(-153). ", "Let j = -97 + i. Which is the closest to 0.2? ", " (a) 5 (b) j (c) 4\nb\nLet w(m) = -m**2 + 9*m + 8. ", "Let l be w(10). ", "Let i(q) = -q**3 - 4*q**2 - 4*q - 4. ", "Let r be i(l). ", "Which is the closest to -1? ", " (a) -0.5 (b) r (c) 3/7\na\nLet a = -1.4 - -1.2. ", "What is the nearest to 7 in a, 2/5, -4?", "\n2/5\nLet w = 2 + -2.3. ", "Let k be (-2)/(6/10 - 1/1). ", "What is the closest to -0.2 in k, w, 0.4?", "\nw\nLet n = 6 + -12. ", "Let x = n - -10. ", "Which is the nearest to 0.1? ", " (a) x (b) 5 (c) 2/7\nc\nLet c be (-1 - (-1 - 0))/(-1). ", "Let v = 18 + -52/3. ", "Let b = -3.4 + -0.6. ", "What is the closest to c in v, -0.3, b?", "\n-0.3\nLet r = 0.489 + -4.479. ", "Let p = 0.01 - r. Let d = 2 - 0. ", "Which is the closest to -2/5? ", " (a) -5 (b) p (c) d\nc\nLet j = 2 - 4. ", "Let p(w) = 2*w**2 + 18*w + 3. ", "Let z be p(-9). ", "Which is the nearest to -0.1? ", " (a) j (b) -4 (c) z\na\nSuppose 0 = -i + 2 - 3. ", "Which is the closest to -0.1? ", " (a) -1/4 (b) i (c) -0.2\nc\nLet q = 52 + -52. ", "Suppose -3*m - 8 + 1 = -y, -y = -m - 5. ", "Which is the closest to m? ", " (a) q (b) 0.2 (c) -0.3\nc\nLet i = -0.11 + -5.89. ", "Let j = -0.19 + -0.21. ", "What is the nearest to 1 in j, 5, i?", "\nj\nLet n(s) = s**3 - 10*s**2 + s - 5. ", "Let j be n(10). ", "Let x = j + -1. ", "Suppose -c - 11 = -x*o, -c = 4*c - 2*o - 17. ", "What is the closest to 1 in 2/7, c, 2?", "\n2/7\nSuppose v = -0*v + 2. ", "Suppose -t - v = -3. ", "What is the closest to t in -2/9, -0.3, 3?", "\n-2/9\nLet k = -3.9 + -0.1. ", "Let v = -1 + 6. ", "Let j = v - 5. ", "What is the closest to j in -0.5, -5, k?", "\n-0.5\nLet a = 0.09 + 0.71. ", "Let h = a - 0.5. ", "Let c = 0.2 + -0.2. ", "What is the nearest to c in h, 2, -0.2?", "\n-0.2\nLet t = -0.42 + 0.29. ", "Let g = 0.37 - t. Which is the closest to 1? ", " (a) g (b) -4 (c) 0\na\nLet d = -2.58 + 2.1. ", "Let u = d - 0.02. ", "Which is the nearest to 1? ", " (a) -3/4 (b) 3 (c) u\nc\nLet m = 0.1 - -0.9. ", "Let r be 23744/204022 - 2/13. ", "Let h = r + -4/59. ", "Which is the nearest to m? ", " (a) -2 (b) 0 (c) h\nb\nLet r be ((-1)/(-2))/((-25)/(-10)). ", "What is the closest to 1 in r, -0.3, 1/11?", "\nr\nLet x = -1 - -1.6. ", "Let k = x - 2.7. ", "Let y = 2 + k. Which is the nearest to -0.1? ", " (a) -0.4 (b) y (c) 1/8\nb\nLet i be 2/(-4)*112/10. ", "Let g = i - -181/35. ", "Let w be (-96)/(-140) - (-1)/(15/(-6)). ", "What is the closest to -1/2 in g, w, 1?", "\ng\nLet o = 81 - 85. ", "Let k = -3.1 + 3. ", "Let u = -6 + 10. ", "Which is the nearest to k? ", " (a) o (b) -5/2 (c) u\nb\nLet g = -0.6 + 2.6. ", "Let f = g + -1.8. ", "Let i = f - 0.1. ", "What is the nearest to -0.1 in -1/2, i, 0.5?", "\ni\nLet u = -3.07 - -0.07. ", "Suppose -g - 2*g + 3*n = -6, -5*g = 4*n + 8. ", "Suppose g = -2*t - 0*t. ", "Which is the nearest to t? ", " (a) u (b) -0.4 (c) 0.5\nb\nLet a = 9 - 9.2. ", "What is the nearest to 1 in 6, 3, a?", "\na\nLet z(p) = -p**2 + 14*p + 3. ", "Let d be z(14). ", "Which is the nearest to 0? ", " (a) -5/6 (b) d (c) -0.8\nc\nLet q = -5.8 + 6. ", "Let v be 2/(0 + 8/(-4)). ", "Let u be ((-1)/(-2))/(3/2). ", "Which is the nearest to u? ", " (a) q (b) v (c) -0.3\na\nSuppose -5*c + 8 = -7, 3*d = 2*c - 6. ", "What is the nearest to 0 in d, 8, 3?", "\nd\nLet n = -83/4 + 21. ", "Let m = 9 - 8. ", "Which is the closest to m? ", " (a) 0.5 (b) n (c) 5\na\nLet j be -3 - (-1 - -4 - 6). ", "Let p be ((-843)/63)/((-1)/1). ", "Let q = p - 41/3. ", "Which is the nearest to j? ", " (a) q (b) -2 (c) 1\na\nLet y = -2.7 - -0.7. ", "Let p = 0.391 + -4.501. ", "Let w = -0.11 - p. Which is the nearest to -1? ", " (a) y (b) w (c) 2/9\na\nLet o = -22 + 22.2. ", "Which is the closest to o? ", " (a) -0.2 (b) 3 (c) 0\nc\nSuppose -z + 19 = -3*a + z, -3*a - 21 = -3*z. ", "Let i = -1.1 - -1. ", "Let r be (2 - 1)/(5*(-12)/30). ", "What is the closest to i in a, 0, r?", "\n0\nSuppose 3*v + 0 - 15 = 0. ", "Let m = -0.857 + -0.113. ", "Let l = 0.03 - m. Which is the nearest to l? ", " (a) v (b) -0.2 (c) 1/2\nc\nSuppose -16 = 4*w + 4*j, -5*j - 10 = -w + 10. ", "Which is the nearest to w? ", " (a) 4 (b) 1/3 (c) -5\nb\nLet j be (-2)/6*(-6)/(-10). ", "Suppose -p = -0*p + 74. ", "Let f = p + 519/7. ", "What is the closest to -1 in j, -2, f?", "\nj\nSuppose -3*n = 2*s + 4, 0 = -s + 2*s + 2. ", "Suppose 6 + 2 = -4*t. ", "Let o be t - 0 - 22/(-6). ", "What is the closest to 1 in -2, n, o?", "\no\nLet r = 2.2 - 2. ", "Let f = -15 - -11. ", "Let j = -2.787 - 0.213. ", "What is the nearest to 2/7 in r, j, f?", "\nr\nLet r(y) = -y**2 + 3*y - 4. ", "Let i be r(3). ", "Which is the closest to 2/5? ", " (a) i (b) -0.3 (c) 0.1\nc\nLet p be 6/4 + -4 + 3. ", "Let s = 8 - 7.9. ", "What is the nearest to 3 in -0.1, s, p?", "\np\nLet n = -85/14 + 46/7. ", "What is the closest to n in -7, -5, 5?", "\n5\nLet p = -32 - -31.6. ", "Which is the nearest to 1/3? ", " (a) 3 (b) p (c) 0.3\nc\nLet q = 19 + -37/2. ", "Let s = 0.2 + -0.3. ", "Let t = -9.2 - -5.2. ", "What is the closest to s in q, 0.4, t?", "\n0.4\nLet x = 0.09 - -0.21. ", "Which is the closest to -0.1? ", " (a) 0.5 (b) 1/11 (c) x\nb\nLet x = -0.4 - 0. ", "Let s = 0.38 + -0.68. ", "Which is the nearest to 2/5? ", " (a) s (b) 0.1 (c) x\nb\nLet l = 63.5 + -49. ", "Let q = l - 19. ", "Let w = q - -4." ]

{ "pile_set_name": "DM Mathematics" }

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[ "Can some one please help me with the Spiral Geographic Society Archives.", "\n\nIf some one can please meet me there in the realm Unicorn on Friday the fifthat 3:30pm. ", "My wizards name is Erica Griffinpetal level 48 storm wizard\n\nThanks\n\nAww. ", "I would really want to help. ", "Is that in Celestia? ", "Or is it a quest from Celestia? ", "But just when I found this post, lol the time JUST passed. ", "Maybe you can change the time. ", ":D Is it a quest only tower or a teleportal dungeon/tower? ", "Though I am only in the Grotto in Celestia. ", "Please reply if you still appreciate help from me. ", "Thanks.", "\n\nIt is a quest involving Celestia but I got it from Halston Balstrom. ", "The tower is in Marlybone. ", "I think it is a quest only dungeon but can not teloport to people in the dungeon. ", "Tell me when and what realm is best for you thanks.", "\n\nIt is a quest involving Celestia but I got it from Halston Balstrom. ", "The tower is in Marlybone. ", "I think it is a quest only dungeon but can not teloport to people in the dungeon. ", "Tell me when and what realm is best for you thanks.", "\n\nNope, you can't port in- when you die, or leave to get potions, you have to come back through the front door alone. ", "If someone new joins you, the instance will reset and you'll have to start over.", "\n\nIf you're looking for another teammate, I've already completed this and wouldn't mind helping you- I'm in the Atlantic time zone, and usually on the Lincoln server (or Wraith, if it's full). ", "If you've since completed it and don't need the help anymore, then best of luck with your other adventures. :)" ]

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[ "Print Club London | Blisters 2017 Submission Call\n\nposted by Amber WeaverApril 24, 2017\n\nNaturally, we’re huge fans of Print Club London, one of the leading printmaking studios in London featuring an assortment of hugely talented print artists and print technicians alike. ", "They’re currently holding the sixth edition of Blisters, their screen-printed poster exhibition and it’s going to be be bigger and better than ever. ", "The show will also include the exciting launch of their first book ‘Screen Printing the Ultimate Guide – From Sketchbook to Squeegee’ published by Thames & Hudson, who are also the same publishers for our People of Print book. ", "Print Club London present their submission call for this exciting exhibition, read on to find the details and how to submit.", "\n\nBlisters: Paperback Edition – The Brief\n\nThis Year, it’s ‘Blisters: The Paperback Edition’ based on BOOKS and will be an entirely hand-pulled screen-print show. ", "Grab inspiration from your favourite book, favourite author or even a favourite line from an iconic book.", "\n\n1. ", "Submit a poster in your own style inspired by your favourite book, favourite author or a favourite line from an iconic book\n\n2. ", "The catch is that, you cannot use the name of the book or author! ", "Use of other text is allowed of course, but this should stand alone as an image/scene/typography\n\n3. ", "Most importantly, your work must be COMPLETELY new and original for this project and never seen before! ", "We will not accept any submissions that are displayed anywhere else, including personal blog or portfolio.", "\n\n4. ", "The artwork specification – It needs to be in B2 format (500 x 700mm) but, can be portrait of landscape.", "\n\n5. ", "When sending the low-res file please ensure it’s saved ‘YourName.jpeg’ and you state in your email the book/author/quote your design is inspired by\n\n6. ", "Submissions must be sent as a low-res .jpeg file to postershow@printclublondon.com and the deadline is Friday 5th May 2017\n\nSuccessful submissions will be allowed to use Print Club London’s printing space for free. ", "Selling at £50 a pop from a range of 50 talented artists, Blisters 2017 will most certainly not one to be missed.", "\n\nSubmissions must be sent as a low-res .jpeg file to postershow@printclublondon.com and the deadline is Monday 8th May 2017.", "\n\nFAQs\n\nQ: If I have book artwork that I’ve used for previous projects, can I reprint this?", "\nA: The artwork for your submission should be original. ", "If there are elements from previous projects this is fine but the submission should appear to be new as a whole.", "\n\nQ: Does the “poster” need to contain text or type?", "\nA: No, this is up to you. “", "Poster” is the format size paper and the term we use to describe this. ", "You can either:\n1. ", "Create artwork that is composed of an illustration or design inspired by a book, author(s) or line from a book\n2. ", "Submit an entry composed entirely of a typographic design (as long as it does not mention the book title/authors name)\n3. ", "Mix the two!", "\n\nQ: If I have several designs, can I submit more than one?", "\nA: You can submit as many designs as you like!", "\n\nQ: When the artwork is printed and signed, do we also need to put a title to it? ", "For example; The book title, author name or not, as it might give the game away?", "\nA: We haven’t decided on this yet. ", "Just email us your entries and let us know your inspiration for the artwork!", "\n\nQ: How much of that goes to the artist?", "\nA: It’s a 50/50 split between the artist and Print Club London. ", "The artist will receive 50% commission as will Print Club London\n\nQ: What happens to prints, which remain unsold?", "\nA: All prints are sold via Print Club London on our online gallery after the show.", "\n\nQ: Do they remain the property of the artist or of London Print Club?", "\nA: They’re owned by the artist/designer, but we retain the right to be the only seller of these prints as they are from a show we have curated.", "\n\nQ: If ownership remains with the artist, can the artist resell them elsewhere – for example, through independent shops?", "\nA: No, the prints can only be sold via Print Club London\n\nQ: If the artist is not producing the prints themselves will Print Club be producing them?", "\nA: The artists are liable for the printing the work. ", "They can use our studios for free if they know how to print! ", "If artists are unable to print, they can ask Tuckshop our bespoke printing service who, will offer a discount for all Blisters artists. ", "This Year we’re sponsored by G.F Smith who are supplying all the paper for the show.", "\n\nQ: Who owns the rights to the image?", "\nA: Artists always own the rights to their work. ", "However a rule of Blisters is that the work cannot be reproduced at a later date as another screen print or giclée\n\nQ: Can the artist/designer use the imagery for, their own products again? ", "For example, using the imagery for t-shirts, greetings cards etc.", "\nA: No, we ask that the image to be just for the show. ", "This is what makes it ‘limited edition’ and this is a key part of Blisters." ]

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[ "Questa Solar Facility\n\nThe Questa Solar Facility is a 1.17 MWp (1.0 MWAC) concentrator photovoltaics (CPV) power station in Questa, New Mexico. ", " Upon its completion in late 2010, it was one of the largest CPV facilities in the world, and the first utility-scale installation of Concentrix Solar technology in the United States. ", " Annual electricity production is expected to average about 2.1 GW·h, and is being sold to the Kit Carson Electric Cooperative under a 20-year power purchase agreement (PPA).", "\n\nFacility details\n\nThe facility was built by Chevron Technology Ventures on a reclaimed site previously used for the collection and storage of molybdenum mine tailings. ", "It consists of 173 dual-axis-tracking CX-P6 systems, each of which supports 90 CX-75 CPV modules. ", " Each module contains 200 fresnel lens to concentrate sunlight 500 times onto multijunction photovoltaic cells. ", " These features enable higher efficiencies - about 40% for cells and 27% for modules - than other photovoltaic technologies.", " \n\nEach of the 173 trackers has its own grid-connected inverter, which also serves as the control system of the mechanical tracking and as the communication port with its own IP address. ", "The inverter technology was developed by Fraunhofer ISE in cooperation with Concentrix Solar and has an efficiency of 96%. ", "For control and monitoring, the facility also includes DNI sensors, GNI sensors and wind sensors. ", "A detailed analysis of the system and power plant performance can be made based on data that is taken at one-minute intervals.", "\n\nElectricity production\n\nSee also\n\n Alamosa Solar Generating Project\n Hatch Solar Energy Center\n Newberry Springs CPV Power Plant\n List of photovoltaic power stations\n Renewable energy in the United States\n Solar power in New Mexico\n Solar power in the United States\n\nExternal links\n VIDEO: Soitec CPV Solar Power Plant near Taos, NM\n VIDEO: Chevron Builds Solar Field in New Mexico\n Field Experience Of Concentrix Solar's CPV Systems In Different Climatic Conditions\n\nReferences\n\nCategory:Energy infrastructure completed in 2010\nCategory:Solar power stations in New Mexico\nCategory:Photovoltaic power stations in the United States" ]

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[ "/*\n * Copyright (c) 2005, 2012, Oracle and/or its affiliates. ", "All rights reserved.", "\n * DO NOT ALTER OR REMOVE COPYRIGHT NOTICES OR THIS FILE HEADER.", "\n *\n * This code is free software; you can redistribute it and/or modify it\n * under the terms of the GNU General Public License version 2 only, as\n * published by the Free Software Foundation. ", " Oracle designates this\n * particular file as subject to the \"Classpath\" exception as provided\n * by Oracle in the LICENSE file that accompanied this code.", "\n *\n * This code is distributed in the hope that it will be useful, but WITHOUT\n * ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or\n * FITNESS FOR A PARTICULAR PURPOSE. ", " See the GNU General Public License\n * version 2 for more details (a copy is included in the LICENSE file that\n * accompanied this code).", "\n *\n * You should have received a copy of the GNU General Public License version\n * 2 along with this work; if not, write to the Free Software Foundation,\n * Inc., 51 Franklin St, Fifth Floor, Boston, MA 02110-1301 USA.", "\n *\n * Please contact Oracle, 500 Oracle Parkway, Redwood Shores, CA 94065 USA\n * or visit www.oracle.com if you need additional information or have any\n * questions.", "\n */\n\n/*\n */\n\n/*\n * (C) Copyright Taligent, Inc. 1996, 1997 - All Rights Reserved\n * (C) Copyright IBM Corp. 1996 - 1998 - All Rights Reserved\n *\n * The original version of this source code and documentation\n * is copyrighted and owned by Taligent, Inc., a wholly-owned\n * subsidiary of IBM. ", "These materials are provided under terms\n * of a License Agreement between Taligent and Sun. ", "This technology\n * is protected by multiple US and International patents.", "\n *\n * This notice and attribution to Taligent may not be removed.", "\n * Taligent is a registered trademark of Taligent, Inc.\n *\n */\n\npackage sun.text.resources.sv;\n\nimport java.util.", "ListResourceBundle;\n\npublic class CollationData_sv extends ListResourceBundle {\n\n protected final Object[][] getContents() {\n return new Object[][] {\n { \"Rule\",\n \"& Z < a\\u030a , A\\u030a\" + // a-ring, aa ligaure\n \"< a\\u0308 , A\\u0308 < a\\u030b, A\\u030b \" + // a-umlaut, a-double-acute\n \"< \\u00e6 , \\u00c6 \" + // ae ligature\n \"< o\\u0308 , O\\u0308 \" + // o-umlaut\n \"< o\\u030b , O\\u030b ; \\u00f8 , \\u00d8 \" + // o-double-acute < o-stroke\n \"& V ; w , W\" +\n \"& Y, u\\u0308 , U\\u0308\" + // u-double-acute\n \"; u\\u030b, U\\u030b \"\n }\n };\n }\n}\n" ]

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[ "Self-help and benzodiazepine withdrawal.", "\nDespite an increased understanding of the potential dangers of benzodiazepines among doctors and patients, and a decline in anxiolytic prescribing, motivating and supporting current benzodiazepine users through withdrawal can be difficult and time consuming for medical services. ", "Self-help organisations offer another approach. ", "This is a study of one such organisation, TRANX (UK), which examined the characteristics of its members and their outcome. ", "The results suggest that this organisation did provide effective counselling and support for its members, and implies that self-help is a realistic alternative or adjunct to orthodox health care for those wishing to withdraw from benzodiazepines." ]

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[ "Professor John T Harvey talks with Christian about the NHS, privatisation and the implications of distributing healthcare via a market mechanism. ", "What conditions need to be met in order to make sellers accountable to buyers in market systems, and are those conditions present in private healthcare systems?", "\n\nPlease help sustain this podcast by donating to our Patreon! ", "Patrons get early access to our episodes and other patron-only content: https://www.patreon.com/MMTpodcast\n\nTickets for Christian’s MMT show in Leicester 5th, 12th and 19th February 2020: https://comedy-festival.co.uk/event/christian-reilly-magic-money-tree/\n\nTickets for Christian’s MMT show in Glasgow 22nd March 2020: http://www.glasgowcomedyfestival.com/shows/2644" ]

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[ "In 2373, Keiko O'Brien was injured when a Pah-wraith that was possessing her caused her to jump from the upper level of Deep Space 9's Promenade in order to impress upon Miles O'Brien the seriousness of the actions that it would take if he attempted to subvert its actions. ", "When Miles was asked what he was doing on the Promenade when he was supposed to be repairing optronic circuitry on level five, he excused it by stating that he was going to the replimat for lunch. (", "DS9: \"The Assignment\")\n\nAfter being injured and having to wait for treatment after a Dominion attack on the USS Defiant in 2374, Garak told Dr. Bashir that he thought he was entitled to preferential treatment by him after all the lunches they had shared together. (", "DS9: \"A Time to Stand\")" ]

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[ "Andrew Ford\n\n@AndrewFordNews\n\nTRENTON - Twice in two weeks, Republican state Sen. Jennifer Beck's push to strip convicted public officials and employees of their government pensions was thwarted by Democrats in floor-vote battle.", "\n\nAt two consecutive Senate voting sessions, Beck, R-Monmouth, attempted to push her pension bill past a committee hearing and onto the floor of the state Senate for a full vote. ", "Citing an Asbury Park Press investigation last year that revealed more than 40 convicted criminals were collecting more than a million dollars in taxpayer-funded retirement checks, Beck said the bill needed to be voted on to save taxpayers money.", "\n\nEach time Beck’s efforts were rejected in a party-line vote of 20-15. ", "An opponent of the bill, state Sen. Jim Whelan, D-Atlantic, who is holding her bill in the committee he chairs, derided Beck’s efforts as “grandstanding.”", "\n\nRepublicans are outnumbered by Democrats 24-16 in the Senate.", "\n\nEXCLUSIVE: Convicts profiting from pensions\n\nOn the floor of the Senate Tuesday, Beck told her fellow senators that, \"Some have been convicted of federal criminal charges, have spent time in jail, and yet our taxpayers are still funding their pensions.\"", "\n\nBeck told the Press afterward that “If you were convicted and went to jail because you were swindling taxpayers, we then should not be forced to fund you in your later years with our hard-earned money.”", "\n\nWhelan expressed skepticism.", "\n\n“I get the feel-good part: let’s be tough on public officials who are corrupt,” Whelan told the Press. “", "I get that. ", "We all feel good. ", "But what’s the net result?”", "\n\nWhelan explained how allowing a corrupt official to keep their pension is a bargaining chip used by prosecutors. ", "Whelan is the chair of the State Government committee responsible for reviewing Beck's bill, S-1557. ", "He hasn't posted her bill for a hearing and said he wouldn't.", "\n\nGallery of New Jersey's crooked politicians\n\n“I’ve talked to a number of prosecutors and frankly having the leverage for enabling someone to keep their pension so that you do a plea or more likely they turn and become helpful in an investigation, you’re taking away that prosecutorial discretion,” Whelan said.", "\n\nWhelan declined to name which prosecutors he spoke to. ", "Beck said she talked to Monmouth County Prosecutor Chris Gramiccioni and \"he said it’s generally not part of the negotiation or plea bargain or anything else.\"", "\n\nGramiccioni did not respond to a request for comment.", "\n\nOcean County Prosecutor Joseph Coronato said he didn't feel the bill would impact the criminal cases his office prosecutes.", "\n\n\"I really don’t think it has any effect one way or the other practically speaking,\" he said.", "\n\nIn July, the Press published its investigation that showed the convicts receiving state pensions. ", "The list read like a who's who of New Jersey corruption: former mayors, an assemblyman, county executives and other politicians convicted of tainting their offices. ", "The crooks ranged from a guard convicted of smuggling drugs to prisoners to a former Ocean Township mayor who admitted to extorting $64,000 from three developers. ", "The ex-guard was still in prison, receiving retirement checks, the Press found.", "\n\nEDITORIAL: No pensions for corrupt officials\n\n“It’s my position that if you have violated the public trust, taxpayers should not be funding your retirement,” Beck said.", "\n\nIn Trenton, as in Washington, the minority party has little power to force debate during sessions when bills are voted on.", "\n\nBeck and GOP colleagues have tried using an ‘’order of the day’’ procedure that would fast-track their bills for consideration, but without success. ", "Democrats tabled the requests in party-line votes.", "\n\n\n\nWhen Beck used the tactic on Monday, Sen. Loretta Weinberg, D-Bergen, called for the vote to table.", "\n\n\"My instinct is, as our residents understand that the people they elected are not acting on their behalf, that they’ll become more vocal,\" Beck said. \"", "This matter is egregious to 99.9% of the residents. ", "And that tenth of one percent is the people that are collecting the pensions, that are the corrupt public officials.\"", "\n\nA rundown of scandal and corruption in New Jersey politics\n\nBeck pointed to legislation passed Jan. 30 in New York proposing an amendment to the state’s constitution to allow for a convicted corrupt public official to have their pension reduced or revoked following a court hearing. ", "That’s similar to how it works in New Jersey now – a convicted crooked official in the garden state goes before a pension review board that determines how much their service was tainted by crime, possibly granting them a portion of their pension for the years they served without breaking the law.", "\n\n“New Jersey’s statutes need to be strengthened,” Beck said. “", "We still have convicted, corrupt public officials that are collecting taxpayer funded pensions.”", "\n\nAndrew Ford: 732-643-4281; aford3@gannettnj.com" ]

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[ "Syria says al-Qaida linked group's leader killed\n\nIn this photo released by the Syrian official news agency SANA, dead bodies of Syrian rebels are seen on the ground after fighting with Syrian government forces according to SANA, near the Otaiba area, near Damascus, Syria, Friday, Oct. 25, 2013. ", "Syrian government troops on Friday ambushed rebels near the capital, Damascus, killing at least 40 opposition fighters, state media reported. ", "The ambush was part of the military's offensive against rebel strongholds around President Bashar Assad's seat of power. (", "AP Photo/SANA)\n\nFriday's one-line report, which could not be immediately confirmed, says Abu Mohammad al-Golani was killed in the coastal province of Latakia. ", "It did not say when or give other details. ", "Opposition groups had no immediate comment on the report.", "\n\nRebels have gained footholds in mountainous regions of Latakia, which is largely loyal to President Bashar Assad.", "\n\nThe extremist group, also known as Nusra Front, is on a U.S. State Department list of terrorist organizations. ", "The group has emerged as one of the most effective among rebel groups fighting Assad.", "\n\nAl-Golani's death would be a huge blow to rebels who have been fragmented and outgunned by Assad's forces." ]

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[ "Testosterone\n\nTestosterone is the primary male sex hormone and anabolic steroid. ", "In male humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of body hair. ", "In addition, testosterone is involved in health and well-being, and the prevention of osteoporosis. ", "Insufficient levels of testosterone in men may lead to abnormalities including frailty and bone loss.", "\n\nTestosterone is a steroid from the androstane class containing a keto and hydroxyl groups at the three and seventeen positions respectively. ", "It is biosynthesized in several steps from cholesterol and is converted in the liver to inactive metabolites. ", " It exerts its action through binding to and activation of the androgen receptor. ", "In humans and most other vertebrates, testosterone is secreted primarily by the testicles of males and, to a lesser extent, the ovaries of females. ", "On average, in adult males, levels of testosterone are about 7 to 8 times as great as in adult females. ", "As the metabolism of testosterone in males is more pronounced, the daily production is about 20 times greater in men. ", "Females are also more sensitive to the hormone.", "\n\nIn addition to its role as a natural hormone, testosterone is used as a medication in the treatment of low testosterone levels in men, transgender hormone therapy for transgender men, and breast cancer in women. ", "Since testosterone levels decrease as men age, testosterone is sometimes used in older men to counteract this deficiency. ", "It is also used illicitly to enhance physique and performance, for instance in athletes.", "\n\nBiological effects\nIn general, androgens such as testosterone promote protein synthesis and thus growth of tissues with androgen receptors. ", "Testosterone can be described as having virilising and anabolic effects (though these categorical descriptions are somewhat arbitrary, as there is a great deal of mutual overlap between them).", "\n Anabolic effects include growth of muscle mass and strength, increased bone density and strength, and stimulation of linear growth and bone maturation.", "\n Androgenic effects include maturation of the sex organs, particularly the penis and the formation of the scrotum in the fetus, and after birth (usually at puberty) a deepening of the voice, growth of facial hair (such as the beard) and axillary (underarm) hair. ", "Many of these fall into the category of male secondary sex characteristics.", "\n\nTestosterone effects can also be classified by the age of usual occurrence. ", "For postnatal effects in both males and females, these are mostly dependent on the levels and duration of circulating free testosterone.", "\n\nBefore birth\nEffects before birth are divided into two categories, classified in relation to the stages of development.", "\n\nThe first period occurs between 4 and 6 weeks of the gestation. ", "Examples include genital virilisation such as midline fusion, phallic urethra, scrotal thinning and rugation, and phallic enlargement; although the role of testosterone is far smaller than that of dihydrotestosterone. ", "There is also development of the prostate gland and seminal vesicles.", "\n\nDuring the second trimester, androgen level is associated with sex formation. ", "Specifically, testosterone, along with anti-Müllerian hormone (AMH) promote growth of the Wolffian duct and degeneration of the Müllerian duct respectively. ", "This period affects the femininization or masculinization of the fetus and can be a better predictor of feminine or masculine behaviours such as sex typed behaviour than an adult's own levels. ", "Prenatal androgens apparently influence interests and engagement in gendered activities and have moderate effects on spatial abilities. ", "Among women with CAH, a male-typical play in childhood correlated with reduced satisfaction with the female gender and reduced heterosexual interest in adulthood.", "\n\nEarly infancy\nEarly infancy androgen effects are the least understood. ", " In the first weeks of life for male infants, testosterone levels rise. ", "The levels remain in a pubertal range for a few months, but usually reach the barely detectable levels of childhood by 4–7 months of age. ", "The function of this rise in humans is unknown. ", "It has been theorized that brain masculinization is occurring since no significant changes have been identified in other parts of the body. ", "The male brain is masculinized by the aromatization of testosterone into estrogen, which crosses the blood–brain barrier and enters the male brain, whereas female fetuses have α-fetoprotein, which binds the estrogen so that female brains are not affected.", "\n\nBefore puberty\nBefore puberty effects of rising androgen levels occur in both boys and girls. ", "These include adult-type body odor, increased oiliness of skin and hair, acne, pubarche (appearance of pubic hair), axillary hair (armpit hair), growth spurt, accelerated bone maturation, and facial hair.", "\n\nPubertal\nPubertal effects begin to occur when androgen has been higher than normal adult female levels for months or years. ", "In males, these are usual late pubertal effects, and occur in women after prolonged periods of heightened levels of free testosterone in the blood. ", " The effects include:\n\nGrowth of spermatogenic tissue in testicles, male fertility, penis or clitoris enlargement, increased libido and frequency of erection or clitoral engorgement occurs. ", "Growth of jaw, brow, chin, and nose and remodeling of facial bone contours, in conjunction with human growth hormone occurs. ", "Completion of bone maturation and termination of growth. ", "This occurs indirectly via estradiol metabolites and hence more gradually in men than women. ", "Increased muscle strength and mass, shoulders become broader and rib cage expands, deepening of voice, growth of the Adam's apple. ", "Enlargement of sebaceous glands. ", "This might cause acne, subcutaneous fat in face decreases. ", "Pubic hair extends to thighs and up toward umbilicus, development of facial hair (sideburns, beard, moustache), loss of scalp hair (androgenetic alopecia), increase in chest hair, periareolar hair, perianal hair, leg hair, armpit hair.", "\n\nAdult\nTestosterone is necessary for normal sperm development. ", "It activates genes in Sertoli cells, which promote differentiation of spermatogonia. ", "It regulates acute HPA (hypothalamic–pituitary–adrenal axis) response under dominance challenge. ", "Androgen including testosterone enhances muscle growth. ", "Testosterone also regulates the population of thromboxane A2 receptors on megakaryocytes and platelets and hence platelet aggregation in humans.", "\n\nAdult testosterone effects are more clearly demonstrable in males than in females, but are likely important to both sexes. ", "Some of these effects may decline as testosterone levels might decrease in the later decades of adult life.", "\n\nHealth risks\nTestosterone does not appear to increase the risk of developing prostate cancer. ", "In people who have undergone testosterone deprivation therapy, testosterone increases beyond the castrate level have been shown to increase the rate of spread of an existing prostate cancer.", "\n\nConflicting results have been obtained concerning the importance of testosterone in maintaining cardiovascular health. ", "Nevertheless, maintaining normal testosterone levels in elderly men has been shown to improve many parameters that are thought to reduce cardiovascular disease risk, such as increased lean body mass, decreased visceral fat mass, decreased total cholesterol, and glycemic control.", "\n\nHigh androgen levels are associated with menstrual cycle irregularities in both clinical populations and healthy women.", "\n\nSexual arousal\n\nTestosterone levels follow a nyctohemeral rhythm that peaks early each day, regardless of sexual activity.", "\n\nThere are positive correlations between positive orgasm experience in women and testosterone levels where relaxation was a key perception of the experience. ", "There is no correlation between testosterone and men's perceptions of their orgasm experience, and also no correlation between higher testosterone levels and greater sexual assertiveness in either sex.", "\n\nSexual arousal and masturbation in women produce small increases in testosterone concentrations. ", "The plasma levels of various steroids significantly increase after masturbation in men and the testosterone levels correlate to those levels.", "\n\nMammalian studies\nStudies conducted in rats have indicated that their degree of sexual arousal is sensitive to reductions in testosterone. ", "When testosterone-deprived rats were given medium levels of testosterone, their sexual behaviors (copulation, partner preference, etc.) ", "resumed, but not when given low amounts of the same hormone. ", "Therefore, these mammals may provide a model for studying clinical populations among humans suffering from sexual arousal deficits such as hypoactive sexual desire disorder.", "\n\nEvery mammalian species examined demonstrated a marked increase in a male's testosterone level upon encountering a novel female. ", "The reflexive testosterone increases in male mice is related to the male's initial level of sexual arousal.", "\n\nIn non-human primates, it may be that testosterone in puberty stimulates sexual arousal, which allows the primate to increasingly seek out sexual experiences with females and thus creates a sexual preference for females. ", "Some research has also indicated that if testosterone is eliminated in an adult male human or other adult male primate's system, its sexual motivation decreases, but there is no corresponding decrease in ability to engage in sexual activity (mounting, ejaculating, etc.).", "\n\nIn accordance with sperm competition theory, testosterone levels are shown to increase as a response to previously neutral stimuli when conditioned to become sexual in male rats. ", "This reaction engages penile reflexes (such as erection and ejaculation) that aid in sperm competition when more than one male is present in mating encounters, allowing for more production of successful sperm and a higher chance of reproduction.", "\n\nMales\nIn men, higher levels of testosterone are associated with periods of sexual activity.", "\n\nMen who watch a sexually explicit movie have an average increase of 35% in testosterone, peaking at 60–90 minutes after the end of the film, but no increase is seen in men who watch sexually neutral films. ", "Men who watch sexually explicit films also report increased motivation, competitiveness, and decreased exhaustion. ", " A link has also been found between relaxation following sexual arousal and testosterone levels.", "\n\nMen's levels of testosterone, a hormone known to affect men's mating behaviour, changes depending on whether they are exposed to an ovulating or nonovulating woman's body odour. ", "Men who are exposed to scents of ovulating women maintained a stable testosterone level that was higher than the testosterone level of men exposed to nonovulation cues. ", "Testosterone levels and sexual arousal in men are heavily aware of hormone cycles in females. ", "This may be linked to the ovulatory shift hypothesis, where males are adapted to respond to the ovulation cycles of females by sensing when they are most fertile and whereby females look for preferred male mates when they are the most fertile; both actions may be driven by hormones.", "\n\nFemales\nAndrogens may modulate the physiology of vaginal tissue and contribute to female genital sexual arousal. ", "Women's level of testosterone is higher when measured pre-intercourse vs pre-cuddling, as well as post-intercourse vs post-cuddling. ", "There is a time lag effect when testosterone is administered, on genital arousal in women. ", "In addition, a continuous increase in vaginal sexual arousal may result in higher genital sensations and sexual appetitive behaviors.", "\n\nWhen females have a higher baseline level of testosterone, they have higher increases in sexual arousal levels but smaller increases in testosterone, indicating a ceiling effect on testosterone levels in females. ", "Sexual thoughts also change the level of testosterone but not level of cortisol in the female body, and hormonal contraceptives may affect the variation in testosterone response to sexual thoughts.", "\n\nTestosterone may prove to be an effective treatment in female sexual arousal disorders, and is available as a dermal patch. ", "There is no FDA approved androgen preparation for the treatment of androgen insufficiency; however, it has been used as an off-label use to treat low libido and sexual dysfunction in older women. ", "Testosterone may be a treatment for postmenopausal women as long as they are effectively estrogenized.", "\n\nRomantic relationships\nFalling in love decreases men's testosterone levels while increasing women's testosterone levels. ", "There has been speculation that these changes in testosterone result in the temporary reduction of differences in behavior between the sexes. ", "However, it is suggested that after the \"honeymoon phase\" ends—about four years into a relationship—this change in testosterone levels is no longer apparent. ", " Men who produce less testosterone are more likely to be in a relationship or married, and men who produce more testosterone are more likely to divorce; however, causality cannot be determined in this correlation. ", "Marriage or commitment could cause a decrease in testosterone levels.", "\n\nSingle men who have not had relationship experience have lower testosterone levels than single men with experience. ", "It is suggested that these single men with prior experience are in a more competitive state than their non-experienced counterparts. ", "Married men who engage in bond-maintenance activities such as spending the day with their spouse and/or child have no different testosterone levels compared to times when they do not engage in such activities. ", "Collectively, these results suggest that the presence of competitive activities rather than bond-maintenance activities are more relevant to changes in testosterone levels.", "\n\nMen who produce more testosterone are more likely to engage in extramarital sex. ", "Testosterone levels do not rely on physical presence of a partner; testosterone levels of men engaging in same-city and long-distance relationships are similar. ", "Physical presence may be required for women who are in relationships for the testosterone–partner interaction, where same-city partnered women have lower testosterone levels than long-distance partnered women.", "\n\nFatherhood\nFatherhood decreases testosterone levels in men, suggesting that the emotions and behavior tied to decreased testosterone promote paternal care. ", "In humans and other species that utilize allomaternal care, paternal investment in offspring is beneficial to said offspring's survival because it allows the parental dyad to raise multiple children simultaneously. ", "This increases the reproductive fitness of the parents, because their offspring are more likely to survive and reproduce. ", "Paternal care increases offspring survival due to increased access to higher quality food and reduced physical and immunological threats. ", "This is particularly beneficial for humans since offspring are dependent on parents for extended periods of time and mothers have relatively short inter-birth intervals.", "\n\nWhile extent of paternal care varies between cultures, higher investment in direct child care has been seen to be correlated with lower average testosterone levels as well as temporary fluctuations. ", "For instance, fluctuation in testosterone levels when a child is in distress has been found to be indicative of fathering styles. ", "If a father's testosterone levels decrease in response to hearing their baby cry, it is an indication of empathizing with the baby. ", "This is associated with increased nurturing behavior and better outcomes for the infant.", "\n\nMotivation\nTestosterone levels play a major role in risk-taking during financial decisions.", "\n\nAggression and criminality \n\nMost studies support a link between adult criminality and testosterone. ", "Nearly all studies of juvenile delinquency and testosterone are not significant. ", "Most studies have also found testosterone to be associated with behaviors or personality traits linked with criminality such as antisocial behavior and alcoholism. ", "Many studies have also been done on the relationship between more general aggressive behavior and feelings and testosterone. ", "About half the studies have found a relationship and about half no relationship. ", "Studies have also found that testosterone facilitates aggression by modulating vasopressin receptors in the hypothalamus.", "\n\nTestosterone is significantly discussed in relation to aggression and competitive behavior. ", "There are two theories on the role of testosterone in aggression and competition. ", "The first one is the challenge hypothesis which states that testosterone would increase during puberty, thus facilitating reproductive and competitive behavior which would include aggression. ", "It is therefore the challenge of competition among males of the species that facilitates aggression and violence. ", "Studies conducted have found direct correlation between testosterone and dominance, especially among the most violent criminals in prison who had the highest testosterone levels. ", "The same research also found fathers (those outside competitive environments) had the lowest testosterone levels compared to other males.", "\n\nThe second theory is similar and is known as \"evolutionary neuroandrogenic (ENA) theory of male aggression\". ", "Testosterone and other androgens have evolved to masculinize a brain in order to be competitive even to the point of risking harm to the person and others. ", "By doing so, individuals with masculinized brains as a result of pre-natal and adult life testosterone and androgens enhance their resource acquiring abilities in order to survive, attract and copulate with mates as much as possible. ", "The masculinization of the brain is not just mediated by testosterone levels at the adult stage, but also testosterone exposure in the womb as a fetus. ", "Higher pre-natal testosterone indicated by a low digit ratio as well as adult testosterone levels increased risk of fouls or aggression among male players in a soccer game. ", "Studies have also found higher pre-natal testosterone or lower digit ratio to be correlated with higher aggression in males.", "\n\nThe rise in testosterone levels during competition predicted aggression in males but not in females. ", "Subjects who interacted with hand guns and an experimental game showed rise in testosterone and aggression. ", "Natural selection might have evolved males to be more sensitive to competitive and status challenge situations and that the interacting roles of testosterone are the essential ingredient for aggressive behaviour in these situations. ", "Testosterone produces aggression by activating subcortical areas in the brain, which may also be inhibited or suppressed by social norms or familial situations while still manifesting in diverse intensities and ways through thoughts, anger, verbal aggression, competition, dominance and physical violence. ", " Testosterone mediates attraction to cruel and violent cues in men by promoting extended viewing of violent stimuli. ", "Testosterone specific structural brain characteristic can predict aggressive behaviour in individuals.", "\n\nTestosterone might encourage fair behavior. ", "For one study, subjects took part in a behavioral experiment where the distribution of a real amount of money was decided. ", "The rules allowed both fair and unfair offers. ", "The negotiating partner could subsequently accept or decline the offer. ", "The fairer the offer, the less probable a refusal by the negotiating partner. ", "If no agreement was reached, neither party earned anything. ", "Test subjects with an artificially enhanced testosterone level generally made better, fairer offers than those who received placebos, thus reducing the risk of a rejection of their offer to a minimum. ", "Two later studies have empirically confirmed these results. ", "However men with high testosterone were significantly 27% less generous in an ultimatum game. ", "The Annual NY Academy of Sciences has also found anabolic steroid use (which increases testosterone) to be higher in teenagers, and this was associated with increased violence. ", "Studies have also found administered testosterone to increase verbal aggression and anger in some participants.", "\n\nA few studies indicate that the testosterone derivative estradiol (one form of estrogen) might play an important role in male aggression. ", "Estradiol is known to correlate with aggression in male mice. ", "Moreover, the conversion of testosterone to estradiol regulates male aggression in sparrows during breeding season. ", "Rats who were given anabolic steroids that increase testosterone were also more physically aggressive to provocation as a result of \"threat sensitivity\".", "\n\nBrain\nThe brain is also affected by this sexual differentiation; the enzyme aromatase converts testosterone into estradiol that is responsible for masculinization of the brain in male mice. ", "In humans, masculinization of the fetal brain appears, by observation of gender preference in patients with congenital diseases of androgen formation or androgen receptor function, to be associated with functional androgen receptors.", "\n\nThere are some differences between a male and female brain (possibly the result of different testosterone levels), one of them being size: the male human brain is, on average, larger. ", "Men were found to have a total myelinated fiber length of 176 000 km at the age of 20, whereas in women the total length was 149 000 km (approx. ", "15% less).", "\n\nNo immediate short term effects on mood or behavior were found from the administration of supraphysiologic doses of testosterone for 10 weeks on 43 healthy men. ", " A correlation between testosterone and risk tolerance in career choice exists among women.", "\n\nAttention, memory, and spatial ability are key cognitive functions affected by testosterone in humans. ", "Preliminary evidence suggests that low testosterone levels may be a risk factor for cognitive decline and possibly for dementia of the Alzheimer's type, a key argument in life extension medicine for the use of testosterone in anti-aging therapies. ", "Much of the literature, however, suggests a curvilinear or even quadratic relationship between spatial performance and circulating testosterone, where both hypo- and hypersecretion (deficient- and excessive-secretion) of circulating androgens have negative effects on cognition.", "\n\nImmune system and inflammation\nTestosteone deficiency is associated with an increased risk of metabolic syndrome, cardiovascular disease and mortality, which are also sequelae of chronic inflammation. ", "Testosterone plasma concentration inversely correlates to multiple biomarkers of inflammation including CRP, interleukin 1 beta, interleukin 6, TNF alpha and endotoxin concentration, as well as leukocyte count. ", "As demonstrated by a meta-analysis, substitution therapy with testosterone results in a significant reduction of inflammatory markers. ", "These effects are mediated by different mechanisms with synergistic action. ", "In androgen-deficient men with concomitant autoimmune thyroiditis, substitution therapy with testosterone leads to a decrease in thyroid autoantibody titres and an increase in thyroid's secretory capacity (SPINA-GT).", "\n\nMedical use\n\nTestosterone is used as a medication for the treatment of males with too little or no natural testosterone production, certain forms of breast cancer, and gender dysphoria in transgender men and non-binary individuals. ", "This is known as hormone replacement therapy (HRT) or testosterone replacement therapy (TRT), which maintains serum testosterone levels in the normal range. ", "Decline of testosterone production with age has led to interest in androgen replacement therapy. ", "It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful.", "\n\nTestosterone is included in the World Health Organization's list of essential medicines, which are the most important medications needed in a basic health system. ", "It is available as a generic medication. ", "The price depends on the form of testosterone used. ", "It can be administered as a cream or transdermal patch that is applied to the skin, by injection into a muscle, as a tablet that is placed in the cheek, or by ingestion.", "\n\nCommon side effects from testosterone medication include acne, swelling, and breast enlargement in males. ", "Serious side effects may include liver toxicity, heart disease, and behavioral changes. ", "Women and children who are exposed may develop virilization. ", "It is recommended that individuals with prostate cancer not use the medication. ", "It can cause harm if used during pregnancy or breastfeeding.", "\n\n2020 guidelines from the American College of Physicians support the discussion of testosterone treatment in adult men with age-related low levels of testosterone who have sexual dysfunction. ", "They recommend yearly evaluation regarding possible improvement and, if none, to discontinue testosterone; physicians should consider intramuscular treatments, rather than transdermal treatments, due to costs and since the effectiveness and harm of either method is similar. ", "Testosterone treatment for reasons other than possible improvement of sexual dysfunction may not be recommended.", "\n\nBiological activity\n\nSteroid hormone activity\nThe effects of testosterone in humans and other vertebrates occur by way of multiple mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. ", "Androgens such as testosterone have also been found to bind to and activate membrane androgen receptors.", "\n\nFree testosterone (T) is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. ", "DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of T. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. ", "The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.", "\n\nAndrogen receptors occur in many different vertebrate body system tissues, and both males and females respond similarly to similar levels. ", "Greatly differing amounts of testosterone prenatally, at puberty, and throughout life account for a share of biological differences between males and females.", "\n\nThe bones and the brain are two important tissues in humans where the primary effect of testosterone is by way of aromatization to estradiol. ", "In the bones, estradiol accelerates ossification of cartilage into bone, leading to closure of the epiphyses and conclusion of growth. ", "In the central nervous system, testosterone is aromatized to estradiol. ", "Estradiol rather than testosterone serves as the most important feedback signal to the hypothalamus (especially affecting LH secretion). ", "In many mammals, prenatal or perinatal \"masculinization\" of the sexually dimorphic areas of the brain by estradiol derived from testosterone programs later male sexual behavior.", "\n\nNeurosteroid activity\nTestosterone, via its active metabolite 3α-androstanediol, is a potent positive allosteric modulator of the GABAA receptor.", "\n\nTestosterone has been found to act as an antagonist of the TrkA and p75NTR, receptors for the neurotrophin nerve growth factor (NGF), with high affinity (around 5 nM). ", "In contrast to testosterone, DHEA and DHEA sulfate have been found to act as high-affinity agonists of these receptors.", "\n\nTestosterone is an antagonist of the sigma σ1 receptor (Ki = 1,014 or 201 nM). ", "However, the concentrations of testosterone required for binding the receptor are far above even total circulating concentrations of testosterone in adult males (which range between 10 and 35 nM).", "\n\nBiochemistry\n\nBiosynthesis\nLike other steroid hormones, testosterone is derived from cholesterol (see figure). ", "The first step in the biosynthesis involves the oxidative cleavage of the side-chain of cholesterol by cholesterol side-chain cleavage enzyme (P450scc, CYP11A1), a mitochondrial cytochrome P450 oxidase with the loss of six carbon atoms to give pregnenolone. ", "In the next step, two additional carbon atoms are removed by the CYP17A1 (17α-hydroxylase/17,20-lyase) enzyme in the endoplasmic reticulum to yield a variety of C19 steroids. ", "In addition, the 3β-hydroxyl group is oxidized by 3β-hydroxysteroid dehydrogenase to produce androstenedione. ", "In the final and rate limiting step, the C17 keto group androstenedione is reduced by 17β-hydroxysteroid dehydrogenase to yield testosterone.", "\n\nThe largest amounts of testosterone (>95%) are produced by the testes in men, while the adrenal glands account for most of the remainder. ", "Testosterone is also synthesized in far smaller total quantities in women by the adrenal glands, thecal cells of the ovaries, and, during pregnancy, by the placenta. ", "In the testes, testosterone is produced by the Leydig cells. ", "The male generative glands also contain Sertoli cells, which require testosterone for spermatogenesis. ", "Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein, sex hormone-binding globulin (SHBG).", "\n\nRegulation\n\nIn males, testosterone is synthesized primarily in Leydig cells. ", "The number of Leydig cells in turn is regulated by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). ", "In addition, the amount of testosterone produced by existing Leydig cells is under the control of LH, which regulates the expression of 17β-hydroxysteroid dehydrogenase.", "\n\nThe amount of testosterone synthesized is regulated by the hypothalamic–pituitary–testicular axis (see figure to the right). ", "When testosterone levels are low, gonadotropin-releasing hormone (GnRH) is released by the hypothalamus, which in turn stimulates the pituitary gland to release FSH and LH. ", "These latter two hormones stimulate the testis to synthesize testosterone. ", " Finally, increasing levels of testosterone through a negative feedback loop act on the hypothalamus and pituitary to inhibit the release of GnRH and FSH/LH, respectively.", "\n\nFactors affecting testosterone levels may include:\n\n Age: Testosterone levels gradually reduce as men age. ", "This effect is sometimes referred to as andropause or late-onset hypogonadism.", "\n Exercise: Resistance training increases testosterone levels, however, in older men, that increase can be avoided by protein ingestion. ", "Endurance training in men may lead to lower testosterone levels.", "\n Nutrients: Vitamin A deficiency may lead to sub-optimal plasma testosterone levels. ", "The secosteroid vitamin D in levels of 400–1000 IU/d (10–25 µg/d) raises testosterone levels. ", "Zinc deficiency lowers testosterone levels but over-supplementation has no effect on serum testosterone. ", "\n Weight loss: Reduction in weight may result in an increase in testosterone levels. ", "Fat cells synthesize the enzyme aromatase, which converts testosterone, the male sex hormone, into estradiol, the female sex hormone. ", " However no clear association between body mass index and testosterone levels has been found. ", "\n Miscellaneous: Sleep: (REM sleep) increases nocturnal testosterone levels. ", "Behavior: Dominance challenges can, in some cases, stimulate increased testosterone release in men. ", "Drugs: Natural or man-made antiandrogens including spearmint tea reduce testosterone levels. ", "Licorice can decrease the production of testosterone and this effect is greater in females.", "\n\nDistribution\nThe plasma protein binding of testosterone is 98.0 to 98.5%, with 1.5 to 2.0% free or unbound. ", "It is bound 65% to sex hormone-binding globulin (SHBG) and 33% bound weakly to albumin.", "\n\nMetabolism\n\nBoth testosterone and 5α-DHT are metabolized mainly in the liver. ", "Approximately 50% of testosterone is metabolized via conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases, respectively. ", "An additional 40% of testosterone is metabolized in equal proportions into the 17-ketosteroids androsterone and etiocholanolone via the combined actions of 5α- and 5β-reductases, 3α-hydroxysteroid dehydrogenase, and 17β-HSD, in that order. ", "Androsterone and etiocholanolone are then glucuronidated and to a lesser extent sulfated similarly to testosterone. ", "The conjugates of testosterone and its hepatic metabolites are released from the liver into circulation and excreted in the urine and bile. ", "Only a small fraction (2%) of testosterone is excreted unchanged in the urine.", "\n\nIn the hepatic 17-ketosteroid pathway of testosterone metabolism, testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive 5β-DHT, respectively. ", "Then, 5α-DHT and 5β-DHT are converted by 3α-HSD into 3α-androstanediol and 3α-etiocholanediol, respectively. ", "Subsequently, 3α-androstanediol and 3α-etiocholanediol are converted by 17β-HSD into androsterone and etiocholanolone, which is followed by their conjugation and excretion. ", "3β-Androstanediol and 3β-etiocholanediol can also be formed in this pathway when 5α-DHT and 5β-DHT are acted upon by 3β-HSD instead of 3α-HSD, respectively, and they can then be transformed into epiandrosterone and epietiocholanolone, respectively. ", "A small portion of approximately 3% of testosterone is reversibly converted in the liver into androstenedione by 17β-HSD.", "\n\nIn addition to conjugation and the 17-ketosteroid pathway, testosterone can also be hydroxylated and oxidized in the liver by cytochrome P450 enzymes, including CYP3A4, CYP3A5, CYP2C9, CYP2C19, and CYP2D6. ", "6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations. ", "The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism. ", "In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites. ", "Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione.", "\n\nTwo of the immediate metabolites of testosterone, 5α-DHT and estradiol, are biologically important and can be formed both in the liver and in extrahepatic tissues. ", "Approximately 5 to 7% of testosterone is converted by 5α-reductase into 5α-DHT, with circulating levels of 5α-DHT about 10% of those of testosterone, and approximately 0.3% of testosterone is converted into estradiol by aromatase. ", "5α-Reductase is highly expressed in the male reproductive organs (including the prostate gland, seminal vesicles, and epididymides), skin, hair follicles, and brain and aromatase is highly expressed in adipose tissue, bone, and the brain. ", "As much as 90% of testosterone is converted into 5α-DHT in so-called androgenic tissues with high 5α-reductase expression, and due to the several-fold greater potency of 5α-DHT as an AR agonist relative to testosterone, it has been estimated that the effects of testosterone are potentiated 2- to 3-fold in such tissues.", "\n\nLevels\nTotal levels of testosterone in the body are 264 to 916 ng/dL in men age 19 to 39 years, while mean testosterone levels in adult men have been reported as 630 ng/dL. Levels of testosterone in men decline with age. ", "In women, mean levels of total testosterone have been reported to be 32.6 ng/dL. In women with hyperandrogenism, mean levels of total testosterone have been reported to be 62.1 ng/dL.\n\nMeasurement\nTestosterone's bioavailable concentration is commonly determined using the Vermeulen calculation or more precisely using the modified Vermeulen method, which considers the dimeric form of sex-hormone-binding-globulin.", "\n\nBoth methods use chemical equilibrium to derive the concentration of bioavailable testosterone: in circulation testosterone has two major binding partners, albumin (weakly bound) and sex-hormone-binding-globulin (strongly bound). ", "These methods are described in detail in the accompanying figure.", "\n\nHistory\nA testicular action was linked to circulating blood fractions – now understood to be a family of androgenic hormones – in the early work on castration and testicular transplantation in fowl by Arnold Adolph Berthold (1803–1861). ", "Research on the action of testosterone received a brief boost in 1889, when the Harvard professor Charles-Édouard Brown-Séquard (1817–1894), then in Paris, self-injected subcutaneously a \"rejuvenating elixir\" consisting of an extract of dog and guinea pig testicle. ", " He reported in The Lancet that his vigor and feeling of well-being were markedly restored but the effects were transient, and Brown-Séquard's hopes for the compound were dashed. ", "Suffering the ridicule of his colleagues, he abandoned his work on the mechanisms and effects of androgens in human beings.", "\n\nIn 1927, the University of Chicago's Professor of Physiologic Chemistry, Fred C. Koch, established easy access to a large source of bovine testicles — the Chicago stockyards — and recruited students willing to endure the tedious work of extracting their isolates. ", "In that year, Koch and his student, Lemuel McGee, derived 20 mg of a substance from a supply of 40 pounds of bovine testicles that, when administered to castrated roosters, pigs and rats, remasculinized them. ", "The group of Ernst Laqueur at the University of Amsterdam purified testosterone from bovine testicles in a similar manner in 1934, but isolation of the hormone from animal tissues in amounts permitting serious study in humans was not feasible until three European pharmaceutical giants—Schering (Berlin, Germany), Organon (Oss, Netherlands) and Ciba (Basel, Switzerland)—began full-scale steroid research and development programs in the 1930s.", "\n\nThe Organon group in the Netherlands were the first to isolate the hormone, identified in a May 1935 paper \"On Crystalline Male Hormone from Testicles (Testosterone)\". ", "They named the hormone testosterone, from the stems of testicle and sterol, and the suffix of ketone. ", "The structure was worked out by Schering's Adolf Butenandt, at the Chemisches Institut of Technical University in Gdańsk.", "\n\nThe chemical synthesis of testosterone from cholesterol was achieved in August that year by Butenandt and Hanisch. ", "Only a week later, the Ciba group in Zurich, Leopold Ruzicka (1887–1976) and A. Wettstein, published their synthesis of testosterone. ", "These independent partial syntheses of testosterone from a cholesterol base earned both Butenandt and Ruzicka the joint 1939 Nobel Prize in Chemistry. ", "Testosterone was identified as 17β-hydroxyandrost-4-en-3-one (C19H28O2), a solid polycyclic alcohol with a hydroxyl group at the 17th carbon atom. ", "This also made it obvious that additional modifications on the synthesized testosterone could be made, i.e., esterification and alkylation.", "\n\nThe partial synthesis in the 1930s of abundant, potent testosterone esters permitted the characterization of the hormone's effects, so that Kochakian and Murlin (1936) were able to show that testosterone raised nitrogen retention (a mechanism central to anabolism) in the dog, after which Allan Kenyon's group was able to demonstrate both anabolic and androgenic effects of testosterone propionate in eunuchoidal men, boys, and women. ", "The period of the early 1930s to the 1950s has been called \"The Golden Age of Steroid Chemistry\", and work during this period progressed quickly. ", "Research in this golden age proved that this newly synthesized compound—testosterone—or rather family of compounds (for many derivatives were developed from 1940 to 1960), was a potent multiplier of muscle, strength, and well-being.", "\n\nOther animals\nTestosterone is observed in most vertebrates. ", "Testosterone and the classical nuclear androgen receptor first appeared in gnathostomes (jawed vertebrates). ", "Agnathans (jawless vertebrates) such as lampreys do not produce testosterone but instead use androstenedione as a male sex hormone. ", "Fish make a slightly different form called 11-ketotestosterone. ", "Its counterpart in insects is ecdysone. ", "The presence of these ubiquitous steroids in a wide range of animals suggest that sex hormones have an ancient evolutionary history.", "\n\nSee also\n List of androgens/anabolic steroids\n\nReferences\n\nFurther reading\n\n \n \n\nCategory:Cyclopentanols\nCategory:Alkene derivatives\nCategory:Androgens and anabolic steroids\nCategory:Androstanes\nCategory:Estrogens\nCategory:GABAA receptor positive allosteric modulators\nCategory:Hormones of the testis\nCategory:Hormones of the ovary\nCategory:Hormones of the hypothalamus-pituitary-gonad axis\nCategory:Hormones of the suprarenal cortex\nCategory:Enones\nCategory:Neuroendocrinology\nCategory:Human hormones\nCategory:Sex hormones" ]

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[ "The preparation of overbased calcium or barium salts of carboxylic acids, alkyl phenols, and sulfonic acids are disclosed in the following U.S. Pat. ", "Nos. ", "2,616,904; 2,760,970; 2,767,164; 2,798,852; 2,802,816; 3,027,325; 3,031,284; 3,342,733; 3,533,975; 3,773,664; and 3,779,922. ", "The use of these overbased metal salts in the halogen-containing organic polymer is described in the following U.S. Pat. ", "Nos. ", "4,159,973; 4,252,698; and 3,194,823. ", "The use of overbased barium salt in stabilizer formulations has increased during recent years. ", "This is due, in the main, to the fact that overbased barium salts possess performance advantages over the neutral barium salts. ", "The performance advantages associated with overbased barium salts are low plate-out, excellent color hold, good long-term heat stability performance, good compatibility with the stabilizer components, etc. ", "Unfortunately, most of the overbased barium salts are dark in color and, while these dark colored overbased barium salts are effective stabilizers for halogen-containing organic polymer, their dark color results in the discoloration of the end product. ", "This feature essentially prohibits the use of dark colored overbased barium salts in applications where a light colored polymer product is desired.", "\nAccording to the teachings of U.S. Pat. ", "No. ", "4,665,117, light colored alkali or alkaline earth metal salts are prepared where alkyl phenol is used as a promoter. ", "However, alkyl phenol is also a major cause for the development of color in the final product. ", "This problem is overcome by the use of propylene oxide which displaces the hydrogen of the phenolic hydroxyl group and thereby restricts the formation of colored species. ", "However, there are disadvantages associated with this approach, principally due to the toxic nature of propylene oxide. ", "Propylene oxide is classified as a possible carcinogen and laboratory animal inhalation studies have shown evidence of a link to cancer. ", "Propylene oxide is also listed as a severe eye irritant, and prolonged exposure to propylene oxide vapors may result in permanent damage to the eye. ", "Furthermore, propylene oxide is extremely flammable and explosive in nature under certain conditions. ", "Propylene oxide boils at 94° F. and flashes at −20° F. As a result, extreme precautions are required to handle propylene oxide at the plant site. ", "Special storage equipment is required for propylene oxide and other safety features are necessary. ", "U.S. Pat. ", "No. ", "4,665,117 describes the use of propylene oxide at 150° C. At this temperature, propylene oxide will be in the gaseous phase. ", "Under these operating conditions, more than stoichiometric amounts of propylene oxide are required to carry the reaction to completion because propylene oxide will escape from the reaction mixture and this requires additional handling of the excess propylene oxide.", "\nWith the movement in the plastics industry to remove heavy metals, liquid calcium-zinc stabilizers are desirous, but not practical, as replacements for barium-cadmium or barium-zinc. ", "Low metal concentrations, poor compatibility, haziness in clear products and plate out during processing in PVC have severely limited the universal acceptance of calcium based liquid stabilizer compositions. ", "Problems are encountered in the stability of these compositions upon standing or storage. ", "Storage stability is due to the incompatibility among the metal salts employed in the composition and is exhibited by increased turbidity, viscosity, or insoluble solids over time. ", "As a result, the liquid calcium compositions are no longer homogeneous or readily pourable and must be specially treated in order to be used. ", "U.S. Pat. ", "No. ", "5,322,872 is directed to stabilized compositions of mixed metal carboxylates having improved storage stability. ", "According to this patent, a complexing agent is added to the mixed metal carboxylate in order to improve shelf stability. ", "Complexing agents disclosed in this patent include phosphines, phosphites, aromatic cyanides, aromatic hydroxy compounds, oximes and other compounds. ", "U.S. Pat. ", "Nos. ", "5,830,935 and 5,859,267 have also issued as directed to processes for improving basic metal salts and stabilizing halogen-containing polymers therewith.", "\nNotwithstanding the state of the art as exemplified by the above patents, there is a need for further improvements in making shelf stable compositions of overbased alkaline earth metal carboxylates and in methods for their use in stabilizing halogen-containing polymers." ]

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[ "<!-- ((! ", "set title A LaTeX plugin example !)) ((! ", "set learn !)) --", ">\n\n# A plugin example for compiling LaTeX\nBesides the example below, another plugin for LaTeX can be found\n[here](https://github.com/ocaml/ocamlunix/blob/master/myocamlbuild.ml#L14)\nit handles\npdfLaTeX, MakeIndex, HeVeA (both monolithic html and html by chapter via\nHaChA) and Pgf/TikZ picture extraction to PNG for the html versions.", "\nHowever as the plugin below it assumes that LaTeX will converge in two\niterations for the PDF and the master tex file chapter dependencies must\nbe explicitly stated.", "\n\n\n```ocaml\nopen Ocamlbuild_plugin\nopen Command\n\nlet pdflatex = ref (A\"pdflatex\")\nlet ocamlweb = ref (A\"ocamlweb\")\n\nlet () =\n dispatch begin function\n \n (* Here one can change the default value of options, they can still\n be updated by a command line option. *)", "\n | Before_options ->\n (* This will put all warnings to \\texttt{ocaml\\{c,opt\\}} by default. *)", "\n Options.ocaml_cflags := [\"-w\";\"A\"]\n \n (* Here one can change the final value of options. *)", "\n | After_options ->\n (* This avoids the creation of symbolic links to the build directory. *)", "\n Options.make_links := false\n \n (* This hook is called before the hygiene phase.", "\n This phase also serve as collecting all the information about the\n source tree. *)", "\n | Before_hygiene ->\n \n (* Here you can dynamically tag some files or directories. *)", "\n (* This is done here by checking the [SOME_COND] variable which is\n impossible in the \\tags file. *)", "\n if getenv \"SOME_COND\" ~default:\"false\" = \"true\" then\n \n (* By setting foo_dir as not_hygienic one say that the foo directory\n can contains non hygienic files (such as \\texttt{.cmi},\n \\texttt{.cmo}\\ldots). *)", "\n tag_file \"foo_dir\" [\"not_hygienic\"]\n \n (* One can also do things after the hygiene step. *)", "\n | After_hygiene -> ()\n \n (* One can setup rules before the standard ones but that's not recommended. *)", "\n | Before_rules -> ()\n \n (* Here one can add or override new rules *)\n | After_rules ->\n (* Rules can be declared by a call of the form\n [rule name ~prod ~dep action].", "\n The first argument is the name of the rule.", "\n [~prod:string] specifies the product of the rule.", "\n Note that [~prods:string list] also exists.", "\n [~dep] and [~deps] are for dependencies *)\n rule \"LaTeX to PDF conversion rule\"\n ~prod:\"%.pdf\"\n ~dep:\"%.tex\"\n begin fun env _build ->\n \n (* The action is a function that receive two arguments:\n [env] is a conversion function that substitutes `%'\n occurrences according to the targets to which the rule\n applies. ", " [_build] can be called to build new things\n (dynamic dependencies). *)", "\n let tex = env \"%.tex\" and _pdf = env \"%.pdf\" in\n \n (* Here we say: ``We compile the file tex form LaTeX to\n PDF''. ", " Note that in fact that is a set of tags, thus\n the order does not matter. ", "But you got the idea. *)", "\n let tags = tags_of_pathname tex++\"compile\"++\"LaTeX\"++\"pdf\" in\n \n (* Here we produce the command to run.", "\n [S] is for giving a sequence of command pieces.", "\n [A] is for atoms.", "\n [P] is for pathnames.", "\n [Px] is a special pathname that should be the main product\n of the rule (for display purposes).", "\n [T] is for tags.", "\n \n The other constructors are given in the documentation of the\n [Command] module in [Signatures.", "COMMAND]. *)", "\n let cmd = Cmd(S[!pdflatex; T tags; P tex; Sh\"< /dev/null\"]) in\n (* Hoping that LaTeX will converge in two iterations *)\n Seq[cmd; cmd]\n end;\n \n (* Here we make an extension of any rule that produces a command\n containing these tags. *)", "\n flag [\"compile\"; \"LaTeX\"; \"pdf\"; \"safe\"] (A\"-halt-on-error\");\n \n (* Here we give an exception: the file ``manual.tex'' is tagged\n ``safe''. ", " With this tag we add the -halt-on-error flag during\n the LaTeX compilation. *)", "\n tag_file \"manual.tex\" [\"safe\"];\n \n (* The generic LaTeX rule could look at the file searching for\n some \\verb'\\input{}' command, but LaTeX is so complex that it\n will be hard to make this solution complete. ", " Here we manually\n inject some dependencies at one particular point. *)", "\n \n (* The [dep] function takes tags and pathnames. ", "This will build\n pathnames if a command contains these tags. ", "Note that every\n file [some_file_name] is tagged [file:some_file_name]. *)", "\n dep [\"compile\"; \"LaTeX\"; \"pdf\"; \"file:manual.tex\"]\n [\"ocamlweb.sty\"; \"myocamlbuild.tex\"];\n \n rule \"OCaml to LaTeX conversion rule (using ocamlweb)\"\n ~prod:\"%.tex\"\n ~dep:\"%.ml\"\n begin fun env _build ->\n let tex = env \"%.tex\" and ml = env \"%.ml\" in\n let tags = tags_of_pathname ml++\"ocamlweb\"++\"LaTeX\" in\n Cmd(S[!ocamlweb; T tags; P ml; A\"-o\"; Px tex])\n end;\n end\n```\n\n## Notes\n\n\n- The (relative and absolute) dependencies of a tex file can be found\n by running latex with `-recorder` and parse the resulting `.fls` file.", "\n Unfortunately as this does execute the tex code this takes too much\n time to sort out the deps.", "\n\n" ]

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[ "About This Game\n\nUnlimited Terraforming and Building in your own Procedurally Generated\n\nSmooth Voxel World.", "\n\nCORE FEATURES\n\nPlay Your Way! ", "Shape Your World! ", "No starting Archetypes – your character, a Planar Warden, grows the way you want them based on your choices(skills) and discoveries(items). ", "Pick from 3 starting races: The Fae, Dark Elf, or Dwarf for character races.", "\n\nUnlimited Terraforming. ", "You have lots of choices for editing your environment using the Kinumon Astra(Magic Cube). ", "The tool is one of your core world powers so gathering materials is not needed. ", "Add or remove land, change textures and more. ", "No restrictions on terraforming.", "\n\nUnlimited Build Tools. ", "You can build using multiple shapes, materials & prefabs. ", "The tool is one of your core world powers so gathering materials is not needed. ", "No grinding required.", "\n\nNext Gen Dynamically Generated Worlds-With a robust modern smooth voxel system, our worlds are generated on the fly every time a player starts a new game (or load up your saved world that you already worked on). ", "Simply put in a seed and see a new world every time!", "\n\nDiscovery & Adventure-Unlock the mysteries of the world through exploration and discovery. ", "Explore underground caves & find rare minerals for crafting.", "\n\nMining & Crafting-Gather ingredients & resources from combat drops OR from mining your land to build new weapons and items. ", "Check our wiki for more details.", "\n\nSkills & XP-Gain XP through combat, harvesting & exploration. ", "Choose skills based on the type of player you want to be. ", "Check our wiki for more detailed spell listings (basic powers and spell tomes available at launch, new advanced skill system coming soon).", "\n\nSurvival & Combat-Fight and kill aggressive mobs that also want to kill you. (", "bloodfiends and grottonoids in caves so far - more coming).", "\n\nSolo & Coop-Play alone in offline single-player mode or Invite friends to join your multiplayer online world via the in-game server browser. ", "If set to public, your friends will see your game and can join you – all done seamlessly without third party software (online private and public mode). ", "Online play is set to a current limit of 10 players per room/world.", "\n\nSTATE OF THE GAME\n\nTerraforming and Terrain Editing Tools (Building, Digging)\n\nDynamic World Generation(with Seeds)\n\n4 different Biomes for the starting Fae Sanctum plane\n\nDay/Night Cycle\n\nResource Harvesting\n\nSimple Crafting System\n\nInteractive Cascading Water, Waterfalls, Rivers, Oceans\n\nUnderground Cave System\n\nBasic Combat, Weapons & Spell Casting\n\nWildlife/Animals\n\nWorld/Home items to place\n\nPlayer Built Housing\n\n3 Starting races with 2 sexes for each race(male or female; Fae, Dark Elf, or Dwarf)\n\nAttributes and XP\n\nSome Survival System Components(hunger/stamina)\n\nAggressive Mobs in caves(Bloodfiends & Grottonoids so far - more coming)\n\nMounts for travel\n\nMultiplayer(cloud hosted, room based MP with up to 10 players per room)\n\nSingle Player Offline Mode\n\nSteam Integration(no 3rd party login required)\n\nFriends list and trade options\n\nCharacter Customization\n\nMore items to craft\n\nMore advanced Combat and Skills\n\nMultiple armor types\n\nSTORY\n\nAstral Terra is a fantasy-themed sandbox world-crafting game for PC with RPG and survival elements. ", "Set in a beautiful smooth voxel world that’s generated on the fly and completely editable, no two players will have the same experience, as everything from the skills you learn to the world you play in is fully unique and customizable. ", "Explore the endless realm of the Fae Sanctum as a Planar Warden and pick out a piece of land to build your fortress via your unlimited power to terraform and build. ", "Gather resources for crafting and building or just explore the various biomes for the sake of discovery. ", "From character progression with abilities and powers, to the terrains and the environments, everything is procedural and editable! ", "Shape your world and your character the way YOU desire! ", "Play alone in single player offline mode or or join friends in multiplayer online mode to collaborate. ", "Astral Terra has automatic online hosting of your world with no external server setup, with options for worlds to be public, password protected or private.", "For most features, we now have the core implemented, these systems just need to be extended upon.---------------------[1 THE BEGINNING]In the beginning there was the formless warm gray.", "There was neither light nor darkness, nor form nor striving.", "Yet in time, there was the slightest movement in the gray.", "So slowly at first, that none might notice, even had there been one to watch.", "Over eons of uncounted time, the gray gathered itself in a single place.", "A thing like a smooth gray egg coalesced, then shrunk and contracted until in an explosive burst,The Two were born: One of Light, the Other of Darkness.", "The Great Lovers, Lakana the White, Goddess of Light and Order, andVisaku the Black, God of Darkness and Chaos, blossomed forth into the universe.[2 THE FIRST CHILDREN]In the fullness of time, the Two begat the First Children. ", "The Firstborn was enigmatic.", "They named him Davanu, and tall and proud,Crowned with mighty horns and lusting always for power.", "Red is his color.", "Next in their line was Da’lea the Green, joyful and merciful,Prone to rapid change in mood, but mighty in her generosity and mirth.", "Finally, in a pregnancy that nearly killed Lakana were born the Four:Ravanyx the Golden, fiery in both temperament and appearance;Vaya the color of Sky, fast and effortless in motion, controlled by none;Nitluru the Brown, dwarfed and sturdy, slow to anger, but mighty in wrath;And Tagaryl, green like the Sea, cold and deep, filled with secrets...Read more and learn all about Planar Wardens and Astral Terra at our wiki!" ]

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[ "Q:\n\nnpm module n emits errors\n\nAfter installing n by command 'sudo npm install -g n',\nI want list all node versions,but some errors come out, even though, n can work normally!", "\nAs bellow:\n$ n list\n/usr/bin/n: line 262: which: command not found\n/usr/bin/n: line 262: which: command not found\n\n0.0.1\n0.0.2\n0.0.3\n0.0.4\n\nI don't know why, there is no need to configure my bin foldeer.", "\n\nA:\n\nI have solved it, after npm install which...\nsudo npm install -g whitch\n\n" ]

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[ "<?", "php\n/*\n * $Id$\n *\n * THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS\n * \"AS IS\" AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT\n * LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR\n * A PARTICULAR PURPOSE ARE DISCLAIMED. ", "IN NO EVENT SHALL THE COPYRIGHT\n * OWNER OR CONTRIBUTORS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL,\n * SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT\n * LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE,\n * DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY\n * THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT\n * (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE\n * OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.", "\n *\n * This software consists of voluntary contributions made by many individuals\n * and is licensed under the LGPL. ", "For more information, see\n * <http://www.doctrine-project.org>.", "\n */\n\n/**\n * Doctrine_Validator_Future\n *\n * @package Doctrine\n * @subpackage Validator\n * @license http://www.opensource.org/licenses/lgpl-license.php LGPL\n * @link www.doctrine-project.org\n * @since 1.0\n * @version $Revision$\n * @author Roman Borschel <roman@code-factory.org>\n */\nclass Doctrine_Validator_Future extends Doctrine_Validator_Driver\n{\n /**\n * checks if the given value is a valid date in the future.", "\n *\n * @param mixed $value\n * @return boolean\n */\n public function validate($value)\n {\n if (is_null($value)) {\n return true;\n }\n $e = explode('-', $value);\n\n if (count($e) !", "== 3) {\n return false;\n }\n \n if (is_array($this->args) && isset($this->args['timezone'])) {\n switch (strtolower($this->args['timezone'])) {\n case 'gmt':\n $now = gmdate(\"U\") - date(\"Z\");\n break;\n default:\n $now = getdate();\n break;\n }\n } else {\n $now = getdate();\n }\n \n if ($now['year'] > $e[0]) {\n return false;\n } else if ($now['year'] == $e[0]) {\n if ($now['mon'] > $e[1]) {\n return false;\n } else if ($now['mon'] == $e[1]) {\n return $now['mday'] < $e[2];\n } else {\n return true;\n }\n } else {\n return true;\n }\n }\n}" ]

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[ "Gourmet trip in the Bay of Cancale\n\nHow about a moment to remember at Cancale? ", "On the programme: a boat trip around the bay aboard the Ausquémé, a traditional sailboat, to explore the hidden beauties of the bay. ", "An unforgettable four hours at sea with tasty seafood to sample on board !", "\n\nOn board the Ausquémé !", "\n\nNext stop is Port-Mer where Jérôme, our tanned and handsome blonde sailor awaits us. ", "Without any hesitation he recruits us all as members of his crew! – ", "Straight away it’s all aboard the Ausquémé. ", "The new crew is in charge of the foresail as the captain patiently explains how to work it. ", "And off we go on a four-hour cruise! ", "Using sheer brawn the crew hoists the huge sail which flutters against the blue sky. ", "The sunlight shimmers on the emerald green water and the boat picks up speed on a lively sea as the wind buffets our faces. ", "Refreshed by the spray we feel reinvigorated. ", "More than ready to explore new horizons!", "\n\nAt the helm\n\n“Ready about!” ", "shouts the sailor and the crew enthusiastically roll up their sleeves. ", "Heave-ho! ", "They seize the rope that controls the position of the sail and pull with all their strength to wind it in – one turn, two turns, three turns; it certainly gets your muscles working. ", "The manoeuvre is a success. ", "No words are necessary – we’re a great crew! ", "Everyone takes their turn at the helm, proud to be steering this beautiful, historic craft.", "\n\nGourmet picnic\n\nThe jewels of this bay are revealed to us in quick succession and include the Cancale rock which harbours nests of egrets, gulls, oyster-catchers and cormorants. ", "Then there’s the Isle of Rimains, and the Herpin lighthouse marking the entrance to Mont Saint-Michel bay. ", "The waves and the wind gently rock the boat along; the experience is enchanting. ", "We drop anchor and picnic on board. ", "A sea hamper full of spices delights our palateall – washed down with a delicious cool Muscadet wine. ", "There’s no denying it – it’s a good life at sea!" ]

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[ "# Copyright 2018 Wallaroo Labs Inc.\n#\n# Licensed under the Apache License, Version 2.0 (the \"License\");\n# you may not use this file except in compliance with the License.", "\n# You may obtain a copy of the License at\n#\n# http://www.apache.org/licenses/LICENSE-2.0\n#\n# Unless required by applicable law or agreed to in writing, software\n# distributed under the License is distributed on an \"AS IS\" BASIS,\n# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or\n# implied. ", "See the License for the specific language governing\n# permissions and limitations under the License.", "\n\n\nimport argparse\nimport struct\nimport time\nimport wallaroo\n\n\ndef application_setup(args):\n parse_delay(args)\n in_name, in_host, in_port = wallaroo.tcp_parse_input_addrs(args)[0]\n out_host, out_port = wallaroo.tcp_parse_output_addrs(args)[0]\n\n nonce_source = wallaroo.", "TCPSourceConfig(in_name, in_host, in_port,\n nonce_decoder)\n ok_sink = wallaroo.", "TCPSinkConfig(out_host, out_port, ok_encoder)\n\n inputs = wallaroo.source(\"Counting Sheep\", nonce_source)\n pipeline = (inputs.", "\n .to(process_nonce)\n .key_by(extract_key)\n .to(busy_sleep)\n .to_sink(ok_sink))\n\n return wallaroo.build_application(\"Counting Sheep\", pipeline)\n\n\n@wallaroo.decoder(header_length=4, length_fmt=\">I\")\ndef nonce_decoder(bytes):\n \"\"\"\n Ignore most of the data and just read a partition key off of the\n message.", "\n \"\"\"\n value = struct.unpack_from(\">I\", bytes)[0]\n return (value, bytes)\n\n\n@wallaroo.encoder\ndef ok_encoder(_):\n \"\"\"\n This encoder always returns a plain-text \"ok\" followed but a newline.", "\n It's useful for checking activity interactively during development.", "\n \"\"\"\n return \"ok\\n\"\n\n\n@wallaroo.computation(name=\"Forward nonce partition\")\ndef process_nonce(nonce):\n \"\"\"\n We could probably do something more interesting but for now we pass\n the entire value forward.", "\n \"\"\"\n return nonce\n\n\n@wallaroo.state_computation(name=\"Count sheep\", state=DreamData)\ndef busy_sleep(data, state):\n delay(delay_ms)\n state.sheep += 1\n return None\n\n\nclass DreamData(object):\n __slots__ = ('sheep')\n\n def __init__(self):\n self.sheep = 0\n\n\npartitions = [str(x) for x in range(0, 60)]\n\n@wallaroo.key_extractor\n def extract_key(tuple):\n global partitions\n return str(partitions[tuple[0] % len(partitions)])\n\n# Set by --delay_ms argument\ndelay_ms = 0\n\n\ndef parse_delay(args):\n parser = argparse.", "ArgumentParser(prog='')\n parser.add_argument('--delay_ms', type=int, default=0)\n a, _ = parser.parse_known_args(args)\n global delay_ms\n delay_ms = a.delay_ms\n\n\ndef delay(ms):\n \"\"\"\n This is an intentional busy sleep which blocks execution instead of allowing\n the GIL to be released.", "\n \"\"\"\n if ms == 0:\n return\n target_time = time.time() + (ms / 1000.0)\n c = 0\n while target_time > time.time():\n c = c + 1\n" ]

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[ "Comedian Nick Whitmer headlines Paulaner NYC!", "\n\nNick Whitmer is a comedian who resides in Brooklyn, New York. ", "He has become a staple in New York's comedy scene performing regularly at Caroline's on Broadway, New York Comedy Club, The Stand, and UCB. ", "He has a weekly podcast called Always Be Closing that can be found on iTunes and Sound Cloud. ", "He was the lead in the Unfringed Festival winning play \"Dan Marmor is God\" in 2016." ]

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[ "Mahalo for supporting Honolulu Star-Advertiser. ", "Enjoy this free story!", "\n\nSomething’s in the water and it’s got fishers worried. ", "Read more\n\nSomething’s in the water and it’s got fishers worried.", "\n\nHawaii’s bottomfish catch is way down for some, and sharks may be the culprit.", "\n\nCommercial bottomfish fishers who go after the valuable “Deep 7” — lehi, ehu, onaga, opakapaka, kalekale, gindai and hapuupuu — caught just under 180,000 pounds of those species in the 2018-2019 season.", "\n\nThat’s more than 50,000 pounds less than what was reported in each of the 2017-2018 and 2016-2017 seasons, representing a roughly 25% drop in catch.", "\n\nThe 2018-2019 season, which started Sept. 1, 2018, and ended Aug. 31, was the worst since 1973, according to data from the National Oceanic and Atmospheric Administration that dates back to 1949.", "\n\nThe fishery averaged about 240,000 pounds annually over the last decade before last year’s anomaly, but that’s still just a sliver of about 35 million pounds of fish that commercial fishers in Hawaii report every year.", "\n\nBottomfishing is not a major industry. ", "Longline fishing brings in the biggest catch, accounting for about 30 million pounds per year; tuna handling nets around 1 million pounds annually; and trolling brings in more than 2 million.", "\n\nBut the drop in the bottomfish catch last season has those fishers worried and some suspect that depredation — when hooked fish get eaten — played a significant role.", "\n\nRoy Morioka, a commercial bottomfish fisher, blames shark depredation for the unusually slow year. ", "He said up to 50% of his hooked catch was taken by sharks, much higher than the 10% or so he said is usually taken.", "\n\n“It happens every year, but not to the extent of 40-50% of our catch,” he said.", "\n\nThough sharks are not the only animals that take hooked fish, Morioka said he knows sharks are responsible because he “can see the sucker come all the way up to the surface.”", "\n\nMorioka has been bottom fishing for 60 years and said this is the first time he’s considered stopping.", "\n\n“Amongst the fishermen, everyone’s saying there’s more sharks,” said Edwin Watamura, who is also a bottomfish fisher. “", "It’s hard to get a fisherman not saying that he’s noticing more sharks.”", "\n\nMorioka attributed the increased shark presence to El Nino, which brings warmer waters to Hawaii, and sharks along with it. ", "He said that although El Nino has ended, the warm water associated with it has persisted.", "\n\nSome commercial fishing data confirms fishers’ observations while others don’t, possibly shedding light on the inconsistencies surrounding fishers’ catch reports.", "\n\nWhile the low fishing catch reports from NOAA support claims of increased depredation, its actual depredation numbers showed the opposite.", "\n\nFor the season, fewer than 1,400 instances of depredation were reported by bottomfish fishers, the lowest since depredation reporting started in 2002. ", "In about half the years since, fishers have reported more than 2,000 instances of depredation, and in one year nearly 3,800.", "\n\nAll commercial fishers are required to submit monthly reports of their catches to the State Department of Land and Natural Resources, and for Deep 7 species that are landed, lost to depredation or released, a report is required five days after the fishing trip is completed.", "\n\nKim Holland, a shark researcher at the University of Hawaii’s Institute of Marine Biology, said that shark depredation is and has been a problem for fishers, and it disproportionately affects bottomfish fishers. ", "However, he said catch reports are inconsistent and unreliable, adding that although fishers are required to report their annual catches, they know that it’s difficult for the state Division of Aquatic Resources to enforce that rule.", "\n\n“I would not put any credence in official records, just because I know for a fact that the way they were collected was not consistent and not reliable,” Holland said. “", "Up until about 10 years ago, all of those records … they may have not been voluntary legally, but there was no enforcement.”", "\n\nHolland has previously said that the department is spread too thinly to enforce fishing-related regulations.", "\n\nThere isn’t any substantial incentive for fishers to provide accurate fishing catch reports, and doing so could even be detrimental to them. ", "Morioka said one of those reasons is that catching too much might be perceived as “pillaging” fish populations.", "\n\nAlthough the new bottomfish season started last month, its peak lasts from about November through January, so fishers will have to wait until then to know definitively whether last season’s problems were the beginning of a trend or a fluke." ]

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[ "United Nations ECOSOC supports U.N. assistance to Territories\n\nSupport to\nNon-Self-Governing Territories by the specialized agencies and international\ninstitutions associated with the United Nations\n\nThe Economic and Social Council,\n\nHaving examined the report of the\nSecretary-General[1] and\nthe report of the President of the Economic and Social Council containing the\ninformation submitted by the specialized agencies and other organizations of\nthe United Nations system on their activities with regard to the implementation\nof the Declaration on the Granting of Independence to Colonial Countries and\nPeoples,[2]\n\nHaving heard the statement by the\nrepresentative of the Special Committee on the Situation with regard to the\nImplementation of the Declaration on the Granting of Independence to Colonial\nCountries and Peoples,[3]\n\nRecalling General Assembly resolutions\n1514 (XV) of 14 December 1960 and 1541 (XV) of 15 December 1960, the\nresolutions of the Special Committee and other relevant resolutions and\ndecisions, including, in particular, Economic and Social Council resolution\n2015/16 of 20 July 2015,\n\nBearing in mind the relevant provisions\nof the final documents of the successive Conferences of Heads of State or\nGovernment of Non-Aligned Countries and of the resolutions adopted by the\nAssembly of Heads of State and Government of the African Union, the Pacific\nIslands Forum and the Caribbean Community,\n\nConscious of the need to facilitate the\nimplementation of the Declaration on the Granting of Independence to Colonial\nCountries and Peoples, contained in General Assembly resolution 1514 (XV),\n\nWelcoming\nthe current participation, in their capacity as observers, of those Non‑Self-Governing\nTerritories that are associate members of the regional commissions in the world\nconferences in the economic and social sphere, subject to the rules of\nprocedure of the General Assembly and in accordance with relevant resolutions\nand decisions of the United Nations, including resolutions and decisions of the\nAssembly and the Special Committee on specific Non-Self-Governing Territories,\n\nNoting that only some specialized\nagencies and organizations of the United Nations system have been involved in\nproviding assistance to Non-Self-Governing Territories,\n\nWelcoming the assistance extended to\nNon-Self-Governing Territories by certain specialized agencies and other\norganizations of the United Nations system,\n\nStressing that, because the development\noptions of the small island Non-Self-Governing Territories are limited, they\nface special challenges in planning for and implementing sustainable\ndevelopment, and that they will be constrained in meeting those challenges\nwithout the continuing cooperation and assistance of the specialized agencies\nand other organizations of the United Nations system,\n\nStressing also the importance of\nsecuring the resources necessary for funding expanded programmes of assistance\nfor the peoples concerned and the need to enlist the support of all the major\nfunding institutions within the United Nations system in that regard,\n\nReaffirming the mandates of the\nspecialized agencies and other organizations of the United Nations system to\ntake all appropriate measures, within their respective spheres of competence,\nto ensure the full implementation of General Assembly resolution 1514 (XV) and\nother relevant resolutions,\n\nExpressing its appreciation to the\nAfrican Union, the Pacific Islands Forum, the Caribbean Community and other\nregional organizations for the continued cooperation and assistance they have\nextended to the specialized agencies and other organizations of the United\nNations system in that regard,\n\nExpressing its conviction that closer\ncontacts and consultations between and among the specialized agencies and other\norganizations of the United Nations system and regional organizations help to\nfacilitate the effective formulation of programmes of assistance for the\nNon-Self-Governing Territories concerned,\n\nMindful of the imperative need to keep\nunder continuous review the activities of the specialized agencies and other\norganizations of the United Nations system in the implementation of the various\ndecisions of the United Nations relating to decolonization,\n\nBearing in mind the extremely fragile\neconomies of the small island Non-Self-Governing Territories and their\nvulnerability to natural disasters, such as hurricanes, cyclones and sea-level\nrise, and recalling the relevant resolutions of the General Assembly,\n\nRecalling General Assembly resolution\n70/231 of 23 December 2015, entitled “Implementation of the Declaration on the\nGranting of Independence to Colonial Countries and Peoples”,\n\n1. ", "Takes\nnote of the report of the President of the Economic and Social Council,2\nand endorses the observations and suggestions arising therefrom;\n\n2. ", "Also\ntakes note of the report of the Secretary-General;1\n\n3. ", "Recommends\nthat all States intensify their efforts within the specialized agencies and\nother organizations of the United Nations system of which they are members to\nensure the full and effective implementation of the Declaration on the Granting\nof Independence to Colonial Countries and Peoples, contained in General\nAssembly resolution 1514 (XV), and other relevant resolutions of the United\nNations;\n\n4. ", "Reaffirms\nthat the specialized agencies and other organizations and institutions of the\nUnited Nations system should continue to be guided by the relevant resolutions\nof the United Nations in their efforts to contribute to the implementation of\nthe Declaration and all other relevant resolutions of the General Assembly;\n\n5. ", "Also\nreaffirms that the recognition by the General Assembly, the Security\nCouncil and other United Nations organs of the legitimacy of the aspirations of\nthe peoples of the Non-Self-Governing Territories to exercise their right to self-determination\nentails, as a corollary, the extension of all appropriate assistance to those\npeoples, on a case-by-case basis;\n\n6. ", "Expresses\nits appreciation to those specialized agencies and other organizations of\nthe United Nations system that have continued to cooperate with the United\nNations and the regional and subregional organizations in the implementation of\nGeneral Assembly resolution 1514 (XV) and other relevant resolutions of the\nUnited Nations, and requests all of the specialized agencies and other\norganizations of the United Nations system to implement the relevant provisions\nof those resolutions;\n\n7. ", "Requests\nthe specialized agencies and other organizations of the United Nations system\nand international and regional organizations to examine and review conditions\nin each Non-Self-Governing Territory so that they may take appropriate measures\nto accelerate progress in the economic and social sectors of those Territories\non a case-by-case basis;\n\n8. ", "Urges\nthose specialized agencies and organizations of the United Nations system that\nhave not yet provided assistance to Non-Self-Governing Territories to do so as\nsoon as possible on a case-by-case basis;\n\n9. ", "Requests\nthe specialized agencies and other organizations and bodies of the United\nNations system and regional organizations to strengthen existing measures of\nsupport and to formulate appropriate programmes of assistance to the remaining\nNon-Self-Governing Territories on a case-by-case basis, within the framework of\ntheir respective mandates, in order to accelerate progress in the economic and\nsocial sectors of those Territories;\n\n10. ", "Recommends\nthat the executive heads of the specialized agencies and other organizations of\nthe United Nations system formulate, with the active cooperation of the regional\norganizations concerned and on a case-by-case basis, concrete proposals for the\nfull implementation of the relevant resolutions of the United Nations and\nsubmit those proposals to their governing and legislative organs;\n\n11. ", "Also\nrecommends that the specialized agencies and other organizations of the\nUnited Nations system continue to review, at the regular meetings of their\ngoverning bodies, the implementation of General Assembly resolution 1514 (XV)\nand other relevant resolutions of the United Nations;\n\n12. ", "Recalls\nthe preparation by the Department of Public Information and the Department of\nPolitical Affairs of the Secretariat, in consultation with the United Nations\nDevelopment Programme, the specialized agencies and the Special Committee on\nthe Situation with regard to the Implementation of the Declaration on the\nGranting of Independence to Colonial Countries and Peoples, of an informational\nleaflet on assistance programmes available to the Non-Self-Governing\nTerritories and its updated online version, and requests that they be\ndisseminated as widely as possible;\n\n13. ", "Welcomes\nthe continuing efforts made by the United Nations Development Programme in\nmaintaining a close liaison between the specialized agencies and other\norganizations of the United Nations system, including the Economic Commission\nfor Latin America and the Caribbean and the Economic and Social Commission for\nAsia and the Pacific, and in providing assistance to the peoples of the\nNon-Self-Governing Territories;\n\n14. ", "Encourages\nthe Non-Self-Governing Territories to take steps to establish or strengthen\ndisaster preparedness and management institutions and policies;\n\n15. ", "Requests the administering Powers\nconcerned to continue their cooperation with the specialized agencies and other\norganizations of the United Nations system, in the framework of the\nresponsibilities established in Article 73 of the Charter of the United\nNations, in particular subparagraph d,\nand to facilitate, when appropriate, the participation of appointed and elected\nrepresentatives of Non‑Self-Governing Territories in the relevant meetings and\nconferences of the specialized agencies and other organizations of the United\nNations system, in accordance with relevant resolutions and decisions of the\nUnited Nations, including the resolutions and decisions of the General Assembly\nand the Special Committee on specific Territories, so that they may benefit\nfrom the related activities of those agencies and organizations;\n\n16. ", "Recommends\nthat all Governments intensify their efforts within the specialized agencies\nand other organizations of the United Nations system of which they are members\nto accord priority to the question of providing assistance to the peoples of\nthe Non-Self-Governing Territories on a case-by-case basis;\n\n17. ", "Draws\nthe attention of the Special Committee to the present resolution and to the\ndiscussion held on the subject at the substantive session of 2016 of the\nEconomic and Social Council;\n\n18. ", "Recalls\nthe adoption by the Economic Commission for Latin America and the Caribbean on\n16 May 1998 of its resolution 574 (XXVII),[4] in\nwhich the Commission called for the mechanisms necessary for its associate\nmembers, including the Non-Self-Governing Territories, to participate, subject\nto the rules of procedure of the General Assembly, in the special sessions of\nthe Assembly convened to review and assess the implementation of the plans of\naction of those United Nations world conferences in which the Territories had\noriginally participated in their capacity as observers, and in the work of the\nCouncil and its subsidiary bodies;\n\n19. ", "Requests\nthe President of the Council to continue to maintain close contact on those\nmatters with the Chair of the Special Committee and to report thereon to the\nCouncil;\n\n20. ", "Requests\nthe Secretary-General to follow up on the implementation of the present\nresolution, paying particular attention to cooperation and integration\narrangements for maximizing the efficiency of the assistance activities\nundertaken by various organizations of the United Nations system, and to report\nthereon to the Council at its 2017 session;\n\n21. ", "Decides\nto keep the above questions under continuous review.", "\n\n* In accordance with rule 72 of the rules of\nprocedure of the Economic and Social Council." ]

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[ "Q:\n\nErro login facebook\n\nQuando tento logar pelo facebook através da minha aplicação, dá o erro:\n\nURL bloqueada: O redirecionamento falhou porque o URl usado não está\n na lista de liberação nas configurações de OAuth do cliente do\n aplicativo. ", "Verifique se o login de OAuth do cliente e da Web está\n ativado e adicione todos os domínios do seu aplicativo como URls\n válidos de redirecionamento de OAuth.", "\n\nPesquisei um pouco, e fala que habilitando o Client OAuth Login no Facebook developers, era pra funcionar o login. ", " Porem, fiz este procedimento e o erro ainda persiste. ", "\nComo faço pra resolver isso ? ", "\n\nA:\n\nEsse erro ocorre porque a URL de retorno não está cadastrada no Facebook.", "\nPara isso, você deve acessar o seu aplicativo e adicionar a URL de retorno. ", "Segue um breve tutorial de como fazer esse procedimento:\n1: Acesse a página de seu aplicativo, por exemplo:\n\nhttps://developers.facebook.com/apps/APPID_AQUI/dashboard/\n\n2: Adicione o produto Login do Facebook.", "\n\n3: Em URIs de redirecionamento do OAuth válidos, adicione a URl de retorno da sua aplicação, ou seja, a URI em que o Facebook deverá chamar ao usuário realizar o login.", "\n\nCaso você tenha uma URI que não seja válida, você deverá criar um aplicativo de testes e substituir a APPID e APPKEY de sua aplicação para a do aplicativo de testes.", "\n\n" ]

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[ "Janet Gourlay\n\nJanet A. Gourlay (1863–1912) was a Scottish Egyptologist, born in Glasgow.", "\n\nShe briefly studied at University College, London, with William Matthew Flinders Petrie, the pioneering archaeologist. ", "She joined Margaret Benson in 1896 in her second season of excavation at the Mut Complex in Karnak, Thebes, in Egypt. ", "She became Margaret's lifelong companion.", "\n\nPublications\n Benson, Margaret and Gourlay, Janet. ", "The Temple of Mut in Asher: An account of the excavation of the temple and of the religious representations and objects found therein, as illustrating the history of Egypt and the main religious ideas of the Egyptians, London, John Murray, 1899\n\nReferences\n\nExternal links\n Janet A. Gourlay biography\n\nCategory:1863 births\nCategory:1912 deaths\nCategory:Scottish Egyptologists\nCategory:Alumni of University College London\nCategory:Women archaeologists\nCategory:British women historians" ]

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[ "1. ", "Field of the Invention\nThe present invention relates to printers.", "\n2. ", "Description of the Related Art\nPrinters are widely used for shop registers and automated teller machines (ATMs) or cash dispensers (CDs) in banks.", "\nSuch printers may include a printer body and a lid pivotably supported on the printer body. ", "The lid is opened to allow a roll of recording sheet, such as recording paper, to be loaded into a paper holder of the printer body.", "\nReference may be made to, for example, Japanese Patent No. ", "2585769 and Japanese Laid-Open Patent Applications No. ", "2003-246104 and No. ", "2009-28910 for related art." ]

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[ "Efficacy of pre-surgical axitinib for shrinkage of inferior vena cava thrombus in a patient with advanced renal cell carcinoma.", "\nThe authors present the first case report of pre-surgical axitinib treatment on primary renal tumor and vena cava thrombus. ", "We report the case of a 78-year-old woman with renal cell carcinoma and inferior vena cava tumor thrombus, successfully downstaged with pre-surgical therapy with axitinib. ", "A significant objective response was observed for tumor size and thrombus. ", "After initiation of axitinib therapy, computed tomography showed a decrease, from 57 to 51 mm, in the maximal renal tumor diameter. ", "The tumor thrombus had shortened to 42 mm and had moved to the inferior hepatic vein (Levels 4-3), thereby obviating the need for thoracotomy. ", "The patient finally accepted surgical treatment. ", "Our case was enabled to perform less surgery for advanced renal cell carcinoma with tumor thrombus using axitinib as a pre-surgical therapy." ]

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[ "<!", "DOCTYPE html>\r\n<head>\r\n <meta http-equiv=\"content-type\" content=\"text/html; charset=UTF-8\" />\r\n <link rel=\"stylesheet\" href=\"${base}/ext/bootstrap/css/bootstrap.min.css\" />\r\n <link rel=\"stylesheet\" href=\"${base}/css/admin.css\"/>\r\n <script src=\"${base}/ext/bootstrap/js/jquery.js\" type=\"text/javascript\"></script>\r\n <script src=\"${base}/js/admin.js\" type=\"text/javascript\"></script>\r\n</head>\r\n<body>\r\n<div class=\"container\" style=\"width: 960px;\">\r\n <div class=\"-header\">\r\n <p>\r\n <a href=\"${base}/\" class=\"btn btn-info\" target=\"_blank\">返回首页</a>\r\n <a href=\"${base}/admin/module\" class=\"btn btn-info\">模块管理</a>\r\n <a href=\"${base}/admin/topicList\" class=\"btn btn-info\">topic列表</a>\r\n <a href=\"${base}/admin/postList\" class=\"btn btn-info\">post列表</a>\r\n <a href=\"${base}/admin/replyList\" class=\"btn btn-info\">reply列表</a>\r\n </p>\r\n <hr>\r\n </div>\r\n ${layoutContent}\r\n</div>\r\n</body>\r\n</html>\r\n" ]

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[ "Cloning and characterization of human Lnk, an adaptor protein with pleckstrin homology and Src homology 2 domains that can inhibit T cell activation.", "\nLnk was originally cloned from a rat lymph node cDNA library and shown to participate in T cell signaling. ", "Human Lnk (hLnk) was cloned by screening a Jurkat cell cDNA library. ", "hLnk has a calculated molecular mass of 63 kDa, and its deduced amino acid sequence indicates the presence of an N-terminal proline-rich region, a pleckstrin homology domain, and a Src homology 2 domain. ", "When expressed in COS cells, hLnk migrates with an apparent molecular mass of 75 kDa. ", "Confocal fluorescence microscope analysis indicates that in COS cells transfected with an expression vector encoding a chimeric Lnk-green fluorescent protein, hLnk is found at the juxtanuclear compartment and also appears to be localized at the plasma membrane. ", "Lnk is tyrosine-phosphorylated by p56lck. ", "Following phosphorylation, p56lck binds to tyrosine-phosphorylated hLnk through its Src homology 2 domain. ", "In COS cells cotransfected with hLnk, p56lck, and CD8-zeta, hLnk associated with tyrosine-phosphorylated TCR zeta-chain through its Src homology 2 domain. ", "The overexpression of Lnk in Jurkat cells led to an inhibition of anti-CD3 mediated NF-AT-Luc activation. ", "Our study reveals a potentially new mechanism of T cell-negative regulation." ]

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[ "Q:\n\nFilter one collection based on another with AngularJS custom filter\n\nI need to filter a collection of objects based on another collection in angularjs. ", " I need to create a custom filter I'm sure but have found no examples that are similar. ", " So I have a list of \"equipmentOptions\" (basically they are product customizations, ex. ", "premium stereo in your car). ", " Some \"equipmentOptions\" are not available unless you have already selected other \"equipmentOptions\". ", " \nThe equipmentOptions available are $scope.product.equipmentOptions.", "\nThe equipmentOptions that have been selected are $scope.product.selectedOptions.", "\nequipmentOptions has a property requiredParents which is a collection of id's for other equipment options. ", " If any of these requiredParents exist in $scope.product.selectedOptions, then the equipmentOption should be shown.", "\nHere's what I've tried so far to no avail:\n<div ng-repeat=\"option in product.equipmentOptions | optionsFilter:product.selectedOptions\">\n\noptionsFilter.js\nmyApp.filter('optionsFilter', function () {\nreturn function (selectedOptions) {\n // I'm just trying to get the list of selected options as well as the current option here for filtering, how do I get the current option?", "\n};\n\n});\n\nA:\n\nYour first argument is the list of product.equipmentOptions. ", "The second argument is product.selectedOptions. ", "Write your filter like this:\nmyApp.filter('optionsFilter', function() {\n return function(equipmentOptions, selectedOptions) {\n var filteredOptions = [];\n angular.forEach(equipmentOptions, function(option) {\n if(/*option meets criteria*/) {\n filteredOptions.push(option);\n }\n });\n return filteredOptions;\n }\n});\n\n" ]

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[ "require \"substitution.k\"\n\nmodule MINPI-SYNTAX\n imports SUBSTITUTION\n \n syntax Var ::= Id\n syntax Zero ::= \"0\"\n syntax For ::= \"for\" \"(\" Var \"<-\" Var \")\" \"{\" Terms \"}\" [binder]\n syntax Send ::= Var \"!\" ", "Var\n syntax New ::= \"new\" Var \".\" \"(\" ", "Terms \")\" [binder]\n syntax Rep ::= \"rep\" \"{\" Terms \"}\"\n syntax Term ::= Zero\n | For\n | Send\n | New\n | Rep\n syntax Terms ::= List{Term, \"|\"}\n syntax KVariable ::= Var\nendmodule\n\nmodule MINPI\n imports MINPI-SYNTAX\n \n configuration <T> \n <ins>\n <in multiplicity=\"*\"> . ", "</in>\n </ins>\n <outs>\n <out multiplicity=\"*\"> . ", "</out>\n </outs>\n <k> $PGM:Terms </k> \n </T>\n\n rule\n <k> _:Zero | Ts:Terms => Ts </k>\n\n rule\n <k> F:For | Ts:Terms => Ts </k>\n <ins> (Is) => (Is <in> F </in>) </ins>\n\n rule\n <k> S:Send | Ts:Terms => Ts </k>\n <outs> (Os) => (Os <out> S </out>) </outs>\n\n rule\n <in> for (Y <- X) { Ts:Terms } => . ", "</in>\n <out> X ! ", "Z => . ", "</out>\n <k> .Terms => Ts[Z / Y] </k>\n\nendmodule" ]

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[ "{\r\n Copyright 1999-2005 ImageMagick Studio LLC, a non-profit organization\r\n dedicated to making software imaging solutions freely available.", "\r\n \r\n You may not use this file except in compliance with the License.", "\r\n obtain a copy of the License at\r\n \r\n http://www.imagemagick.org/script/license.php\r\n \r\n Unless required by applicable law or agreed to in writing, software\r\n distributed under the License is distributed on an \"AS IS\" BASIS,\r\n WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.", "\r\n See the License for the specific language governing permissions and\r\n limitations under the License.", "\r\n\r\n Pixel Iterator Methods.", "\r\n}\r\n\r\ntype\r\n PixelIterator = record\r\n id: culong;\r\n\r\n name: array[0..MaxTextExtent] of char;\r\n\r\n exception: ExceptionInfo;\r\n\r\n view: PViewInfo;\r\n\r\n region: RectangleInfo;\r\n\r\n y: cint;\r\n\r\n pixel_wand: PPPixelWand;\r\n\r\n debug: MagickBooleanType;\r\n\r\n signature: culong;\r\n end;\r\n \r\n PPixelIterator = ^PixelIterator;\r\n\r\n\r\nfunction PixelGetIteratorException(const iterator: PPixeliterator;\r\n severity: PExceptionType): PChar; cdecl; external WandExport;\r\n\r\nfunction IsPixelIterator(const iterator: PPixeliterator): MagickBooleanType; cdecl; external WandExport;\r\nfunction PixelClearIteratorException(iterator: PPixeliterator): MagickBooleanType; cdecl; external WandExport;\r\nfunction PixelSetIteratorRow(iterator: PPixeliterator;\r\n const row: cint): MagickBooleanType; cdecl; external WandExport;\r\nfunction PixelSyncIterator(iterator: PPixeliterator): MagickBooleanType; cdecl; external WandExport;\r\n\r\nfunction DestroyPixelIterator(iterator: PPixeliterator): PPixelIterator; cdecl; external WandExport;\r\nfunction NewPixelIterator(wand: PMagickWand): PPixelIterator; cdecl; external WandExport;\r\nfunction NewPixelRegionIterator(\r\n wand: PMagickWand; const x, y: cint; const columns, rows: culong;\r\n const modify: MagickBooleanType): PPixelIterator; cdecl; external WandExport;\r\n\r\nfunction PixelGetNextIteratorRow(iterator: PPixeliterator; var wandCount: culong): PPPixelWand; cdecl; external WandExport;\r\nfunction PixelGetPreviousIteratorRow(iterator: PPixeliterator; var wandCount: culong): PPPixelWand; cdecl; external WandExport;\r\n\r\nprocedure ClearPixelIterator(iterator: PPixeliterator); cdecl; external WandExport;\r\nprocedure PixelResetIterator(iterator: PPixeliterator); cdecl; external WandExport;\r\nprocedure PixelSetFirstIteratorRow(iterator: PPixeliterator); cdecl; external WandExport;\r\nprocedure PixelSetLastIteratorRow(iterator: PPixeliterator); cdecl; external WandExport;\r\n\r\n{\r\n Deprecated.", "\r\n}\r\n{extern WandExport char\r\n *PixelIteratorGetException(const PixelIterator *,ExceptionType *);\r\n\r\nextern WandExport PixelWand\r\n **PixelGetNextRow(PixelIterator *);}\r\n\r\n" ]

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[ "Q:\n\nhow to retrieve text from an xml\n\nI want to try an retrieve the name of a hotel (in this example the hotel is called 'Test Hotel'), but I am unsure how to do it because I believe to get a @node it's using @ but how do I retrieve a text?", "\nBelow is the xml:\n<xxx xmlns:soap=\"xxx\" xmlns:xsi=\"xxx\" xmlns:xsd=\"xxx\">\n <xxx>\n <xxxxmlns=\"xxx\">\n <AvailabilityRS Url=\"xxx\" IntCode=\"xxx\">\n <Results>\n <HotelResult Code=\"xxx\"DestinationZone=\"xxx\">\n <HotelInfo>\n <Name>Test Hotel</Name>\n\nBelow is the script:\ndef response = testRunner.testCase.getTestStepByName(\"xxx\").getProperty(\"Response\").getValue()\ndef parsedxml = new XmlSlurper().parseText(response)\n\ndef hotelName = parsedxml.", "'soap:Body'.", "HotelAvailResponse[0].xxx[0].Results[0].xxxx[0].xxx[0].Name[0].toString()\n\nA:\n\nInstead of using toString(), you should be able to just use text()\ndef hotelName = parsedxml.", "Body\n .HotelAvailResponse\n .AvailabilityRS\n .Results\n .HotelResult\n .HotelInfo\n .Name.text()\n\n" ]

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[ "Solubility soluble in water.", "Aqueous solution is colorless transparent to translucent, transparency influenced greatly by concentration and temperature. ", "Generally, as the concentration increases, the opacity will increases; as the temperature decreases, the opacity will also increases." ]

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[ "Transcript\n\n1.", "\nJan Rojthana\nCross Cultural Issues\nConflictCase Study March 2011\n1\nThai and Cambodia\nPart 1: Introductionto the conflict.", "\nThe Phra Viharn Temple is located on the Thailand-Cambodia border. ", "It is known in\nCambodia as Khao Phra Viharn. ", "There has been a temple since the early 9th Century which is a\nplace of Hindu worship it moved overto Buddhism during the centuries.", "\nThe temple has been a source of conflict between Thailand and Cambodia for more than a\nhundred years. ", "It seemed that a peaceful solution was arrived at in 1963 when Cambodia took\n'official' possession and agreed to freedom of access by Thai citizens and agreeing that they could\nretain ownership of any removed artifacts. ", "However, in 2008 the Temple was to be declared a\nWorld Heritage site with the agreement of Thailand and Cambodia but it did not go according to\nplan as Thailand backed out. ", "Another redrawing of the border started an argument amongst Thai\npolitical parties. ", "This current disagreement has led to a continuing heavy presence of troops from\nboth sides of the border. ", "Shooting, rockets, many deaths and wound are becoming all to frequent\nas is the war of words between the two countries.", "\nIn this case, Thailand and Cambodia has conflicts of whose the Phra Viharn temple belongs\nto, which lead to the problem that who has the right to take the temple. ", "It is true that the main part\nof the temple is on Cambodia side, but the path of the entrance of the temple is on the Thailand side.", "\nHowever, people from both side need to talk to agree with each other conflict even though there\nwill be many problems after that.", "\n\n2.", "\nJan Rojthana\nCross Cultural Issues\nConflictCase Study March 2011\n2\nPart 2: Causes of the Conflict. ", "Students must use two ideas from our list of why does\nconflict happen? ", "To explain the original causes of the conflict they are examining. ", "Use specific\ninformation from research to support your analysis.", "\nConflict is a necessity of life for people to learn and grow. ", "It occurs when individuals fail to\nagree to disagree fairly simple complex. ", "In this case, the conflict between Thailand and Cambodia is\nNationalism and the miscommunication. ", "Cambodia has presented Phra Viharn Temple to be the\nworld heritage as the path of the temple.", "\nThe first idea of how does the conflict happen is that Cambodia’s main rationale for helping\nTaksin is that the Thai justice system is unjust and not fair in which there is a recent Thai poll says\nthat most Thais see that the Thai justice system that is going after Taksin is not fair. ", "However, the\ngovernment is reported that it will build Nationalism feelings in Thailand to shore up failing\npopularity, and the Thai support for a war with Cambodia is expected to be firm in which there are\nmany opinions from the government that says that Cambodia’s helping Taksin is about weakening\nthe Thais. ", "Furthermore, People from Thailand and Cambodia have their own nationalism which\nmakes them think that they are right to possess, causing a conflict that whose will the Phra Vihear\nbelongs to? ", "Due to that conflict, people start to gather together in their country to protest that , in\nCambodia, Phra Viharn Temple belongs to them while, in Thailand, people want to make sure that it\ndoes not belong to anyone but both. ", "Another idea of the cause of the occurrence of conflict is the\nmiscommunication between two countries that it is important for both sides to have a talk to\nunderstand each other’s conflict and come up with a solution to solve it. ", "Thai prime minister has\ntried so many times to talk with the Cambodian prime minister and every times are failed. ", "This is\nbecause of the Cambodia refuses to talk and try to solve problem with Thailand and in the same\ntime refuse to understand Thai’s problem. ", "Therefore, those that are mentioned can lead to the\nescalation of conflictswhichmake the conflictsget worstby the time.", "\n\n3.", "\nJan Rojthana\nCross Cultural Issues\nConflictCase Study March 2011\n3\nPart 3. ", "Escalation of the Conflict. ", "Students must use two ideas from our list of How / Why do\nconflicts \"escalate\"? ", "to explain how this conflict has gotten worse over time. ", "Students may want\nto include media examples in this section.", "\nThere were the escalation of conflicts which cause the loss of Thai citizens which causes by border\nconflict between Thai and Cambodian. ", "The first example of how or why does the conflicts escalates\nis when one side \"Loses Face\" or suffers a public embarrassment, it becomes more difficult to\ncompromise. ", "This is especially true when leaders feel they need to maintain backing of supporters.", "\nFrom the conflict, Cambodia has put the sign on the Watt Kaew as Kmer’s temple but in fact it is on\nThailand side in which it is not clearly claimed as an overlapped area so Thai people ask to put\ndown the sign. ", "At last Cambodian agreed to put down but it takes long time for the argument.", "\nAnother example of escalation of the conflict is the loss of life (or some other \"offense\") puts\npressure on leadership to \"win\" and makes it difficult to compromise in which Cambodia started to\nfire into Thai territory during the night time which has hurt and kill many solders and several\npeople. ", "Furthermore, they have also destroyed the school in the Thai area as well. ", "However, they\nhave put on forcesat PhraViharn Temple side whichagainst the international regulation.", "\n\n4.", "\nJan Rojthana\nCross Cultural Issues\nConflictCase Study March 2011\n4\nPart 4. ", "Conclusion - Students must offer their ideas on what is going to need to happen in order\nfor this conflict to end. ", "This can include general comments based on our Conflict Resolution ideas\ndiscussed in class however, students also must include specific idea/proposals from their research.", "\nStudents are also encouraged to include at least one example of someone working to try and reduce\ntension and/or solve the conflict.", "\nCambodia proposed Thailand military left the area of Phra Viharn and each side\npulled back its military by 10 km, but Thai rejected the move on basis of Cambodia has no\nright to suggest to Thai any military movements. ", "Cambodia military personals have shown\nintentions on crossing into clearly defined Thai territories on several occasions, according\nto Thai military.", "\nConflict usually occurs when there are differences within a person or between two\nor more people that touches them in a significant way. ", "Therefore, if people agree to listen\nto other side and try to understand each other than the conflicts between there will not be\nsuch a big problem like this. ", "For what happen between Thailand and Cambodia is that\npeople from either side, Thailand and Cambodia, do not have a well communication to\nunderstand their conflict in which it can create the misunderstanding of things in which it\ncan lead to a big problem in the future such as loss of people because people from each side\nmight agree that they do not do anything wrong so that it is not their faults." ]

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[ "A Review Of case study assistance\n\nA Review Of case study assistance\n\nYou will require the next provides for every injection of HUMIRA. ", "Look for a clean up, flat area to position the materials on. ", "one Liquor swab\n\nIn Study PCD-I, allergic reactions ended up observed in 5% of children which had been all non-significant and were generally localized reactions.", "\n\nOnce the vessel broke in two and the fires burned out, responders resumed salvage efforts around the bow part, which was finally towed out to sea and sunk in deep drinking water (see Reference [one]) for particulars of the operation).", "\n\nBenefits from each research shown statistically major reduction of the risk of therapy failure in individuals handled with HUMIRA compared to patients obtaining placebo.", "\n\nHUMIRA has been examined in 1696 subjects with plaque psoriasis (Ps) in placebo-managed and open-label extension scientific studies. ", "The safety profile for topics with Ps taken care of with HUMIRA was comparable to the safety profile noticed in topics with RA with the following exceptions.", "\n\nEach time a file is deleted in Windows NT, the file will probably be renamed by OS and moved it to Recycle bin with a unique identification. ", "OS shops details about the first path and first file name in info2 file. ", "However, if a file is deleted within the Recycle bin, then connected clusters are marked as accessible for new knowledge. ", "NTFS is much more economical than Extra fat, as it is faster in reclaiming its deleted Area. ", "NTFS disks are a knowledge stream, which means they can be appended into A different current file. ", "An information stream file could be stored as follows:\n\nWill not contact this location again right before offering the injection. ", "Enable the skin to dry before injecting. ", "Will not admirer or blow within the clean up space.", "\n\nCumulative case experiments. ", "These provide to combination information from a number of internet sites collected at diverse times.", "\n\nPopper himself used the now well-known example: \"All swans are white\", and proposed that just one observation of only one black swan would falsify this proposition and in this way have basic significance and promote even more investigations and idea-setting up. ", "this link The case study is like minded for figuring out \"black swans\" because of its in-depth method: what appears to generally be \"white\" generally seems on nearer assessment to generally be \"black\".", "\n\nAt SKF, iPhone and iPad join manufacturing unit operators to colleagues as well as production line, enabling employees to collaborate and quickly remedy complications.", "\n\nIn clients with moderately to seriously Energetic UC, the rate of antibody progress in individuals acquiring check my source HUMIRA was five%. ", "However, because of the limitation in the assay ailments, antibodies to adalimumab may very well be detected only when serum adalimumab amounts were < 2 mcg/mL.\n\nIn pediatric sufferers with Crohn's condition, the rate of antibody development in sufferers acquiring HUMIRA was three%. ", "However, mainly because of the limitation of the assay disorders, antibodies to adalimumab could be detected only when serum adalimumab ranges ended up < two mcg/mL.\n\nOught to continue to keep holding the HUMIRA Pen versus their squeezed, raised skin right until most of the medicine is injected. ", "This will take as many as ten seconds.", "\n\nNonetheless, an evaluation of your case check my site delivers insight to engineers and incident responders to the envisioned structural conduct of these types of seriously stranded vessels, and highlights possible implications with the in-situ oil burning technique." ]

{ "pile_set_name": "Pile-CC" }

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[ "---\nabstract: 'Various authors have investigated the problem of light deflection by radially moving gravitational lenses, but the results presented so far do not appear to agree on the expected deflection angles. ", "Some publications claim a scaling of deflection angles with $1-v$ to first order in the radial lens velocity $v$, while others obtained a scaling with $1-2v$. In this paper we generalize the calculations for arbitrary lens velocities and show that the first result is the correct one. ", "We discuss the seeming inconsistency of relativistic light deflection with the classical picture of moving test particles by generalizing the lens effect to test particles of arbitrary velocity, including light as a limiting case. ", "We show that the effect of radial motion of the lens is very different for slowly moving test particles and light and that a critical test particle velocity exists for which the motion of the lens has no effect on the deflection angle to first order. ", "An interesting and not immediately intuitive result is obtained in the limit of a highly relativistic motion of the lens towards the observer, where the deflection angle of light reduces to zero. ", "This phenomenon is elucidated in terms of moving refractive media. ", "Furthermore, we discuss the dragging of inertial frames in the field of a moving lens and the corresponding Lense-Thirring precession, in order to shed more light on the geometrical effects in the surroundings of a moving mass. ", "In a second part we discuss the effect of transversal motion on the observed redshift of lensed sources. ", "We demonstrate how a simple kinematic calculation explains the effects for arbitrary velocities of the lens and test particles. ", "Additionally we include the transversal motion of the source and observer to show that all three velocities can be combined into an effective relative transversal velocity similar to the approach used in microlensing studies.'", "\nauthor:\n- Olaf Wucknitz\n- Ulrich Sperhake\ndate: 19 Jan 2004\ntitle: Deflection of light and particles by moving gravitational lenses\n---\n\nIntroduction\n============\n\nThe subject of gravitational lenses (light deflection by gravitational fields in the Universe) is a well-established field in modern astrophysical research (see, e.g., [@blandford92; @refsdal94; @narayan99; @sef]). ", "Applications include cosmology, dark matter, the large scale structure in the Universe, clusters of galaxies, galactic structure, the structure of the Milky Way, and even the search for extrasolar planets. ", "Not to be forgotten, light deflection by the Sun’s gravitation was the first test of the then new theory of general relativity [@dyson20].", "\n\nIn almost all of the studies, the deflecting masses are treated as being at rest in the cosmological Robertson-Walker metric or (in the limit of noncosmological lensing) at rest with respect to the source and observer. ", "This is well justified since most sufficiently massive astronomical lenses have velocities very small compared to the velocity of light, which leads only to minor gravitomagnetic corrections.", "\n\nIn addition to the potential astrophysical relevance, our main motivation to study moving lenses is the desire to understand the fundamental physics governing the light deflection caused by such systems in an intuitive and possibly Newtonian interpretation. ", "This leads us to the comparison of the deflection of light with the deflection of slowly moving particles and especially the effect any motion of the lens has on either.", "\n\nIn contrast to most previous work, we do not only consider effects to first order in velocity ([FOV]{}) but for the first time calculate the deflection for arbitrary velocities of both lens and deflected particle (including light in the ultrarelativistic limit).", "\n\nTo our knowledge, the first calculations of the deflection of light in gravitational fields were done by Cavendish (see @will88) and @soldner1801. ", "This early work is based on the ansatz of Newtonian particles moving with the speed of light. ", "@einstein11 used the principle of equivalence to avoid the physically unsound picture of classical particles for the description of light. ", "The result is naturally the same. ", "Only after the formulation of general relativity the result had to be revised to be *twice* as large as expected from classical theory [@einstein15]. ", "This relativistic result has been confirmed by numerous tests with very high accuracy, see, e.g., [@robertson91; @lebach95].", "\n\nEarlier studies in the context of moving gravitational lenses were undertaken by several authors. ", "In 1993 @pyne93 calculated the effects of the lens’ motion on the deflection in a Minkowski background metric. ", "For radial motion with velocity $v$ they found the deflection angle to scale with a factor $1-v$ in [FOV]{} approximation. ", "The deflection increases if light and lens are moving in opposite directions (as seen by the observer). ", "Interestingly, the leading term is of first order; i.e., the effect is not merely a consequence of scaling with the special-relativistic parameter $\\gamma=1/\\sqrt{1-v^2}$.\n\nIn contrast to this, @capozziello99 found a different scaling behavior of $1-2v$ for point-mass lenses. ", "They later generalized their calculations to other mass distributions with the remarkable but questionable result that the scaling of the deflection caused by a rigidly moving lens does not only depend on the mass distribution and velocity of the lens but also on its internal parameters [@capozziello01]. ", "This is of particular significance because it would enable us to derive information from such observations about the inner structure of lenses beyond their mass and momentum. ", "The same scaling for point mass lenses was found by @sereno02a and later generalized for other mass distributions in [@sereno02b].", "\n\nAn alternative analytic method was used by @frittelli02a which confirmed the result of [@pyne93]. ", "@frittelli02b also discusses the discrepancy between the two results, again favoring [@pyne93]. ", "Below we will demonstrate how we find our results to agree with those of [@pyne93; @frittelli02a; @frittelli02b; @molnar02], whereas our velocity corrections differ by a factor of 2 from the values of [@capozziello99; @capozziello01; @sereno02a; @sereno02b].", "\n\nA further interesting result of [@pyne93] concerns the effect of a *transversal* motion of the lens on the observed redshift of the source. ", "We believe this to be the most promising possibility of actually measuring gravitomagnetic effects in gravitational lensing and even utilizing them for astrophysical studies. ", "Concrete practical scenarios are discussed by @molnar02.", "\n\n@kopeikin99 presented an exhaustive calculation of light propagation in the field of an ensemble of arbitrarily moving point masses in terms of retarded Liénard-Wiechert potentials, covering effects on both deflection angles and redshifts.", "\n\nAside from gravitational lenses of standard astronomical origin, the deflection of light by topological defects in the universe, such as cosmic strings, has stimulated a great deal of scientific investigation. ", "Of most interest in the context of our work is the study of moving cosmic strings (see, for example, @deLaix1996 and @uzan). ", "Below we will discuss the similarities and differences arising from such different types of lenses and motions.", "\n\nThis paper is organized as follows. ", "After a summary of the notation and approximations used in this work, we begin our discussion with the analysis of purely radial motion of the gravitational lens in Sec.", " \\[sec:radial\\]. ", "In view of the fact that the gravitational lensing effect is commonly described in the framework of Newtonian physics, it will be important to verify to what extent this approximation remains valid for *moving* lenses. ", "For this purpose we will present a Newtonian calculation of the deflection of massive test particles in Sec.", " \\[sec:class\\] and contrast the results with the relativistic expressions derived in Secs.", " \\[sec:obs frame\\] and \\[sec:lens frame\\]. ", "The dependency of the deflection on the test particle’s velocity will be studied in detail in Sec.", " \\[sec:disc radial\\]. ", "We then turn our attention to the effect of transversal motion of the lens in Sec.", " \\[sec:transverse\\] and conclude in Sec.", " \\[sec:conclusions\\].", "\n\nA comparison of our analytic results for radial motion with more accurate numerical simulations is presented in Appendix \\[sec:geoexac\\]. ", "An illustration of how some of the calculated effects can be understood in a more intuitive fashion in terms of moving refractive media is given in Appendix \\[sec:refrindex\\]. ", "Finally we discuss in Appendix \\[sec:framedrag\\] the dragging of inertial frames in the field of a moving lens by calculating the Lense-Thirring precession in this case.", "\n\nNotation and approximations\n===========================\n\nIn this work we will measure velocities in units of the speed of light, i.e., we set $c=1$. The velocity of the lens is denoted by $v$ and that of the test particle by $w$. The deflection of light is obtained in the limit $w=1$. Without loss of generality we perform all calculations in “2+1” dimensions, described by Cartesian coordinates $y$ and $z$ and time $t$. For all relativistic calculations we will use the metric signature $(+--)$.\n\nUnless stated otherwise we use the weak-field and small-angle approximation as is common in gravitational lens theory. ", "We restrict our discussion to thin lenses so that it is sufficient to calculate the deflection of light in a cosmologically small region around the lens only. ", "We are thus able to describe the surroundings of the lens by the Minkowski metric. ", "The local deflection angle calculated in this way can then be used as part of the cosmological lens equation in which it is related with cosmological distances and the *observed* positional displacement, see, e.g., [@sef].", "\n\nIn the weak-field limit, the line element in the *rest frame of the lens* can be written as $${\\mathrm{d}}s^2 = \\left(1+2\\Phi\\right){\\mathrm{d}}t'^2 -\n\\left(1-2\\Phi\\right)\\left({\\mathrm{d}}y'^2+{\\mathrm{d}}z'^2\\right) \n{\\hspace{0.4em}\\text{.}}", "\n\\label{eq:metric static}$$ Here we have used primed coordinates to distinguish the rest frame of the lens from that of the observer (unprimed coordinates). ", "The static Newtonian gravitational potential $\\Phi$ is linear in the mass distribution and satisfies $|\\Phi|\\ll1$.\n\nThe unperturbed light/particle is traveling in the positive $z$ direction at $y=0$ with velocity $w$ as measured in the unprimed observer system. ", "The deflected trajectories will therefore be directed at small angles relative to the $z$ axis. ", "The only requirement we impose on the velocity of the test particle is that it travels faster than the lens, i.e., $w>v$, so that it passes the lens in the usual direction.", "\n\nThe approximations imply that deviations of $y$ from the unperturbed path $y\\equiv 0$ need to be calculated to first order only. ", "This “first order in deflection” ([FOD]{}) approximation is not to be confused with [FOV]{}. ", "Below, these approximations will allow us to integrate along the unperturbed path instead of the deflected (and then still unknown) path itself. ", "We will further be able to compare the deflection of light for lenses at different velocities without changing the light path close to the lens, i.e., without changing the impact parameter. ", "In this approximation we can also relate the coordinates along the path of the test particle by $${\\mathrm{d}}z = w\\,{\\mathrm{d}}t\n{\\hspace{0.4em}\\text{.}}", "\n\\label{eq:dz=wdt}$$\n\nThe deflection angle is the difference of the propagation directions before and after passing the lens. ", "For small angles and propagation close to the $z$ direction, this can be written as $$\\alpha = \\left.\\frac{{\\mathrm{d}}y}{{\\mathrm{d}}z}\\right|{_\\text{out}} -\n\\left.\\frac{{\\mathrm{d}}y}{{\\mathrm{d}}z}\\right|{_\\text{in}} {\\hspace{0.4em}\\text{.}}", "\n\\label{eq:def defl}$$ For the ingoing path we have $z\\to-\\infty$, for the outgoing $z\\to+\\infty$.\n\nFor the radial velocity of the lens and the test particle we will adopt the sign-convention that they are positive if directed towards the observer so that $v$ and $w$ are measured in the same direction. ", "This definition is opposite to the usual astronomical definition of radial velocities but is commonly used in the literature on moving gravitational lenses.", "\n\nRadial motion {#sec:radial}\n=============\n\nNonrelativistic calculation based on\\\nthe principle of equivalence\\[sec:class\\]\n-----------------------------------------\n\nWe begin our discussion of the effect of purely radial motion of the lens on the resulting deflection angle with a Newtonian discussion. ", "Aside from providing an intuitive insight into the effect, the results thus obtained will also enable us below to highlight the quantitative and qualitative modifications arising in a general relativistic treatment.", "\n\nIn order to avoid a description of light in terms of classical particles, we follow the lines of @einstein11 and apply the principle of equivalence to the gravitational effects and use nonrelativistic kinematics otherwise. ", "At each point of the path of a test particle, we can define a freely falling observer who is momentarily at rest and who views the deflected path in her vicinity as a straight line. ", "The equations of motion of this observer are given by $$\\begin{aligned}\n{2}\n\\frac{{\\mathrm{d}}^2 y}{{\\mathrm{d}}t^2} &= - \\Phi_y {\\hspace{0.4em}\\text{,}} &\n\\qquad \\frac{{\\mathrm{d}}^2 z}{{\\mathrm{d}}t^2} &= - \\Phi_z {\\hspace{0.4em}\\text{,}}\n\\label{eq:motion obs}\\end{aligned}$$ where $\\Phi_y$ and $\\Phi_z$ denote partial derivatives of the potential with respect to $y$ and $z$, respectively. ", "In the frame of this observer, the acceleration of the test particles vanishes, so that they follow the same equations of motion as the falling observer.", "\n\nIn order to calculate the deflection angle defined in Eq.", "  we need to calculate ${\\mathrm{d}}y/{\\mathrm{d}}z$. In [FOD]{}this is obtained from Eq.", "  by replacing time derivatives with $z$ derivatives according to Eq.", "  and integrating once over $z$. We thus obtain for the deflection angle $$\\alpha{^\\text{cl}}_w(v) = -\\frac{1}{w^2}\\int_{-\\infty}^\\infty{\\mathrm{d}}z \\, \\Phi_{y}\n (y,z){\\hspace{0.4em}\\text{.}}$$ Next we transform the integral to primed coordinates. ", "First we note that the boost does not affect the $y$ direction, so that $\\Phi_y(y,z)=\\Phi_{y'}(y',z')$. Secondly we can use Eq.", "  together with the nonrelativistic limit of the Lorentz transformation below to obtain ${\\mathrm{d}}z'=(1-v/w)\\,{\\mathrm{d}}z$. This gives us the deflection angle as $$\\alpha{^\\text{cl}}_w(v) = -\\frac{1}{w(w-v)}\\int_{-\\infty}^\\infty{\\mathrm{d}}z' \\, \\Phi_{y'} (y',z'){\\hspace{0.4em}\\text{.}}$$ The integral is now expressed entirely in terms of the coordinates of the lens’ rest frame and is therefore independent of the velocity $v$ (the perturbation of the gradient $\\Phi_{y'}$ on a perturbed path is of second order in the deflection angle and is thus ignored in [FOD]{}). ", "We can therefore express the dependency of the deflection angle on the velocity $v$ of the lens in [FOV]{} approximation as $$\\begin{aligned}\n\\frac{\\alpha{^\\text{cl}}_w(v)}{\\alpha{^\\text{cl}}_w(0)} &= \\frac{w}{w-v}\n{\\hspace{0.4em}\\text{,}}\n\\label{eq:alpha class i}\n\\\\\n\\alpha{^\\text{cl}}_w(0) &= - \\frac{1}{w^2}\\int_{-\\infty}^\\infty{\\mathrm{d}}z' \\,\n\\Phi_{y'}{\\hspace{0.4em}\\text{.}}", "\n\\label{eq:alpha class ii}\\end{aligned}$$ The factor $1/w^2$ in the last equation can be interpreted as follows. ", "One factor $1/w$ originates from Eqs.", "  and and represents the geometrical effect that the transversal acceleration due to the gradient $\\Phi_{y'}$ and the resulting change in velocity along the $y$ direction $\\Delta w_\\bot$ correspond to a larger deflection angle the smaller the velocity-component $w$ along the $z$ direction. ", "The second factor $1/w$ is due to the interaction time which scales inversely with the velocity $w$. The first contribution is unchanged for moving lenses while the interaction time now scales inversely with the *relative* velocity $w-v$, leading to the correction factor in Eq.", " .", "\n\nThis result is not only exact in the nonrelativistic limit ($w \\rightarrow 0$) but still provides a decent approximation for the deflection angle of *light* for lenses *at rest*: The only modification caused by general relativity is an additional factor of 2. ", "One may ask whether this remains true for *moving* lenses — can one simply apply the missing scaling factor of 2 to the deflection angle of light in the moving case as well? ", "Below we will learn that this is not the case.", "\n\nAs a qualitative result for slowly moving particles, we find from Eq.", "  that the deflection increases (due to the change in interaction time) if the test particle and lens are moving in the same direction. ", "We will see that the opposite holds for light, so there exists a test particle velocity ${w{_\\text{c}}}$ for which motion of the lens has no effect on the deflection angle in [FOV]{}approximation. ", "We will study this feature in more detail in the next sections when we calculate the deflection in the framework of general relativity.", "\n\nRelativistic calculation in the observer frame\\[sec:obs frame\\]\n---------------------------------------------------------------\n\nIn order to calculate the trajectories of test particles in the observer’s rest frame, in which the lens is moving, we need to find the line element in this system. ", "For this purpose we transform the line element from the rest frame of the lens (primed) to that of the observer (unprimed coordinates). ", "The corresponding Lorentz transformation is given by $$\\begin{aligned}\n{\\mathrm{d}}t' &= \\gamma \\left({\\mathrm{d}}t- v \\, {\\mathrm{d}}z\\right) {\\hspace{0.4em}\\text{,}}\n\\label{eq:lotra i}\n \\\\\n{\\mathrm{d}}y' &= {\\mathrm{d}}y {\\hspace{0.4em}\\text{,}} \\\\\n{\\mathrm{d}}z' &= \\gamma \\left({\\mathrm{d}}z - v \\, {\\mathrm{d}}t\\right) {\\hspace{0.4em}\\text{,}} \n\\label{eq:lotra iii}\\end{aligned}$$ where $\\gamma=1/\\sqrt{1-v^2}$. We drop the [FOV]{} approximation for this calculation so that the line element for arbitrary velocity $v$ in the observer’s rest frame is given by $$\\begin{aligned}\n{\\mathrm{d}}s^2 = &\n\\left[1+2\\left(1+v^2\\right)\\gamma^2\\Phi\\right]{\\mathrm{d}}t^2 -\n \\left(1-2\\Phi\\right)\\,{\\mathrm{d}}y^2 \\notag \\\\\n& - \n\\left[1-2\\left(1+v^2\\right)\\gamma^2\\Phi\\right]\\,{\\mathrm{d}}z^2 - 8 v\\gamma^2\\Phi \\,{\\mathrm{d}}t\\, {\\mathrm{d}}z{\\hspace{0.4em}\\text{.}}", "\n\\label{eq:metric moving}\\end{aligned}$$ In the limit of small $v$ this metric reduces to the [FOV]{} result of @sef.", "\n\nThe geodesic equation with a given metric is equivalent to an Euler-Lagrange system of equations with Lagrange function $$L= \\left(\\frac{{\\mathrm{d}}s}{{\\mathrm{d}}\\lambda}\\right)^2 {\\hspace{0.4em}\\text{,}}\n\\label{eq:lagrange}$$ where $\\lambda$ is an affine parameter of the test particle’s world line. ", "We denote the derivative with respect to this parameter by a dot, e.g., ${\\mathrm{d}}y/{\\mathrm{d}}\\lambda=\\dot{y}$. Using the line element , the equation for $y$ in [FOD]{}approximation becomes $$\\begin{gathered}\n\\frac{{\\mathrm{d}}}{{\\mathrm{d}}\\lambda} \\frac{\\partial L}{\\partial \\dot y} -\n\\frac{\\partial L}{\\partial y} = 0 {\\hspace{0.4em}\\text{,}}\n\\label{eq:elg y}\n\\\\\n\\ddot y = -\\left[ \\left(1+v^2\\right)\\left(\\dot t^2+\\dot\n z^2\\right) - 4v\\,\\dot t\\dot z \\right] \\gamma^2 \n\\Phi_y {\\hspace{0.4em}\\text{.}}", "\n\\label{eq:ddot y}\\end{gathered}$$ Terms like $\\dot{\\Phi}\\dot y$, $\\Phi\\ddot{y}$ and ${\\dot y}^2$ are neglected here because they are of higher order in the deflection.", "\n\nFrom the corresponding equations for $z$ and $t$ we learn that deviations from the undeflected path in these coordinates are of the same order as the deflection in $y$ so that they become insignificant after multiplication with $\\Phi_y$ in Eq.", " . ", "We can therefore apply $\\dot t=\\dot z/w$ from Eq.", "  for the undeflected path and use $\\lambda=z$ as the affine parameter. ", "Equation  can then be written as $$\\frac{{\\mathrm{d}}^2 y}{{\\mathrm{d}}z^2} = -\\left[ (1+v^2)(1+w^{-2}) -\n 4\\frac{v}{w} \\right] \\gamma^2 \\Phi_y \\label{eq: d2ydz2_rel}\n{\\hspace{0.4em}\\text{.}}$$ After integration we can use Eq.", "  and find the deflection angle $$\\begin{aligned}\n\\alpha_w (v) &= \\int_{-\\infty}^\\infty {\\mathrm{d}}z \\, \n\\frac{{\\mathrm{d}}^2 y}{{\\mathrm{d}}z^2} \\label{eq: integral_rel} \\\\\n&= \\frac{1}{(1-v/w)\\gamma} \\int_{-\\infty}^\\infty {\\mathrm{d}}z' \\, \\frac{{\\mathrm{d}}^2\n y}{{\\mathrm{d}}z^2} {\\hspace{0.4em}\\text{.}}", "\n\\label{eq:factor scale 2}\\end{aligned}$$ In the final step we applied a parameter transformation from $z$ to $z'$ using the unperturbed particle path and the Lorentz transformation . ", "This result can again be written as a correction to the deflection angle $\\alpha_w(0)$ caused by a lens at rest, so that we obtain $$\\begin{aligned}\n\\frac{\\alpha_w (v)}{\\alpha_w(0)} &= \\frac{\\gamma}{1-v/w} \\left( 1+v^2 -\n \\frac{4vw}{1+w^2} \\right) {\\hspace{0.4em}\\text{,}}\n\\label{eq:alpha c}\n\\\\\n\\alpha_w (0) &= -(1+w^{-2}) \\int_{-\\infty}^\\infty {\\mathrm{d}}z'\n\\, \\Phi_{y'}{\\hspace{0.4em}\\text{.}}", "\n\\label{eq:alpha 0 c}\\end{aligned}$$ As before the integral in Eq.", "  is evaluated to [FOD]{} by using the unperturbed path. ", "We emphasize that in this approximation the impact parameter, and thus the integral in Eq.", " , is a background quantity, i.e. remains constant for different values of $v$ and $w$. In all our comparisons of deflection angles obtained for different velocities we will therefore consider the impact parameter as being kept constant, even in the numerical calculations below which go beyond [FOD]{}.", "\n\nFor the special case of light and a lens at rest ($w=1$, $v=0$), the comparison of Eq.", "  with the classical result yields the additional factor of 2 introduced by general relativity. ", "In the nonrelativistic limit $|v|,w\\ll1$ we recover the classical result .", "\n\nRelativistic calculation in the lens frame\\[sec:lens frame\\]\n------------------------------------------------------------\n\nIn view of the discrepancy between the results presented in the literature (see, e.g., [@pyne93] and [@capozziello99]), we consider it appropriate to calculate the same effect again in the lens’ reference frame.", "\n\nFor this purpose we consider Eq.", "  which remains valid *in the rest frame of the lens* even for nonzero $v$ and which can be derived directly from the usual static weak-field metric .", "\n\nWe must take into account in that case, however, that the particle velocity now is $w'$ (instead of $w$) and that the resulting deflection angle will be $\\alpha'$, i.e., the angle as viewed in the lens’ system. ", "In order to facilitate a comparison with the results of the previous section we need to Lorentz-transform both quantities into the observer’s rest frame. ", "We first consider the velocity $w'$.\n\nBecause of the [FOD]{} approximation we can consider the velocities $w$, $w'$ as the components along the $z$ axis for this transformation. ", "This is reflected by Eq.", "  and its analogue in primed coordinates ${\\mathrm{d}}z'=w'{\\mathrm{d}}t'$. Combining these relations with the Lorentz transformation – we directly obtain the relativistic addition of velocities $$w' = \\frac{w-v}{1-vw}{\\hspace{0.4em}\\text{.}}", "\n\\label{eq:vel comp}$$ We simplify the transformation of the deflection angle $\\alpha$ by defining the direction of the ingoing path as that of zero deflection. ", "We therefore need to transform the outgoing path only which is parametrized by $$\\begin{aligned}\n{\\mathrm{d}}z' &= w' \\, {\\mathrm{d}}t' {\\hspace{0.4em}\\text{,}} \\\\\n{\\mathrm{d}}y' &= \\alpha'_{w'}(0) \\, {\\mathrm{d}}z'\\end{aligned}$$ \\[cf.", " Eqs.", "  and \\]. ", "Again we use the Lorentz transformation – to eliminate the primed coordinate differentials and Eq.", "  to express the result in terms of the deflection angle in the *observer’s rest frame*. ", "We thus obtain $$\\begin{aligned}\n\\frac{\\alpha_w(v)}{\\alpha'_{w'}(0)} = \\left(1-\\frac{v}{w}\\right)\\gamma\n{\\hspace{0.4em}\\text{.}} ", " \n\\label{eq:lorentz contrib}\\end{aligned}$$ Eventually we want to compare deflection angles for *equal test particle velocities* $w$, so that we still need to express $\\alpha'_{w'}(0)$ in terms of $\\alpha_w(0)$. From Eq.", "  we directly obtain $$\\begin{aligned}\n\\frac{\\alpha'_{w'}(0)}{\\alpha_w(0)} &=& \\frac{1+w'^{-2}}{1+w^{-2}} \\nonumber\\\\\n&=& \\left(1-\\frac{v}{w}\\right)^{-2} \\left(1+v^2-\\frac{4vw}{1+w^2}\\right) \n{\\hspace{0.4em}\\text{,}}\n\\label{eq:w w'}\\end{aligned}$$ which becomes unity in the special case of light ($w=w'=1$). ", "The combination of Eqs.", "  and confirms the above result calculated directly from the viewpoint of the observer.", "\n\nDiscussion of radial motion\\[sec:disc radial\\]\n----------------------------------------------\n\n### Rigidly moving lenses\n\nWe now turn our attention to the interpretation of the deflection of light for a rigidly moving gravitational lens to [FOD]{}. ", "For this purpose we consider the limit of Eq.", "  for $w\\to1$. In that case the scaling has the simple form $$\\begin{aligned}\n\\frac{\\alpha(v)}{\\alpha(0)} = (1-v)\\,\\gamma =\\sqrt{\\frac{1-v}{1+v}} {\\hspace{0.4em}\\text{.}}", "\n\\label{eq:scaling light}\\end{aligned}$$ To [FOV]{} this becomes $1-v$ which confirms the result of [@pyne93] while it differs by a factor of 2 from that given in [@capozziello99]. ", "We further note that the quotient $\\alpha(v)/\\alpha(0)$ diverges for $v\\to -1$ but vanishes in the limit $v\\to +1$. Thus, rather surprisingly, a lens approaching the observer with a highly relativistic velocity will *not* deflect the passing light at all even though the effective mass-energy of the lens as viewed by the observer diverges in this limit.", "\n\nIn view of the counterintuitive nature of this result one may ask whether the approximation of small deflection angles (FOD) underlying this calculation is still justified in the limit of $v \\rightarrow 1$. In order to clarify this point we have numerically solved the full geodesic equations, e.g., Eq., ", "for the case of a point mass ($\\Phi=-M/r$) *without* FOD approximation. ", "Instead of Eq.", "  we obtain in this case a system of three nontrivial second order ordinary differential equations for $t$, $y$, and $z$. These equations together with more details of the numerical treatment are listed in Appendix \\[sec:geoexac\\]. ", "Note that the only approximation in this numerical calculation is the assumption of a weak gravitational field in the *rest frame of the lens*. ", "In Fig.", " \\[fig:deflexac\\] we plot the resulting geodesics and the deflection angles obtained for different velocities of the lens together with the analytic result in FOD approximation as given by Eq.", " . ", "For these calculations source and observer are located at $z= \\pm 10\\,000\\,M$, respectively, while the impact parameter, which equals the $y$ position of the source with high accuracy, is $150\\,M$. The precise values of these parameters do not affect our results. ", "The lens is always positioned at $y=0$ and moves along the $z$ axis, so that it reaches $z=0$ at the same time as the null-geodesics. ", "Note that the $y$ position of the observer depends on the deflection angle since the impact parameter is kept constant as the lens’ velocity $v$ is varied.", "\n\nThe excellent agreement between the numerical deflection angle and that predicted by the approximate FOD result demonstrates the validity of the FOD approximation in our calculations even for strongly relativistic velocities $v$.\n\n![", "\\[fig:v\\] The deflection angle caused by a moving lens in units of that arising from a lens at rest as given by Eq.", "  is shown as a function of $v$. The graphs are obtained for $w=1$ (light), $0.9$, $0.577=1/\\sqrt{3}$ ($=w_{\\rm c}$), and $0.1$. We note that the curve for $w={w{_\\text{c}}}$ is stationary at $v=0$, i.e., small lens velocities have no effect for this critical test particle velocity. ](", "figv.eps){width=\"\\figwidth\"}\n\nWith regard to the deflection of light by cosmic strings we first note that such types of lenses induce vector and tensor perturbations of the metric in addition to the scalar perturbations in our Eq. ", "\\[cf.", " Eq.(38) of @uzan\\] which can be combined into an effective deflecting potential. ", "The deflection angle can be expressed in terms of this deflection potential and our result \\[Eqs.", " , \\] corresponds to the limit of their Eq.(45) for purely scalar perturbations and linear motion of the lens. ", "In general, [@uzan] find the vector and tensor perturbations to be neglegible as long as the thin lens approximation is valid but not necessarily for the case of extended lenses. ", "A time dependence of the deflecting potential which is of particular interest for string type lenses (because they are expected to move with relativistic velocities) is that of an oscillating loop. ", "For this scenario the deflection of light passing sufficiently far outside the loop has been found to be identical to that of a point mass source (see [@deLaix1996; @uzan] for details). ", "In contrast, the linear motion studied in this work gives rise to a vector perturbation of the metric, which manifests itself in the ${\\mathrm{d}}t\\,{\\mathrm{d}}z$ cross term of the boosted line element . ", "The analogy between this term and rotational effects will be studied in more detail in Appendix\\[sec:framedrag\\].", "\n\nIt remains therefore to obtain a better understanding of how the deflection vanishes in the limit of a lens moving towards the observer at highly relativistic velocities. ", "For this purpose we provide in Appendixes \\[sec:refrindex\\] and \\[sec:framedrag\\] a description in terms of refractive media and the dragging of inertial frames similar to the frame dragging close to rotating bodies.", "\n\nWe now return to the general behavior of the deflection angle for arbitrary velocities $v$ and $w$ which is shown in Fig.", " \\[fig:v\\]. ", "This graphic demonstrates the singular behavior of the deflection angle at $v=-1$ and (provided $w\\ne 1$) $v=w$. The singularity at $-1$ arises from the diverging factor $\\gamma$ while the second singularity is a consequence of the vanishing relative velocities which causes the interaction time to become infinitely large.", "\n\nWe next discuss the limit of small lens velocities $v$ ([FOV]{}) combined with a comparatively larger, but otherwise arbitrary speed of the test particle, i.e., $w \\gg v$. In this case the scaling of Eq.", "  simplifies to $$\\frac{\\alpha_w(v)}{\\alpha_w(0)} = 1- \\frac{3w^2-1}{1+w^2} \\, \\frac{v}{w}\n{\\hspace{0.4em}\\text{.}} ", "\n\\label{eq:scaling slow}$$ We have already mentioned above that the deflection of light scales with $1-v$ to [FOV]{} whereas the Newtonian result of Eq.", "  predicts a scaling of $1+v/w$ for nonrelativistic test particles satisfying $w \\gg v$. Hence there must be a critical velocity ${w{_\\text{c}}}$ of the test particle for which the deflection angle is independent of the lens’ velocity $v$ to [FOV]{}. ", "From Eq.", "  we see that this critical particle velocity is ${w{_\\text{c}}}=1/\\sqrt 3$. We illustrate the functional behavior of Eq.", "  in Fig.", " \\[fig:c\\].", "\n\n![", "\\[fig:c\\][Effect of small lens velocities $v$ on the deflection angle. ", "According to Eq.", "  the deflection scales with $1-(v/w)\\,f$, where]{} $f=(3w^2-1)/(1+w^2)$. The graph shows $f$ as a function of the test particle velocity $w$. The effect has opposite signs for $w\\to \n 0$ and $w=1$ and there is a critical particle velocity ${w{_\\text{c}}}=1/\\sqrt 3$ for which the lens motion has no effect to [FOV]{}.](figc.eps){width=\"\\figwidth\"}\n\nOnly after finishing our calculations we learned that special properties of the velocity $1/\\sqrt3$ have been discussed before by Carmeli \\[[@carmeli72] and problem 5.5.1 in [@carmeli82]\\]. ", "There it was found that the coordinate velocity of a massive particle approaching the center of a Schwarzschild metric in a radial direction *increases* only for asymptotic starting velocities smaller than $1/\\sqrt3$ but *decreases* otherwise, all in a [FOD]{}approximation. ", "The same was later independently rediscovered by @blinnikov01 [@blinnikov03]. ", "It can indeed be shown easily that the same is true for any 1+1 dimensional weak field with a metric of ${\\mathrm{d}}s^2=(1+2\\Phi) {\\mathrm{d}}t^2 - (1-2\\Phi){\\mathrm{d}}r^2$. To first order in $\\Phi$, there is no coordinate acceleration for $w={w{_\\text{c}}}$. This effect can in principle be detected by measuring round trip travel times.", "\n\nWith regard to the observation of the deflection caused by a radially moving lens we note that it is not possible to distinguish the scaling of the deflection angle with $\\alpha_w(v)/\\alpha_w(0)$ from a scaling with the total mass of the lens. ", "For a given test particle, the effect can therefore be used to infer a radial motion of the lens only if an accurate and independent estimate of the lens’ mass is available. ", "An alternative way to disentangle the two effects would consist of measuring deflection angles of test particles with *different* velocities $w$. Unfortunately, appropriate test particles other than light are currently not available in astrophysics. ", "Even if we could measure the direction of cosmic rays consisting of massive particles with higher accuracy than is possible with existing instruments, they would not serve our purpose as they travel at highly relativistic speeds and would be subject to practically the same deflection as light. ", "Furthermore they are also deflected by electric and magnetic fields.", "\n\n### Compound lenses\n\nIt is an interesting question whether the gravitomagnetic correction to the deflection of light or particles could be used to deduce information about the inner structure (e.g., the velocity field) of a lens as suggested by the results of @capozziello01 for the deflection of light. ", "We address this question by considering a compact (relative to the impact parameter $r$) lens which we treat as a collection of point masses located close to each other. ", "In terms of our formalism, the argument in favor of the possibility to probe the inner structure of the lens can be summarized as follows. ", "Consider a lens with two components of equal mass $m$ moving in opposite directions with the same speed. ", "Compared to a lens at rest with mass $2m$, we expect a deflection angle larger by a factor $\\gamma$ because the compound lens will appear as a lens of mass $2m\\gamma$ in the observer’s rest frame. ", "Because of the more complicated dependence of its right-hand side on $v$, however, Eq.", "  will predict a different deflection angle for this scenario. ", "It appears therefore that the deflection is not uniquely determined by the total four-momentum of the lens.", "\n\nThis argument is not valid, however, because the compound lens must be compact not only momentarily but for the whole interval during which the test particle passes by and is deflected significantly. ", "Otherwise the lens would effectively be extended so that the deflection would test rather the mass distribution than the internal velocity field of the lens. ", "Measurable effects are not surprising in that case.", "\n\nThe time scale for the passage is $r/w$ and the displacements of the lens’ components during this interval are $r v/w$. Because these displacements must be $\\ll r$ to preserve the compactness of the lens, we obtain an upper limit for the velocities of its components, $|v|\\ll w$. In this limit, however, the right-hand side of Eq.", "  becomes approximately $\\gamma (1 + \\mathrm{const}\\,\\, v)$ and the total deflection is indeed determined by the total four-momentum. ", "We thus conclude that no information about the internal structure beyond the mass and total momentum of a compact lens can be obtained from the lensing effect. ", "In the case of light ($w \\rightarrow 1$) this is also demonstrated by Eq.", " , where the deflection is always determined by the total four-momentum, $\\alpha\\propto p_t - p_z = \\sum_j (1-v_j)\\gamma_j m_j$.\n\nComparison with previous results\\[sec:compar\\]\n----------------------------------------------\n\nWe will now address the question of what causes the discrepancies between our results and those in [@capozziello99; @sereno02a] where the velocity effects appear to be overestimated by a factor of 2. ", "Note that this also affects the ensuing results published in [@capozziello01; @sereno02b] which generalize to mass distributions other than point masses. ", "Both these groups exclusively use light as test particles, work in a [FOV]{} approximation and use essentially the same approach as @sef in formulating the problem.[^1] Following this approach, we use the equivalent formulation of light propagation in an Euclidean metric with an effective index of refraction $n$ (cf.", " Appendix \\[sec:refrindex\\]). ", "For a rigidly moving lens with gravitational potential $\\Phi$, this index can be calculated from setting $\\theta = 0$ in Eqs.", "  and and is given by $$n-1=-2\\,(1-2v)\\Phi{\\hspace{0.4em}\\text{,}}$$ which does indeed contain the factor $1-2v$. In order to obtain the correct scaling, however, we must further take into account that the motion of the lens affects the potential $\\Phi$ which now becomes time-dependent in the observer’s rest frame. ", "It is most convenient to calculate the total deflection integral over the path of light in the primed coordinates of the lens’ rest frame. ", "We thus replace $\\Phi(t,y,z) = \\Phi(y',z')$ with $z'=z-vt$ from Eq.", "  and substitute $z'$ for $z$ in the integral. ", "The same procedure has been used in Eq.", "  for the classical and in Eq.", "  for the relativistic calculation. ", "This correction describes the scaling of time of interaction caused by the different relative velocity. ", "The resulting additional factor $1+v$ was *not* applied in [@capozziello99] and [@sereno02a] but would otherwise have changed their scaling factor $1-2v$ to the correct result of a $1-v$ scaling of light deflection in [FOV]{}approximation. ", "@frittelli02b, on the other hand, *did* apply this factor in her Eqs.", " (33) and (34) and arrives at the same result as we do in Secs.", " \\[sec:obs frame\\] and \\[sec:lens frame\\] above.", "\n\nTransversal motion\\[sec:transverse\\]\n====================================\n\nDeflection angle\n----------------\n\nUntil now we have restricted our discussion to a radial motion of the lens, because this velocity component is the only one affecting the deflection angle to [FOV]{}. ", "In this section we will discuss the effects of transversal motion. ", "For this purpose we use the same approximations as in the discussion of radial velocity effects, i.e. we allow for weak deflections only and work in the [FOD]{} approximation. ", "For radially moving lenses, the light path across the lens does not depend on the velocity so that a nonzero velocity merely gives rise to an overall scaling factor. ", "This is no longer the case for large transversal velocities. ", "Due to aberration, the direction of light propagation in the lens’ rest frame *does* depend on the velocity so that an additional term involving the radial derivative $\\Phi_{z'}$ appears in the geodesic equation. ", "The resulting scaling law would therefore depend on the mass distribution and is not of general validity and immediate interest.", "\n\nBy using the methods of Secs.", " \\[sec:obs frame\\] and \\[sec:lens frame\\], however, it can be shown that to [FOV]{} the deflection angle is *not* modified at all by transversal motion.", "\n\nRedshift\n--------\n\nEven though a transversal motion of the lens does not affect the deflection angle to [FOV]{}, there is an interesting effect on the observed redshift of the source. ", "This can be illustrated as follows. ", "When the test particle approaches the lens it falls into the potential well and gains energy. ", "During the passage, the lens is moving, so that the potential experienced by the particle as it climbs out of the potential well will differ from that before. ", "The associated loss in energy of the test particle will therefore not exactly compensate for its earlier gain. ", "The resulting net change in energy can be measured as a change in the velocity of the test particle or the energy, i.e., wavelength, in the case of a photon.", "\n\nAlternatively one can view the effect in the following way. ", "The test particle traveling on the rear side of the lens (with respect to the transversal motion) will be deflected towards the lens and slow down the motion of the lens so as to preserve total momentum. ", "The energy loss of the lens (which is proportional to its initial velocity, see below) has to be transferred to the particle. ", "For particles passing on the other side of the lens, this effect has the opposite sign. ", "We will now quantify these ideas straightforwardly by calculating the effect in the framework of special relativistic kinematics.", "\n\nThe transversal momentum transferred from the lens to the test particle in the course of the deflection is given by $$\\Delta p_\\bot = \\alpha\\, p_\\|{\\hspace{0.4em}\\text{,}}\n\\label{eq:alpha delta p}$$ where $p_\\|$ is the radial momentum of the particle. ", "We can calculate the accompanying transfer of energy $\\Delta E$ by using the fundamental equations of special-relativistic kinematics $$\\begin{aligned}\n{3}\nE^2&=m^2+p^2 {\\hspace{0.4em}\\text{,}}\\qquad &\n{\\mathbf{p}}&=E {\\mathbf{v}} {\\hspace{0.4em}\\text{,}}\\qquad &\nE&= m\\gamma {\\hspace{0.4em}\\text{.}}", "\n\\label{eq:kinem}\\end{aligned}$$ From the first of these equations we derive $E\\Delta E={\\mathbf{p}}\\cdot \\Delta {\\mathbf{p}}$ to first order in $\\Delta E$ and thus, together with the second one, $$\\Delta E={\\mathbf{v}} \\cdot\\Delta {\\mathbf{p}}\n{\\hspace{0.4em}\\text{.}}", "\n\\label{eq:kinem2}$$ We now apply this equation both to the lens and the test particle to write the equation of energy conservation as $$v_\\|\\,\\Delta p_\\| + v_\\bot \\, \\Delta p_\\bot = w\\,\\Delta p_\\|\n{\\hspace{0.4em}\\text{.}} ", "\\label{eq:energy balance}$$ The left-hand side is the energy loss of the lens, written in terms of a possible radial velocity component of the lens $v_\\|$ and its transversal velocity $v_\\bot$. On the right-hand side we have the energy gain of the test particle. ", "Here the transversal part is of higher order in the deflection and can be neglected. ", "Combining Eqs.", "  and we directly obtain the relative change in radial momentum of the particle $$\\frac{\\Delta p_\\|}{p_\\|} = \\alpha \\frac{v_\\bot}{w-v_\\|}\n{\\hspace{0.4em}\\text{.}}", "\n\\label{eq:redshift lens}$$ Even though this relation is valid for arbitrary values of the velocities, we will assume $v_{\\|}=0$ for the following discussion.", "\n\n![", "\\[fig:geom\\]The lensing geometry. ", "The solid line shows the deflected light path while the horizontal axis is the undeflected light path from the source to the observer. ", "The deflection angle is $\\alpha$ and the apparent position of the source is $\\Delta\\theta$. The true position would be at an angle of zero. ", "As shown in the figure, $\\alpha$ is negative while $\\Delta\\theta$, $\\Delta\\phi$, and $y{_\\text{d}}$, $y'{_\\text{s}}$ are positive.](geom.eps){width=\"\\xfigwidth\"}\n\nIn the case of light and assuming $v_\\|=0$ we can relate the relative change in momentum to a shift in frequency or an additional redshift of $\\Delta z=-\\alpha\\, v_\\bot$, which agrees with the [FOV]{} results of @pyne93 and @kopeikin99. ", "In spite of the remarkably simple derivation, however, our results remain valid for arbitrary lens potentials and lens and particle velocities. ", "Equations – do not even depend on the physical process which causes the deflection but instead are valid for any kind of scattering by a massive moving target.", "\n\nGeometry\n--------\n\nSo far we have only considered a transversal motion *of the lens* but assumed that source and observer are at rest. ", "In reality, source, lens, and observer will all be moving relative to the cosmological Robertson-Walker background metric. ", "It is therefore necessary to also take into account the motion of source and observer. ", "We will calculate the resulting total redshift in the framework of the [FOV]{} approximation. ", "The fundamental geometry is shown in Fig.", " \\[fig:geom\\]. ", "If the source is moving with a transversal velocity $v{_\\text{s}}$, this will lead to a velocity component in the direction of the real path of light and, thus, a Doppler velocity of $v{_\\text{s}} \\Delta\\phi$. We have already seen in the discussion of Eq.", "  that a transverse velocity $v{_\\text{d}}$ of the lens leads to a Doppler shift analogous to an apparent radial velocity $v{_\\text{d}} \\alpha$ of the source. ", "The motion of the observer themself gives rise to an additional contribution corresponding to a radial velocity of $v{_\\text{o}} \\Delta \\theta$. In [FOV]{} approximation, the net Doppler effect is obtained by linear addition of these velocities because $(1+\\Delta z)$ acts multiplicatively, see Eq.", "  below.", "\n\nIf we denote the apparent size distance parameter[^2] from $a$ to $b$ (angle measured at $a$, size measured at $b$) with $D_{ab}$, we can use two equations each to express the apparent position of the source $y'{_\\text{s}}$ and the position of the lens $y{_\\text{d}}$ using different angles and distances (cf.", "Fig.", " \\[fig:geom\\]) $$\\begin{aligned}\n{2}\ny'{_\\text{s}} &= \\quad - \\alpha \\, D{_\\text{ds}} &\\quad&= \\quad \\Delta\\theta \\,\nD{_\\text{os}} {\\hspace{0.4em}\\text{,}} \\\\ \ny{_\\text{d}} &= \\quad \\Delta\\theta \\, D{_\\text{od}} &\\quad&= \\quad \\Delta\\phi \\,\nD{_\\text{sd}}.\\end{aligned}$$ These equations can be used to express $\\alpha$ and $\\Delta\\phi$ in terms of the apparent displacement $\\Delta\\theta$ (also called apparent deflection angle) to write the total Doppler velocity in terms of this angle. ", "Because of the expansion of the Universe, distance parameters depend on the direction, i.e., $D{_\\text{sd}}\\ne D{_\\text{ds}}$. The two can easily be related, however, using the redshifts $z{_\\text{s}}$ and $z{_\\text{d}}$ of source and lens so that we obtain $$\\frac{D{_\\text{sd}}}{D{_\\text{ds}}} = \\frac{1+z{_\\text{s}}}{1+z{_\\text{d}}} {\\hspace{0.4em}\\text{.}}$$ This leads to the final expression for the total Doppler velocity $$\\begin{aligned}\n{v{_\\text{Dopp}}}= \\left( \\frac{1+z{_\\text{d}}}{1+z{_\\text{s}}} \\frac{D{_\\text{od}}}{D{_\\text{ds}}}\n v{_\\text{s}} -\\frac{D{_\\text{os}}}{D{_\\text{ds}}} v{_\\text{d}} + v{_\\text{o}} \\right)\n\\Delta\\theta\n{\\hspace{0.4em}\\text{.}}", "\n\\label{eq:v eff}\\end{aligned}$$ Remember that our sign convention for ${v{_\\text{Dopp}}}$ is opposite to that commonly used for astronomical radial velocities, so that the observed redshift $z'{_\\text{s}}$ is given as a modification of the unperturbed redshift $z{_\\text{s}}$ in the following way: $$1+z'{_\\text{s}} = (1+z{_\\text{s}}) (1+\\Delta z) = (1+z{_\\text{s}})(1-{v{_\\text{Dopp}}})\n\\label{eq:zs' vdopp}$$ In the case of a surrounding Minkowski metric, the redshift factors become unity and the distance parameters become additive. ", "In this case Eq.", "  predicts a zero Doppler velocity if source, lens and observer are all moving with the same velocity, as expected. ", "The combination of velocities is very similar to the effective transversal velocity $V$ defined by @krs86 [Eq.", " (B9)] to discuss effects of microlensing. ", "The only difference (besides the multiplication with $\\Delta\\theta$) is that their $V$ is projected into the source plane and incorporates a cosmological time dilation factor, so that $${v{_\\text{Dopp}}}= (1+z{_\\text{d}}) \\frac{D{_\\text{od}}}{D{_\\text{ds}}} \\, V \\Delta\\theta \n{\\hspace{0.4em}\\text{.}}$$\n\nIf more than one lensed image of the source is observed, the effect of the transversal motion can be separated from the [*a priori*]{} unknown radial velocity (including cosmological redshift) of the source, which usually contributes a much larger Doppler effect. ", "In this case the radial velocity will have the same effect on all images while the effect of transversal motion depends on the position of the image. ", "The latter can therefore be measured unambiguously by comparing the Doppler shifts of at least two images. ", "This possibility makes the situation conceptually very different from the effects of radial motion on deflection angles which cannot be distinguished from a scaling of the total mass of the lens.", "\n\nUnfortunately the effects are so small that it is hardly possible to detect them with current state-of-the-art instruments, see e.g., [@molnar02]. ", "However, telescopes planned for the future, in particular radio arrays like ALMA (“Atacama Large Millimeter Array”) or SKA (“Square Kilometer Array”), will provide sufficient sensitivity and spectral resolution to measure the effect for sources with sharp spectral features to facilitate a sufficiently accurate determination of redshifts.", "\n\nSummary {#sec:conclusions}\n=======\n\nIn this work we used different methods to calculate the effect of *radially* moving lenses on the deflection of light as well as test particles with arbitrary velocity. ", "These calculations are valid for arbitrary lens velocities and thus generalize the results of previous publications (e.g., [@pyne93; @frittelli02a; @frittelli02b; @molnar02]) dealing with the deflection of light by slowly moving lenses (FOV). ", "At the same time we have demonstrated how neglecting the time dependence of the potential of a moving lens (which is equivalent to the scaling of the interaction time) accounts for the discrepancy between our results and those of [@capozziello99; @sereno02a; @capozziello01; @sereno02b]. ", "In agreement with [@frittelli02b] we find the inclusion of this time dependence essential for obtaining correct deflection angles.", "\n\nOur study of the deflection of light and particles by radially moving lenses has revealed some rather surprising results. ", "While a motion of the lens parallel to the test particle velocity increases the deflection of slowly moving particles, as is intuitively expected from the decreasing relative velocity and increasing interaction time, the opposite is true for the deflection of light. ", "As a consequence there exists a critical particle velocity of ${w{_\\text{c}}}=1/\\sqrt 3$ for which the motion of the lens does not have any effect on the deflection to first order. ", "These results imply that the classical approach of treating light as classical particles, while providing qualitatively correct results for lenses at rest (see e.g., @soldner1801), does not facilitate a satisfactory description for the case of radially moving lenses. ", "This behavior seems to be related to the effects found by @carmeli72 [@carmeli82] and @blinnikov01 [@blinnikov01; @blinnikov03] for radial motion in the Schwarzschild metric where massive particles are accelerated when approaching the center only for $w<{w{_\\text{c}}}$ but decelerated otherwise.", "\n\nAs a further surprising result we find that the deflection angle of light vanishes in the limit of gravitational lenses approaching the observer with highly relativistic velocities, even though the effective mass-energy of the lens diverges in this limit. ", "Intuitively one would have rather expected a diverging deflection angle in this scenario. ", "In Appendix \\[sec:refrindex\\] we provide a descriptive explanation of this effect by demonstrating how gravitational lensing can be formulated in terms of light propagating in a refractive medium, both for static *and* moving lenses. ", "In this picture the coordinate velocity of light is reduced in the rest frame of the lens. ", "For the case of a relativistically moving lens, however, this reduction is effectively compensated by the motion of the rest frame of the lens with respect to the observer, so that the net reduction vanishes. ", "The unchanged velocity of light in turn implies a vanishing deflection angle.", "\n\nWe have addressed the question whether the deflection of test particles or light can provide information about the internal structure of a rigidly moving, compact lens beyond its mass and total momentum. ", "We find that this is not possible in the case of lenses that remain compact during the passage of the test particle.", "\n\nIn Appendix \\[sec:framedrag\\] we additionally extend our discussion beyond the pure deflection of test particles and calculate the effects of a moving lens on the inertial system of an observer at rest. ", "We find the motion of the lens to give rise to a dragging of this local inertial frame similar to the frame dragging known in the case of rotating stars or Kerr black holes.", "\n\nIn order to study the effects caused by *transversally* moving lenses we have used kinematic arguments in the framework of special relativity. ", "These calculations predict a change of the radial momentum of the deflected test particle. ", "In the case of light this manifests itself in a change of wavelength. ", "In spite of their simplicity our kinematic calculations extend previous discussions (using general relativistic integrations along the geodesics) to arbitrary velocities of the lens and the test particles.", "\n\nFinally, we have investigated the total Doppler shift arising from a moving lens in combination with a transversal motion of the source and the observer. ", "The resulting effective Doppler velocity is similar to the total effective transversal velocities as commonly defined in studies of microlensing effects in cosmological lenses. ", "We have thus been able to directly relate observable quantities with transversal velocities of source, lens, and observer. ", "The required accuracy to apply this method to measure transversal velocities of astronomical objects, especially galaxies, is beyond the capability of current astronomical instruments but will be reached with the next generation of telescopes.", "\n\nO.W. was supported by the BMBF/DLR Verbundforschung under grant 50OR0208. ", "U.S. acknowledges the support of the Center for Gravitational Wave Physics funded by the National Science Foundation under Cooperative Agreement PHY-0114375. ", "Work partially supported by NSF grant PHY-9800973 to Pennsylvania State University.", "\n\nThe geodesic equations without FOD approximation {#sec:geoexac}\n================================================\n\nWe consider the boosted weak-field limit of the Schwarzschild metric Eq.", " . ", "The geodesic equations are derived from the Euler-Lagrange equation and the analogues for $t$ and $z$. In contrast to the analytic treatment of Sec.", " \\[sec:obs frame\\] we do not use the FOD approximation and obtain the equations\n\n$$\\begin{aligned}\n \\begin{split}\n 0 =& \\left(2 + 4\\frac{1+v^2}{1-v^2} \\Phi\\right) \\ddot{t} -\n 8\\frac{v}{1-v^2} \\Phi \\ddot{z} -2\\frac{v(1+v^2)}{(1-v^2)^{3/2}}\n \\Phi_{z'} \\dot{t}^2 + 4\\frac{1+v^2}{1-v^2} \\Phi_{y'}\n \\dot{t} \\dot{y} \\\\ & + 4\\frac{1+v^2}{(1-v^2)^{3/2}} \\Phi_{z'} \\dot{t} \\dot{z}\n + 2\\frac{v}{\\sqrt{1-v^2}}\\Phi_{z'} \\dot{y}^2\n - 8\\frac{v}{1-v^2} \\Phi_{y'} \\dot{y} \\dot{z}\n - 2\\frac{v(3-v^2)}{(1-v^2)^{3/2}} \\Phi_{z'} \\dot{z}^2{\\hspace{0.4em}\\text{,}} \\label{eq:GEOT}\n \\end{split} \\\\ \\begin{split}\n 0 =& \\left(-2+4\\Phi \\right) \\ddot{y}\n - 2\\frac{1+v^2}{1-v^2}\\Phi_{y'} \\dot{t}^2\n - 4\\frac{v}{\\sqrt{1-v^2}}\\Phi_{z'} \\dot{t}\\dot{y}\n + 8\\frac{v}{1-v^2} \\Phi_{y'} \\dot{t}\\dot{z} \\\\ & + 2\\Phi_{y'} \\dot{y}^2\n + 4\\frac{1}{\\sqrt{1-v^2}}\\Phi_{z'} \\dot{y}\\dot{z}\n - 2\\frac{1+v^2}{1-v^2} \\Phi_{y'} \\dot{z}^2{\\hspace{0.4em}\\text{,}}\n \\end{split} \\\\ \\begin{split}\n 0 =& -8\\frac{v}{1-v^2} \\Phi \\ddot{t}\n +\\left( -2+4\\frac{1+v^2}{1-v^2} \\Phi \\right) \\ddot{z}\n - 2\\frac{1-3v^2}{(1-v^2)^{3/2}}\\Phi_{z'} \\dot{t}^2\n - 8\\frac{v}{1-v^2} \\Phi_{y'} \\dot{t} \\dot{y} \\\\ & - 4 \\frac{v(1+v^2)}{(1-v^2)^{3/2}} \\Phi_{z'} \\dot{t} \\dot{z}\n - 2\\frac{1}{\\sqrt{1-v^2}}\\Phi_{z'} \\dot{y}^2\n + 4\\frac{1+v^2}{1-v^2}\\Phi_{y'} \\dot{y}\\dot{z}\n + 2\\frac{1+v^2}{(1-v^2)^{3/2}} \\Phi_{z'} \\dot{z}^2{\\hspace{0.4em}\\text{.}} ", "\\label{eq:GEOZ}\n \\end{split}\\end{aligned}$$\n\nIn order to complete this set of equations we still need one further condition which is given by the requirement that the geodesics be null: $$\\begin{aligned}\n 0 &= g_{tt}\\dot{t}^2 + g_{yy} \\dot{y}^2 + g_{zz}\\dot{z}^2 + 2g_{tz}\n \\dot{t} \\dot{z} {\\hspace{0.4em}\\text{.}} ", "$$\n\nThe potential of the lens is assumed to be that of a point mass given in the weak-field limit by $$\\begin{aligned}\n \\Phi(t', y', z') &= -\\frac{M}{\\sqrt{y'^2+z'^2}}$$ in the lens’ rest frame. ", "The resulting potential in the observer’s frame is obtained from Lorentz transformation. ", "For the derivatives that implies $$\\begin{aligned}\n \\Phi_{y} &= \\Phi_{y'} {\\hspace{0.4em}\\text{,}} \\\\ \\Phi_{z} &= \\gamma \\, \\Phi_{z'} {\\hspace{0.4em}\\text{,}} \\\\ \\Phi_{t} &= -v\\gamma \\, \\Phi_{z'} {\\hspace{0.4em}\\text{,}}\\end{aligned}$$ which has already been incorporated into Eqs.", " –. ", "In order to numerically obtain a solution we need to specify boundary conditions for the null geodesic. ", "At the point of emission of the light we demand $$\\begin{aligned}\n t &= 0 {\\hspace{0.4em}\\text{,}} \\\\ z &= z{_\\text{s}}{\\hspace{0.4em}\\text{,}} \\\\ y &= y{_\\text{s}}{\\hspace{0.4em}\\text{,}} \\\\ \\dot{y} &= 0{\\hspace{0.4em}\\text{,}}\\end{aligned}$$ where $z{_\\text{s}}$ and $y{_\\text{s}}$ give the position of the source and have been set to $-10\\,000$ and $150$, respectively, in our calculations. ", "At the observer’s position we impose the boundary condition $$\\begin{aligned}\n z &= z{_\\text{o}}\\end{aligned}$$ with the position of the observer being set to $z{_\\text{o}}=10\\,000$ in our calculation. ", "Note that the $y$ position of the observer depends on the deflection of the light ray and cannot be freely specified.", "\n\nWe solve this two-point-boundary value problem with a second order accurate relaxation scheme. ", "For our calculations we have set the mass of the lens to $M=1$, so that all distances are given in units of the lens’ mass (remember that $c=1=G$). ", "These parameters lead to deflection angles much larger than those observed in astronomical lenses. ", "We therefore expect this test of the [FOD]{} approximation to provide upper bounds on the error and the [FOD]{} approximation to be even more accurate in all scenarios of practical interest.", "\n\nIndex of refraction\\[sec:refrindex\\]\n====================================\n\nIn this section we will provide an alternative descriptive explanation of the counterintuitive result obtained in Secs.", " \\[sec:obs frame\\] and \\[sec:lens frame\\] that a gravitational lens moving towards the observer at highly relativistic speed leads to a vanishing deflection angle. ", "We have not found an intuitive explanation for this effect based on the components of the energy momentum tensor which diverge in the limit of $v \\rightarrow 1$, but whose contributions must cancel to explain the vanishing total effect. ", "Instead we describe the deflection in terms of light moving in a refractive medium.", "\n\nIt is a well known fact that the deflection of light in weak *static* gravitational fields can be described by the analogous scenario of light moving in Euclidean space filled with a refractive medium. ", "We therefore consider a refractive medium in the rest frame of the lens. ", "We denote the propagation speed of light in the medium by $c'$ so that the refractive index is given by $$\\begin{aligned}\n n' &= \\frac{1}{c'} = \\frac{{\\mathrm{d}}t'}{{\\mathrm{d}}l'} {\\hspace{0.4em}\\text{.}}", "\n \\label{eq:n'}\\end{aligned}$$ As before we use primed coordinates for the rest frame of the lens. ", "Note, however, that the spatial geometry is viewed as Euclidian now, so that ${\\mathrm{d}}l'^2={\\mathrm{d}}y'^2+{\\mathrm{d}}z'^2$. The gravitational effect on the light propagation is absorbed in the refractive index $$\\begin{aligned}\n n'-1 &= -2\\Phi {\\hspace{0.4em}\\text{,}}\n \\label{eq:n'2}\\end{aligned}$$ which follows from the combination of Eq.", "  and the line element for the case of light (i.e., ${\\mathrm{d}}s^2=0$). ", "This description can be extended to the nonstatic scenario in the rest frame of the observer either by applying the Lorentz transformation – or by directly calculating $n$ as before but now using the unprimed analogue of Eq.", "  and the metric for the moving lens. ", "Both approaches lead to the rather simple scaling law $$\\begin{aligned}\n \\frac{n-1}{n'-1} &= \\gamma^2 (1-v\\cos\\theta)^2 {\\hspace{0.4em}\\text{.}}", "\n \\label{eq:n n'}\\end{aligned}$$ Here $\\theta$ defines the direction of light propagation relative to the lens’ motion as seen by the observer, i.e., $\\cos\\theta={\\mathrm{d}}z/{\\mathrm{d}}l$, $\\sin\\theta={\\mathrm{d}}y/{\\mathrm{d}}l$. This result is the generalization of the [FOV]{} expression of @sef. ", "It is also valid for arbitrary directions $\\theta$, even though we are still working in the [FOD]{} approximation.", "\n\nWe emphasize that we have obtained a description of a moving gravitational potential in terms of a refractive medium at rest but with an anisotropic refractive index $n$ given by Eqs.", "  and . ", "In particular this scaling law demonstrates that the refractive index $n$ approaches unity in the limit of the gravitational lens moving towards the observer with highly relativistic velocity ($\\theta=0$, $v\\rightarrow1$). ", "Translated back to the deflection of light, however, a constant refractive index $n\\equiv1$ implies a vanishing of the deflection angle.", "\n\nIt is now not surprising at all that the refractive index becomes unity in this limit. ", "The coordinate velocity of light is reduced *in the rest frame of the lens,* but as the lens itself is moving highly relativistically, the resulting net velocity *in the observer’s frame* is obtained from relativistic velocity addition \\[cf.", " Eq.", " \\] and approaches $1$. In the limit $v\\rightarrow 1$ we thus have no reduction of the velocity of light in the refractive medium and consequently no deflection.", "\n\nFrame dragging\\[sec:framedrag\\]\n===============================\n\nThe fact that the velocity of light is reduced *in a moving frame of reference* (cf.", " Appendix \\[sec:refrindex\\]) suggests effects analogous to the “dragging of inertial frames” in the field of a rotating body with its extreme consequences close to Kerr black holes. ", "A discussion of this effect helps in understanding the geometric effects in the field of a linearly moving mass and is therefore included in this appendix. ", "@gabriel88 showed that the gravitomagnetic light deflection of rotating bodies can be expressed as an integral over the Lense-Thirring rotation rate which demonstrates the close relation between both effects.", "\n\nTo simplify the discussion we consider regions with a stationary (static in the lens frame) gravitational field in $y$ direction, i.e., $\\Phi_z=\\Phi_t=0$. It can be shown easily that a freely falling particle will gain a velocity component in the $z$ direction (parallel to the direction of motion of the lens) as a result of its motion in the $y$ direction. ", "This transversal acceleration is similar to magnetic Lorentz forces and shows the gravitomagnetic effects directly. ", "Such effects are, however, coordinate dependent and thus not easy to interpret in a general way. ", "We therefore want to discuss effects on a body *at rest with respect to the outside world,* i.e., with constant $y$ and $z$ coordinates.", "\n\nThe tetrad of a local Minkowski coordinate system can be derived by starting at one point of the world line and transforming the direction vectors $T^\\nu$ with the Fermi-Walker transport which is defined by a vanishing Fermi derivative, $$\\begin{aligned}\n\\frac{{\\mathrm{D}}T^\\alpha}{{\\mathrm{D}}\\tau} + g_{\\mu\\nu} \\left( u^\\alpha\n \\frac{{\\mathrm{D}}u^\\mu}{{\\mathrm{D}}\\tau} - u^\\mu\n \\frac{{\\mathrm{D}}u^\\alpha}{{\\mathrm{D}}\\tau} \\right) T^\\nu = 0 {\\hspace{0.4em}\\text{.}}", "\n\\label{eq:fermi}\\end{aligned}$$ Here the four-velocity of the test particle is denoted by $u^\\alpha={\\mathrm{d}}x^\\alpha/{\\mathrm{d}}\\tau$ (with $\\tau$ being the proper time along the trajectory of the test particle) and the covariant derivatives by an uppercase ${\\mathrm{D}}$: $$\\begin{aligned}\n\\frac{{\\mathrm{D}}T^\\alpha}{{\\mathrm{D}}\\tau} &= \\frac{{\\mathrm{d}}T^\\alpha}{{\\mathrm{d}}\\tau} +\n\\Gamma^\\alpha_{\\mu\\nu} T^\\mu u^\\nu\n\\label{eq:covder}\\end{aligned}$$ In order to derive the Christoffel symbols we write the Euler-Lagrange equations \\[e.g., ", "Eq.", " \\] for the Lagrange function in Eq.. On the other hand we write the equations of motion by setting the covariant derivative of the velocity vector $T^\\alpha=u^\\alpha$ in Eq. ", "to zero. ", "Even though we still work in the [FOD]{} approximation, we now do allow for arbitrary directions of test particle velocities. ", "By comparing coefficients, we find the following nonvanishing Christoffel symbols: $$\\begin{aligned}\n\\Gamma^t_{ty} &= (1+v^2)\\gamma^2\\Phi_y {\\hspace{0.4em}\\text{,}} & \\Gamma^t_{yz} &= -2v\\gamma^2\\Phi_y {\\hspace{0.4em}\\text{,}}\n \\\\[1ex]\n\\Gamma^y_{tt} &= (1+v^2)\\gamma^2\\Phi_y {\\hspace{0.4em}\\text{,}} & \\Gamma^y_{yy} &= -\\Phi_y {\\hspace{0.4em}\\text{,}} \\notag \\\\\n\\Gamma^y_{zz} &= (1+v^2)\\gamma^2\\Phi_y {\\hspace{0.4em}\\text{,}}&\n\\Gamma^y_{tz} &= -2v\\gamma^2\\Phi_y {\\hspace{0.4em}\\text{,}}\\\\[1ex]\n\\Gamma^z_{ty} &= 2v\\gamma^2\\Phi_y {\\hspace{0.4em}\\text{,}}& \\Gamma^z_{yz} &= -(1+v^2)\\gamma^2\\Phi_y {\\hspace{0.4em}\\text{,}}\\end{aligned}$$ as well as those following from the symmetry properties. ", "The four-velocity $u^\\alpha$ of a particle at rest is needed only to zeroth order of the deflection (i.e., potential) and is given by $u^t=1$, $u^z=u^y=0$ in unprimed coordinates. ", "For the covariant derivative of $u^\\alpha$ for the particle at rest, we obtain in [FOD]{} approximation $$\\begin{aligned}\n\\frac{{\\mathrm{D}}u^y}{{\\mathrm{D}}\\tau} = (1+v^2)\\gamma^2\\Phi_y\\end{aligned}$$ while all other components are vanishing. ", "This covariant derivative for the particle at rest is equivalent to the force needed to support the particle and prevent it from falling towards the lens.", "\n\nIn the next step we apply Eqs. ", "and to derive the transformation of the components of an arbitrary vector $T^\\alpha$. For the metric $g_{\\mu\\nu}$, the zeroth order approximation (i.e., the Minkowski metric) is sufficient in this case. ", "We arrive at the final equations for the Fermi-Walker transport: $$\\begin{aligned}\n\\frac{{\\mathrm{d}}T^\\alpha}{{\\mathrm{d}}\\tau} &=\nM^\\alpha{}_\\beta T^\\beta \\\\\n(M^\\alpha{}_\\beta) &= \n2v\\gamma^2\\Phi_y \\begin{pmatrix} 0 & 0 & 0 \\\\ 0 & 0 & 1 \\\\ 0 & -1 & 0\n \\end{pmatrix} {\\hspace{0.4em}\\text{.}}\\end{aligned}$$ The ordering of indices is $t,y,z$, the row index is $\\alpha$, and the column index $\\beta$. We note that the velocity vector $u^\\alpha$ itself remains constant as required. ", "Furthermore, we see that the $y$ and $z$ coordinates evolve in a way which is equivalent to a rotation. ", "Modulo an arbitrary time offset, the fundamental solution of this part is $$\\begin{aligned}\nT^y&=\\cos(\\omega \\tau) {\\hspace{0.4em}\\text{,}} & T^z&=\\sin(\\omega \\tau) \\end{aligned}$$ with an angular velocity of $\\omega=-2v\\gamma^2\\Phi_y$. As a consequence a gyroscope (or any other device capable of sustaining a locally nonrotating reference system) will precess relative to the outside world with this angular velocity. ", "This precession can be observed from great distance and represents a coordinate independent measure of the frame dragging caused by the linear motion of the lens.[^3]\n\nWithout presenting the calculations we note that the precession of a gyroscope could be obtained more directly by solving the equation of motion for the different parts of the rotating mass. ", "The mass elements approaching the lens will be dragged with the lens’ motion while elements moving parallel to the lens will feel a reduced gravitational attraction. ", "It is easy to show that this leads exactly to the precession which we derived in a more formal but general way.", "\n\nThe effect is analogous to Lense-Thirring precession in the field of rotating bodies, especially in the field of a Kerr black hole. ", "There is, however, one important difference. ", "In our case, all gravitomagnetic terms of the metric vanish in the rest frame of the lens. ", "The precession due to the frame dragging does of course not disappear when viewed in this system. ", "It would instead be interpreted as an incarnation of geodesic precession of a *moving* particle in a *static* gravitational field. ", "In the case of the Kerr metric, such a transformation is possible locally only as has been shown by @ashby90.", "\n\n[29]{} natexlab\\#1[\\#1]{}bibnamefont \\#1[\\#1]{}bibfnamefont \\#1[\\#1]{}citenamefont \\#1[\\#1]{}url \\#1[`#1`]{}urlprefix\\[2\\][\\#2]{} \\[2\\]\\[\\][[\\#2](#2)]{}\n\n, ****, ().", "\n\n, ****, ().", "\n\n, in **, edited by (, ), p. , .", "\n\n, , , ** (, ).", "\n\n, , , ****, ().", "\n\n, ****, ().", "\n\n, in ** (, ), p. .", "\n\n, ****, ().", "\n\n, in ** (), p. .", "\n\n, , , ****, ().", "\n\n, ****, ().", "\n\n, ****, ().", "\n\n, , , , ****, (), .", "\n\n, ****, (), .", "\n\n, ****, (), .", "\n\n, ****, (), .", "\n\n, , , ****, (), .", "\n\n, ****, (), .", "\n\n, ****, (), .", "\n\n, ****, ().", "\n\n, ****, ().", "\n\n, ****, ().", "\n\n, ****, ().", "\n\n, ** (, ).", "\n\n, , (), .", "\n\n, , (), .", "\n\n, , , ****, ().", "\n\n, , , ****, ().", "\n\n, ****, ().", "\n\n[^1]: An alternative derivation based on integration of the geodesic equation is presented additionally in [@capozziello99]. ", "Our arguments are valid for this approach as well.", "\n\n[^2]: The apparent size distance $D$ is defined as the relation between the physical size of a distant object $l$ and the (small) angle $\\theta$ under which it is seen by an observer: $D=l/\\theta$\n\n[^3]: The assumption of constant spatial coordinates for the test particle is not coordinate dependent because it can be defined in the way that the test particle appears to be at rest when observed by a distant observer whose coordinates are fixed by the background Minkowski metric.", "\n" ]

{ "pile_set_name": "ArXiv" }

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[ "Supreme business win on immigration\n\nJune 25 - The U.S. Supreme Court came down hard on Arizona's tough immigration law, making it clear the issue is a federal one, and giving businesses a sigh of relief. ", "Bobbi Rebell reports.", "\n\n▲ Hide Transcript\n\n▶ View Transcript\n\nPLEASE NOTE: THIS EDIT CONTAINS 4:3 MATERIAL\nBusinesses can now breathe a sigh of relief now that the Supreme Court has essentially gutted Arizona's tough immigration law.", "\nThe ruling effectively puts immigration squarely back into the federal government's court.", "\nDecision Economics Cary Leahey:\nSOUNDBITE: CARY LEAHEY, SENIOR U.S. AND GLOBAL ECONOMIST, DECISION ECONOMICS (ENGLISH) SAYING:\n\"That's the big plus is they don't have to worry about having a sort of a state by state liaison which would increase their costs of just dealing with the work force.\"", "\nIt also gives a level of comfort to foreign businesses and investors that might have been hesitant when it comes to doing business here.", "\nBoston University Law Professor Susan Akram:\nSOUNDBITE: SUSAN AKRAM, PROFESSOR, BOSTON UNIVERSITY SCHOOL OF LAW (ENGLISH) SAYING:\n\"Foreign investors want to have uniformity of laws of employment laws in particular so for them to have to figure out among the 50 contiguous states a different employment authorization requirement is again a nightmare. ", "So I think it's very good both for international investment and for national business.\"", "\nMore liberal immigration policies are also good for the economy in general, according to Leahey:\nSOUNDBITE: CARY LEAHEY, SENIOR US AND GLOBAL ECONOMIST, DECISION ECONOMICS (ENGLISH) SAYING:\n\"Economies benefit from a wide-open immigration because you bring in people that you want. ", "Someone that is willing to go to the trouble to come to a new country and make a new life is generally the kind of person that you want in your country because they are showing you know a lot of grit initiative and hard work.\"", "\nOf note: The provision that has attracted many protests- requiring police checks for immigration status- was upheld.", "\nBobbi Rebell, Reuters.", "\n\nReuters, the news and media division of Thomson Reuters, is the world’s largest international multimedia news provider reaching more than one billion people every day. ", "Reuters provides trusted business, financial, national, and international news to professionals via Thomson Reuters desktops, the world's media organizations, and directly to consumers at Reuters.com and via Reuters TV. ", "Learn more about Thomson Reuters products:" ]

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[ "2007 in Canada\n\nEvents from the year 2007 in Canada.", "\n\nIncumbents\n\nCrown \n Monarch – Elizabeth II\n\nFederal government \n Governor general – Michaëlle Jean \n Prime minister – Stephen Harper\n Chief Justice – Beverley McLachlin (British Columbia)\n Parliament – 39th\n\nProvincial governments\n\nLieutenant governors \nLieutenant Governor of Alberta – Norman Kwong\nLieutenant Governor of British Columbia – Iona Campagnolo (until October 1) then Steven Point\nLieutenant Governor of Manitoba – John Harvard \nLieutenant Governor of New Brunswick – Herménégilde Chiasson \nLieutenant Governor of Newfoundland and Labrador – Edward Roberts \nLieutenant Governor of Nova Scotia – Mayann Francis\nLieutenant Governor of Ontario – James Bartleman (until September 5) then David Onley\nLieutenant Governor of Prince Edward Island – Barbara Oliver Hagerman\nLieutenant Governor of Quebec – Lise Thibault (until June 7) then Pierre Duchesne\nLieutenant Governor of Saskatchewan – Gordon Barnhart\n\nPremiers \nPremier of Alberta – Ed Stelmach\nPremier of British Columbia – Gordon Campbell\nPremier of Manitoba – Gary Doer \nPremier of New Brunswick – Shawn Graham \nPremier of Newfoundland and Labrador – Danny Williams \nPremier of Nova Scotia – Rodney MacDonald \nPremier of Ontario – Dalton McGuinty \nPremier of Prince Edward Island – Pat Binns (until June 12) then Robert Ghiz\nPremier of Quebec – Jean Charest\nPremier of Saskatchewan – Lorne Calvert (until November 21) then Brad Wall\n\nTerritorial governments\n\nCommissioners \n Commissioner of Yukon – Geraldine Van Bibber \n Commissioner of Northwest Territories – Tony Whitford\n Commissioner of Nunavut – Ann Meekitjuk Hanson\n\nPremiers \nPremier of the Northwest Territories – Joe Handley (until October 18) then Floyd Roland\nPremier of Nunavut – Paul Okalik \nPremier of Yukon – Dennis Fentie\n\nEvents\n\nJanuary to March\nJanuary 5 – The domed roof of BC Place Stadium in Vancouver collapses.", "\nJanuary 11 – A major blizzard rips through Central Saskatchewan.", "\nFebruary 3 – At a Calgary Flames game, young Cree singer Akina Shirt becomes the first person to perform \"O Canada\" in an Aboriginal language at a major league sporting event.", "\nFebruary 8 – Ontario provincial by-election in Burlington; Markham; and York South–Weston electoral districts.", "\nFebruary 19 – During a live interview on CKRS in Saguenay, Quebec, talk radio host Louis Champagne attacks Parti Québécois candidate Sylvain Gaudreault and leader André Boisclair, both openly gay, in an interview with PQ candidate Alexandre Cloutier, asking \"In Jonquière, listen, aren't you going to face the question, 'Is the Parti Québécois a club of fags?'\"", "\nFebruary 20 – The Canadian government, along with American billionaire Bill Gates, announce the Canadian HIV Vaccine Initiative, a $139 million dollar plan to fight the AIDS virus.", "\nMarch 13 – Canada 2006 Census data is released; the population of Canada in 2006 was 31,612,897. ", "Notably, the census also indicates that for the first time in Canadian history, the three territories (Yukon, Northwest Territories and Nunavut) have a combined population of over 100,000.", "\nMarch 26 – Quebec general election.", "\n\nApril to June\nApril 3 – Royal Assent is granted to the Veterans' Bill of Rights.", "\nApril 27 – Three new Laval metro stations are inaugurated. (", "see Montreal Metro)\nApril 30 – Prince Andrew, fourth in line to the Canadian throne, arrives in Canada to undertake duties in Halifax, Toronto and Cambridge\nMay 3 – Fixed election dates introduced. ", "The Prime Minister can no longer advise the Governor General to call an election unless a non-confidence motion is passed.", "\nMay 18 – Governor General Michaëlle Jean appoints Pierre Duchesne as Lieutenant Governor of Quebec\nMay 22 – The general election in Manitoba is won by the governing New Democrats.", "\nMay 23 – Jordan Manners is the first Torontonian killed in a school shooting.", "\nMay 28 – Prince Edward Island election. ", "Robert Ghiz's Liberals win a majority, defeating Premier Pat Binns' Progressive Conservatives\nJune 2 – Prince Harry, third in line to the Canadian throne, arrives at CFB Suffield to train for a possible deployment to Afghanistan\nJune 2 – Princess Anne arrives in Saskatchewan to undertake various official duties\nJune 7 – Pierre Duchesne becomes Lieutenant Governor of Quebec, replacing Lise Thibault\nJune 12 – Robert Ghiz becomes Premier of Prince Edward Island, replacing Pat Binns\nJune 18 – Passenger Protect went into effect\nJune 22 – CTVglobemedia's takeover of CHUM Limited (excepting Citytv, which is slated for sale to Rogers Communications) is completed.", "\nJune 29 – A national Aboriginal Day of Protest, including blockades of several major transportation routes in Ontario and Quebec, is held to protest the state of First Nations relations with the federal government.", "\n\nJuly to September\nJuly 13 – Conrad Black is found guilty on three charges of fraud and one charge of obstruction of justice in Chicago.", "\nJuly 19 – Jesse Imeson begins a murderous rampage in Ontario, prompting an international manhunt.", "\nAugust 8 - A suspect, Gaétan Bissonnette, was arrested in relation to the business Denise Morelle, an actress who was murdered in Montreal in 1984. ", "He later plead guilty to murder.", "\nAugust 20 – First incident of severed feet finding on British Columbia coast.", "\nAugust 23 – Quebec Provincial Police admit to inserting \"agents provocateurs\" into the group protesting against the Montebello meeting.", "\nAugust 28 – Steven Truscott is acquitted by the Court of Appeal for Ontario in a hearing to review his 1959 conviction for the murder of Lynne Harper.", "\nSeptember 5 – The Governor General appoints David Onley as Lieutenant Governor of Ontario, replacing James Bartleman\nSeptember 11 – Stephen Harper becomes the first Canadian Prime Minister since Confederation to address the Parliament of Australia.", "\nSeptember 17 – Three by-elections in Quebec in Roberval—Lac-Saint-Jean, Saint-Hyacinthe—Bagot, and Outremont.", "\n\nOctober to December\nOctober 1 – General election in Northwest Territories.", "\nOctober 1 – The Governor General appoints Steven Point as Lieutenant Governor of British Columbia, replacing Iona Campagnolo\nOctober 9 – The general election in Newfoundland and Labrador is won by the governing Progressive Conservatives.", "\nOctober 9 – A series of small earthquakes start in the British Columbia Interior that expressed interest in the adjacent 7,200-year-old Nazko Cone.", "\nOctober 10 – The general election in Ontario is won by the governing Liberals.", "\nOctober 13 – Roger Duguay is chosen as the new leader of the New Brunswick New Democratic Party at the party's leadership convention.", "\nOctober 14 – The Royal Canadian Mounted Police (RCMP) taser a man, who died shortly thereafter, at the Vancouver Airport. ", "The incident is videotaped and eventually released to the public.", "\nOctober 17 – Floyd Roland is selected as the new Premier of the Northwest Territories.", "\nOctober 19 – In Surrey, British Columbia, six people are murdered in a highrise apartment. ", "Chris Mohan, and Ed Schellenburg, were innocent victims in the murder. ", "The other four were drug dealers. ", "This is known as the Surrey Six slayings.", "\nOctober 25 – The Government of Canada announces the creation of the Lake Superior National Marine Conservation Area, the largest freshwater marine protected area in the world.", "\nOctober 31 – The Conservative Party of Canada drops Mark Warner as its candidate in the pending Toronto Centre byelection, citing unspecified differences.", "\nOctober 31 – Rogers Communications officially takes ownership of Citytv.", "\nNovember 1 – A provincewide Amber Alert is issued in Ontario after a newborn baby is abducted from the Sudbury Regional Hospital in Greater Sudbury. ", "A Kirkland Lake resident, Brenda Batisse, is arrested later the same evening; the baby is recovered safely.", "\nNovember 7 – The general election in Saskatchewan is won by the opposition Saskatchewan Party.", "\nNovember 21 – Brad Wall is sworn in as Premier of Saskatchewan, succeeding Lorne Calvert.", "\nNovember 30 – A fire destroys much of the beachfront shopping area in the resort town of Wasaga Beach, Ontario.", "\n\nArts and literature\n\nMusic\nMarch 30 – Final concert by influential Canadian rock band Rheostatics.", "\n\nNew books\nTodd Babiak, The Book of Stanley\nDavid Chariandy, Soucouyant\nBarbara Fradkin, Dream Chasers\nBarbara Gowdy, Helpless\nDon Hannah, Ragged Islands\nNalo Hopkinson, The New Moon's Arms\nNaomi Klein, The Shock Doctrine\nBob Mersereau, The Top 100 Canadian Albums\nMichael Ondaatje, Divisadero\nM. G. Vassanji, The Assassin's Song\nMichael Winter, The Architects Are Here\nAlissa York, Effigy\n\nLiterary awards\nHeather O'Neill's 2006 novel Lullabies for Little Criminals wins the 2007 edition of Canada Reads\nBarbara Fradkin's 2006 novel Honour Among Men wins the 2007 Arthur Ellis Award for Best Novel\nElizabeth Hay's 2007 novel Late Nights on Air wins the 2007 Scotiabank Giller Prize\n2007 Governor General's Awards: TBA\n\nTelevision\n\nSport\n\nJanuary 9–15 – 2007 Canadian Figure Skating Championships\nMen's medalists – Jeffrey Buttle, Gold; Christopher Mabee, Silver; Emanuel Sandhu, Bronze.", "\nWomen's medalists – Joannie Rochette, Gold; Mira Leung, Silver; Lesley Hawker, Bronze.", "\nPairs' medalists – Jessica Dubé / Bryce Davison, Gold; Valérie Marcoux / Craig Buntin, Silver; Anabelle Langlois / Cody Hay, Bronze.", "\nDance medalists – Marie-France Dubreuil / Patrice Lauzon, Gold; Tessa Virtue / Scott Moir, Silver; Kaitlyn Weaver / Andrew Poje, Bronze.", "\nJanuary 14 - Toronto's Christian Cage (Jay Reso) won his Second NWA World Heavyweight Championship by defeating Abyss(Chris Parks) at the TNA Impact! ", "Zone in Orlando at Total Nonstop Action's Genesis 2006 \nMarch 23 – Marie-France Dubreuil / Patrice Lauzon won the silver medal in Ice Dancing at the World Figure Skating Championships in Tokyo.", "\nMay 13 - Cage is awarded the First TNA Heavyweight Championship when Total Nonstop Action severs ties with National Wrestling Alliance \nMay 27 - Vancouver Giants won their First Memorial Cup by defeating the Medicine Hat Tigers 3 to 1. ", "The Tournament was played at the Pacific Coliseum in Vancouver\nJune 6 - Anaheim Ducks won their First Stanley Cup by defeating the Ottawa Senators 4 games to 1. ", "Edmonton's Scott Niedermayer was awarded the Conn Smythe Trophy\nNovember 23 - Manitoba Bisons won their Third Vanier Cup by defeating the Saint Mary's Huskies by a score of 28 to 14 in the 43rd Vanier Cup played at the Rogers Centre in Toronto\nNovember 25 – Saskatchewan Roughriders won their Third (and First since 1989) Grey Cup by defeating the Winnipeg Blue Bombers 23 to 19 in the 95th Grey Cup played at the Rogers Centre in Toronto. ", "Chatham, Ontario's Andy Fantuz is awarded the game's Most Valuable Canadian\n\nBirths\n\nDeaths\n\nJanuary to March\nJanuary 3 – Earl Reibel, ice hockey player (born 1930)\nJanuary 6 – Charmion King, actress (born 1925)\nJanuary 8 – Yvonne De Carlo, actress, dancer and singer (born 1922)\nJanuary 15\nJames Hillier, scientist and inventor, jointly designed and built first electron microscope (born 1915)\nPercy Saltzman, meteorologist and television personality, first English-speaking weatherman in Canadian television history (born 1915)\nJanuary 18 – Julie Winnefred Bertrand, supercentenarian, oldest living Canadian and oldest verified living recognized woman at the time of her death (born 1891)\nJanuary 19 – Denny Doherty, singer and songwriter (born 1940)\nJanuary 20\nCyril Lloyd Francis, politician and Speaker of the House of Commons of Canada (born 1920)\n Richard Vollenweider, limnologist (born 1922)\nJanuary 26 – Gump Worsley, ice hockey player (born 1929)\nFebruary 14 – Ryan Larkin, animator, artist and sculptor (born 1943)\nFebruary 17 – Dermot O'Reilly, musician, producer and songwriter (born 1942)\nFebruary 19 – Celia Franca, ballet dancer and founder and artistic director of the National Ballet of Canada (born 1921)\nFebruary 27 – Myron Wolf Child, youth activist, public speaker and politician (born 1983)\nMarch 2 – Doris Anderson, author, journalist and women's rights activist (born 1925)\nMarch 23 – Agnes Benidickson, first female chancellor of Queen's University at Kingston, Ontario (born 1920)\n\nApril to June\nApril 10 – Charles Philippe Leblond, pioneer of cell biology and stem cell research (born 1910)\nApril 14 – June Callwood, journalist, author and social activist (born 1924)\nApril 23 – Jim Walding, politician (born 1937)\nApril 28\nLloyd Crouse, businessman, politician and Lieutenant Governor of Nova Scotia (born 1918)\n Bertha Wilson, jurist and first female Puisne Justice of the Supreme Court of Canada (born 1923)\nMay 7 – Myfanwy Pavelic, artist (born 1916)\nJune 15 – Richard Bell, musician (born 1946)\nJune 21 – Peter Liba, journalist and Lieutenant-Governor of Manitoba (born 1940)\nJune 24 – Chris Benoit, wrestler (born 1967)\nJune 27 – William Hutt, actor (born 1920)\n\nJuly to September\nJuly 9 - Sean Collins, son of politician Chris Collins (born 1994)\nJuly 11 – Ed Mirvish, businessman, philanthropist and theatrical impresario (born 1914)\nJuly 15 – Bluma Appel, philanthropist and patron of the arts (b. c1920)\nJuly 31 – Margaret Avison, poet (born 1918)\nAugust 17 – Elmer MacFadyen, politician (born 1943)\nAugust 22 – Gilles Beaudoin, politician and mayor of Trois-Rivières (born 1919)\nAugust 23 – William John McKeag, politician and Lieutenant-Governor of Manitoba (born 1928)\nAugust 24 – Andrée Boucher, politician and 39th Mayor of Quebec City (born 1937)\nSeptember 8 – George Crum, conductor, pianist, vocal coach and musical arranger (born 1926)\nSeptember 23 – Ken Danby, artist (born 1940)\n\nOctober to December\nOctober 24 – David Adams, ballet dancer (born 1928)\nOctober 30 – Robert Goulet, singer and actor (born 1933)\nNovember 24 – Antonio Lamer, lawyer, jurist and 16th Chief Justice of Canada (born 1933)\nNovember 25 – Neil Hope, actor (born 1972)\nNovember 27 – Jane Rule, novelist and non-fiction writer (born 1931)\nNovember 29 – James Barber, cookbook author and television chef (born 1923)\nDecember 4 – Norval Morrisseau, artist (born 1932)\nDecember 10 – Aqsa Parvez, murder victim (born 1991)\nDecember 23 – Oscar Peterson, jazz pianist and composer (born 1925)\n\nSee also\n 2007 in Canadian music\n 2007 in Canadian television\n List of Canadian films of 2007\n\nReferences\n\n \n\n \nCategory:Years of the 21st century in Canada" ]

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[ "Pediatric patient-reported outcome instruments for research to support medical product labeling: report of the ISPOR PRO good research practices for the assessment of children and adolescents task force.", "\nPatient-reported outcome (PRO) instruments for children and adolescents are often included in clinical trials with the intention of collecting data to support claims in a medical product label. ", "The purpose of the current task force report is to recommend good practices for pediatric PRO research that is conducted to inform regulatory decision making and support claims made in medical product labeling. ", "The recommendations are based on the consensus of an interdisciplinary group of researchers who were assembled for a task force associated with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). ", "In those areas in which supporting evidence is limited or in which general principles may not apply to every situation, this task force report identifies factors to consider when making decisions about the design and use of pediatric PRO instruments, while highlighting issues that require further research. ", "Five good research practices are discussed: 1) Consider developmental differences and determine age-based criteria for PRO administration: Four age groups are discussed on the basis of previous research (<5 years old, 5-7 years, 8-11 years, and 12-18 years). ", "These age groups are recommended as a starting point when making decisions, but they will not fit all PRO instruments or the developmental stage of every child. ", "Specific age ranges should be determined individually for each population and PRO instrument. ", "2) Establish content validity of pediatric PRO instruments: This section discusses the advantages of using children as content experts, as well as strategies for concept elicitation and cognitive interviews with children. ", "3) Determine whether an informant-reported outcome instrument is necessary: The distinction between two types of informant-reported measures (proxy vs. observational) is discussed, and recommendations are provided. ", "4) Ensure that the instrument is designed and formatted appropriately for the target age group. ", "Factors to consider include health-related vocabulary, reading level, response scales, recall period, length of instrument, pictorial representations, formatting details, administration approaches, and electronic data collection (ePRO). ", "5) Consider cross-cultural issues. ", "Additional research is needed to provide methodological guidance for future studies, especially for studies involving young children and parents' observational reports. ", "As PRO data are increasingly used to support pediatric labeling claims, there will be more information regarding the standards by which these instruments will be judged. ", "The use of PRO instruments in clinical trials and regulatory submissions will help ensure that children's experience of disease and treatment are accurately represented and considered in regulatory decisions." ]

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[ "/* sysdep.h -- handle host dependencies for the GNU linker\n Copyright (C) 1995-2016 Free Software Foundation, Inc.\n\n This file is part of the GNU Binutils.", "\n\n This program is free software; you can redistribute it and/or modify\n it under the terms of the GNU General Public License as published by\n the Free Software Foundation; either version 3 of the License, or\n (at your option) any later version.", "\n\n This program is distributed in the hope that it will be useful,\n but WITHOUT ANY WARRANTY; without even the implied warranty of\n MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. ", " See the\n GNU General Public License for more details.", "\n\n You should have received a copy of the GNU General Public License\n along with this program; if not, write to the Free Software\n Foundation, Inc., 51 Franklin Street - Fifth Floor, Boston,\n MA 02110-1301, USA. ", " */\n\n#ifndef LD_SYSDEP_H\n#define LD_SYSDEP_H\n\n#ifdef PACKAGE\n#error sysdep.h must be included in lieu of config.h\n#endif\n\n#include \"config.h\"\n\n#include <stdio.h>\n#include <sys/types.h>\n#include <sys/stat.h>\n#include <stdarg.h>\n\n#ifdef STRING_WITH_STRINGS\n#include <string.h>\n#include <strings.h>\n#else\n#ifdef HAVE_STRING_H\n#include <string.h>\n#else\n#ifdef HAVE_STRINGS_H\n#include <strings.h>\n#else\nextern char *strchr ();\nextern char *strrchr ();\n#endif\n#endif\n#endif\n\n#ifdef HAVE_STDLIB_H\n#include <stdlib.h>\n#endif\n\n#ifdef HAVE_UNISTD_H\n#include <unistd.h>\n#endif\n\n#ifdef HAVE_REALPATH\n# define REALPATH(a,b) realpath (a, b)\n#else\n# define REALPATH(a,b) NULL\n#endif\n\n#ifdef USE_BINARY_FOPEN\n#include \"fopen-bin.h\"\n#else\n#include \"fopen-same.h\"\n#endif\n\n#ifdef HAVE_FCNTL_H\n#include <fcntl.h>\n#else\n#ifdef HAVE_SYS_FILE_H\n#include <sys/file.h>\n#endif\n#endif\n\n#ifdef HAVE_DLFCN_H\n#include <dlfcn.h>\n#endif\n\n#ifndef O_RDONLY\n#define O_RDONLY 0\n#endif\n#ifndef O_WRONLY\n#define O_WRONLY 1\n#endif\n#ifndef O_RDWR\n#define O_RDWR 2\n#endif\n#ifndef O_ACCMODE\n#define O_ACCMODE (O_RDONLY | O_WRONLY | O_RDWR)\n#endif\n/* Systems that don't already define this, don't need it. ", " */\n#ifndef O_BINARY\n#define O_BINARY 0\n#endif\n\n#ifndef SEEK_SET\n#define SEEK_SET 0\n#endif\n#ifndef SEEK_CUR\n#define SEEK_CUR 1\n#endif\n#ifndef SEEK_END\n#define SEEK_END 2\n#endif\n\n#if !", "HAVE_DECL_STRSTR\nextern char *strstr ();\n#endif\n\n#if !", "HAVE_DECL_FREE\nextern void free ();\n#endif\n\n#if !", "HAVE_DECL_GETENV\nextern char *getenv ();\n#endif\n\n#if !", "HAVE_DECL_ENVIRON\nextern char **environ;\n#endif\n\n#endif /* ! ", "defined (LD_SYSDEP_H) */\n" ]

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[ "Q:\n\nHow to redirect to an ASP.net MVC action for url with hash parameter\n\nI am using ASP.Net core 2.2. ", "I redirect to an identity server instance, which then redirects back to my MVC app. ", "The redirect back url is of the form: \n\nhttp://localhost:8081/home/fetchtokenresponse#id_token=longtokenvalue&token_type=Bearer&expires_in=3600&scope=myscopes&session_state=jizlw_6DiGhYvkGk6fKRKkhZQoFlYKJ5v1_2Lwd-caI.MN0g0HwpGuulkwKleHtJCg\n\nIn my action I want to be able to read the parameters like\npublic IActionResult FetchTokenResponse(string id_token)\n\nWhat I have tried\nI tried adding a new route with a has tag, but this appears to be illegal:\nroutes.", "MapRoute(\n name: \"default\",\n template: \"{controller=Home}/{action=Index}#{id?}\");", "\n\nIs there another way to intercept the path and redirect to my action?", "\n\nA:\n\nYou will need to modify your authentication request to IdentityServer to use response_mode=form_post or response_mode=query.", "\nFragments are not sent to the server, as defined in: https://blog.httpwatch.com/2011/03/01/6-things-you-should-know-about-fragment-urls/.\nFragment response mode is used when you want your front-end JavaScript to grab the tokens.", "\n\n" ]

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[ "/*\n Simple DirectMedia Layer\n Copyright (C) 1997-2018 Sam Lantinga <slouken@libsdl.org>\n\n This software is provided 'as-is', without any express or implied\n warranty. ", " In no event will the authors be held liable for any damages\n arising from the use of this software.", "\n\n Permission is granted to anyone to use this software for any purpose,\n including commercial applications, and to alter it and redistribute it\n freely, subject to the following restrictions:\n\n 1. ", "The origin of this software must not be misrepresented; you must not\n claim that you wrote the original software. ", "If you use this software\n in a product, an acknowledgment in the product documentation would be\n appreciated but is not required.", "\n 2. ", "Altered source versions must be plainly marked as such, and must not be\n misrepresented as being the original software.", "\n 3. ", "This notice may not be removed or altered from any source distribution.", "\n*/\n#include \"../SDL_internal.h\"\n\n/* Clipboard event handling code for SDL */\n\n#include \"SDL_events.h\"\n#include \"SDL_events_c.h\"\n#include \"SDL_clipboardevents_c.h\"\n\n\nint\nSDL_SendClipboardUpdate(void)\n{\n int posted;\n\n /* Post the event, if desired */\n posted = 0;\n if (SDL_GetEventState(SDL_CLIPBOARDUPDATE) == SDL_ENABLE) {\n SDL_Event event;\n event.type = SDL_CLIPBOARDUPDATE;\n\n posted = (SDL_PushEvent(&event) > 0);\n }\n return (posted);\n}\n\n/* vi: set ts=4 sw=4 expandtab: */\n" ]

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[ "Q:\n\nBad Company 2 engineer antitank mine cap\n\nSo the mines you plant as engineer stays even if you die. ", "But is there a cap of how much mines you can have at once in a map? ", "I've planted mines in a few places before, and some time later I go back and the mines disappeared.", "\nActually, I assumed it disappeared, because right where it should be there were no holes or burn marks from the explosion that would result if ran over by vehicles or shot by someone.", "\n\nA:\n\nYes, you can only have 6 Mines or C4s planted at any one time. ", " When you plant your 7th, the 1st one you planted is removed.", "\nAlso, I believe if you die they also disappear.", "\n\n" ]

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[ "Wife Gets Death for Killing Husband\n\nThe Montebello woman poisoned her spouse with antifreeze to collect insurance money.", "\n\nThree months after Angelina and Frank Rodriguez got married, the Montebello woman took out a $250,000 life insurance policy on her husband and began trying to kill him.", "\n\nFirst, authorities said, she fed him poisonous oleander plants, sending him to the hospital with an upset stomach. ", "Then, she allegedly loosened the gas cap on the clothes dryer at their home before leaving to visit a friend in San Luis Obispo. ", "Finally, Rodriguez spiked her husband's Gatorade with shots of green antifreeze.", "\n\nFrank Rodriguez, a special education teacher, died on Sept. 9, 2000, with a lethal amount of antifreeze in his body. ", "Three years later, Angelina Rodriquez was convicted of his murder.", "\n\nLos Angeles County Superior Court Judge William R. Pounders on Monday sentenced Rodriguez to death, saying that she killed her husband in an \"exceptionally cruel and callous\" way and that her guilt had been proved to \"an absolute certainty.\"", "\n\n\"In the past 20 years, I have never seen a colder heart,\" Pounders told the defendant.", "\n\nRodriguez, 35, begged for leniency Monday, insisting she didn't kill her husband and at times clashing with the judge.", "\n\n\"I have lived my life with integrity,\" she said in an hourlong speech in court. \"", "I broke and made a few terrible, stupid mistakes that I regret very much.... But murder is not on that list.\"", "\n\nRodriguez blamed her attorney for preventing her from testifying during her trial and said there was no way she could have made her husband drink antifreeze.", "\n\n\"Are you suggesting he took it on his own?\" ", "Judge Pounders asked incredulously.", "\n\n\"I know he did,\" Rodriguez replied. ", "Then she challenged the judge: \"Would your wife be able to hand you a cup of antifreeze?\"", "\n\nPounders denied motions for a new trial and reduction of sentence. ", "As he pronounced the death sentence, making Rodriguez the 15th woman on California's death row, she let out a heavy sigh and tapped her foot rapidly.", "\n\nLos Angeles County Deputy Dist. ", "Atty. ", "Doug Sortino said outside court that Rodriguez blamed the slaying on a former co-worker and fabricated evidence in a failed attempt to get investigators to arrest him. \"", "She's a remorseless, coldblooded killer, and that's why she's in the position she is in today,\" he said.", "\n\nCourt-appointed defense attorney David Houchin said he tried to remain objective and present the best possible defense, despite his client's constant accusations against him. \"", "No one wants to have one on death row,\" he said outside court.", "\n\nHours after her husband's death, Rodriguez called her insurance company, but an agent told her she wouldn't receive any money until the coroner determined the cause of death. ", "She later called an investigator and said she had received an anonymous phone call suggesting that her husband died from antifreeze poisoning, prosecutors said. ", "Cellphone records show that she never received such a call, authorities said.", "\n\nPolice arrested Rodriguez in Paso Robles in February 2001. \"", "Her relentlessness in her effort to pursue her goals was matched only by her stupidity,\" Sortino said Monday.", "\n\nDuring the trial, prosecutors presented evidence that Rodriguez had complained to a friend about her marital problems and talked of killing her husband instead of divorcing him in order to receive the life insurance money. ", "Prosecutors also charged her with soliciting someone to kill that witness scheduled to testify against her. ", "The jurors deadlocked on that count but found her guilty of threatening the witness.", "\n\nWitnesses also testified about the 1993 death of Rodriguez's 13-month-old baby, who died after swallowing part of a pacifier. ", "The judge said Rodriguez received 60% of a $710,000 settlement in her daughter's death, after filing a civil suit against the manufacturer. ", "But a prosecution expert testified that medical records indicated that Rodriguez broke the pacifier herself and pushed part of it into her baby's throat to suffocate her, authorities said.", "\n\nRodriguez has not been charged in connection with her daughter's death. ", "Los Angeles prosecutors said Monday that they sent information on the case to investigators in Santa Barbara County, where the death occurred. ", "But Pounders called the baby's death a \"calculated murder\" that reflected Rodriguez's \"desire to murder family members for financial gain.\"", "\n\nJurors convicted Rodriguez of murder in October, along with the special allegations that she killed her husband for financial gain and used poison as the murder weapon. ", "Those allegations made her eligible for the death penalty.", "\n\nAfter returning a verdict of death in November, during the trial's penalty phase, jurors said they were influenced by Rodriguez's lack of remorse. ", "Pounders echoed that sentiment.", "\n\nRodriguez apologized for lying and pointing the finger at somebody else, but said without emotion, \"I don't have remorse for a murder I didn't do.\"", "\n\nThe case automatically goes to the California Supreme Court on appeal." ]

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[ "Through the thousands of photos online regarding Day Bed Frame, choices the best collections with greatest resolution only for you, and this photos is one of pictures collections within our ideal pictures gallery regarding Day Bed Frame. ", "I’m hoping you may enjoy it.", "\n\nThat image (Best Day Beds The Independent throughout Recent Bed Frame noa nani 2) earlier mentioned can be labelled with:put up simply by @Wadeframes.com from July, 24 2018. ", "To determine almost all pictures with Day Bed Frame pictures gallery you need to comply with Day Bed Frame.", "\n\nGallery Of Best Day Beds The Independent throughout Recent Bed Frame noa nani 2" ]

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[ "99mTechnetium-methylene diphosphonate bone imaging using low-intensity pulsed ultrasound: promotion of bone formation during mandibular distraction osteogenesis in dogs.", "\nOur objective was to assess the value of (99m)technetium-methylene diphosphonate ((99m)Tc-MDP) bone imaging in the use of low-intensity pulsed ultrasound to promote bony formation during mandibular distraction osteogenesis in dogs. ", "The body of the mandibles in 7 dogs were cut between the first and the second premolar and were lengthened at the rate of 1mm/day, twice a day, for 20 days. ", "During the period of distraction one lateral distraction gap was irradiated with low-intensity pulsed ultrasound (LIPUS) for 10min twice a day, and the other side was used as control. ", "Serial radiographic inspections were made at different periods (0, 1, 2, 4, 6, 8, and 12 weeks) during the consolidation phase, followed by a plain radiograph and histological examination. ", "The (99m)Tc-MDP imaging showed that the ratio of bone formation on the LIPUS-treated side was significantly higher than that on the control side during the early period of consolidation (before the 4th week), but later this was reversed and there were no significant differences between the two sides by the 12th week. ", "Plain radiographs and histological examination showed that the new bone on the experimental side had matured earlier than that on the control side. ", "Radionuclide bone imaging is a good way to assess the formation of bone after distraction osteogenesis." ]

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[ "Q:\n\nSelenium - count number of elements with matching class\n\nI have the following test code:\n it('count elements by class', async t => {\n let count = await driver.findElements(By.css('my-questions-class')).then(v => v.length);\n assert.equal(count, 3); // count is 0, but I expect 3\n });\n\nin my HTML, it's clear that there are some matching elements:\n<div class=\"panel panel-default my-questions-class\">\n\nis there a good reason why the Selenium code should not pick up these HTML elements? ", "\nI also tried this selector instead:\nBy.css('div[class=\\'my-questions-class\\']')\n\nneither one picked up any elements from the page. ", "But I can tell from observation that it is loading the correct page, so not sure what's going on here.", "\n\nA:\n\nYou want to use By.className the way you have it written. ", "i.e.\nBy.className('my-questions-class')\n\nWhen using By.css, you should use the CSS selector.", "\nBy.css('.my-questions-class')\n\nOr\nBy.css('div.my-questions-class')\n\n" ]

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[ "\n167 U.S. 43 (1897)\nDAVIS\nv.\nMASSACHUSETTS.", "\nNo. ", "229.", "\nSupreme Court of United States.", "\nArgued and submitted March 25, 1897.", "\nDecided May 10, 1897.", "\nERROR TO THE SUPERIOR COURT OF SUFFOLK COUNTY, MASSACHUSETTS.", "\n*46 Mr. James F. Pickering for plaintiff in error submitted on his brief.", "\nMr. Hosea M. Knowlton, Attorney General of Massachusetts, for defendant in error. ", "Mr. George C. Travis was on his brief.", "\nMR. ", "JUSTICE WHITE, after stating the case, delivered the opinion of the court.", "\nIn the brief of counsel for plaintiff in error many presumed errors are elaborately discussed, all of which when analyzed rest on the assumption that there was a right in the plaintiff in error to use the common of the city of Boston free from legislative or municipal control or regulation. ", "It is argued that —\n\"Boston Common is the property of the inhabitants of the city of Boston, and dedicated to the use of the people of that city and the public in many ways, and the preaching of the gospel there has been, from time immemorial to a recent period, one of these ways. ", "For the making of this ordinance in 1862 and its enforcement against preaching since 1885, no reason whatever has been or can be shown.\"", "\nThe record, however, contains no evidence showing the manner in which the ordinance in question had been previously enforced, nor does it include any proof whatever as to the nature of the ownership in the common from which it can be deduced that the plaintiff in error had any particular right to use the common apart from the general enjoyment which he was entitled, as a citizen, to avail of along with others and to the extent only which the law permitted. ", "On the contrary, the legislative act and the ordinance passed in pursuance thereof, previously set out in the statement of facts, show an assumption by the State of control over the common in question. ", "Indeed, the Supreme Judicial Court, in affirming the conviction, placed its conclusion upon the express ground that the common was absolutely under the control of the legislature, which, in the exercise of its *47 discretion, could limit the use to the extent deemed by it advisable, and could and did delegate to the municipality the power to assert such authority. ", "The court said:\n\"There is no evidence before us to show that the power of the legislature over the common is less than its power over any other park dedicated to the use of the public or over public streets the legal title to which is in a city or town. ", "Lincoln v. Boston, 148 Mass. 578, 580. ", "As representative of the public it may and does exercise control over the use which the public may make of such places, and it may and does delegate more or less of such control to the city or town immediately concerned. ", "For the legislature absolutely or conditionally to forbid public speaking in a highway or public park is no more an infringement of the rights of a member of the public than for the owner of a private house to forbid it in his house. ", "When no proprietary right interferes the legislature may end the right of the public to enter upon the public place by putting an end to the dedication to public uses. ", "So it may take the less step of limiting the public use to certain purposes. ", "See Dillon Mun. ", "Corp. secs. ", "393, 407, 651, 656, 666; Brooklyn Park Commissioners v. Armstrong, 45 N.Y. 234, 243, 244.", "\n\"If the legislature had power under the constitution to pass a law in the form of the present ordinance, there is no doubt that it could authorize the city of Boston to pass the ordinance, and it is settled by the former decision, Commonwealth v. Davis, 140 Mass. 485, that it has done so.\"", "\nIt is, therefore, conclusively determined there was no right in the plaintiff in error to use the common except in such mode and subject to such regulations as the legislature in its wisdom may have deemed proper to prescribe. ", "The Fourteenth Amendment to the Constitution of the United States does not destroy the power of the States to enact police regulations as to the subjects within their control, Barbier v. Connolly, 113 U.S. 27, 31; Minneapolis & St. Louis Railway Co. v. Beckwith, 129 U.S. 26, 29; Giozza v. Tiernan, 148 U.S. 657; Jones v. Brim, 165 U.S. 180, 182, and does not have the effect of creating a particular and personal right in the *48 citizen to use public property in defiance of the constitution and laws of the State.", "\nThe assertion that although it be conceded that the power existed in the State or municipality to absolutely control the use of the common, the particular ordinance in question is nevertheless void because arbitrary and unreasonable in that it vests in the mayor the power to determine when he will grant a permit, in truth, whilst admitting on the one hand the power to control, on the other denies its existence. ", "The right to absolutely exclude all right to use, necessarily includes the authority to determine under what circumstances such use may be availed of, as the greater power contains the lesser. ", "The finding of the court of last resort of the State of Massachusetts being that no particular right was possessed by the plaintiff in error to the use of the common, is in reason, therefore, conclusive of the controversy which the record presents, entirely aside from the fact that the power conferred upon the chief executive officer of the city of Boston by the ordinance in question may be fairly claimed to be a mere administrative function vested in the mayor in order to effectuate the purpose for which the common was maintained and by which its use was regulated. ", "In re Kollock, 165 U.S. 526, 536, 537. ", "The plaintiff in error cannot avail himself of the right granted by the State and yet obtain exemption from the lawful regulations to which this right on his part was subjected by law.", "\nAffirmed.", "\n" ]

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[ "The 6th Circuit just handed down a major ruling kneecapping Planned Parenthood.", "\n\nOhio passed a law in 2016 requiring that the Ohio Department of Health “ensure” that all of the funds it receives for six government-sponsored health and education programs targeting sexually transmitted diseases, breast cancer and cervical cancer, teen pregnancy, infant mortality, and sexual violence not be used to do any of the following:\n\n(1) Perform non-therapeutic abortions;\n\n(2) Promote non-therapeutic abortions;\n\n(3) Contract with any entity that performs or promotes non-therapeutic abortions;\n\n(4) Become or continue to be an affiliate of any entity that performs or promotes non-therapeutic abortions.", "\n\nPlanned Parenthood sued and a district judge affirmed the right of that company to suckle at the public teat for as long as it wished. ", "The State of Ohio appealed and the 6th Circuit ruled decisively in favor of Ohio.", "\n\nVia the Twitter feed of HotAir colleague Gabriel Malor:\n\n(Link is to Scribd as the court doesn't have the decision up on its webpage yet. ", "Usually up around 1pm.) — ", "Friendly Gabriel Malor (@gabrielmalor) March 12, 2019\n\nThe dissenting judges would hold that PP's right to perform abortions is derivative of the right to receive an abortion, and that ceasing to perform abortions would necessarily be an undue burden on women seeking to exercise their right. ", "pic.twitter.com/CWJSoD04Sl — Friendly Gabriel Malor (@gabrielmalor) March 12, 2019\n\nThe Ohio Planned Parenthood decision is now up on the 6th Cir. ", "website: https://t.co/1kLh9JE78f — Friendly Gabriel Malor (@gabrielmalor) March 12, 2019\n\nSingificantly, by using non-therapeutic abortions as the wedge, the court cracked wide open the death grip Planned Parenthood has on federal money that is a) fungible and b) lets Planned Parenthood troll for patients using other programs. ", "Now other organizations have a chance to provide those same services without performing abortions.", "\n\nThis is how POLITICO sees it:\n\nA majority of the 6th Circuit Court of Appeals ruled Tuesday that Ohio can cut state funding to Planned Parenthood because the organization performs abortions, overturning a lower court ruling that blocked the state from stripping about $1.5 million of annual support from the network of clinics. ", "The case was one of several across the country addressing attempts to cut public dollars to Planned Parenthood and other providers who offer abortions in addition to a range of health care services. ", "The 6th Circuit’s ruling affects six state public health programs in Ohio, but doesn’t touch Medicaid. ", "The Supreme Court in December declined to review a case brought by other Republican-led states seeking to cut off Medicaid funding for Planned Parenthood and other reproductive health organizations that offer abortions. ", "More than 20 states additionally have brought legal challenges over a Trump administration rule cutting tens of millions of dollars in Title X funding from Planned Parenthood and other abortion providers.", "\n\nRight now, as Malor says, there is no circuit split and Planned Parenthood may not appeal because of the nationwide ramifications if they lose in the Supreme Court.", "\n\nSix of the seventeen judges on the Sixth are now Trump appointees but only four of them were appointed in time to participate in this decision. ", "The other two judges voted with the minority in this decision. ", "It is not hard to see how this could have gone from an 11-6 against Planned Parenthood to a 10-7 for them. ", "It always was difficult to take seriously the Never Trump people who thought “but Gorsuch” was a killer comeback to anyone who said something complimentary of Trump. ", "Day by day we are seeing that the contribution made by Trump to conservatism in appointing at least to Supreme Court justices and dozens of appeals court judges far exceeds anything the Bulwark crowd will ever accomplish.", "\n\n=========\n\n=========\n\nLike what you see? ", "Then visit my story archive.", "\n\nFollow @streiffredstate\n\nI’m on Facebook. ", "Drop by and join the fun there.", "\n\n=========\n\n=========" ]

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[ "Implementation of an electronic medical record system in previously computer-naïve primary care centres: a pilot study from Cyprus.", "\nThe computer-based electronic medical record (EMR) is an essential new technology in health care, contributing to high-quality patient care and efficient patient management. ", "The majority of southern European countries, however, have not yet implemented universal EMR systems and many efforts are still ongoing. ", "We describe the development of an EMR system and its pilot implementation and evaluation in two previously computer-naïve public primary care centres in Cyprus. ", "One urban and one rural primary care centre along with their personnel (physicians and nurses) were selected to participate. ", "Both qualitative and quantitative evaluation tools were used during the implementation phase. ", "Qualitative data analysis was based on the framework approach, whereas quantitative assessment was based on a nine-item questionnaire and EMR usage parameters. ", "Two public primary care centres participated, and a total often health professionals served as EMR system evaluators. ", "Physicians and nurses rated EMR relatively highly, while patients were the most enthusiastic supporters for the new information system. ", "Major implementation impediments were the physicians' perceptions that EMR usage negatively affected their workflow, physicians' legal concerns, lack of incentives, system breakdowns, software design problems, transition difficulties and lack of familiarity with electronic equipment. ", "The importance of combining qualitative and quantitative evaluation tools is highlighted. ", "More efforts are needed for the universal adoption and routine use of EMR in the primary care system of Cyprus as several barriers to adoption exist; however, none is insurmountable. ", "Computerised systems could improve efficiency and quality of care in Cyprus, benefiting the entire population." ]

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[ "James W. Henderson\n\nJames W. Henderson is the Ben H. Williams Professor in Economics at Baylor University and is the author of Health Economics and Policy (2005), The Financial Analyst's Deskbook (1989), and Obtaining Venture Financing (1988)." ]

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[ "Imagine a car that runs on the same power as a toaster.", "\n\nThat's what the student-run Stanford Solar Car Project claims to have done. ", "The project designs, builds, tests and races solar-powered vehicles as part of the World Solar Challenge, a 2,000-mile (3,200 kilometre) trek across the Australian Outback. ", "The aim is to develop fuel-efficient, lighter and more aerodynamic vehicles.", "\n\nAs the video above shows, the lightweight vehicle, which cruises at 55mph (89km/h), operates on only one battery pack’s charge. ", "Its bulbous shape is designed to minimise drag, but it was a huge challenge to build.", "\n\nThe team’s engineering philosophy is that they can repurpose traditional designs to make them more efficient and sustainable. ", "Their car won’t ever make it on to the roads however – it is too fragile to survive a crash with another vehicle, and had to be escorted by other cars during the Australian race.", "\n\nRachel Abril, a member of the project’s mechanical team, spoke to BBC Future at the team’s Stanford workshop.", "\n\nAdditional video courtesy: Mark Shwartz, Precourt Institute for Energy, Stanford University: http://energy.stanford.edu.", "\n\nFollow us on Facebook, Twitter, Google+ and LinkedIn" ]

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[ "As computer-based systems, such as monitoring systems, training systems, game consoles, appliances, personal computers (“PCs”), servers, personal digital assistants (“PDAs”), cellular phones, become more prevalent in recent years, intuitive human-machine communications have become increasingly important. ", "Human-machine communications generally can be categorized into user interface device and machine interface device, wherein user interface device provides a mechanism for a user to talk to a machine while machine interface device is a mechanism for a machine to talk to a user. ", "Many conventional user interface devices have been well developed over the years, such as keyboard, voice recognition, touch panel, joystick, and the like. ", "Machine interface, however, is typically limited to audible cues and visual cues.", "\nAn audible cue typically is a sound or voice initiated by a machine or a computer to notify or to respond to a user's request(s). ", "For example, audible cues may be a beep, a voice, a ring, etc. ", "and it is used to remind, acknowledge, and/or warn the user(s). ", "Audible cues have been effectively used by the machines to communicate with the user(s). ", "For example, a machine initiates a beep when a user tries to choose a menu item that is currently not available.", "\nA visual cue typically includes a graphical cue or a textual cue enabling a machine to communicate to a user. ", "Visual cues typically allow users to see the results of their interaction with the machine or computer immediately. ", "For example, when a user clicks to open a file, the computer responds to user's click by providing context of the file in a text format on the display. ", "Graphical cues typically assist and/or indicate user actions. ", "For example, a cursor on a screen is a graphical cue to indicate or assist user action.", "\nA problem associated with machine interface is that audible cues are not effective in certain scenarios while visual cues may not be available in some occasions. ", "For example, a marathon runner may have a difficult time noticing visual cues via a display. ", "Also, the runner may not be able to notice audible cues in a noisy environment." ]

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[ "The role of neoadjuvant chemotherapy in the management of patients with advanced stage ovarian cancer: survey results from members of the Society of Gynecologic Oncologists.", "\nRecent randomized controlled data suggest that neoadjuvant chemotherapy (NACT) with interval debulking (ID) may produce similar overall survival and progression free survival compared to standard primary cytoreduction followed by chemotherapy. ", "The object of our study was to assess current patterns of care among members of the Society of Gynecologic Oncologists (SGO), specifically collating their opinions on and use of NACT for advanced stage ovarian cancer. ", "A 20-item questionnaire was sent to all working e-mail addresses of SGO members (n=1137). ", "The data was collected and analyzed using descriptive statistics with commercially available online survey software. ", "The Chi-square test for independence was used to determine differences in responses between groups. ", "Of 339 (30%) responding members, most rarely employ NACT, with 60% of respondents using NACT in less than 10% of advanced stage ovarian cancer cases. ", "Respondents did not consider available evidence sufficient to justify NACT followed by ID (82%), nor did most think it should be preferred (74%). ", "Sixty-two percent of respondents thought it was impossible to accurately predict preoperatively whether an optimal cytoreduction is possible. ", "Thirty-nine percent believed that women with bulky upper abdominal disease on preoperative imaging would benefit from NACT versus primary debulking. ", "If gross disease were found at ID, 43% would continue to treat with IV chemotherapy, and 42% would place an IP port if optimally cytoreduced. ", "When ID reveals microscopic disease, 51% would continue IV treatment and the remaining IP therapy. ", "Eighty-six percent of the respondents believed that both biological and surgical factors determine patient outcomes. ", "The majority of responding SGO members do not treat patients with NACT followed by ID. ", "Currently available studies of NACT/ID have been insufficient to convince most gynecologic oncologists to incorporate it into practice. ", "Our results provide a benchmark against which further research can assess the penetration of NACT/ID into clinical practice." ]

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[ "Comparison of direct versus indirect determination of zinc concentration in erythrocytes in euthyroid and hyperthyroid subjects.", "\nZinc concentration in erythrocytes is a suitable marker of peripheral tissue response to thyroid hormones. ", "Therefore, the determination of erythrocyte zinc concentration has become an important marker for duration of preexisting hyperthyroidism in the clinical laboratory. ", "We compared a new indirect erythrocyte zinc determination method with a commonly used direct method in 42 euthyroid and 14 hyperthyroid subjects. ", "Zinc concentrations (median and range) obtained by direct and indirect methods were 172.8 (134.4-241.1) and 176.8 (143-243.9) mumol/l erythrocytes in the euthyroid group and 117.1 (71-141.9) and 118.5 (73-137) mumol/l erythrocytes in the hyperthyroid group. ", "Values measured by the indirect method were slightly higher in both groups. ", "Regression analysis showed a good correlation (r = 0.967, p = 0.0001). ", "The influence of the anticoagulants, potassium EDTA and heparin, on erythrocyte and plasma zinc values was studied, and zinc concentrations in serum and plasma were compared. ", "No statistically significant differences were found. ", "Thus, the indirect determination of erythrocyte zinc concentration is a simple and rapid technique well suited for use in clinical laboratory work, yielding accurate and reliable results. ", "For the indirect method reference concentrations were established in a collective of 102 thyroid healthy subjects. ", "An erythrocyte zinc concentration of 176.3 +/- 23.9 mumol/l (mean +/- SD) was found with a cut-off limit of 138 mumol/l to hyperthyroidism." ]

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[ "Peripheral osteopenia in adult patients with insulin-dependent diabetes mellitus.", "\nAlterations in bone metabolism in diabetes mellitus is a topic of special interest. ", "Bone blood flow is increased in the distal limb of diabetic patients, which is believed to increase osteoclastic activity. ", "We measure bone mineral density using dual-photon absorptiometry in the distal lower limb, the femoral neck, and the lumbar spine in 41 IDDM patients and in 30 control persons. ", "In the diabetic group there was a 10% reduction of bone mineral density in the femoral neck (p < 0.01) and a 12% reduction in the distal limb (p < 0.001) compared with the control group. ", "No significant difference was found in the lumbar spine (p = 0.22). ", "Our data yield incidence for peripheral osteopenia in IDDM-patients, independent of any systemic bone disease such as osteoporosis. ", "A link between decreased bone mineral density and diabetic neuropathy has been observed for the femoral neck (p < 0.001), but not for the distal limb or axial skeleton. ", "Whether there is a common aetiological link or a casual connection between diabetic neuropathy and bone mineral density has still to be determined." ]

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[ "Dave Wommack\n\nDave Wommack (born May 9, 1956) is a former American football coach. ", " He is the former defensive coordinator at the University of Mississippi. ", " Wommack was formerly the defensive coordinator for Arkansas State University and at the Georgia Institute of Technology. ", "On January 8, 2010, Wommack was let go from his position as Georgia Tech by head coach Paul Johnson. ", "A native of Kimberling City, Missouri, Wommack played college football at Missouri Southern State University. ", " Wommack lettered three years, as a center. ", " He is married, with two children. ", "Wommack retired after the 2016 season.", "\n\nReferences\n\nCategory:1956 births\nCategory:Living people\nCategory:American football centers\nCategory:Arkansas Razorbacks football coaches\nCategory:Arkansas State Red Wolves football coaches\nCategory:Bemidji State Beavers football coaches\nCategory:Georgia Tech Yellow Jackets football coaches\nCategory:Missouri State Bears football coaches\nCategory:Missouri Southern Lions football players\nCategory:Missouri Tigers football coaches\nCategory:Ole Miss Rebels football coaches\nCategory:South Carolina Gamecocks football coaches\nCategory:Southern Miss Golden Eagles football coaches\nCategory:UNLV Rebels football coaches\nCategory:People from Kimberling City, Missouri" ]

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[ "runtime: go\nservice: get\napi_version: go1\n\nhandlers:\n- url: /.*\n script: _go_app\n" ]

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[ "http://www.ceaescrow.org/The vision of the California Escrow Association is to both lead and support the escrow settlement services and real estate and financial industries through our commitment to the professional and personal growth of the escrow practitioner." ]

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[ "Q:\n\nSingleton causing linker errors: \"already defined\"\n\nI wrote a simple class which manages the current execution session. ", "Therefore, I decided to use a singleton pattern but the compilation crashes at linked step. ", "This is the error:\nerror LNK2005: \"class Session * session\" (?", "session@@3PAVSession@@A) already defined in ClientTsFrm.obj\n(...)client\\FrmSaveChat.obj TeamTranslate\nerror LNK2005: \"class Session * session\" (?", "session@@3PAVSession@@A) already defined in ClientTsFrm.obj\n(...)client\\Login.obj TeamTranslate\nerror LNK2019: unresolved external symbol \"protected: __thiscall Session::Session(void)\" (??", "0Session@@IAE@XZ)\n referenced in function \"public: static class Session * __cdecl Session::Instance(void)\" (?", "Instance@Session@@SAPAV1@XZ)\n(...)client\\Session.obj TeamTranslate\nerror LNK2001: unresolved external symbol \"private: static char const * const Session::_nick\" (?_", "nick@Session@@0PBDB)\n(...)client\\Session.obj TeamTranslate\nerror LNK2001: unresolved external symbol \"private: static char const * const Session::_service\" (?_", "service@Session@@0PBDB)\n(...)client\\Session.obj TeamTranslate\nerror LNK2001: unresolved external symbol \"private: static char const * const Session::_serverAddress\" (?_", "serverAddress@Session@@0PBDB)\n(...)client\\Session.obj TeamTranslate\nerror LNK2001: unresolved external symbol \"private: static char const * const Session::_googleAPI\" (?_", "googleAPI@Session@@0PBDB)\n(...)client\\Session.obj TeamTranslate\nerror LNK2001: unresolved external symbol \"private: static char const * const Session::_language\" (?_", "language@Session@@0PBDB)\n(...)client\\Session.obj TeamTranslate\nerror LNK2001: unresolved external symbol \"private: static int Session::_numbLanguageSelected\" (?_", "numbLanguageSelected@Session@@0HA)\n(...)client\\Session.obj TeamTranslate\nerror LNK2001: unresolved external symbol \"private: static char const * const Session::_translationEngine\" (?_", "translationEngine@Session@@0PBDB)\n(...)client\\Session.obj TeamTranslate\nerror LNK1120: 8 unresolved externals\n(...)client\\bin\\TeamTranslate.exe TeamTranslate\nIntelliSense: identifier \"wxZipStreamLink\" is undefined\n(..)\\include\\wx\\zipstrm.h 417 5\n\nsession.h (singleton)\n#ifndef __SESSION_H__\n#define __SESSION_H__\n\n#include <cstring>\n#include <stdio.h>\n\nclass Session {\npublic:\n static Session* Instance();\n\n void setNick(char* nick);\n const char* getNick();\n\n void setService(char* serv);\n const char* getService();\n\n void setLanguage(char* lang);\n const char* getLanguage();\n\n const char* getServerAddress();\n void setServerAddress(char *sv);\n\n void setGoogleAPIKey(char* code);\n const char* getGoogleAPIKey();\n\n void setNumbLanguageSelected(int v);\n int getNumbLanguageSelected();\n\n const char* Session::getTranslationEngine();\n void Session::setTranslationEngine(char *sv);\n\n char* Session::getGoogleURLTranslation();\n\n void update();\n bool read();\nprotected:\n Session();\nprivate:\n static Session* _instance;\n static const char* _nick; // client nickname\n static const char* _service; // service used to translation (Google, Bing,....)\n static const char* _serverAddress;\n static const char* _googleAPI;\n static const char* _language;\n static int _numbLanguageSelected;\n static const char* _translationEngine;\n};\n\n#endif\n\nSession.cpp\n#include \"Session.h\"\n\nSession* Session::_instance = 0;\n\nSession* Session::Instance() {\n if (_instance == 0) {\n _instance = new Session;\n _instance->read();\n }\n return _instance;\n}\n\nvoid Session::setGoogleAPIKey(char* code){\n _googleAPI = strdup(code);\n}\n\nconst char* Session::getGoogleAPIKey(){\n return _googleAPI;\n}\n\nvoid Session::setLanguage(char* lang){\n _language = strdup(lang);\n}\n\nconst char* Session::getLanguage(){\n return _language;\n}\n\nvoid Session::setNick(char* nick){\n _nick = strdup(nick);\n}\n\nconst char* Session::getNick(){\n return _nick;\n}\n\nvoid Session::setService(char* serv){\n _service = strdup(serv);\n}\n\nconst char* Session::getService(){\n return _service;\n}\n\nconst char* Session::getServerAddress(){\n return _serverAddress;\n}\n\nvoid Session::setServerAddress(char *sv){\n _serverAddress = strdup(sv);\n}\n\nvoid Session::setNumbLanguageSelected(int v){\n this->_numbLanguageSelected = v;\n}\nint Session::getNumbLanguageSelected(){\n return _numbLanguageSelected;\n}\n\nconst char* Session::getTranslationEngine(){\n return _translationEngine;\n}\n\nvoid Session::setTranslationEngine(char* sv){\n _translationEngine = strdup(sv);\n}\n\nvoid Session::update(){\n FILE* config = fopen(\"conf\\\\config.txt\", \"w\");\n fprintf(config, \"%s\\n\", _serverAddress);\n fprintf(config, \"%s\\n\", _nick);\n fprintf(config, \"%d\\n\", _numbLanguageSelected);\n fprintf(config, \"%s\\n\", _language);\n fprintf(config, \"%s\", _translationEngine);\n fflush(config);\n fclose(config);\n}\n\nbool Session::read(){\n FILE * config;\n if (config = fopen(\"conf\\\\config.txt\", \"r\"))\n {\n fscanf(config, \"%s\", _serverAddress);\n fscanf(config, \"%s\", _nick);\n fscanf(config, \"%d\", _numbLanguageSelected);\n fscanf(config, \"%s\", _language);\n fscanf(config, \"%s\", _translationEngine);\n fflush(config);\n fclose(config);\n return true;\n } else\n return false;\n}\n\n char* Session::getGoogleURLTranslation(){\n return \"https://www.googleapis.com/language/translate/v2?key=\";\n}\n\nExample about how I call the singleton:\n#include \"../data/Session.h\"\n\nstatic Session* session = Session::Instance();\n\nCan you help me to fix the errors? ", "\nthanks in advance.", "\n\nA:\n\nOne of your headers (which you didn't show, but it is included in both \"ClientTsFrm.cpp\" and \"FrmSaveChat.cpp\") defines a variable called \"session\" of type Session*.", "\nThe other errors are caused by your forgetting to define most static members of Session.", "\n\n" ]

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[ "The announcer in League of Legends reports important events in the game, usually kills, deaths and objectives, both on Gameplay and Spectator Mode." ]

{ "pile_set_name": "OpenWebText2" }

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[ "Efficacy of Enteral Access in Patients with Esophageal Squamous Cell Carcinoma Under Neoadjuvant Therapy.", "\nEnteral feeding tubes used to manage the nutritional status of esophageal cancer were evaluated regarding their effectiveness in patients receiving neoadjuvant therapy. ", "A retrospective study evaluating patients with esophageal squamous cell carcinoma undergoing neoadjuvant therapy between 2001 and 2014 was conducted at a medical center. ", "Hospital patients' records for enteral access (EA) insertion and treatment outcomes were statistically analyzed. ", "Patients with EA at initial diagnosis had lower body mass index than the group without EA (p=0.012). ", "Chemotherapy-related adverse events with grade 3-4 mucositis were significantly less frequent in the EA group (p=0.008), and grade 3-4 anemia was significantly more frequent (p=0.012). ", "The 4-year mortality rate was 63.0% in the EA group and 67.7% in the group without EA (pnon-inferiority=0.035), which met the non-inferiority criterion with a non-inferiority margin of 10%. ", "Patients with esophageal squamous cell carcinoma with malnutrition status undergoing neoadjuvant therapy with EA showed an improved outcome at maintaining nutritional status, reduced severity of mucositis and improved survival rate." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Q:\n\nGDB grep info sources files\n\nIs it possible to grep or filter the output of info sources in gdb?", "\nSomething like:\n(gdb) info sources | grep bob.cpp\n\nThanks\n\nA:\n\nIs it possible to grep or filter the output of info sources in gdb?", "\n\nNo. ", "This could be considered a bug: info shared takes an optional regex to filter shared libraries, but info sources does not.", "\nWorkaround:\n(gdb) set logging on # GDB output will now be copied into gdb.txt\n(gdb) info sources\n(gdb) set logging off\n(gdb) shell grep bob.cpp gdb.txt\n(gdb) shell rm gdb.txt\n\nIf you need to do this often, you could put above commands into a user-defined command.", "\n\n" ]

{ "pile_set_name": "StackExchange" }

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[ "Alcohol and anesthetic actions on excitatory amino acid-activated ion channels.", "\nThe actions of alcohol and anesthetics have been studied on excitatory amino acid activated ion channels in mammalian neurons. ", "Ethanol inhibits NMDA-activated current over a concentration range that produces intoxication, and the potency of several alcohols for inhibiting the NMDA-activated current is correlated with their intoxicating potency, suggesting that alcohol-induced inhibition of responses to NMDA receptor activation may contribute to the neural and cognitive impairments associated with intoxication. ", "Studies on the mechanism of ethanol inhibition of NMDA-activated current indicate that ethanol does not appear to block the ion channel, alter the ion selectivity of the channel, or interact with previously described binding sites on the NMDA receptor/ionophore complex. ", "The linear relation between the potency of several alcohols for inhibiting the NMDA-activated current and the hydrophobicity of the alcohols suggests that ethanol may inhibit the NMDA-activated ion current by a novel type of interaction with a hydrophobic site associated with the NMDA channel. ", "In addition, different types of general anesthetic agents exhibit different inhibitory actions on NMDA-, kainate-, and quisqualate-activated currents, suggesting that differences in the profile of inhibition of excitatory amino acid neurotransmission in the CNS among different classes of general anesthetics may contribute to the differences in their behavioral and physiological effects." ]

{ "pile_set_name": "PubMed Abstracts" }

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[]

[ "// Copyright (c) 2012 The Chromium Authors. ", "All rights reserved.", "\n// Use of this source code is governed by a BSD-style license that can be\n// found in the LICENSE file.", "\n\n#include \"ppapi/cpp/dev/file_chooser_dev.h\"\n\n#include <stddef.h>\n#include <string.h>\n\n#include \"ppapi/c/dev/ppb_file_chooser_dev.h\"\n#include \"ppapi/c/pp_errors.h\"\n#include \"ppapi/cpp/completion_callback.h\"\n#include \"ppapi/cpp/file_ref.h\"\n#include \"ppapi/cpp/instance_handle.h\"\n#include \"ppapi/cpp/module.h\"\n#include \"ppapi/cpp/module_impl.h\"\n\nnamespace pp {\n\nnamespace {\n\ntemplate <> const char* interface_name<PPB_FileChooser_Dev_0_5>() {\n return PPB_FILECHOOSER_DEV_INTERFACE_0_5;\n}\n\ntemplate <> const char* interface_name<PPB_FileChooser_Dev_0_6>() {\n return PPB_FILECHOOSER_DEV_INTERFACE_0_6;\n}\n\n} // namespace\n\nFileChooser_Dev::FileChooser_Dev(const InstanceHandle& instance,\n PP_FileChooserMode_Dev mode,\n const Var& accept_types) {\n if (has_interface<PPB_FileChooser_Dev_0_6>()) {\n PassRefFromConstructor(get_interface<PPB_FileChooser_Dev_0_6>()->Create(\n instance.pp_instance(), mode, accept_types.pp_var()));\n } else if (has_interface<PPB_FileChooser_Dev_0_5>()) {\n PassRefFromConstructor(get_interface<PPB_FileChooser_Dev_0_5>()->Create(\n instance.pp_instance(), mode, accept_types.pp_var()));\n }\n}\n\nFileChooser_Dev::FileChooser_Dev(const FileChooser_Dev& other)\n : Resource(other) {\n}\n\nint32_t FileChooser_Dev::Show(\n const CompletionCallbackWithOutput< std::vector<FileRef> >& callback) {\n if (has_interface<PPB_FileChooser_Dev_0_6>()) {\n return get_interface<PPB_FileChooser_Dev_0_6>()->Show(\n pp_resource(),\n callback.output(),\n callback.pp_completion_callback());\n }\n if (has_interface<PPB_FileChooser_Dev_0_5>()) {\n // Data for our callback wrapper. ", "The callback handler will delete it.", "\n ChooseCallbackData0_5* data = new ChooseCallbackData0_5;\n data->file_chooser = pp_resource();\n data->output = callback.output();\n data->original_callback = callback.pp_completion_callback();\n\n return get_interface<PPB_FileChooser_Dev_0_5>()->Show(\n pp_resource(), PP_MakeCompletionCallback(&CallbackConverter, data));\n }\n return callback.", "MayForce(PP_ERROR_NOINTERFACE);\n}\n\n// static\nvoid FileChooser_Dev::CallbackConverter(void* user_data, int32_t result) {\n ChooseCallbackData0_5* data = static_cast<ChooseCallbackData0_5*>(user_data);\n\n // Get all of the selected file resources using the iterator API.", "\n std::vector<PP_Resource> selected_files;\n if (result == PP_OK) {\n const PPB_FileChooser_Dev_0_5* chooser =\n get_interface<PPB_FileChooser_Dev_0_5>();\n while (PP_Resource cur = chooser->GetNextChosenFile(data->file_chooser))\n selected_files.push_back(cur);\n }\n\n // Need to issue the \"GetDataBuffer\" even for error cases & when the\n // number of items is 0.", "\n void* output_buf = data->output.", "GetDataBuffer(\n data->output.user_data,\n static_cast<uint32_t>(selected_files.size()), sizeof(PP_Resource));\n if (output_buf) {\n if (!", "selected_files.empty()) {\n memcpy(output_buf, &selected_files[0],\n sizeof(PP_Resource) * selected_files.size());\n }\n } else {\n // Error allocating, need to free the resource IDs.", "\n for (size_t i = 0; i < selected_files.size(); i++)\n Module::Get()->core()->ReleaseResource(selected_files[i]);\n }\n\n // Now execute the original callback.", "\n PP_RunCompletionCallback(&data->original_callback, result);\n delete data;\n}\n\n} // namespace pp\n" ]

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[ "---\nabstract: 'Every day millions of users are connected through online social networks, generating a rich trove of data that allows us to study the mechanisms behind human interactions. ", "Triadic closure has been treated as the major mechanism for creating social links: if Alice follows Bob and Bob follows Charlie, Alice will follow Charlie. ", "Here we present an analysis of longitudinal micro-blogging data, revealing a more nuanced view of the strategies employed by users when expanding their social circles. ", "While the network structure affects the spread of information among users, the network is in turn shaped by this communication activity. ", "This suggests a link creation mechanism whereby Alice is more likely to follow Charlie after seeing many messages by Charlie. ", "We characterize users with a set of parameters associated with different link creation strategies, estimated by a Maximum-Likelihood approach. ", "Triadic closure does have a strong effect on link formation, but shortcuts based on traffic are another key factor in interpreting network evolution. ", "However, individual strategies for following other users are highly heterogeneous. ", "Link creation behaviors can be summarized by classifying users in different categories with distinct structural and behavioral characteristics. ", "Users who are popular, active, and influential tend to create traffic-based shortcuts, making the information diffusion process more efficient in the network.'", "\nauthor:\n- |\n Lilian Weng$^1$, Jacob Ratkiewicz$^2$, Nicola Perra$^3$, Bruno Gonçalves$^4$, Carlos Castillo$^5$, Francesco Bonchi$^6$, Rossano Schifanella$^7$, Filippo Menczer$^1$, Alessandro Flammini$^1$\\\n \\\n \\\n \\\n \\\n \\\nbibliography:\n- 'references.bib'\ntitle:\n- Modeling social network evolution with user activity dynamics\n- 'Coupling user activity and structure evolution: a new model of social networks'\n- |\n Efficient information diffusion\\\n and the evolution of social networks\n- |\n Diverse Link Creation Mechanisms\\\n in the Evolution of Social Networks\n- |\n User Activity and Link Creation\\\n in the Evolution of Social Networks\n- |\n Does Traffic Matter?\\\n User Activity and Link Creation in Online Social Networks\n- |\n Why does Alice follow Bob?\\\n User Activity and Traffic in Online Social Networks\n- 'User Activity, Traffic, and Link Creation in Information Diffusion Networks'\n- 'User Activity, Traffic, and Link Creation in Online Social Networks'\n- |\n The Role of Information Diffusion\\\n in the Evolution of Social Networks\n---\n\nIntroduction\n============\n\n![", "The dynamics *of* and *on* the network are strongly coupled. ", "The bottom layer illustrates the social network structure, where the blue arrows represent “follow” relationships with the direction of information flow. ", "The dashed red arrow marks a newly created link. ", "The upper layer depicts the flow of information between people in the same group, leading to the creation of the new link. []{", "data-label=\"fig:illustration\"}](illustration){width=\"\\columnwidth\"}\n\nUser activity in online social networks is exploding. ", "Social and micro-blogging networks such as Facebook, Twitter, and Google Plus every day host the information sharing activity of billions of users. ", "Using these systems, people communicate ideas, opinions, videos, and photos among their circles of friends and followers across the world. ", "These interactions generate an unprecedented amount of data that can be used as a social observatory, providing a unique opportunity to shed light on the mechanisms of human communication with a quantitative approach [@lazer-09; @cho-09; @kumar-06; @angelina; @vespignani2009; @vespignani2011modelling].", "\n\nResearch on social media revolves around two main themes: communication and its social network substrate. ", "Most network models focus on either the structural growth of the system — the dynamics *of* the network — or information diffusion processes — the dynamics *on* the network. ", "The present work establishes a feedback loop between these two dynamics.", "\n\nMuch effort has been devoted to modeling the evolution of social networks [@Wasserman-F; @Alexlibro; @Newmanlibro; @angelina]. ", "Among proposed mechanisms of how a link is created, *triadic closure* [@simmel; @Granovetter] is a simple but powerful principle to model the evolution of social networks based on shared friends: two individuals with mutual friends have a higher than random chance to establish a link. ", "In directed networks, such as Twitter or Yahoo! ", "Meme, triadic closure implies a particular order with respect to the direction of links: once Alice follows Bob and Bob follows Charlie, Alice will follow Charlie. ", "Triadic closure has been observed in both undirected and directed online social networks and incorporated into several network growth models [@Leskovec-08; @Krackhardt; @shi2007; @romero2010closure]. ", "However, most existing models do not take user activity — or how information spreads on the network — into consideration.", "\n\nSocial micro-blogging networks, such as Twitter, Google Plus, Sina Weibo, and Yahoo! ", "Meme, are designed for information sharing. ", "As illustrated in Fig.", " \\[fig:illustration\\], the social network structure constrains communication patterns, but information propagated through the network also affect how agents behave and ultimately how the network changes and grows. ", "In this paper we study the role of information diffusion in shaping the evolution of the network structure, and the individual strategies that bring about this effect by way of creating social links.", "\n\nThe major contribution of this paper is to present clear evidence that information diffusion affects network evolution at both system-wide and individual levels. ", "In particular, we find that a considerable portion of new links are *shortcuts based on information flow* (§ \\[sec:4\\]). ", "There is significant statistical evidence for triadic closure as a link creation mechanism, but also that users tend to link to people who have generated content they have seen (§ \\[sec:4.1\\]). ", "Furthermore, not all users apply the same strategy to grow their social connections; users with high in-degree tend to pay more attention to traffic (§ \\[sec:4.2\\]). ", "However, shortcuts are not equally probable; we find that users follow the most active sources of content; purely topological mechanisms cannot account for these shortcuts (§ \\[sec:4.3\\]). ", "As a result, traffic-based shortcuts can make the social network more efficient in terms of information diffusion (§ \\[sec:4.4\\]). ", "In § \\[sec:5\\], we perform a Maximum Likelihood Estimation analysis to quantify the system-wide prevalence of different link creation strategies. ", "Finally, the categorization of users suggests the existence of several distinct link formation behaviors (§ \\[sec:6\\]). ", "Our findings identify information diffusion dynamics as a key factor in the evolution of social networks.", "\n\nBackground\n==========\n\nEarly models concerning communication dynamics were inspired by studies of epidemics, assuming that a piece of information could pass from one individual to another through social contacts [@rapoport53; @goffman64; @daley64; @bailey75; @SIR]. ", "These models have been extended to include cascade phenomena [@goldenberg01], factors that influence the speed of spreading such as information recency [@moreno04], the heterogeneity in connectivity patterns [@Romu01-1], clustering [@onnela06-1], user-created content [@bakshy09], and temporal connectivity patterns [@morris95-1; @butts08-1; @butts09-1; @perra12-1]. ", "An alternative class of models is based on the idea of a threshold; you propagate an idea when some number of friends communicate it to you [@threshold_model; @Morris00]. ", "These models are believed to be relevant in the diffusion of rumors, norms, and behaviors [@centola2010], and have been extended to study the role of competition for finite attention [@Weng:2012scirep]. ", "The large majority of these studies consider either a *static* or *annealed* underlying social network, under the assumption that the network evolves on a longer (slower) time scale than the information spread. ", "Recent research has addressed the modeling of intermediate cases, in which the two time scales are comparable. ", "These approaches consider the two dynamics as either independent [@Rocha:2010; @perra12-2] or coupled [@volz09-1; @schwartz10-2]. ", "The foundations of this last class of models are very similar to those explored in this paper. ", "However, thus far, these models have focused mainly on epidemic processes in which links are deleted or rewired according to the disease status of each node [@volz09-1; @schwartz10-2]. ", "The social systems considered in this paper are governed by quite different underlying mechanisms.", "\n\nModels devoted to reproducing the growth and evolution of network topology have traditionally focused on defining basic mechanisms driving link creation [@Wasserman-F; @Newmanlibro; @Alexlibro]. ", "From the first model proposed in 1959 by Erdös and Rényi [@Erdos], many others have been introduced capturing different properties observed in real networks, such as the small-world phenomenon [@Watts-S; @Leskovec-08; @Krackhardt; @shi2007; @romero2010closure], large clustering coefficient [@Watts-S; @Leskovec-08; @Krackhardt; @shi2007; @romero2010closure], temporal dynamics [@perra12-1; @Rocha:2010], and heterogeneous distributions in connectivity patterns [@BA; @Kleinberg-K-R-R; @kumar2000stochastic; @Krapivsky-R; @Dorogo-M-S00a; @santo-PRL]. ", "In particular, this latter property was first described by the preferential attachment [@BA] and copy models [@kumar2000stochastic].", "\n\nIn the social context, the rationale behind preferential attachment mechanisms is that people prefer linking to well connected individuals [@BA]. ", "Although very popular, this prescription alone is not sufficient to reproduce other important features of social networks. ", "Other models have been put forth to fill this gap, including ingredients such as homophily [@holme2006opinion; @McPherson2001homophily; @papa2012similarity; @Aiello2011Friendship; @gallos2012people] and triadic closure [@simmel; @Granovetter; @Leskovec-08; @Krackhardt; @shi2007; @romero2010closure].", "\n\nHomophily describes the tendency of people to connect with others sharing similar features [@McPherson2001homophily; @holme2006opinion]. ", "Its impact on link creation in large-scale online networks is a recent topic of discussion [@papa2012similarity; @Aiello2011Friendship; @gallos2012people].", "\n\nThe triadic closure mechanism is based on the intuition that two individuals with mutual friends have a higher probability to establish a link [@simmel; @Granovetter]. ", "This tendency has been observed in both undirected and directed online social networks and incorporated into several network growth models [@Leskovec-08; @Krackhardt; @shi2007; @romero2010closure]. ", "In particular Leskovec *et al.* ", "have tested triadic closure against many other mechanisms in four different large-scale social networks [@Leskovec-08]. ", "By using Maximum Likelihood Estimation (MLE) [@cowan] they have identified triadic closure as the best rule, among those considered, to explain link creation.", "\n\nAlthough similar in spirit, our approach is different from this large body of literature. ", "We do not consider agent based simulations in which the structural behavior of each user is modeled by a set of rules. ", "We adopt the MLE framework extending the work of Leskovec *et al.*", " [@Leskovec-08]. ", "We extend the notion of triadic closure by considering mechanisms based on traffic, or more in general, users activity. ", "We explicitly study the coupling between the dynamics *of* and *on* the network, connecting these two previously separated themes of research, in the context of online social networks.", "\n\nMeme Dateset {#sec:3}\n============\n\nWe study *Yahoo! ", "Meme,* a social micro-blogging system similar to Twitter, which was active between 2009 and 2012. ", "We have access to the entire history of the system, including full records of every message propagation and link creation event, from April 2009 until March 2010. ", "A user $j$ following a user $i$ is represented in the follower network by a directed edge $\\ell = (i,j)$, indicating $j$ can receive messages posted by $i$. We adopt this notation, in which the link creator is the target, to emphasize the direction of information flow. ", "Edges are directed to account for asymmetric relations between users; a node can follow another without being followed back. ", "In our notation, the in-degree of a node $i$ is the number of people followed by $i$, and the out-degree is the number of $i$’s followers. ", "Users can repost received messages, which become visible to their followers. ", "When user $j$ reposts content from $i$, we infer a flow of information from $i$ to $j$. Each link is weighted by the numbers of messages from $i$ that are reposted or seen by $j$.\n\nAt the end of the observation period, the Yahoo! ", "Meme follower network consisted of 128,199 users with at least one edge, connected by a total of 3,485,361 directed edges. ", "Fig.", " \\[fig:stats\\] displays general statistics about the growth and structure of the network.", "\n\n![", "General statistics of the Yahoo! ", "Meme system. (", "A) The growth of the system in time, the number of users (red circles), links (blue squares) and messages (green triangles). (", "B) Broad distributions of in-degree and out-degree in the follower network of Yahoo! ", "Meme. ", "Users were not allowed to follow more than 1,000 people, which is the maximum in-degree a node can attain. []{", "data-label=\"fig:stats\"}](basic_stats){width=\"\\columnwidth\"}\n\nLink Creation Mechanisms {#sec:4}\n========================\n\n![ (", "A) Illustration of the link creation mechanisms. (", "B) Venn digram of the proportions of grandparent, origin, and triadic closure links among all existing edges.[]{data-label=\"fig:definition\"}](definition){width=\"\\columnwidth\"}\n\nWhen users post or repost messages, all their followers can see these posts and might decide to repost them, generating paths that together form cascade networks. ", "When receiving a reposted message, a user in such a path can see both the *grandparent* ($G$, the user two steps ahead in the path) and the *origin* ($O$, original source). ", "A user may decide to follow a grandparent or origin, receiving their future messages directly. ", "These new links create *shortcuts* connecting users at any distance in the network. ", "A triadic closure occurs when a user follows a *triadic node* ($\\Delta$, the user two steps away in the follower network). ", "The definitions of different types of link creation mechanisms are illustrated in Fig.", " \\[fig:definition\\](A).", "\n\nThe Venn diagram in Fig.", " \\[fig:definition\\](B) shows the proportions of links of different types and the logical relationships between these sets of links. ", "We observe that 84.8% of new edges consist of triadic closures, 21.5% form shortcuts to grandparent, and 19.5% to origins. ", "Note that not all the grandparents are triadic nodes, because users are allowed to repost messages from people they are not following in Yahoo! ", "Meme. ", "This account for 0.03% of links. ", "There is a large overlap between triadic closure links and traffic-based shortcuts. ", "This can be explained by the phenomenon that most real-world information cascades are shallow [@bakshy2011everyone] and thus triadic closure links and traffic-based shortcuts coincide.", "\n\nThis evidence suggests that traffic-based link creation mechanisms are an important complement to the triadic closure in modeling network evolution. ", "Actions of posting and reposting induce the creation of shortcuts, shaping the structure of the network. ", "Newly created links in turn determine what messages are seen by users, making the network more efficient at spreading information.", "\n\nStatistical Analyses of Shortcuts {#sec:4.1}\n---------------------------------\n\nTo quantify the statistical tendency of users to create shortcuts, let us consider every single link creation in the data as an independent event. ", "We test the null hypotheses that links to grandparents, origins, and triadic nodes are generated by choosing targets at random among the users not already followed by the creator.", "\n\nWe label each link $\\ell$ by its creation order, $1 \\leq \\ell \\leq L$, where $L$ is the total number of links. ", "For each link, we can compute the likelihood of following a grandparent by chance: $$p_G(\\ell)=\\frac{N_G(\\ell)}{\\ell - k(\\ell)-1}$$ where $N_G(\\ell)$ is the number of distinct grandparents seen by the creator of $\\ell$ at the moment when $\\ell$ is about to be created; $k(\\ell)$ is the in-degree of $\\ell$’s creator at the same moment; and the denominator is the number of potential candidates to be followed. ", "The indicator function for each link $\\ell$ denotes whether the link connects with a grandparent or not in the real data: $$\\begin{aligned}\n\\mathbf{1}_G (\\ell)&= \\left\\{ \n \\begin{array}{l l}\n 1 & \\text{if $\\ell$ links to a grandparent} \\\\\n 0 & \\text{otherwise.} \\\\", "\n \\end{array}\\right.\\end{aligned}$$ The expected number of links to grandparents according to the null hypothesis can be then computed as: $$E_G=\\sum_{\\ell=1}^{L} p_G(\\ell)$$ and its variance is given by: $$\\sigma^2_G = \\sum_{t=1}^{L} p_{G}\\left(\\ell \\right)\\left(1-p_{G}\\left(\\ell \\right)\\right)$$ while the corresponding empirical number is: $$S_G= \\sum_{\\ell=1}^{L} \\mathbf{1}_G(\\ell).$$ According to the Lyapunov central limit theorem,[^1] the variable $z_G=(S_G - E_G)/\\sigma_G$ is distributed according to a standard normal $\\mathcal{N}(0,1)$. For linking to origins ($O$) or triadic nodes ($\\Delta$), we can define $z_O$ and $z_{\\Delta}$ similarly. ", "In all three cases, using a $z$-test, we can reject the null hypotheses with high confidence ($p < 10^{-10}$). ", "We conclude that links established by following grandparents, origins or triadic nodes happen much more frequently than by random connection. ", "These link creation mechanisms have important roles in the evolution of the social network.", "\n\nUser Preference {#sec:4.2}\n---------------\n\nTo study the dependence of the link formation tendencies on the different stages of an individual’s lifetime, let us compute $z^k_G$, $z^k_O$ and $z^k_{\\Delta}$ for links created by users with in-degree $k$, that is, those who are following $k$ users at the time when the link is created. ", "Fig.", " \\[fig:preference\\] shows that the principle of triadic closure dominates user behavior when one follows a small number of users ($k < 75$). ", "In the early stages, one does not receive much traffic, so it is natural to follow people based on local social circles, consistently with triadic closure. ", "However, users who have been active for a long time and have followed many people ($k > 75$) have more channels through which they monitor traffic. ", "This creates an opportunity to follow others from whom they have seen messages in the past.", "\n\n![", "Individual preferences for following grandparents (red circles), origins (blue squares) and triadic nodes (green triangles) change with the in-degree of the link creator.[]{data-label=\"fig:preference\"}](preference_ink){width=\"\\columnwidth\"}\n\nTraffic Bias {#sec:4.3}\n------------\n\n![ ", "Probability density of followed grandparents (red circles) or origins (blue squares) having a certain rank percentile. ", "Link targets are ranked so that the link creator has seen more messages from a user with smaller rank percentile. []{", "data-label=\"fig:weights\"}](Rank_vs_Problink1){width=\"\\columnwidth\"}\n\nFurther inspection of the empirical data reveals that not all shortcuts are equally likely; users tend to follow those who have often been sources of seen messages. ", "To investigate this, consider all new shortcuts to grandparents or origins. ", "For each shortcut, we rank all the available grandparent or origin candidates according to how many of their messages have been seen by the creator prior to the link formation. ", "We plot the probability of a followed grandparent or origin having a certain rank percentile in Fig.", " \\[fig:weights\\]. ", "The plot clearly demonstrates that repeated exposure to contents posted by a user increases the probability of following that user. ", "This is analogous to the way in which we are more likely to adopt a piece of information or behavior to which we are exposed multiple times [@bakshy09; @centola2010; @romero_differences_2011; @Hodas2012_attention]. ", "This observation shows that topology alone is insufficient to explain the evolution of the network; activity patterns — the dynamics *on* the network — are a necessary ingredient in describing the formation of new links.", "\n\nLink Efficiency {#sec:4.4}\n---------------\n\nIn information diffusion networks like Twitter and Yahoo! ", "Meme, social links may have a key efficiency function of shortening the distance between information creators and consumers. ", "An efficient link should be able to convey more information to the follower than others. ", "Hence we define the *efficiency* of link $\\ell$ as the average number of posts seen or reposted through $\\ell$ during one time unit after its creation: $$\\eta_\\mathrm{seen} = \\frac{w_\\mathrm{seen}(\\ell)}{T - t(\\ell)}, \\quad \\eta_\\mathrm{repost} = \\frac{w_\\mathrm{repost}(\\ell)}{T - t(\\ell)}$$ where $w(\\ell)$ is the number of messages seen or reposted through $\\ell$; $t(\\ell)$ is the time when $\\ell$ was created; and $T$ is the time of the last action recorded in our dataset. ", "Both seen and reposted messages are considered, as they represent different types of traffic; the former are what is visible to a user, and the latter are what a user is willing to share. ", "We compute the link efficiency of every grandparent, origin, and triadic closure link. ", "As shown in Fig.", " \\[fig:eff\\], both grandparent and origin links exhibit higher efficiency than triadic closure links, irrespective of the type of traffic. ", "By shortening the paths of information flows, more posts from the content generators reach the consumers.", "\n\nRules of Network Evolution {#sec:5}\n==========================\n\nTo infer the different link creation strategies from the observed data, we characterize users with a set of probabilities associated with different actions, and approximate these parameters by Maximum-Likelihood Estimation (MLE) [@cowan]. ", "For each link $\\ell$, we know the actual creator and the target; we can thus compute the likelihood $f(\\ell | \\Gamma, \\Theta)$ of the target being followed by the creator according to a particular strategy $\\Gamma$, given the network configuration $\\Theta$ at the time when $\\ell$ is created. ", "The likelihoods associated with different strategies can be mixed according to the parameters to obtain a model of link creation behavior. ", "Finally, assuming that link creation events are independent, we can derive the likelihood of obtaining the empirical network from the model by the product of likelihoods associated with every link. ", "The higher the value of the likelihood function, the more *accurate* the model.", "\n\nSingle Strategies\n-----------------\n\nLet us consider five link creation mechanisms and their combinations:\n\nRandom (Rand):\n\n: follow a randomly selected user who is not yet followed.", "\n\nTriadic closure ($\\Delta$):\n\n: follow a randomly selected triadic node.", "\n\nGrandparent ($G$):\n\n: follow a randomly selected grandparent.", "\n\nOrigin ($O$):\n\n: follow a randomly selected origin.", "\n\nTraffic shortcut ($G \\cup O$):\n\n: follow a randomly selected grandparent or origin.", "\n\nTo model link creation with a single strategy, we can use a parameter $p$ for the probability of using that strategy, while a random user is followed with probability $1-p$.\n\nThe calculation of maximum likelihood, taking the single strategy of grandparents as an example, is as follows: $$\\begin{aligned}\n\\mathcal{L}_{G}(p)\n &= \\prod_{\\ell=1}^{L} \\left( pf(\\ell | G, \\Theta) + (1-p)f(\\ell | \\text{Rand}, \\Theta) \\right)\\\\\n &= \\prod_{\\ell=1}^{L} \\left( p\\frac{\\mathbf{1}_{G}(\\ell)}{N_G(\\ell)} + (1-p)\\frac{1}{\\ell - k(\\ell) - 1} \\right)\\\\\n &= \\prod_{\\mathbf{1}_{G}(\\ell)=1} \\left( \\frac{p}{N_G(\\ell)} + \\frac{1-p}{l- k(\\ell) - 1} \\right) \\\\\n & \\quad \\prod_{\\mathbf{1}_{G}(\\ell)=0} \\frac{1-p}{\\ell - k(\\ell) - 1}. ", "\\end{aligned}$$ Note that since a follow action can be ascribed to multiple strategies, it can contribute to multiple terms in the log-likelihood expression. ", "For instance, a link could be counted in both $f(\\ell | G, \\Theta)$ and $f(\\ell | \\text{Rand}, \\Theta)$. For numerically stable computation, we maximize the log-likelihood: $$\\begin{gathered}\n\\log \\mathcal{L}_{G}(p)\n = \\sum_{\\mathbf{1}_{G}(\\ell)=1} \\ln \\left( \\frac{p}{N_G(\\ell)} + \\frac{1-p}{\\ell - k(\\ell) - 1} \\right) + \\\\\n \\sum_{\\mathbf{1}_{G}(\\ell)=0} \\ln \\frac{1-p}{\\ell - k(\\ell) - 1}.\\end{gathered}$$ Similar expressions of log-likelihood can be obtained for other strategies ($\\Delta$, $O$, and $G \\cup O$).", "\n\nIt is not trivial to obtain the best $p$ analytically, so we explore the values of $p \\in (0,1)$ numerically (Fig.", " \\[fig:model1\\]). ", "Triadic closure dominates as a single strategy, with $p_\\mathrm{\\Delta}=0.82$, consistently with the large number of triadic closure links observed in the data. ", "Traffic-based strategies alone account for about 20% of the links.", "\n\n![", "Efficiency of links created according to different mechanisms, or average number of messages (A) seen or (B) reposted per time unit. ", "Each box shows data within lower and upper quartile. ", "Whiskers represent the 99th percentile. ", "The triangle and line in a box represent the median and mean, respectively. ", "Note that the mean can fall outside the shown quantiles for skewed distributions. ", "The grey area and the black line across the entire figure mark the interquartile range and the median of the measure across all links, respectively. []{", "data-label=\"fig:eff\"}](boxplot_by_type){width=\"0.859\\columnwidth\"}\n\n{width=\"\\textwidth\"}\n\nCombined Strategies\n-------------------\n\nFor a more realistic model of the empirical data, let us consider combined strategies with both triadic closure and traffic-based shortcuts. ", "For each link $\\ell$, the follower with probability $p_1$ creates a shortcut by linking to a grandparent ($G$), an origin ($O$), or either of them ($G \\cup O$); with probability $p_2$ follows a triadic node ($\\Delta$); and with probability $1-p_1-p_2$ connects to a random node.", "\n\nTaking the combined strategy with grandparent as an example, we compute the log-likelihood as:\n\n&\\_[G+]{}(p\\_1,p\\_2)\\\n& = \\_[=1]{}\\^[L]{} \\[ p\\_1 f(| G, ) + p\\_2 f(| , )\\\n& + (1-p\\_1-p\\_2) f(| , ) \\]\\\n& = \\_ ( + + )\\\n& + \\_ ( + )\\\n& + \\_ ( + )\\\n& + \\_ .", "\n\nOnce again, many follow actions can create both triadic closure links and traffic shortcuts, so they can contribute to multiple terms in the log-likelihood expression.", "\n\nIt is hard to obtain the optimal solution analytically. ", "We numerically explore the values of $p_1$ and $p_2$ in the unit square to maximize the log-likelihood. ", "The best combined strategy is the one considering both grandparents and origins as well as triadic closure (see Fig.", " \\[fig:model12\\]). ", "The parameter settings and the maximum likelihood values for all tested models are listed in Table \\[table:models\\]. ", "We can compare the quality of these models by comparing their maximized $\\log \\mathcal{L}$’s. ", "The combined models with both traffic shortcuts and triadic closure yield the best accuracy. ", "In these models, triadic closure accounts for 71% of the links, grandparents and origins for 12%, and the rest are created at random.", "\n\n![", "The contour plot of log-likelihood $\\log \\mathcal{L}(p_1, p_2)$ for the combined strategy of creating traffic shortcuts ($G \\cup O$) with probability $p_1$ and triadic closure links ($\\Delta$) with probability $p_2$. The black triangle marks the optimum.[]{data-label=\"fig:model12\"}](model2_GO){width=\"\\columnwidth\"}\n\nThus far we have assumed that each user has the same behavior; in the next section we model each user separately.", "\n\n Strategy Model Parameters $\\max\\log\\mathcal{L}$\n ---------- ------------------- ------------ -----------------------\n Baseline $\\mathrm{Rand}$ – $-3.75\\times 10^7$\n $\\Delta$ $p=0.82$ $-3.15\\times 10^7$\n $G$ $p=0.19$ $-3.64\\times 10^7$\n $\\mathrm{O}$ $p=0.17$ $-3.65\\times 10^7$\n $G\\cup\\mathrm{O}$ $p=0.21$ $-3.63\\times 10^7$\n $p_1=0.12$ \n $p_2=0.71$ \n $p_1=0.10$ \n $p_2=0.73$ \n $p_1=0.12$ \n $p_2=0.71$ \n\n : The best parameters in different models and corresponding values of maximized log-likelihood function.", "\n\n\\[table:models\\]\n\nUser Behavior {#sec:6}\n=============\n\nThe MLE models for describing the system behavior can be similarly employed to characterize the strategy of an individual user. ", "Let us focus on the model $G \\cup O +\\Delta$ that best reproduces the empirical data at the global level. ", "We run MLE to explain the links created by each user independently. ", "We consider users with at least 20 in-links, such that MLE is meaningful. ", "To facilitate the interpretation of the parameters, let us call $p_\\mathrm{traffic} = p_1$, $p_\\mathrm{structure} = p_2$ and $p_\\mathrm{random} = 1-p_1-p_2$. Each user has her own set of parameters.", "\n\nUser Strategy Classification\n----------------------------\n\nUsing the Expectation-Maximization (EM) algorithm [@celeux1992classification; @dempster1977maximum], users are clustered into several classes based on $p_\\mathrm{traffic}$, $p_\\mathrm{structure}$ and $p_\\mathrm{random}$. EM iteratively preforms an expectation step to compute the probability that each instance belongs to each class, and a maximization step in which latent variables of classes are altered to maximize the expected likelihood of the observed data. ", "EM decides how many clusters to create by cross validation. ", "This procedure yields five classes:\n\n**Information-Oriented** (Info):\n\n: People prefer to follow someone from whom or through whom they have received messages.", "\n\n**Friend of a Friend** (Friend):\n\n: People follow users two steps away to form triadic closure, almost exclusively.", "\n\n**Casual Friendship** (CFrd):\n\n: People tend to follow a set of users their friends are following; they also link to random users occasionally.", "\n\n**Mixture** (Mix):\n\n: Miscellaneous behavior of creating traffic shortcuts, connecting others by triadic closure, and following random people.", "\n\n**Random Browsing** (Rand):\n\n: People have a much higher preference for following a random user who is not close in either the follower network or the message flow network. “", "Random” does not necessarily imply the absence of any rule; there can be other strategies not explored in our model, i.e., following a celebrity on purpose (similar to preferential attachment).", "\n\nTable \\[table:behavior\\_class\\] displays the parameter averages for users in each class, representing the overall behavior pattern in that class. ", "Users in the mixture category behave similarly to the average across all users. ", "Fig.", " \\[fig:behavior\\_ternary\\] illustrates how users in different classes are mapped into the parameter space with the probability of each link creation strategy as one dimension.", "\n\n Class \\#Users $\\langle p_\\mathrm{traffic}\\rangle$ $\\langle p_\\mathrm{structure}\\rangle$ $\\langle p_\\mathrm{random}\\rangle$\n ----------- --------- ------------------------------------- --------------------------------------- ------------------------------------\n All Users 45,708 0.07 0.77 0.17\n Info 4,750 0.52 0.36 0.13\n Friend 12,797 0.00 0.96 0.04\n CFrd 23,469 0.01 0.80 0.19\n Mix 2,524 0.07 0.63 0.30\n Rand 2,168 0.09 0.32 0.59\n\n : Classes of user link creation strategy\n\n\\[table:behavior\\_class\\]\n\nCharacterization of User Classes\n--------------------------------\n\nTo further differentiate users with different link creation strategies, let us look at several structural and behavioral characteristics of each class. ", "Figs.", " \\[fig:behavior\\_boxplot\\](A-C) show how users in different classes create social links by comparing $p_\\mathrm{traffic}$, $p_\\mathrm{structure}$ and $p_\\mathrm{random}$.\n\nAs shown in Fig.", " \\[fig:behavior\\_boxplot\\](D), information-oriented users have been active longer than users in friendship classes. ", "Similarly, information-oriented users tend to follow more people (Fig.", " \\[fig:behavior\\_boxplot\\](E)). ", "Information-oriented users have even more followers compared to friendship-driven users (Fig.", " \\[fig:behavior\\_boxplot\\](F)). ", "This suggests that they tend to be more influential, as confirmed by considering the number of times that their messages are reposted (Fig.", " \\[fig:behavior\\_boxplot\\](G)). ", "Friendship-driven users follow a few people while essentially nobody is following them. ", "Such a passive role can be explained by their short lifetime. ", "All of these results are consistent with Fig.", " \\[fig:preference\\].", "\n\nFinally, Figs.", " \\[fig:behavior\\_boxplot\\](H-I) suggest that, while information-oriented users tend to produce more messages, their role is more that of spreaders than producers of information compared to other classes.", "\n\nConclusion\n==========\n\nThe study of the feedback loop between the dynamics *of* and *on* the network — how the network grows and how the information spreads — offers a promising framework for understanding social influence, user behavior, and network efficiency in the context of micro-blogging systems.", "\n\nThe results presented in this paper show that while triadic closure is the dominant mechanism for social network evolution, it is mainly relevant in the early stages of a user’s lifetime. ", "As time progresses, the traffic generated by the dynamics of information flow on the network becomes an indispensable component for user linking behavior. ", "As users become more active and influential, their links create shortcuts that make the spread of information more efficient in the network. ", "Users whose following behavior is driven by the information they see are a minority of the population, but play a key role in the information diffusion process. ", "They produce more information, but, even more importantly, they act as spreaders of the information they collect widely across the network.", "\n\nWe believe our findings apply generally to techno-social networks, and in particular information diffusion networks and (micro)blogs. ", "Analyses of other micro-blogging systems, such as Twitter, would be needed to confirm this, but will be challenging due to the difficulty of obtaining full longitudinal data about user actions on the social network.", "\n\nWe are looking at the possibility to share with the community an anonymized dataset along with source code that would allow to reproduce and extend our analyses. ", "A URL for download will be included in the camera-ready version of the paper.", "\n\n![", "Ternary plot of users according to $p_\\mathrm{traffic}$, $p_\\mathrm{structure}$ and $p_\\mathrm{traffic}$.[]{data-label=\"fig:behavior_ternary\"}](user_ternary \"fig:\"){width=\"\\columnwidth\"}\\\n\n{width=\"\\textwidth\"}\n\n**Acknowledgments.** ", "This project is a collaboration between the Center for Complex Networks and Systems (CNetS) at Indiana University and Yahoo! ", "Research Barcelona. ", "During the project, CC was at Yahoo!; ", "NP and BG were at CNetS; RS was visiting CNetS; and JR was visiting Yahoo! ", "as a PhD student at CNetS. We are grateful to Alessandro Vespignani for helpful discussion and to Ricardo Baeza-Yates for support and access to the Yahoo! ", "Meme data. ", "This project was funded in part by the James S. McDonnell Foundation, NSF Grant No. ", "1101743, and the Indiana University School of Informatics and Computing.", "\n\n[^1]: Lyapunov’s condition, $\\frac{1}{\\sigma_{n}^4} \\sum_{\\ell=1}^n E[(X(\\ell) - p(\\ell))^4] \\overset{n\\to\\infty}{\\longrightarrow} 0$ where $X(\\ell)$ is a random Bernoulli variable with success probability $p(\\ell)$ [@billingsleyprobability], is consistent with numerical tests. ", "Details are omitted for brevity.", "\n" ]

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[ "Functional dissociation of CD8 alpha's Ig homologue and connecting peptide domains.", "\nThe contribution of the CD8 alpha.", "IgV homologue domain to class I MHC binding was evaluated using a series of chimeric human CD8 alpha:Fc polypeptides incorporating alternative CD8 alpha extracellular domain components. ", "Using a nonisotopic cellfree physical binding assay, those Fc chimeras encompassing the CD8 alpha.", "IgV homologue domain only (dissociated from the 48-amino acid CD8 alpha connecting peptide) were shown to retain the capacity of the complete CD8 alpha extracellular domain to bind to a recombinant soluble class I MHC alpha 3 domain unit or to intact class I MHC. ", "The specificity of the CD8 alpha:class I MHC alpha 3 domain interaction was verified by mAb and soluble polypeptide blocking experiments. ", "Furthermore, co-precipitation of an Fc chimera incorporating only the CD8 alpha.", "IgV homologue domain and a recombinant soluble class I MHC alpha 3 domain unit was accomplished. ", "In addition, a glycosylphosphatidylinositol (GPI)-modified variant of the CD8 alpha.", "IgV homologue domain was generated via chimerization with the GPI signal sequence from decay-accelerating factor. ", "GPI anchorage for this truncated CD8 alpha polypeptide was verified, and its capacity to promote intercellular adhesion through class I MHC binding was shown in a cell:cell binding assay. ", "The findings indicate that the CD8 alpha.", "IgV homologue domain acts as an independent structural unit when dissociated from the CD8 alpha connecting peptide, and in so doing retains class I MHC binding capacity. ", "This further establishes the principle that Ig superfamily domains from receptor:counter-receptor pairs can interact with each other as isolated units, providing an experimental path for tailoring therapeutically useful IgSF protein derivatives." ]

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[ "Q:\n\ndrawer menu fonts are not changed programatically\n\nMy code is shown below:\npublic class QuFlipActivity extends AppCompatActivity {\n\n @Override\n protected void onCreate(Bundle savedInstanceState) {\n super.onCreate(savedInstanceState);\n initNavigationDrawer();\n\n....\n\n}\n\npublic void initNavigationDrawer() {\n\n NavigationView navigationView = (NavigationView) findViewById(R.id.navigation_view);\n overrideFonts(QuFlipActivity.this, navigationView);\n....\n}\n\npublic static void overrideFonts(final Context context, final View v) {\n Typeface typeface = Typeface.createFromAsset(context.getAssets(), Consts.montserrat_regular);\n try {\n if (v instanceof ViewGroup) {\n ViewGroup vg = (ViewGroup) v;\n for (int i = 0; i < vg.getChildCount(); i++) {\n View child = vg.getChildAt(i);\n overrideFonts(context, child);\n }\n } else if (v instanceof TextView) {\n ((TextView) v).setTypeface(typeface);\n }\n } catch (Exception e) {\n }\n }\n\nNow, here even If I write the code to change the default fonts, it is not able to change it, what modifications can I make to make it work?", "\n\nA:\n\nI had similar problem and I solved it by changing the font inside a Runnable. ", "Try to call the override font function like below and see if it works for you\nnavigationView.post(new Runnable() {\n @Override\n public void run() {\n overrideFonts(QuFlipActivity.this, navigationView);\n }\n});\n\n" ]

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[ "In any case, Stelter asked Miller whether Trump wanted the debate dates changed:\n\nJason Miller: We would not like the debates not be head to head against major NFL games. ", "We like to see some—that's something we'll be discussing as we got into negotiations.", "\n\n\n\nBrian Stelter: Will Trump skip the debates if they are continued to be scheduled on football nights?", "\n\n\n\nMiller: Brian, we want as many people to be watching the debates as possible. ", "That's our spirit of it. ", "The Clinton camp would like these debates to be head-to-head with the NFL games. ", "So, we're going to go in and start negotiations...\n\nIn other words, Miller was unwilling to commit to Trump debating. ", "Stelter pressed Miller further, pointing out that there was no evidence that Clinton wanted the debates head-to-head with NFL games. “", "Why did Mr. Trump say that Clinton is trying to rig the debates?” ", "Stelter asked. ", "Miller replied:\n\nBrian, if you take a look back at Hillary Clinton's track record in the primary, numerous times they had pushed to go on and have debates at the same time as other big events that were going on, head to head against things that would be big conflicts and keep voters excluded. ", "Our focus, we want as many people involved as possible.", "\n\nMiller is right that the Democratic debates were scheduled for mysteriously low-profile times. ", "Many observers presented this as evidence of the Democratic National Committee trying to engineer low-profile meetings to aid Hillary Clinton. ", "If so, the decision may not have paid off: Clinton ended up having a tough race against Senator Bernie Sanders, but she consistently performed well in debates.", "\n\nBut all of that is irrelevant to the presidential debates. ", "Unlike primary debates, which are scheduled with cooperation between the candidates and their campaigns, their respective party committees, and the networks that will broadcast them, the general-election debates are produced by the Commission on Presidential Debates. ", "It’s an independent organization created after the 1984 elections, which has run the debates in every presidential-election year since. ", "The debates are shot by pooled press, and they’re available to networks to air but have to be aired in their entirety, without commercials, on the premise that they’re providing a national public service and shouldn’t be monetized.", "\n\nThe idea that the CPD is working to throw the debates doesn’t bear much scrutiny. ", "CPD announced the dates for the debates in September 2015. ", "And while the commission studiously insists it’s nonpartisan, it is in practice mostly a bipartisan body, made of former political hands of both parties. ", "The chairs are Frank Fahrenkopf, a former head of the RNC, and Mike McCurry, former press secretary under Bill Clinton. ", "Other Republicans on the commission include former Indiana Governor Mitch Daniels and former Senator Olympia Snowe. ", "It’s not a body that seems likely to throw the debates in favor of Clinton. (", "McCurry even publicly counseled her against running.) ", "Neither of the parties gets a role in scheduling or planning the debates, nor do the candidates, although the candidates typically negotiate some mutually agreed-upon rules." ]

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[ "太平洋と大西洋を結ぶ中米パナマ運河で6月26日、拡張工事が完了した記念式典が行われた。新しい運河では従来の3倍近い貨物量の大型船の通航が可能になり、通航第1号は9427個のコンテナを積んだ中国のコスコグループ（中国援用運輸集団）の大型船だった。ガーディアンなどが報じた。", "\n\nパナマ運河とは、パナマ共和国のパナマ地峡を横断して大西洋と太平洋を結ぶ運河で1914年に開通。全長は約80キロ、約9時間かけて通過する。これまでは閘門（こうもん）という水面を昇降させるシステムを使って船を通過させてきたが、長さ294.1メートル、幅 32.3メートルまでの船にしか対応できず、船舶の大型化が進むにつれて通過できない船が増加していた。", "\n\n2007年からより約54億ドル（約5500億円）かけて大型の閘門を建設する工事が始まり、新しい閘門では長さ366メートル、幅49メートルまでの大型船に対応できるようになった。", "\n\nパナマ運河は、エジプトのスエズ運河を建設したレセップスが掘削を試みて失敗し、その後アメリカが建設。当初の運河条約で運河の両側5マイル（約8キロ）のパナマ運河地帯は事実上アメリカ領土となった。1968年の軍事クーデターで実権を握ったトリホス将軍が条約改定交渉を行い、1977年の新パナマ運河条約で運河はパナマに返還されることになった。", "\n\n1981年にトリホス将軍が航空機事故で死亡し、軍司令官のノリエガ将軍が軍政を敷いたが、アメリカは1989年に軍事侵攻し、ノリエガ将軍を麻薬密輸の容疑で逮捕した。1999年にはパナマ運河が返還され、駐留していたアメリカ軍も全面撤退した。", "\n\n登録する 選りすぐりのニュースやブログをお届けします（広告などが掲載される場合もございます） 続きを読む メールマガジン 有効なメールアドレスを入力してください ご登録ありがとうございます。ご登録内容を記載したメールが送信されますので、ご確認ください。 ", "登録中に何か問題が発生したようです。後ほど再度お試しください。 ", "Twitter\n\nFacebook\n\nLine\n\nInstagram" ]

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[ "[Margin eyelid reconstruction with hard palate graft].", "\nTo investigate the advantages and the complications of the use of hard palate graft in the reconstruction of the inferior eyelids with large basocelular carcinoma. ", "Review of specialized articles and report of the technique used in the Oculoplastic Department of the \"Hospital Santa Casa de Porto Alegre\". ", "The hard palate graft is an excellent replacement for posterior lamellar defects in eyelid reconstruction, because it presents the benefit of a mucous layer in addition to a semirigid support. ", "The sandwich technique using hard palate was shown to be efficient, with good functional and esthetic results." ]

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[ "This invention relates, in general, to semiconductor devices, and more particularly, to electronic components formed in a glass-type package.", "\nConventional discrete devices such as diodes, resistors, capacitors, etc., ", "are typically packaged into ceramic or opaque glass packages. ", "A package is formed by placing the individual components of a discrete device, such as the leads, slug, and semiconductor die, in a glass tube. ", "The components are then heated to over 600.degree. ", "Celsius (C.) so that the glass tube melts and encapsulates the individual components to form the protective package of the discrete device.", "\nOne problem with this technique is that there is no commercially available process utilizing drawn glass tubing that allows a semiconductor package to be formed under 590.degree. ", "C. that is also optically transparent. ", "This is a problem because advanced semiconductor devices often include metal interconnect or doped structures that are extremely sensitive to temperature. ", "For example, if a semiconductor die used to form the semiconductor device includes aluminum for junction material or contact metallization, care must be taken not to exceed a package assembly temperatures above 600.degree. ", "C. or else the aluminum may melt and diffuse into the semiconductor die.", "\nAccordingly, it would be advantageous to provide a method for forming a semiconductor package that is formed at a lower temperature than conventional packages. ", "It would also be advantageous if the package were clear so that the individual components of the semiconductor device could be visually inspected." ]

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[ "Nurses' experiences of prehospital care encounters with children in pain.", "\nPain relief in children is a complex issue, partly an ethical dilemma and due to a lack of nursing competence. ", "There are few studies regarding prehospital care encounters with children in pain. ", "The aim of this study was to describe nurses' experiences in prehospital care encounters with children in pain and the specific related challenges. ", "This study has a qualitative design. ", "Eighteen Swedish nurses participated in three focus group interviews analysed using qualitative content analysis. ", "The findings consist of a theme, \"A challenge to shift focus and adjust to the child\", and three categories describing prehospital care encounters with children in pain: \"Being receptive and focusing on care,\" \"Developing a trusting relationship,\" and \"Providing professional nursing care.\" ", "Caring for children in pain was stressful for the nurses. ", "The nurses described how they had to shift focus and used different methods to build trust, such as playfulness, making eye contact, attracting curiosity, and using the parents to create trust. ", "The also had to adjust to the child regarding dosages and materials. ", "Nurses has to be practically, mentally, and theoretically prepared to care for children with prehospital pain. ", "It is essential to evaluate the administration of adequate pain relief to children, and more evidence-based knowledge is necessary concerning the different modes of administering pain-relieving drugs to prehospital children." ]

{ "pile_set_name": "PubMed Abstracts" }

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[ "Q:\n\nPut focus back on a gridview's selected row after postback\n\nIs it possible to put focus back on a gridview row after that a selection of the row generates a postback?", "\nI'm trying to add an onkeydown handler on the gridview rows in order to use the keyboard for navigation. ", "My problem, I believe, is that after the first postback, the selected cell loses focus, and so the next key stroke is not caught by the cell.", "\nI have the following code\nThe grid view\n <asp:GridView runat=\"server\" ID=\"gdvPersons\" AutoGenerateColumns=\"false\" \n onrowcreated=\"gdvPersons_RowCreated\" onselectedindexchanged=\"gdvPersons_SelectedIndexChanged\">\n <Columns>\n <asp:TemplateField HeaderText=\"Name\">\n <ItemTemplate>\n <%# ((GridviewFocus.", "Person) Container.", "DataItem).Name %>\n </ItemTemplate>\n </asp:TemplateField>\n <asp:TemplateField HeaderText=\"Age\">\n <ItemTemplate>\n <%# ((GridviewFocus.", "Person) Container.", "DataItem).Age %>\n </ItemTemplate>\n </asp:TemplateField>\n </Columns>\n </asp:GridView>\n\nThe Code behind\n protected void Page_Load(object sender, EventArgs e)\n {\n var persons = new List<Person> {new Person() {Name = \"Fikre\", Age = 24}, \n new Person() {Name = \"Mike\", Age = 29},\n new Person() {Name = \"Mark\", Age = 35}};\n gdvPersons.", "DataSource = persons;\n gdvPersons.", "DataBind();\n }\n\n protected void gdvPersons_RowCreated(object sender, System.", "Web.", "UI.WebControls.", "GridViewRowEventArgs e)\n {\n if (e.Row.", "RowType == DataControlRowType.", "DataRow)\n e.Row.", "Attributes.", "Add(\"onkeydown\", ClientScript.", "GetPostBackEventReference((Control)sender, \"Select$\" + e.Row.", "DataItemIndex));\n }\n\n protected void gdvPersons_SelectedIndexChanged(object sender, EventArgs e)\n {\n gdvPersons.", "SelectedRow.", "Focus();\n }\n\nA:\n\nOn your onkeydown script code copy the id of the cell to a hidden input field.", "\n<input type=\"text\" id=\"gridviewcell_id\" onkeydown=\"lastcell.value = this.id\" />\n<input type=\"hidden\" id=\"lastcell\" runat=\"server\" />\n\nthe example above is plain html, and you would have to add the proper onkeydown code to your gridview.", "\nIn your postback (for example onclick) event handler code you can retrieve the id from the hidden fields value property and register javascript to execute once the page is refreshed. ", "If you have a button which is clicked which performs the postback you could do something like this:\nprotected void MyButton_Click(object sender, EventArgs e)\n{\n string id = lastcell.", "Value;\n string script = \"var ctrl = document.getElementById('\" + lastcell.", "Value + \"');\";\n script += \"ctrl.focus();\";\n ClientScript.", "RegisterClientScriptBlock(this.", "GetType(), \n \"focusScript\", script, true);\n\n}\n\nThis should make your page execute the following script once it's loaded, and the control should retrive focus:\nvar ctrl = document.getElementById(\"yourid\"); \nctrl.focus();\n\n" ]

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[ "Jariyeh-e Seyyed Mohammad\n\nJariyeh-e Seyyed Mohammad (, also Romanized as Jarīyeh-e Seyyed Moḩammad; also known as Qal‘eh Seyyed Moḩammad, Qal‘eh-ye Moḩammad, Shahīd Mofatteh, and Shahrak-e Mofatteh) is a village in Hoseynabad Rural District, in the Central District of Shush County, Khuzestan Province, Iran. ", "At the 2006 census, its population was 763, in 118 families.", "\n\nReferences \n\nCategory:Populated places in Shush County" ]

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[ "Certain metals commonly referred to as shape memory alloys exhibit characteristic material properties that make them desirable for use in actuators. ", "Shape memory alloy actuation provides greater force per volume than electromagnetic-type actuation, and is also less complex. ", "These characteristics make shape memory alloy actuation highly desirable for use in fuel injectors, particularly automotive fuel injectors.", "\nShape memory alloys (hereinafter \"SMAs\") undergo a temperature-related phase change which is characterized by the memory of any mechanical configuration imposed on the material in its austenitic crystalline phase. ", "In particular, SMAs have two different crystal structures that are determined by temperature. ", "In its low temperature state the material exhibits a martensitic crystal structure which has a relatively low modulus of elasticity, and which can be easily deformed. ", "However, when the alloy is heated above a temperature threshold, the transition temperature, its crystal structure changes to austenite and the alloy returns to its original configuration.", "\nThis temperature-dependent memory characteristic is exploited in actuators for fuel injectors by providing a bias mechanism, for example a spring, to deform the SMA element while it is in the low temperature state, then raising the SMA element's temperature, for example by resistance heating, in order to induce a return to the element's original configuration. ", "The return to the SMA element's original conformation thereby creates motion in the spring, which in conjunction with the remainder of the actuator assembly results in opening or closing of the fuel injector valve. ", "Cooling of the SMA element returns the element to its low temperature, easily deformed phase. ", "The bias spring force results in mechanical motion in the actuator which closes or opens the fuel injector valve. ", "A major challenge in the use of SMAs in automotive fuel injectors has been to reduce the response time of the alloy so that the opening or closing cycle of the actuator is reduced to one millisecond or less. ", "This fast response time is required in order to provide the necessary minimum flow control necessary under light load engine conditions.", "\nIt is known in the art that the response time is affected by the rate of heat transfer (i.e., cooling) of the SMA element, and that the geometry of the alloy element has a direct affect on this heat transfer rate. ", "SMA actuator geometries comprising small-diameter wires, ribbons, or thin films, for example, have been shown to maximize the heat transfer rate of the alloy, thereby achieving faster response times. ", "Such geometries have been described in U.S. Pat. ", "No. ", "4,806,815 to Homma; U.S. Pat. ", "No. ", "4,973,024 to Homma; U.S. Pat. ", "No. ", "5,061,914 to Busch, et al.; ", "U.S. Pat. ", "No. ", "5,211,371 to Coffee; and U.S. Pat. ", "No. ", "5,325,880 to Johnson et al. ", "The width-to-thickness ratios disclosed in the prior art are in the range from 50:1 to 4:1, and resulted in best minimum response times of about 10 milliseconds. ", "However, none of these geometries yield the requisite degree of heat transfer effective to provide response times at the 1 millisecond level required for fuel injector applications.", "\nIt is further known in the art that the response time is affected by the energy input (e.g., resistance heating) into the SMA element. ", "Ordinarily, a high energy input into the SMA element is desirable, in order to decrease the response time. ", "This energy input has an inherent limitation, however, due to the nature of the materials suitable for shape memory alloys. ", "An \"over-temperature\" condition results in strain recovery loss or destruction of the alloy. ", "The response time of SMA actuators in the prior art have accordingly been limited in the amount of input power which may be applied to the SMA elements, and again, are limited to response times of no less than 10 milliseconds. ", "There thus remains a need in the art for economical methods and apparatus for controlling the operating conditions of shape memory alloy actuators for fuel injectors so as to provide response times of less than 10 milliseconds, and preferably less than about 1 millisecond." ]

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[ "Меня зовут Moses. ", "Я был комментатором последние несколько лет.", "\nСегодня я делаю объявление, что становлюсь главным тренером состава по CS:GO.", "\nВолнующий момент. ", "Так много можно сделать, так многого достичь с такой командой.", "\nИметь возможность наблюдать за тем, как развивается их карьера, я определенно не мог такое пропустить.", "\nМоя история с Counter-Strike началась очень давно. ", "Я играл с 1999.", "\nЭто значит, что я играл в нее большую часть жизни, более двадцати лет.", "\nСначала я был игроком одной из лучших команд Северной Америки в Counter-Strike 1.6.", "\nЗатем я вернулся в Counter-Strike в качестве комментатора.", "\nБыл практически на каждом Мейджоре за последние пять лет.", "\nЯ живу и дышу Counter-Strike на протяжении этих пяти лет.", "\nПришло время в моей карьере, когда нужно переключиться на что-то другое.", "\nЗдорово переходить на следующий уровень.", "\nПосмотреть на что ты способен как тренер.", "\nТы был игроком и комментатором.", "\nНо что ты можешь сделать наставляя команду?", "\nЭтот челлендж мотивирует меня больше всего.", "\nЯ видел, как они растут с каждым изменением в составе.", "\nЯ видел, как они были близки к победе на Мейджоре в 2016 году в Кёльне.", "\nЯ видел, как они взяли Grand Slam.", "\nЯ видел, все их взлеты и падения.", "\nУ Team Liquid невероятная история в CS:GO Северной Америки.", "\nИ хочется быть частью этого.", "\nИдея о стремлении выиграть Мейджор.", "\nО возможности поднять этот трофей в CS:GO с Team Liquid, с этими ребятами.", "\nЭто самая захватывающая перспектива.", "\nЯ видел, как они справляются с поражениями, видел как они воспринимают победы.", "\nДумаю, эти парни все еще ждут того, чтобы узнать, на что они способны.", "\nЯ здесь именно за этим.", "\nЭто как смена караула в Team Liquid.", "\nЯ прямо чувствую, что это будет эра изменений.", "\nОгромный шаг вперед от тех Team Liquid, какими они были, к тем, какими становятся.", "\nДля меня это ответственность. ", "Большая ответственность.", "\nВывести Team Liquid в следующую эру.", "\nЭто цель, которую я поставил перед собой и командой.", "\nВывести Team Liquid на следующие пять лет в CS:GO.", "\nБольшинство в этой команде видят своих главных соперников в себе самих.", "\nПреодоление этого препятствия это то, над чем я буду работать, чтобы вывести их на новый уровень.", "\nЭти игроки могут поставить такие рекорды, которые никто потом не побьет за всю историю CS:GO.", "\nГлавная задача научить их преодолевать те трудности, которые накопились за эти годы.", "\nВот что, мы увидим, когда Team Liquid выйдет на новый уровень.", "\nСейчас время онлайнового CS:GO, где все не так понятно.", "\nВсе только и говорят о том, что практика неэффективна.", "\nСоревнования проходят не на том уровне.", "\nПоэтому сложно работать над собой, найти, что можно улучшить в команде.", "\nПервостепенная задача — это максимально подготовиться к ближайшим турнирам.", "\nИспользовать это время в онлайне с умом.", "\nБыть тренером этой команды и не сделать так, чтобы они подняли трофей Мейджора.", "\nЭто будет провалом.", "\nЭто самое важное, что не уходит из моей головы.", "\nЗабрать еще один Мейджор в Северную Америку.", "\nВсе фанаты, которые следили за мной эти пять лет. ", "Для меня это было огромной честью.", "\nХочу сказать огромное спасибо тем, кто поддерживал меня и кому нравилось то, что я делаю в качестве комментатора.", "\nНадеюсь, я вас не разочарую в качестве тренера Team Liquid.", "\nТренера команды, которую я считаю самой лучшей в мире.", "\nДавайте это выясним.", "\n" ]

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[ "High-resolution droplet-based fractionation of nano-LC separations onto microarrays for MALDI-MS analysis.", "\nWe present a robust droplet-based device, which enables the fractionation of ultralow flow rate nanoflow liquid chromatography (nano-LC) eluate streams at high frequencies and high peak resolution. ", "This is achieved by directly interfacing the separation column to a micro T-junction, where the eluate stream is compartmentalized into picoliter droplets. ", "This immediate compartmentalization prevents peak dispersion during eluate transport and conserves the chromatographic performance. ", "Subsequently, nanoliter eluate fractions are collected at a rate of one fraction per second on a high-density microarray to retain the separation with high temporal resolution. ", "Chromatographic separations of up to 45 min runtime can thus be archived on a single microarray possessing 2700 sample spots. ", "The performance of this device is demonstrated by fractionating the separation of a tryptic digest of a known protein mixture onto the microarray chip and subsequently analyzing the sample archive using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). ", "Resulting peak widths are found to be significantly reduced compared to standard continuous flow spotting technologies as well as in comparison to a conventional nano-LC-electrospray ionization-mass spectrometry interface. ", "Moreover, we demonstrate the advantage of our high-definition nanofractionation device by applying two different MALDI matrices to all collected fractions in an alternating fashion. ", "Since the information that is obtained from a MALDI-MS measurement depends on the choice of MALDI matrix, we can extract complementary information from neighboring spots containing almost identical composition but different matrices." ]

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[ "About\n\nDr Eberhard Mandishona ‘’Ebe’’ – MBChB, FRACGP (Fellow of the Australian College of general Practice] and DRANZCOG (Australian Diploma in Obstetrics and Gynaecology), PGCME\n\nDr Mandishona trained and worked in Zimbabwe, before moving to England (UK) where he worked in Obstetrics and Gynaecology, and then as a GP in the East Midlands from 2005. ", "He has been working as a GP in Geraldton since April 2014.", "\n\nDr Mandishona has special interests in Obstetrics, Gynaecology, reproductive health, fertility medicine, sexual health, men and women’s health, contraception, chronic disease management, substance misuse treatment (C-POP provider), mental health, minor surgery (small skin excision and removal of lesions) and medical education. ", "He is a former GP tutor at the Graduate Entry Medical School of the University of Nottingham in Derby UK.", "\n\nDr Yollanda Chikari “Yollanda” – MBChB, DRANZCOG [Australian Diploma in Obstetrics and Gynaecology], FRACGP[Fellow of the Australian College of General Practice] (FRACGP)\n\nDr Chikari trained and worked in Zimbabwe, before moving to England to continue her training in Psychiatry and later on in General Practice. ", "Yollanda moved to Geraldton in 2014 to join her husband and enjoys working in Mental health and general practice.", "\n\nDr Chikari’s special interests are sexual health, reproductive health, women’s health, contraception, chronic disease management and mental health. ", "She was credentialed to work in Psychiatry[Mental Health] as a Visiting Medical Officer at the Geraldton Regional Hospital from 2014 to 2018." ]

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[ "1-1I53 system, Providence region. ", "On the 27th of January at 8:52 EVE Standard Time, Providence Bloc forces managed to destroy WAFFLES. [", "N0MAD] Revenant and Wyvern supercarriers.", "\n\nThe Revenant in question had been hunting ships in the Providence region alongside a sister ship for a couple of months. ", "Thus it was no surprise that the region’s residents would seek to strike back against them. ", "The plan was to use a Raven battleship as bait for the ships, then drop on them using a mix of capital and supercapital ships. ", "Both a Raven and an interdictor had been prepared in the 1-1I53 system, each equipped with a cynosural beacon in order to spring the trap.", "\n\nThe Raven itself started clearing sites in space while the interdictor held back, waiting for a signal. ", "In the meantime, Providence Bloc started assembling pilots for the actual killing fleet, pulling around 30 pilots which included a supercapital squadron, a capital squadron and more interdictors, heavy interdictors and other assorted subcapitals.", "\n\nHowever, before the fleet could properly organize, intel networks flared up with sightings of a known hunter character used by the Revenants. ", "This led Providence Bloc to frantically organize its fleet, getting everyone in range of the system as well as getting a titan bridge ready. ", "As preparations were underway, the hunter in an interceptor found the Raven in a site and tackled it, lighting its cynosural beacon.", "\n\nInto the system jumped a Revenant and a Wyvern, rather than the second Revenant Providence Bloc expected, as well as a Nidhoggur combat carrier. ", "As the ships launched their fighters, the Providence Bloc interdictor warped to the site, launched its own interdiction probe trapping the ships and lit its cynosural beacon. ", "Into the field materialized the Providence Bloc subcapital squadron. ", "Interdictors raced to launch secondary interdiction probes while heavy interdictors used focused scripts to tackle the actual ships. ", "The Raven then lit its own beacon to let the Providence Bloc capital force through.", "\n\nThe WAFFLES. ", "supercarriers didn’t panic and focused their fighters on destroying the ships carrying the cynosural beacons. ", "They then started to target tackle ships as they attempted to clear the interdiction probes but to no avail. ", "With the capitals in, many of them dreadnoughts, they had little chance of survival. ", "Even worse, the capitals lit their own cynosural beacon to let through the super carriers which sealed the WAFFLES’ ships’ fate. ", "The Providence Bloc supercarriers launched their own fighter bombers that quickly overwhelmed the shields of both hostile ships. ", "Without their shields, the vessels lost their remaining hit points rapidly, resulting in their ultimate destruction.", "\n\nThe only ship from the drop to escape was the Nidhoggur, which managed to burn away from the hostile fleet, outrunning a Hel super carrier that attempted to keep tackle on it. ", "Free of tackle, the combat carrier managed to flee the slaughter, leaving Providence Bloc to loot the field and take stock of its losses.", "\n\nWith the field under their control, Providence Bloc forces extracted, leaving 5 sub capitals dead for 1.36 billion ISK loss in exchange for 2 WAFFLES. ", "super carriers worth a combined 145.2 billion in ISK damage.", "\n\nA battle report can be found here.", "\n\nFeatured image credit: razorien" ]

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[ "Marchesan JT, Girnary M, Moss K, et al. ", "Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics. ", "Periodontol 2000. ", "2020;82:93‐114. ", "10.1111/prd.12269 31850638\n\n1. ", "INTRODUCTION {#prd12269-sec-0001}\n===============\n\nThe innate immune response is the body\\'s first line of defense against pathogens. ", "The innate immune system recognizes pathogens, including bacteria and viruses, by engagement of the germline encoded pattern recognition receptors (PRR). ", "There are five families of PRRs that are able to sense a vast array of microbial components, referred to as pathogen‐associated molecular patterns (PAMP) and damage‐associated molecular patterns (DAMP), that are host cell components produced during inflammation or environmentally derived, such as exposure to silica. ", "Although PRRs are predominately expressed by innate immune cells, many of the PRRs are also found on other cells, including epithelial, endothelial and cells of the adaptive immune system. ", "PRR engagement by its ligand induces downstream signaling cascades that induce multiple effects, including activation of innate immune cells and cytokine/chemokine production for the recruitment of immune cells to the site of infection or tissue damage.", "\n\nA key function of the innate immune system is inflammasome activation. ", "In response to PAMPs or DAMPS, some PRRs assemble inflammasomes (Figure [1](#prd12269-fig-0001){ref-type=\"fig\"}) for the activation of cellular caspases that, in turn, induce the maturation of the proinflammatory cytokines interleukin‐1β and interleukin‐18 together with the induction of inflammation‐induced programmed cell death (pyroptotic). ", "Although it had been known since the early 1990s that caspase‐1 was able to cleave pro‐interleukin‐1β and trigger cell death (later termed pyroptosis in contrast to apoptosis), it was not until a decade later, with a seminal paper by Martinon et al[1](#prd12269-bib-0001){ref-type=\"ref\"} that the details of how caspase‐1 is activated were unraveled with the discovery of the inflammasome.", "\n\n{ref-type=\"ref\"}](PRD-82-93-g001){#prd12269-fig-0001}\n\nInflammasomes are multimeric protein structures composed of a sensor molecule (the PRR), typically the adapter molecule apoptosis‐associated speck‐like protein containing a caspase‐recruitment domain (CARD), and the protease caspase‐1. ", "There are multiple inflammasomes that can be formed, which are named for their sensor PRR that induces its activation. ", "Inflammasome sensor molecules cross multiple PRR families, including a nucleotide‐binding domain, leucine‐rich repeat‐containing proteins (NLR, also known as NOD‐like receptors), absent in melanoma 2 (AIM2)‐like receptors (ALRs) and retinoic acid‐inducible gene I (Rig‐I)‐like receptors (RLR; Figure [2](#prd12269-fig-0002){ref-type=\"fig\"}). ", "Although inflammasomes are widely recognized to be activated in myeloid cells, including monocytes, macrophages, dendritic cells and neutrophils, they can also be activated in keratinocytes, gingival and dermal fibroblasts,[2](#prd12269-bib-0002){ref-type=\"ref\"} and mucosal epithelial cells.", "\n\n{ref-type=\"ref\"}](PRD-82-93-g002){#prd12269-fig-0002}\n\nInflammasome activation is a highly inflammatory process that is often initiated during pathogen infections (in communicable diseases) or during sterile inflammation by detection of proinflammatory debris (in noncommunicable diseases). ", "Inflammasome activation induces the maturation of the proinflammatory cytokines interleukin‐1β and interleukin‐18 through their cleavage by caspase‐1. ", "Recognition of mature interleukin‐1β and interleukin‐18 by their receptors has pleiotropic actions, including: (a) recruitment of neutrophils and other innate immune cells, (b) activation of B cells and antibody production and (c) differentiation of T cells. ", "Additionally, activation of the inflammasome induces pyroptosis in immune cells. ", "Pyroptosis occurs when the cytoplasmic protein, gasdermin D, is cleaved by caspase‐1, inducing the N‐terminal gasdermin D fragment to oligomerize and insert into the plasma membrane forming pores. ", "N‐terminal gasdermin D pore formation causes cell lysis and the release of intracellular components (DAMPS) into the intracellular milieu, perpetuating inflammation.", "\n\nAlthough insufficient inflammation can lead to persistent infection of pathogens, excessive inflammation can cause chronic or systemic inflammatory diseases. ", "Therefore, it is important that the host balances inflammasome activation. ", "Because inflammasome activation is highly inflammatory, it is tightly regulated to prevent aberrant activation. ", "With the exception of human monocytes, inflammasome activation is a two‐step process; the cell must respond to two sequential signals in order for inflammasome formation and activation to occur (Figure [2](#prd12269-fig-0002){ref-type=\"fig\"}). ", "The first step is cell priming, which serves two purposes. ", "The first purpose of priming is the transcriptional and translational upregulation of inflammasome components, including the sensing PRR, caspase‐1 and interleukin‐1β. ", "The second purpose of priming is the post‐translational modification of the PRR and adaptor molecule, ASC. ", "Inflammasome priming occurs through recognition of various PAMPs or DAMPS that engage a subset of multiple toll‐like receptors, NOD1 or NOD2, or by the cytokines, tumor necrosis factor and interleukin‐1β, that lead to transcriptional upregulation of inflammasome components mostly through the activation of the transcription factor nuclear factor‐κB (Figure [2](#prd12269-fig-0002){ref-type=\"fig\"}). ", "Importantly, most aspects of inflammasome priming are not specific to the inflammasome being activated. ", "Priming leaves the cells poised to respond to a second signal (step 2). ", "The second step is recognizing a PAMP or DAMP specific to each inflammasome, which then induces inflammasome formation and activation.", "\n\nInflammasome formation and activation are initiated through PRR recognition of a PAMP or DAMP specific for the PRR, inducing oligomerization of the PRR (Figure [2](#prd12269-fig-0002){ref-type=\"fig\"}). ", "This PRR oligomerization then sets into motion the continued assembly of the inflammasome by the PRR binding to the adapter ASC followed by caspase‐1 binding to ASC. ", "All inflammasome‐inducing PRRs, ASC and caspase‐1 are multidomain‐containing proteins, whose domains are important to the assembly of the inflammasome. ", "Inflammasome assembly occurs by protein‐protein interactions at homotypic (structurally similar) domains. ", "For instance, protein‐protein interactions between many PRRs and ASC occur at pyrin domains found in both proteins, inducing the oligomerization of ASC. ", "Additionally, ASC and caspase‐1 bind at their respective caspase activation and recruitment domain (CARD). ", "Binding of caspase‐1 to the CARD of ASC induces caspase‐1 to oligomerize and autoactivate through self‐cleavage.", "\n\nIt is still not clear how many sensors are capable of forming inflammasomes, with strong literature support for over 10 different inflammasomes, including NLRP1, NLRP3, NLRP6, NLRP12, pyrin, NAIP/NLRC4, RIG‐I AIM2, IFI16, NLRC3, NLP6, recently reviewed elsewhere.[3](#prd12269-bib-0003){ref-type=\"ref\"}, [4](#prd12269-bib-0004){ref-type=\"ref\"}, [5](#prd12269-bib-0005){ref-type=\"ref\"} Here we will focus on discussing the clinical and preclinical data supporting a potential role of NRRP1, NLRP3, pyrin, AIM2 and IFI16 in the context of periodontal disease pathogenesis. ", "Additionally, we will discuss the role of the cytokines matured during inflammasome activation, interleukin‐1β and interleukin‐18. ", "Lastly, we will review the potential of interfering with inflammasome activation and its cytokines for therapeutic purposes.", "\n\n2. ", "NLR INFLAMMASOMES {#prd12269-sec-0002}\n====================\n\nIn the early 2000s, Ting and collaborators[6](#prd12269-bib-0006){ref-type=\"ref\"} recognized that a handful of related immune regulatory proteins belonged to a large family of mostly uncharacterized proteins recognized by the presence of nucleotide‐binding domains and leucine‐rich repeats.[6](#prd12269-bib-0006){ref-type=\"ref\"} This led to a standardization of the nomenclature, with the agreement of the PRR family name, NLR (formerly CATERPILLARs, NODs and NACHT‐leucine‐rich repeats).[7](#prd12269-bib-0007){ref-type=\"ref\"} NLRs are a large family of intracellular proteins that either positively or negatively regulate innate immune responses.[7](#prd12269-bib-0007){ref-type=\"ref\"} NLRs are found in all animal species and have structural similarity to disease‐resistant proteins in plants. ", "The human genome encodes 23 NLRs, whereas the mouse genome encodes 34. ", "With few exceptions, NLR proteins have tripartite domain organization, including a variable N‐terminal domain, the central nucleotide‐binding domain (also called NACHT) and C‐terminal leucine‐rich repeats. ", "They are divided into four subfamilies dependent upon their N‐terminal domains. ", "These four N‐terminal domains include: (a) acidic transactivator domain, (b) baculoviral inhibition of apoptosis protein repeat (BIR)‐like domain, (c) CARD and (d) pyrin domain.", "\n\n2.1. ", "NLRP1 INFLAMMASOME {#prd12269-sec-0003}\n-----------------------\n\nAlthough NLRP1 was the first inflammasome described, exactly how it is activated is still unclear.[1](#prd12269-bib-0001){ref-type=\"ref\"}, [8](#prd12269-bib-0008){ref-type=\"ref\"} Although the human genome encodes for a single NLRP1 protein, mice express eight paralogs, *Nlrp1a‐f* and *Nlrp1b2*.[9](#prd12269-bib-0009){ref-type=\"ref\"} Additionally, murine Nlrp1b has five different alleles that respond differentially to stimuli. ", "The human NLRP1 domain structure deviates from the typical tripartite domain structure and contains an N‐terminal pyrin domain, followed by a nucleotide‐binding domain, leucine‐rich repeats, function to find domain (FIND) and C‐terminal CARD. ", "The mouse domain structure lacks the N‐terminal pyrin domain. ", "Proteolytic cleavage in FIND must occur for NLRP1 to recognize its stimulus, although both portions remain associated. ", "Anthrax lethal toxin is sensed by multiple murine Nlrp1b alleles. ", "This toxin is a protease and N‐terminally processes Nlrp1b, leading to its activation in mice. ", "Although human NLRP1 is neither cleaved nor activated by lethal toxin, experimental cleavage of its N‐terminal sequence is sufficient to activate NLRP1.[10](#prd12269-bib-0010){ref-type=\"ref\"} This suggests that human NLRP1 may detect pathogen infection by an as yet unknown protease. *", "Toxoplasma gondii* activates some alleles of rat Nlrp1b. ", "Although polymorphisms in human NLRP1 are linked to congenital toxoplasmosis, there is no evidence that *T. gondii* activates NLRP1 inflammasome.[11](#prd12269-bib-0011){ref-type=\"ref\"} Muramyl dipeptide has been proposed as the ligand for human NLRP1, although this remains controversial and unsubstantiated.", "\n\n2.2. ", "NLRP3 INFLAMMASOME {#prd12269-sec-0004}\n-----------------------\n\nThe NLRP3 inflammasome responds to structurally and chemically diverse stimuli, including pathogen infections, tissue damage and metabolic changes. ", "Thus, it has been shown to contribute to a substantial number of inflammatory diseases, including diabetes mellitus, obesity and atherosclerosis. ", "The NLRP3 inflammasome is the most highly studied of all the inflammasomes.", "\n\nAlthough NLRP3 is activated during a variety of infections and inflammatory diseases, no direct agonist for NLRP3 has been found. ", "Instead, NLRP3 recognizes cell stress in a currently unknown manner. ", "Cellular stressors that are able to activate the NLRP3 inflammasome induce multiple upstream signaling events that are critical for NLRP3 activation. ", "These signaling events include: (a) K^+^, Ca^2+^ and Cl^−^ ion fluxes, (b) lysosomal disruption, (c) mitochondrial damage or dysfunction, (d) production of reactive oxygen species, (e) release of oxidized‐mitochondrial DNA (ox‐mtDNA) and (f) metabolic changes. ", "Although many of these signaling events are not mutually exclusive, it is not clear if they occur in single or multiple signal pathways that then converge upon the activation of NLRP3. ", "Most of these stressors converge on mtROS and ox‐mtDNA, but it is still unclear whether ox‐mtDNA is the direct ligand for NLRP3. ", "Additionally, mitochondrial antiviral signaling protein, an adaptor protein in RNA sensing pathways, has been shown to be important for NLRP3 inflammasome activation during infections by several different RNA viruses and after stimulation with the synthetic RNA poly I:C.[12](#prd12269-bib-0012){ref-type=\"ref\"}, [13](#prd12269-bib-0013){ref-type=\"ref\"}, [14](#prd12269-bib-0014){ref-type=\"ref\"}, [15](#prd12269-bib-0015){ref-type=\"ref\"} The location of the mitochondrial antiviral signaling protein in the mitochondrial outer membrane protein substantiates a role for NLRP3 sensing of mitochondrial perturbations.", "\n\nThe NLRP3 inflammasome has an additional protein that is unique to it and not found to be associated with other inflammasomes. ", "It was recently recognized that NIMA‐related kinase 7 (NEK7), a serine‐threonine kinase known to be involved in mitosis, is also essential for NLRP3 inflammasome activation.[16](#prd12269-bib-0016){ref-type=\"ref\"}, [17](#prd12269-bib-0017){ref-type=\"ref\"}, [18](#prd12269-bib-0018){ref-type=\"ref\"} The upstream signaling events that induce inflammasome activation also induce NEK7‐NLRP3 interaction. ", "Upon sensing cellular stress, NLRP3 oligomerizes at its nucleotide‐binding domains in a helical manner (Figure [3](#prd12269-fig-0003){ref-type=\"fig\"}). ", "NLRP3 oligomerization clusters the pyrin domain of NLRP3, inducing pyrin domain‐pyrin domain‐mediated ASC polymerization. ", "It is not clear whether NEK7 binding occurs prior to NLRP3 oligomerization or after, although recent evidence suggests that it is critical for ASC polymerization.[19](#prd12269-bib-0019){ref-type=\"ref\"}\n\n{#prd12269-fig-0003}\n\nActivation of the NLRP3 inflammasome is further regulated by post‐translational modifications of NLRP3 and ASC. ", "Multiple post‐translational modifications of NLRP3 occur that are necessary for NLRP3 inflammasome activation, including its phosphorylation, ubiquitination and sumoylation. ", "Additionally, phosphorylation of ASC also occurs and is a necessary step for the activation of the NLRP3 inflammasome.[20](#prd12269-bib-0020){ref-type=\"ref\"} Thus, the appropriate post‐translational modifications of NLRP3 with the phosphorylation of ASC act to fine tune the NLRP3 inflammasome response and prevent aberrant activation.", "\n\n2.3. ", "NOD1 AND NOD2 {#prd12269-sec-0005}\n------------------\n\nNOD1 and NOD2 are CARD‐containing members of the NLR family. ", "NOD1 is ubiquitously expressed, whereas NOD2 is found in myeloid cells, as well as epithelial cells and osteoblasts. ", "NOD1 and NOD2 both recognize different bacterial peptidoglycan components. ", "NOD1 recognizes γ [d]{.smallcaps}‐glutamyl‐meso‐diaminopimelic acid (iE‐DAP), whereas NOD2 recognizes muramyl dipeptide, both leading to the activation of nuclear factor‐κB.[21](#prd12269-bib-0021){ref-type=\"ref\"}, [22](#prd12269-bib-0022){ref-type=\"ref\"}, [23](#prd12269-bib-0023){ref-type=\"ref\"} In addition to the well‐known peptidoglycan sensing, NOD receptors were recognized for perceiving perturbations of cellular processes, such as regulation of the actin cytoskeleton and maintenance of endoplasmic reticulum homeostasis.[24](#prd12269-bib-0024){ref-type=\"ref\"} Although NOD2 does not activate its own inflammasome, activation of NOD2 has been shown to promote activation of both NLRP3 and NLRP1 inflammasomes, both dependent upon muramyl dipeptide recognition.[25](#prd12269-bib-0025){ref-type=\"ref\"}, [26](#prd12269-bib-0026){ref-type=\"ref\"} Because activation of NOD1 and NOD2 through recognition of peptidoglycan components leads to nuclear factor‐κB activation, which is necessary for priming the inflammasome, it may be that enhancement of inflammasomes by NOD1 and NOD2 is at least partially due to increased priming effects. ", "Additional pathogen‐sensing mechanisms involving actin cytoskeletal dynamics are attributed to NOD1 and NOD2, although it is not clear if these contribute to enhanced NLRP1 and NLRP3 inflammasome activation.", "\n\n3. ", "ALR {#prd12269-sec-0006}\n======\n\nThe ALRs are a family of DNA‐binding proteins that contain pyrin domains and DNA‐binding domains (hematopoietic expression, interferon‐inducible nature and nuclear localization \\[HIN200 or HIN\\]). ", "They are also referred to as the PYHIN (PYD HIN200) family, based on their domain structure. ", "Humans express four ALRs (AIM2, IFI16, PYHIN1 and MNDA), whereas mice express 13. ", "ALRs are activated through binding DNA at their HIN domains. ", "Of the four human ALRs, only AIM2 and IFI16 form inflammasomes.", "\n\nALRs function in both the nucleus and the cytoplasm, where they detect nuclear double‐stranded DNA breaks and sense cytoplasmic DNA. ", "Cytoplasmic DNA is detected by two major sensing pathways leading to different outcomes. ", "The first is the GMP‐AMP (cGAMP)‐synthase (cGAS)‐STING pathway that leads to the production of type I interferons. ", "The second is the activation of inflammasomes. ", "ALRs have been shown to function in both pathways, which leads to type I interferons and interleukin‐1β secretion. ", "Additionally, there is cross‐talk between the cGAS‐STING and inflammasome pathways. ", "ALRs are upregulated by type I interferons induced during activation of the cGAS‐STING pathway (inflammasome priming). ", "Furthermore, activation of cGAS produces the second‐messenger cGAMP, which binds to STING for cGAS‐STING activation, but also enhances activation of the AIM2 inflammasome.[27](#prd12269-bib-0027){ref-type=\"ref\"}\n\n3.1. ", "AIM2 INFLAMMASOME {#prd12269-sec-0007}\n----------------------\n\nMost of the literature on the AIM2 inflammasome centers on it being a protective mechanism during bacterial or viral infections, including *Fransicella tularensis*, vaccinia virus and *Listeria monocytogenes*.[3](#prd12269-bib-0003){ref-type=\"ref\"} AIM2 resides in an inactive state, with the HIN200 domain folded over the pyrin domain, thus preventing its inadvertent activation. ", "Double‐stranded cytoplasmic DNA from bacterial, viral or self‐DNA binds to the AIM2 HIN200 domain, releasing the HIN200‐pyrin domain association. ", "Multiple AIM2 proteins bind to a single double‐stranded DNA, resulting in the oligomerization of AIM2. ", "This DNA‐induced oligomerization causes clustering of the pyrin domain, which through self‐pyrin domain‐pyrin domain interactions stabilize the assembly and allows for ASC oligomerization and caspase‐1 activation as in other inflammasomes (Figure [4](#prd12269-fig-0004){ref-type=\"fig\"}). ", "In addition to its role in inflammasome activation, AIM2 was initially found to be a tumor suppressor and induce cell cycle arrest, and also found to regulate colon cancer tumorigenesis through suppression of AKT, a regulator of cellular proliferation.[28](#prd12269-bib-0028){ref-type=\"ref\"}, [29](#prd12269-bib-0029){ref-type=\"ref\"}, [30](#prd12269-bib-0030){ref-type=\"ref\"}\n\n{#prd12269-fig-0004}\n\n3.2. ", "IFI16 INFLAMMASOME {#prd12269-sec-0008}\n-----------------------\n\nAlthough most inflammasomes form in the cytosol, IFI16 is the only sensor that has been reported to form an inflammasome in the nucleus. ", "Nuclear IFI16 binds to episomal viral DNA genomes and induces an inflammasome, specifically in response to Listeria monocytogens, herpesvirus and lentivirus infections.[31](#prd12269-bib-0031){ref-type=\"ref\"}, [32](#prd12269-bib-0032){ref-type=\"ref\"}, [33](#prd12269-bib-0033){ref-type=\"ref\"} Structurally, IFI16 has two HIN200 domains, HINa and HINb, which are connected via a linker region. ", "In addition to double‐stranded DNA, IFI16 also binds single‐stranded DNA via the HINa domain, and preferentially binds quadraplex DNA structures that are intrinsic to many viral genomes and GC‐rich DNA.[34](#prd12269-bib-0034){ref-type=\"ref\"} Although IFI16 is predominately located in the nucleus, it can shuttle between the nucleus and the cytoplasm, where it has other functions.[32](#prd12269-bib-0032){ref-type=\"ref\"} Although IFI16 has additional DNA sensing roles in the cytoplasm, there is no evidence that it forms an inflammasome from detection of cytosolic DNA.", "\n\nIFI16 is a multifunctional protein due to its ability to bind to various target proteins and, in turn, modulate a variety of cell functions, including cell cycle regulation, apoptosis/pyroptosis, DNA damage responses and inflammation.[35](#prd12269-bib-0035){ref-type=\"ref\"}, [36](#prd12269-bib-0036){ref-type=\"ref\"} Although there is not a murine homolog for IFI16, murine Ifi204 and Ifi205 have shown similar structures and functions in innate immune responses, cell differentiation and proliferation.[37](#prd12269-bib-0037){ref-type=\"ref\"}, [38](#prd12269-bib-0038){ref-type=\"ref\"}, [39](#prd12269-bib-0039){ref-type=\"ref\"}, [40](#prd12269-bib-0040){ref-type=\"ref\"}, [41](#prd12269-bib-0041){ref-type=\"ref\"} Differing from the human ALRs, however, the murine homologs do not function in the cGAS‐STING pathway.[42](#prd12269-bib-0042){ref-type=\"ref\"}\n\nAmong the different functions it can perform, IFI16 is shown to have inflammasome antagonizing functions. ", "Although it can promote AIM2 inflammasome formation by upregulating AIM2 expression during priming, it is also shown to antagonize the AIM2 inflammasome.[43](#prd12269-bib-0043){ref-type=\"ref\"} IFI16 lacks the N‐terminal pyrin domain and it can bind to the same DNA as AIM2 and inhibit AIM2 inflammasome formation. ", "IFI16 is also shown to heterodimerize with AIM2 and, therefore, modulate inflammation.[43](#prd12269-bib-0043){ref-type=\"ref\"}, [44](#prd12269-bib-0044){ref-type=\"ref\"}, [45](#prd12269-bib-0045){ref-type=\"ref\"}, [46](#prd12269-bib-0046){ref-type=\"ref\"} Thus, IFI16 has multiple roles related to inflammasomes that are dependent upon the protein binding, location and splice variation.", "\n\n4. ", "PYRIN INFLAMMASOME {#prd12269-sec-0009}\n=====================\n\nPyrin was first recognized as the initiator of familial Mediterranean fever, the most common monogenic autoinflammatory disease.[47](#prd12269-bib-0047){ref-type=\"ref\"}, [48](#prd12269-bib-0048){ref-type=\"ref\"} These mutations in familial Mediterranean fever lessen the threshold of activation for the pyrin inflammasome, translating into a hyperinflammatory response.[49](#prd12269-bib-0049){ref-type=\"ref\"}, [50](#prd12269-bib-0050){ref-type=\"ref\"} Pyrin is unique among PRRs in that it does not fit into any of the known PRR families. ", "It is the protein for which the pyrin domain was named. ", "It has an N‐terminal pyrin domain, then a long linker, followed by a B‐box, a coil‐coil domain and finally a B30.2 at the C‐terminus.[51](#prd12269-bib-0051){ref-type=\"ref\"} The pyrin inflammasome recognizes inhibition of the Rho family of GTPases. ", "The RhoA family regulates actin cytoskeletal dynamics that many bacterial pathogens modify in order to invade host cells for their survival. ", "Pyrin does not directly sense modified RhoA, but rather senses impairment of RhoA activity from RhoA modifications, sequestration of RhoA or stimulation of its GTPase activity.[51](#prd12269-bib-0051){ref-type=\"ref\"} Like the other inflammasomes described here, activation of pyrin recruits the linker ASC binding through pyrin domain‐pyrin domain binding. ", "ASC then oligomerizes, followed by caspase‐1 recruitment and activation.", "\n\n5. ", "INFLAMMASOMES AND DISEASE PATHOGENESIS {#prd12269-sec-0010}\n=========================================\n\nThe same innate immune signaling receptors that are critical for protective anti‐infectious immune responses are also the mediators of the heightened inflammatory state that is found in several noncommunicable diseases.[52](#prd12269-bib-0052){ref-type=\"ref\"} Therefore, multiple studies have explored inflammasomes in the context of several inflammatory, autoinflammatory and autoimmune diseases.[5](#prd12269-bib-0005){ref-type=\"ref\"}, [53](#prd12269-bib-0053){ref-type=\"ref\"} Inflammasomes are primed and activated by PAMPs and, therefore, involved with infection. ", "However, the presence/accumulation of sterile danger signals (DAMPs) in tissues that occurs in many common diseases that present later in life also upregulates inflammasome proteins in diseased tissues. ", "This suggests that the priming step of inflammasome activation has occurred during infection and disease, with a potential for further inflammasome activation and inflammatory cytokine secretion.", "\n\nGenetic alterations of inflammasome components and increased tissue expression of inflammasome‐related proteins are clinically correlated with several disease phenotypes.[4](#prd12269-bib-0004){ref-type=\"ref\"}, [5](#prd12269-bib-0005){ref-type=\"ref\"}, [54](#prd12269-bib-0054){ref-type=\"ref\"} In this section we will discuss the current evidence from clinical and preclinical studies supporting a role for inflammasomes in some of these conditions, including periodontitis. ", "The diseases discussed in this section were selected based on reports of clinical disease comorbidity with periodontal disease and the current evidence supporting inflammasome involvement. ", "Clinical comorbidity can suggest similar underlying biological principals of different entities that predispose patients for the development of different conditions. ", "We will not discuss data from studies reporting only in vitro results. ", "We have included only selected candidate gene studies due to the false‐positive results and reporting bias that can occur with these studies.", "\n\nBefore we start, it is important to clarify that autoinflammatory diseases differ from autoimmune diseases, in which the first is the innate immune system directly causing tissue inflammation and the latter is the adaptive immune system that directly causes the damage.[53](#prd12269-bib-0053){ref-type=\"ref\"} Autoinflammatory disorders were first recognized nearly 20 years ago as distinct immunological entities in which there is an innate immune dysregulation that lacks high titers of autoantibodies and self‐reactive T cells.[54](#prd12269-bib-0054){ref-type=\"ref\"} The hereditary periodic fever syndromes were the first described examples of autoinflammatory diseases and comprise a group of rare, multisystem disorders characterized by recurrent episodes of fever in association with inflammation that affects many tissues.[54](#prd12269-bib-0054){ref-type=\"ref\"} Skin and mucosal inflammation is a common feature of many autoinflammatory diseases. ", "These syndromes result from different genetic alterations and include familial Mediterranean fever, Crohn\\'s disease and Behcet disease, among many others.[54](#prd12269-bib-0054){ref-type=\"ref\"}\n\n5.1. ", "NOD1 AND NOD2 {#prd12269-sec-0011}\n------------------\n\nNOD receptors have been included in this section because, in addition to microbial and damage sensing, NOD receptors also promote activation of NLRP3 and NLRP1 inflammasomes.[24](#prd12269-bib-0024){ref-type=\"ref\"}, [25](#prd12269-bib-0025){ref-type=\"ref\"}, [26](#prd12269-bib-0026){ref-type=\"ref\"} The importance of NOD2 in inflammatory diseases is most strongly supported by the association of mutations in NOD2 and the increased risk for developing Crohn\\'s disease, an autoinflammatory disorder of the gastrointestinal tract. ", "The most common polymorphisms associated with Crohn\\'s disease are located in the leucine‐rich repeat domain of NOD2 and include R702W, G908R and L1007fsinsC.[24](#prd12269-bib-0024){ref-type=\"ref\"}, [55](#prd12269-bib-0055){ref-type=\"ref\"}, [56](#prd12269-bib-0056){ref-type=\"ref\"} Individuals with these variants have an increased risk for developing Crohn\\'s disease. ", "Although the exact mechanisms by which these mutations lead to disease is still not clear; data indicate that these mutations impair the mucosal barrier function due to a deficiency in bacterial clearance and activation of toll‐like receptors and Th1 immune responses.[54](#prd12269-bib-0054){ref-type=\"ref\"}, [57](#prd12269-bib-0057){ref-type=\"ref\"} Recent studies suggest that these defects may also alter the recognition of endoplasmic reticulum stress‐induced NOD1/NOD2 activation and further contribute to the development of Crohn\\'s disease.[24](#prd12269-bib-0024){ref-type=\"ref\"}, [54](#prd12269-bib-0054){ref-type=\"ref\"}\n\nCrohn\\'s disease and ulcerative colitis are classified under the umbrella of inflammatory bowel diseases. ", "Although the pathogeneses are distinct, both diseases have multiple similarities, including the chronic debilitating inflammation of the gastrointestinal tract that is partly driven by defects in the innate immune system in response to commensal gut bacteria. ", "It has been suggested that inflammatory bowel disease and periodontal disease share similar immunopathogenic pathways, in that both entities show tissue‐destructive mucosal inflammation directed against commensal microbiota.[58](#prd12269-bib-0058){ref-type=\"ref\"} Therefore, we propose that some individuals may have a systemic abnormal defensive inflammasome response that is initiated during the sensing of the commensal microbiota by NOD receptors. ", "A recent meta‐analysis of nine cross‐sectional studies (n = 1297) concluded that inflammatory bowel disease was associated with increased risk of periodontitis (332 more diseased individuals per 1000 individuals; *P* \\< .001) compared with noninflammatory bowel disease individuals.[59](#prd12269-bib-0059){ref-type=\"ref\"} Individuals with inflammatory bowel disease (either Crohn\\'s disease or ulcerative colitis) had an average of one tooth less (*P* = .090) than noninflammatory bowel disease individuals. ", "Other oral mucosa manifestations of inflammatory bowel disease reported include aphthous ulcers, cobblestoning (fissures/ulcers in separate islands of mucosa with the appearance reminiscent of cobblestones) and pyostomatitis. ", "These additional findings support an alteration in the epithelial barrier and/or host response in oral mucosal tissues that could be parallel to what is observed in the gut.", "\n\nThere is a paucity of information regarding the relevance of NOD1 and NOD2 in periodontitis. ", "Healthy and diseased human gingival tissues are shown to express high levels of NOD1 and NOD2 in epithelial cells and inflammatory cells, with no difference reported among different periodontal conditions.[60](#prd12269-bib-0060){ref-type=\"ref\"}, [61](#prd12269-bib-0061){ref-type=\"ref\"}, [62](#prd12269-bib-0062){ref-type=\"ref\"} In a preclinical study Nod2^−/−^ and Rip2^−/−^ (downstream kinase of Nod1 and Nod2) mice showed a significant reduction of experimental alveolar bone resorption and osteoclastogenesis, supporting NOD2 as a driver of periodontal bone loss.[63](#prd12269-bib-0063){ref-type=\"ref\"} This result is contradictory to the findings of a collaborative effort developed by the authors in which Nod2^−/−^ mice showed no difference in the amount of bone loss compared with controls.[64](#prd12269-bib-0064){ref-type=\"ref\"} This could be attributed to the different types of model used to study experimental periodontitis (injection of heat‐killed *Aggregatibacter actinomycetemcomitans* into murine gingival tissues in their study vs ligature model developed by Jiao et al).[64](#prd12269-bib-0064){ref-type=\"ref\"} Although the inflammatory infiltrate in the gingival tissues did not seem to be affected by Nod2, the osteoclastogenesis was significantly reduced in mice lacking Nod2 in the gavage model.[63](#prd12269-bib-0063){ref-type=\"ref\"} We speculate that Nlrp3 inflammasome assembly was affected in Nod2‐ablated mice, as signals originating from the bone matrix can act as DAMPs, activate the NLRP3 inflammasome and promote osteoclast differentiation.[65](#prd12269-bib-0065){ref-type=\"ref\"} Neither study evaluated the effect of Nod2 in the mucosal barrier function of the gingival tissues, as reported to be the main effect on the development of Crohn\\'s disease.[54](#prd12269-bib-0054){ref-type=\"ref\"}, [57](#prd12269-bib-0057){ref-type=\"ref\"} In the ligature model of periodontitis, Nod1 (rather than Nod2) drives the alveolar bone resorption, with decreased bone loss (approximately one‐third less compared with wild‐type), decreased interleukin‐β levels, decreased osteoclast numbers and decreased neutrophil migration observed in mice lacking Nod1 and Ripk2 (a mediator of NOD1 and NOD2 signaling).[64](#prd12269-bib-0064){ref-type=\"ref\"} In summary, the current data demonstrate potential involvement of NOD1 and NOD2 in the pathogenesis of periodontitis. ", "Additional studies involving NOD receptors, DAMPs and epithelial barrier integrity are needed to clarify further the role of these receptors in periodontal disease.", "\n\n5.2. ", "NLRP1 {#prd12269-sec-0012}\n----------\n\nNLRP1 is the main inflammasome in the skin.[54](#prd12269-bib-0054){ref-type=\"ref\"} Genetic mutations associated with some autoinflammatory diseases are present in either NLRP1\\'s pyrin domain or leucine‐rich repeats domain and lead to constitutive activation of NLRP1. ", "Although NLRP1 is the founding member of the inflammasome family,[8](#prd12269-bib-0008){ref-type=\"ref\"} most of the studies that have explored its role have centered on autoinflammatory diseases, with no information on the periodontal status of the individuals, and can be reviewed elsewhere.[54](#prd12269-bib-0054){ref-type=\"ref\"} It should also be noted that although NLRP1, which has many genetic variants in mice and rats, forms well‐defined inflammasomes in these rodent models, the activation of the human NLRP1 into an inflammasome is less well understood.[5](#prd12269-bib-0005){ref-type=\"ref\"} A meta‐analysis evaluating a total of 37 candidate gene studies among 37 033 cases and 54 716 controls of 10 genetic variants found NLRP1 rs12150220 (odds ratio = 0.71, 95% CI = 0.55‐0.92, *P* = .01) to be significantly associated with type 1 diabetes.[66](#prd12269-bib-0066){ref-type=\"ref\"} Because it is known that individuals with type 1 diabetes have increased susceptibility to periodontitis,[67](#prd12269-bib-0067){ref-type=\"ref\"} it leads to further speculation as to whether the alteration of NLRP1 could partially contribute to the clinical comorbidity in particular individuals. ", "Only one clinical study so far has evaluated NLRP1 in the context of periodontal disease.[68](#prd12269-bib-0068){ref-type=\"ref\"} NLRP1 was shown to be expressed at very low levels in the gingival tissues of healthy, chronic and aggressive periodontitis, with expression more frequently observed in the epithelium and connective tissue of individuals with aggressive periodontitis (n = 65).[68](#prd12269-bib-0068){ref-type=\"ref\"} The data indicate that NLRP1 function is still not well defined in periodontal disease.", "\n\n5.3. ", "NLRP3 {#prd12269-sec-0013}\n----------\n\nBeing the most studied inflammasome in clinical diseases, NLRP3 has been implicated as having a role in several inflammatory and autoimmune diseases, including atherosclerosis, diabetes mellitus, obesity and rheumatoid arthritis,[4](#prd12269-bib-0004){ref-type=\"ref\"}, [5](#prd12269-bib-0005){ref-type=\"ref\"} all of which are diseases known for their clinical association with periodontal disease.[67](#prd12269-bib-0067){ref-type=\"ref\"}, [69](#prd12269-bib-0069){ref-type=\"ref\"} The data indicate that in these four conditions there is a dysregulation of the inflammatory response that is partly driven by NLRP3.[5](#prd12269-bib-0005){ref-type=\"ref\"} In atherosclerosis, the formation of cholesterol crystals that accumulate on arterial walls can become intracellular and appear to lead to vascular inflammation.[70](#prd12269-bib-0070){ref-type=\"ref\"}, [71](#prd12269-bib-0071){ref-type=\"ref\"}, [72](#prd12269-bib-0072){ref-type=\"ref\"} In diabetes mellitus type 2, endogenous and exogenous stimulators of NLRP3 inflammasome have been shown to accumulate in the pancreas, including glucose, islet amyloid polypeptides, reactive oxygen species, neuromodulatory lipids (endocannabinoids) and saturated fatty acids that arise from a high‐fat diet.[73](#prd12269-bib-0073){ref-type=\"ref\"}, [74](#prd12269-bib-0074){ref-type=\"ref\"}, [75](#prd12269-bib-0075){ref-type=\"ref\"}, [76](#prd12269-bib-0076){ref-type=\"ref\"}, [77](#prd12269-bib-0077){ref-type=\"ref\"} The accumulation of these stimulators can induce NLRP3 activation and subsequent cytokine expression.[5](#prd12269-bib-0005){ref-type=\"ref\"} In obesity, NLRP3 and ASC are reported to be upregulated in adipocytes from obese individuals.[78](#prd12269-bib-0078){ref-type=\"ref\"} Obesity‐associated inflammation leads to functional abnormalities of adipocytes, resulting in elevated circulating levels of free fatty acids in human blood that induces pro‐interleukin‐1β production through toll‐like receptors, providing the first signal (priming) for inflammasome activation.[77](#prd12269-bib-0077){ref-type=\"ref\"}, [79](#prd12269-bib-0079){ref-type=\"ref\"} Although the data supporting interleukin‐1β as a driver of rheumatoid arthritis disease pathogenesis are strong,[80](#prd12269-bib-0080){ref-type=\"ref\"} the data supporting the role of the NLRP3 inflammasome are more limited. ", "In rheumatoid arthritis, individuals with active rheumatoid arthritis have increased expression of NLRP3 and NLRP3‐mediated interleukin‐1β secretion in whole blood cells.[81](#prd12269-bib-0081){ref-type=\"ref\"} In experimental arthritis, deletion of Nlrp3, caspase‐1 and the interleukin‐1 receptor markedly protects against rheumatoid arthritis‐associated inflammation and cartilage destruction.[82](#prd12269-bib-0082){ref-type=\"ref\"} Together, the data strongly indicate that NLRP3 inflammasome deregulation is implicated in the pathogenesis of atherosclerosis, diabetes mellitus type 2 and obesity and, to a lesser extent, rheumatoid arthritis.", "\n\nLimited clinical studies have explored the presence of NLRP3 as it relates to periodontal disease. ", "Analyses of human gingival tissue samples showed a significant four‐ to five‐fold increased NLRP3 mRNA expression in chronic periodontitis and approximately a seven‐fold increased expression in aggressive periodontitis when compared with healthy gingival samples.[68](#prd12269-bib-0068){ref-type=\"ref\"}, [83](#prd12269-bib-0083){ref-type=\"ref\"} Immunohistochemical results confirmed these findings and showed that the increased NLRP3 expression is more pronounced in the epithelial layer, which could indicate that the epithelium uses NLRP3 to assist the host innate immunity in the resistance to the constant bacterial invasion in the gingival sulcus and tissues.[68](#prd12269-bib-0068){ref-type=\"ref\"} It appears that even when the inflammation is only present in the gingival tissues and not yet involving bone resorption, NLRP3 levels are already increased (7.7‐fold increased expression in gingivitis gingival samples compared with healthy controls).[83](#prd12269-bib-0083){ref-type=\"ref\"} Whole saliva samples of individuals with chronic periodontitis and aggressive periodontitis also demonstrate significantly increased levels of NLRP3 compared with healthy individuals, with 3.20 ± 3.12 ng/mL in aggressive periodontitis, 1.56 ± 1.55 ng/mL in chronic periodontitis and 0.530 ± 0.40 ng/mL in saliva from healthy individuals.[84](#prd12269-bib-0084){ref-type=\"ref\"} Salivary levels of ASC are also reported to have significant differences among individuals with different periodontal status, with 43.62 ± 21.62 pg/mL in healthy individuals, 74.44 ± 63.31 pg/mL in chronic periodontitis and 82.82 ± 73.10 pg/mL in aggressive periodontitis.[84](#prd12269-bib-0084){ref-type=\"ref\"} Additionally, a positive correlation has been reported between *NLRP3* mRNA levels with *IL1B* and *IL18* mRNA expression levels in gingival tissues.[83](#prd12269-bib-0083){ref-type=\"ref\"} Data from ligature‐induced periodontitis further support NLRP3 upregulation in experimental periodontitis (Figure [5](#prd12269-fig-0005){ref-type=\"fig\"}). ", "Together, the current limited data support the priming of NLRP3 inflammasome components in tissues and saliva samples in the presence of periodontal inflammation.", "\n\n{ref-type=\"ref\"} Representative images of maxilla micro‐computed tomography showing (A) baseline (no ligature) and (B) alveolar bone loss that developed with disease induction. (", "C) Alveolar bone quantification shows significant bone loss after 10 days of ligature placement. (", "D) mRNA expression of inflammasome components are significantly higher in gingival tissues at 10 days postligature when compared with nonligated animals. *", "\\*P *\\<* *.05, *\\*\\*P *\\<* *.01 as compared with no ligature control](PRD-82-93-g005){#prd12269-fig-0005}\n\nEvidence also suggests that genetic variants in the *NLRP3* gene are associated with increased risk for developing autoinflammatory Crohn\\'s disease.[85](#prd12269-bib-0085){ref-type=\"ref\"} A predicted regulatory region on chromosome 1q44 downstream of NLRP3 (rs10733113) was strongly associated with the risk of Crohn\\'s disease (odds ratio = 1.78, confidence interval = 1.47‐2.16) and was consistently replicated in four sample sets from individuals with European descent.[85](#prd12269-bib-0085){ref-type=\"ref\"} No study so far has reported genetic defects or variants in NLRP3 correlated with periodontal disease.", "\n\n5.4. ", "PYRIN {#prd12269-sec-0014}\n----------\n\nMutations in the gene *MEFV* that encodes the protein pyrin leads to familial Mediterranean fever, the prototypic periodic fever syndrome. ", "This group of diseases was the first described examples of autoinflammatory disease and initiated the path to a deeper understanding of the mediation of proinflammatory cytokine interleukin‐1β release that later led to the inflammasome discovery.[54](#prd12269-bib-0054){ref-type=\"ref\"} Individuals with familial Mediterranean fever experience recurrent episodes of fever with inflammation of serosal membranes in the abdomen, heart and lungs. ", "As the name suggests, this disease is most prevalent in Mediterranean populations, with a relatively high prevalence in Turkey (1:1000).[86](#prd12269-bib-0086){ref-type=\"ref\"} Approximately one‐third of people with clinical symptoms of familial Mediterranean fever have only one identified mutation in *MEFV*, despite extensive searches for a second mutation.[87](#prd12269-bib-0087){ref-type=\"ref\"} Five (M694V, V726A, M680I, M694I and E148Q) out of 68 acknowledged MEFV mutations have been reported to be the most common.[88](#prd12269-bib-0088){ref-type=\"ref\"}, [89](#prd12269-bib-0089){ref-type=\"ref\"} The spatial arrangement and relocalization of pyrin and NLRP3 inflammasome components during activation are driven by microtubulin dynamics.[90](#prd12269-bib-0090){ref-type=\"ref\"}, [91](#prd12269-bib-0091){ref-type=\"ref\"} Colchicine is a highly effective and specific treatment for familial Mediterranean fever and NLRP3 inflammasome that works by binding to tubulin, preventing microtubule polymerization. ", "Additionally, colchicine activates RhoA and suppresses pyrin inflammasome activation.[54](#prd12269-bib-0054){ref-type=\"ref\"}, [92](#prd12269-bib-0092){ref-type=\"ref\"}\n\nFew studies have been conducted evaluating the periodontal condition of individuals with familial Mediterranean fever. ", "The type of classification selected for familial Mediterranean fever is reported to affect the periodontal clinical findings.[93](#prd12269-bib-0093){ref-type=\"ref\"}, [94](#prd12269-bib-0094){ref-type=\"ref\"}, [95](#prd12269-bib-0095){ref-type=\"ref\"} Individuals with familial Mediterranean fever (n = 81) were shown to have significantly higher clinical measures of periodontal disease severity compared with systemically healthy controls (n = 85), although the clinical magnitude of difference was small (mean, SD probing depth in systemically healthy controls was 2.73 ± 0.86 vs 3.00 ± 0.93 mm in familial Mediterranean fever, *P* = .044; mean clinical attachment level in systemically healthy controls was 2.96 ± 1.10 vs 3.15 ± 1.22 mm in familial Mediterranean fever, *P* = .032). ", "However, several salivary oxidative stress parameters were significantly higher in individuals with familial Mediterranean fever compared with systemically healthy controls (up to six times higher, mean, SD 8OHdG in healthy controls was 12.78 ± 19.88 pg/mL vs 82.80 ± 82.09 pg/mL in familial Mediterranean fever, *P* = .001).[93](#prd12269-bib-0093){ref-type=\"ref\"} This suggests that periodontal disease in individuals with familial Mediterranean fever may have oxidative stress regulation as a stronger underlying biological driver when compared with systemically healthy individuals. ", "It is also possible that particular genetic mutations of *MEFV* may be more detrimental to the oral microflora environment. ", "Of all the *MEFV* gene mutations, individuals with the M694V mutation showed a higher prevalence of severe familial Mediterranean fever development with early emergence, frequent attacks, need for treatment with higher colchicine doses and frequent amyloidosis occurrence in untreated patients.[96](#prd12269-bib-0096){ref-type=\"ref\"}, [97](#prd12269-bib-0097){ref-type=\"ref\"}, [98](#prd12269-bib-0098){ref-type=\"ref\"} Interestingly, individuals with familial Mediterranean fever with this same pyrin mutation, M694V, were reported to be \\~3.5 times more likely to present with periodontitis than individuals with other pyrin mutations.[96](#prd12269-bib-0096){ref-type=\"ref\"}, [99](#prd12269-bib-0099){ref-type=\"ref\"} These studies provide clinical indications that pyrin proteins are probably important in the pathogenesis of periodontal disease. ", "No preclinical studies using *Mefv* ^−/−^ mice were identified in the periodontal field.", "\n\n5.5. ", "AIM2 AND IFI16 {#prd12269-sec-0015}\n-------------------\n\nThe ALR family contains four human proteins, of which IFI16 and AIM2 are the only inflammasome‐forming members. ", "Although AIM2 binds to double‐stranded DNA, IFI16 binds to both single‐stranded and double‐stranded DNA encountered during infection by different viruses and intracellular bacteria.[37](#prd12269-bib-0037){ref-type=\"ref\"}, [100](#prd12269-bib-0100){ref-type=\"ref\"} Both have additional functions in the detection of DNA beyond their role in inflammasome activation. ", "Importantly, some of IFI16\\'s additional functions include modulation of the AIM2 inflammasome.[44](#prd12269-bib-0044){ref-type=\"ref\"}, [45](#prd12269-bib-0045){ref-type=\"ref\"}, [101](#prd12269-bib-0101){ref-type=\"ref\"}\n\nIncreased expression of AIM2 has been reported in a number of inflammatory diseases, including inflammatory bowel disease and the skin conditions of psoriasis, atopic dermatitis and venous ulcers.[102](#prd12269-bib-0102){ref-type=\"ref\"}, [103](#prd12269-bib-0103){ref-type=\"ref\"}, [104](#prd12269-bib-0104){ref-type=\"ref\"} In the skin, AIM2 upregulation is seen at sites of individuals with acute and chronic skin barrier disruption‐related inflammation, which can be as striking as more than a 300‐fold increase.[103](#prd12269-bib-0103){ref-type=\"ref\"} AIM2 priming/upregulation upon skin barrier disruption serves as a first line of defense against invading pathogens. ", "This is beneficial during wound healing, which is usually temporary in the absence of disease. ", "However, the prolonged barrier disruption with AIM2‐interleukin‐1β secretion may contribute to the chronicity of inflammatory skin lesions.[103](#prd12269-bib-0103){ref-type=\"ref\"} Although less explored in other inflammatory diseases, IFI16 also shows higher expression in inflammatory bowel disease, including Crohn\\'s disease and ulcerative colitis. ", "In active inflammatory bowel disease, a significant two‐fold higher expression of AIM2 and IFI16 is observed in the intestinal mucosa compared with controls,[104](#prd12269-bib-0104){ref-type=\"ref\"}, [105](#prd12269-bib-0105){ref-type=\"ref\"} indicating priming/upregulation of these proteins in certain conditions involving barrier function integrity.", "\n\nThere are limited data exploring the role of IFI16 and AIM2 in periodontal disease pathogenesis. ", "Current data report differences in tissue expression based on periodontal disease status, limited tissue characterization and correlation of specific gene variants with periodontitis.[106](#prd12269-bib-0106){ref-type=\"ref\"}, [107](#prd12269-bib-0107){ref-type=\"ref\"} In human gingival tissues, AIM2 levels were approximately two‐fold higher in the lamina propria and epithelium of chronic periodontitis compared with healthy controls and aggressive periodontitis.[68](#prd12269-bib-0068){ref-type=\"ref\"} In that study, AIM2 was mainly expressed in epithelial cells. ", "Previously we have shown that IFI16 and AIM2 are expressed in multiple cells of human gingival tissues, with a homogeneous distribution in the epithelial layer.[106](#prd12269-bib-0106){ref-type=\"ref\"} In the connective tissue, inflammatory cells and endothelial cells show expression of both IFI16 and AIM2.[106](#prd12269-bib-0106){ref-type=\"ref\"} Further characterization by our group shows that IFI16 expression in the gingival inflammatory infiltrate coincides with CD14^+^ monocytes/macrophages (Figure [6](#prd12269-fig-0006){ref-type=\"fig\"}). ", "In addition, gingival tissues derived from ligature‐induced periodontitis shows a significant two‐fold increase in *AIM2* and *IFI204* expression compared with controls (Figure [5](#prd12269-fig-0005){ref-type=\"fig\"}). ", "Together, these studies and preliminary data support a potential inflammasome priming/upregulation of IFI16 and AIM2 in periodontal tissues with disease.", "\n\n{#prd12269-fig-0006}\n\nInterestingly, our group has shown that variants in *IFI16* and *AIM2* regions correlate with periodontal disease (genome‐wide association study from n = 4766 European Americans).[106](#prd12269-bib-0106){ref-type=\"ref\"}, [107](#prd12269-bib-0107){ref-type=\"ref\"} We further characterized the microbial, biological and periodontal disease clinical parameters of these individuals. ", "Haplotype blocks rs1057028 and rs6940 in the *IFI16* region were significantly correlated with dramatic increases in levels of plaque‐adjusted periodontal microorganisms that ranged from 33% to 275%, with the highest increase associated with plaque levels of *Porphyromonas gingivalis, Tannerella forsythia* and *Campylobacter rectus*. ", "Levels of gingival crevicular fluid‐interleukin‐1β were also significantly higher in individuals with variants on the *IFI16/AIM2* region, ranging from 3% to 5% increases even after plaque adjustment.[106](#prd12269-bib-0106){ref-type=\"ref\"} Interestingly, individuals with one of the variants, *IFI16* variants (rs6940), are reported to be at a higher risk for developing autoinflammatory Behcet disease, suggesting that alterations in IFI16 may affect the oral mucosal host response.[108](#prd12269-bib-0108){ref-type=\"ref\"} In addition to genital ulcers, individuals with Behcet disease commonly show oral aphthous ulcers and show increased periodontal clinical parameters of disease.[109](#prd12269-bib-0109){ref-type=\"ref\"}, [110](#prd12269-bib-0110){ref-type=\"ref\"}, [111](#prd12269-bib-0111){ref-type=\"ref\"} Because the recurrent oral ulcers are also known to affect oral hygiene habits, both the bacterial plaque ecology and/or the immune responses to these microorganisms may be affected in Behcet disease. ", "In sum, current literature indicates that inflammasome proteins IFI16 and AIM2 are upregulated in diseased tissues with an epithelial barrier function disruption and *IFI16* and *AIM2* variants that affect the expression or function of these proteins may lead to periodontal disease predisposition and development that may impact the composition of the oral microbiome.", "\n\n5.6. ", "INTERLEUKIN‐1Β {#prd12269-sec-0016}\n-------------------\n\nInterleukin‐1 is one of the most studied cytokines in periodontology, having a central role in the host response as a mediator of local tissue destruction and bone resorption.[112](#prd12269-bib-0112){ref-type=\"ref\"} Both interleukin‐1α and interleukin‐1β are reported to be at least 10 times more potent on a molar basis than tumor necrosis factor‐α, parathyroid hormone or prostaglandin E2 in the induction of bone demineralization.[113](#prd12269-bib-0113){ref-type=\"ref\"} Clinically, elevated interleukin‐1β levels have been associated with many human diseases In addition, extensive literature supports that gingival crevicular fluid‐interleukin‐1β is associated with different periodontal disease phenotypes. [", "2](#prd12269-bib-0002){ref-type=\"ref\"}, [114](#prd12269-bib-0114){ref-type=\"ref\"}, [115](#prd12269-bib-0115){ref-type=\"ref\"} Regardless of the oral condition, the average level of interleukin‐1β in gingival crevicular fluid is reported as 136.8 ± 1.4 (mean, SE) ng/mL, with a high range of variation among individuals.[114](#prd12269-bib-0114){ref-type=\"ref\"}\n\nOffenbacher and collaborators[114](#prd12269-bib-0114){ref-type=\"ref\"} have previously evaluated gingival crevicular fluid‐interleukin‐1β levels in 5809 individuals from the Dental Atherosclerosis Risk in Communities study, which is a cross‐sectional study that took place during Visit 4 of the Dental Atherosclerosis Risk in Communities study of community‐dwelling adults aged 45‐64 years conducted in four US communities. ", "In this study, individual average gingival crevicular fluid‐interleukin‐1β was positively correlated to maximum probing depth and bleeding on probing, supporting an association between gingival crevicular fluid‐interleukin‐1β levels and clinical signs of periodontal disease. ", "It is reported that a 22.8‐150 ng/mL concentration range is observed in healthy individuals and 85.8‐882.2 ng/mL in moderate/severe periodontitis.[116](#prd12269-bib-0116){ref-type=\"ref\"} The 2017 World Workshop on Periodontal Disease Classification (WW17) has proposed a new classification system that involves stages and grades of disease. ", "We evaluated the association of gingival crevicular fluid‐interleukin‐1β levels according to the WW17 classification system[117](#prd12269-bib-0117){ref-type=\"ref\"}, [118](#prd12269-bib-0118){ref-type=\"ref\"} and the periodontal profile class stages described in the references.[119](#prd12269-bib-0119){ref-type=\"ref\"}, [120](#prd12269-bib-0120){ref-type=\"ref\"}, [121](#prd12269-bib-0121){ref-type=\"ref\"} No differences were observed in gingival crevicular fluid‐interleukin‐1β levels across the WW17 stages (incipient, moderate, severe and advanced disease), potentially because of the lack of consideration of the grades that requires longitudinal analysis of the individual (Figure [7](#prd12269-fig-0007){ref-type=\"fig\"}). ", "The periodontal profile class stages (health/incidental, mild, moderate, severe, mild tooth loss/high gingival inflammation, moderate tooth loss/reduced periodontium and severe tooth loss) showed that individuals in all disease categories were significantly different from stage I (health/incidental disease), which had the lowest concentration (mean, SE 83.75 \\[1.02\\] pg/mL), with the exception of stage VII (severe tooth loss; mean, SE 89.84 \\[1.03\\] pg/mL; Figure [7](#prd12269-fig-0007){ref-type=\"fig\"}). ", "This could be attributed to the fact that most of the diseased teeth of individuals in stage VII (severe tooth loss) have already been lost. ", "Interestingly, individuals in stage VI (severe disease) showed the highest levels of gingival crevicular fluid‐interleukin‐1β (mean, SE 135.25 \\[1.04\\] pg/mL). ", "Individuals in this category show mild tooth loss, usually missing six to 10 teeth, and extensive gingival inflammation, but very minimal bleeding on probing. ", "The analysis indicates that high gingival crevicular fluid‐interleukin‐1β is associated with the periodontal disease phenotypes represented by the periodontal profile class stages, but not the phenotypes represented by the WW17 stages.", "\n\n{ref-type=\"ref\"}, [118](#prd12269-bib-0118){ref-type=\"ref\"} B, periodontal profile phenotype.[119](#prd12269-bib-0119){ref-type=\"ref\"}, [120](#prd12269-bib-0120){ref-type=\"ref\"}, [121](#prd12269-bib-0121){ref-type=\"ref\"} Generalized linear models adjusted for age, sex, study center, race, smoking and diabetes history. ", "The data were log‐transformed because they were not normally distributed. ", "WW17 stages were as follows: incipient, moderate, severe and advanced disease; periodontal profile class classification was as follows: stage I --health/incidental disease; stage II -- mild disease; stage III -- moderate disease; stage IV -- severe disease; stage V -- mild tooth loss/hi GI; stage VI -- moderate tooth loss; stage VII -- severe tooth loss. *", "\\*\\*\\*P *\\<* *.001 as compared with stage I](PRD-82-93-g007){#prd12269-fig-0007}\n\nThe influence of genetic control on interleukin‐1β production has been previously supported by twin studies, with an estimated 86% of the variance for interleukin‐1β production being genetically determined.[122](#prd12269-bib-0122){ref-type=\"ref\"} Among all genetic variations, two *IL1* gene variations (*IL1A* \\[−889; rs1800587\\] or the concordant *IL1A* \\[+4845; rs17561\\] and *IL1B* \\[+3954; rs1143634\\]) are the ones most studied and consistently associated with the progression and severity of periodontitis in Caucasians, with significant associations between the *IL1* variants and periodontitis reported for 19 of 27 studies and validated in two meta‐analyses.[123](#prd12269-bib-0123){ref-type=\"ref\"}, [124](#prd12269-bib-0124){ref-type=\"ref\"} A recent study correlated *IL1B* variations with periodontal disease in other non‐Caucasian ethnicities, including African‐Americans, Hispanic and Asians.[125](#prd12269-bib-0125){ref-type=\"ref\"} Data indicate that the *IL1* gene cluster, including *IL1A*,*IL1B* and *IL1RN* loci, impacts the amount of interleukin‐1β secretion.[126](#prd12269-bib-0126){ref-type=\"ref\"} It is suggested that the variants cause interleukin‐1 to be secreted at higher levels in gingival tissues, therefore contributing to the development and progression of disease. ", "A recent genome‐wide association study analysis carried out by our group in 4910 European‐American adults identified loci significantly (*P* \\< 5 × 10^−8^) associated with high gingival crevicular fluid‐interleukin‐1β in the *IL1* gene complex area of chromosome 2.[127](#prd12269-bib-0127){ref-type=\"ref\"} In this study, 72 single nucleotide polymorphisms were correlated with high gingival crevicular fluid‐interleukin‐1β (upper quartile), including 16 variants in the *IL1B* region (Table [1](#prd12269-tbl-0001){ref-type=\"table\"}). *", "IL1B* \\[+3954; rs1143634\\], which is part of the *IL1* genotype previously associated with periodontitis, is among the variants associated with high gingival crevicular fluid‐interleukin‐1β. ", "However, the periodontal phenotype of these individuals was not described in a genome‐wide association study data set. ", "Subjects with high interleukin‐1β levels were also more likely to have severe periodontitis, diabetes, high carotid intima‐media wall thickness, higher body mass index and to be heavier smokers.[127](#prd12269-bib-0127){ref-type=\"ref\"} To date, variants in the *IL1A‐IL1B* regions have been associated with coronary artery disease,[128](#prd12269-bib-0128){ref-type=\"ref\"} rheumatoid arthritis[129](#prd12269-bib-0129){ref-type=\"ref\"} and Behcet disease[130](#prd12269-bib-0130){ref-type=\"ref\"} in three meta‐analyses of candidate gene studies. ", "Together, this further supports that variants of the *IL1* gene can potentially alter the inflammatory response and predispose for diseases.", "\n\n###### \n\nIL1B gene variants significantly associated with high gingival crevicular fluid‐interleukin‐1β (upper quartile)[127](#prd12269-bib-0127){ref-type=\"ref\"}\n\n SNP ID Chromosome Closest gene reference *P*‐value\n --------------- ------------ ------------------------ --------------\n rs16944 2 *IL1B* 6.53E‐19\n rs1143627 2 *IL1B* 6.70E‐19\n rs2708916 2 *IL1B* 7.73E‐19\n rs10169916 2 *IL1B* 7.76E‐19\n rs2708914 2 *IL1B* 8.00E‐19\n rs2466446 2 *IL1B* 8.29E‐19\n rs13013349 2 *IL1B* 1.79E‐18\n rs6735739 2 *IL1B* 5.75E‐18\n rs12621220 2 *IL1B* 3.70E‐17\n rs1143623 2 *IL1B* 4.91E‐17\n rs12053091 2 *IL1B* 7.92E‐17\n rs13008855 2 *IL1B* 3.43E‐16\n rs11674397 2 *IL1B* 2.62E‐14\n rs4334503 2 *IL1B* 2.74E‐14\n **rs1143634** **2** ***IL1B*** **9.94E‐12**\n rs7596684 2 *IL1B* 4.08E‐10\n\nBold represents *IL1B* single nucleotide polymorphisms (SNPs) previously identified as a risk for periodontitis in candidate gene studies.", "\n\nJohn Wiley & Sons, Ltd\n\n5.7. ", "INTERLEUKIN‐18 {#prd12269-sec-0017}\n-------------------\n\nInterleukin‐18 belongs to the interleukin‐1 superfamily that was originally discovered as an interferon γ‐inducing factor.[131](#prd12269-bib-0131){ref-type=\"ref\"} It is secreted by a variety of cell types and strongly augments interferon‐γ production in natural killer cells and Th1 cells.[132](#prd12269-bib-0132){ref-type=\"ref\"} Although it is also a cytokine matured through inflammasome activation, the role of interleukin‐18 in diseases is significantly less explored as compared with interleukin‐1β.[2](#prd12269-bib-0002){ref-type=\"ref\"}, [132](#prd12269-bib-0132){ref-type=\"ref\"} The majority of studies exploring the impact of interleukin‐18 levels in diseases are related to a group of diseases named cryopyrin‐associated periodic syndromes, which are associated with gain‐of‐function mutations in NLRP3 mediated primarily by interleukin‐1β effects.[52](#prd12269-bib-0052){ref-type=\"ref\"}, [54](#prd12269-bib-0054){ref-type=\"ref\"}, [133](#prd12269-bib-0133){ref-type=\"ref\"} There is currently no study reporting periodontal disease parameters and cryopyrin‐associated periodic syndromes.", "\n\nInterleukin‐18 levels have previously been measured in gingival tissues and saliva samples of individuals with different oral disease status in small clinical studies. ", "Gingival tissues showed no difference in the levels of interleukin‐18 when comparing chronic periodontitis (n = 18), aggressive periodontitis (n = 12) and healthy (n = 9) individuals.[134](#prd12269-bib-0134){ref-type=\"ref\"} Saliva samples from nonsmoking individuals with chronic periodontitis showed significantly higher levels of interleukin‐18 (275.05 ± 289.46 pg/mL; mean ± SD) when compared with healthy controls (143.71 ± 103.68 pg/mL; mean ± SD).[135](#prd12269-bib-0135){ref-type=\"ref\"} Candidate gene studies evaluating polymorphisms have not identified single nucleotide polymorphisms in the *IL18* region correlated with periodontal disease.[136](#prd12269-bib-0136){ref-type=\"ref\"}\n\nThe current evidence suggests that biological alterations of the inflammasome, either by genetic variations or priming, are correlated with the development of different complex diseases. ", "Inflammasome dysregulation appears to lead to a defective bacterial clearance and impaired epithelial/mucosal barrier function that is translated to disease predisposition. ", "Clinical comorbidity of some inflammasome‐driven entities with periodontal disease further supports this concept. ", "Although previous twin studies suggest that 50% of the variance of periodontal disease has a genetic composition, it is clear that this will not be explained by a single altered protein. ", "A genome‐wide association study and candidate gene studies in type 2 diabetes concluded that all associated variants identified affected the risk of disease by \\<40%, and most affected risk by closer to 15%.[137](#prd12269-bib-0137){ref-type=\"ref\"}, [138](#prd12269-bib-0138){ref-type=\"ref\"}, [139](#prd12269-bib-0139){ref-type=\"ref\"} As previously suggested, it appears that periodontal disease is actually a group of distinct biological conditions with similar overlapping clinical presentations.[127](#prd12269-bib-0127){ref-type=\"ref\"} The challenge is to identify these different groups of periodontal disease in order to target individual biological alterations that will lead to improved and tailored therapies.", "\n\n6. ", "THERAPEUTICS TARGETING THE INFLAMMASOME {#prd12269-sec-0018}\n==========================================\n\nThe host response is well recognized as a major contributor to periodontal tissue damage by supporting a nonresolving inflammation and dysbiosis.[140](#prd12269-bib-0140){ref-type=\"ref\"} It is acknowledged that most of the biological approaches to improve periodontal treatment have been focusing on direct microbial management (antibiotic treatments) rather than approaches that will modulate the host response.[141](#prd12269-bib-0141){ref-type=\"ref\"} The inappropriate inflammasome activity with continuous production of proinflammatory cytokines is believed to contribute to the development of many diseases. ", "Therefore, inhibitors/antagonists targeting inflammasome components, activation status and cytokine production are an attractive approach for treating periodontal disease.", "\n\nIt is important to clarify that upregulation (priming) of inflammasome components (NLRP3, AIM2, IFI16, caspase‐1, pro‐interleukin‐1β) in a tissue is only the first step of inflammasome activation (Figure [2](#prd12269-fig-0002){ref-type=\"fig\"}). ", "Multiple PAMPs and DAMPs will cause these priming events by binding to their cognate receptors and inducing upregulation. ", "Although this does not imply inflammasome activation, protein overexpression (priming) in diseased tissues is currently used as an indicator for a rationale of therapeutic targeting of inflammasome activation in several diseases.[5](#prd12269-bib-0005){ref-type=\"ref\"}, [52](#prd12269-bib-0052){ref-type=\"ref\"}\n\nAlthough most of these inhibitor/antagonist treatments are given via oral/subcutaneous routes, as reaching most inflamed tissues requires systemic processing and access to diseased tissues, the easy access to a periodontal pocket provides the opportunity for direct drug delivery that is potentially possible depending on the chemical composition of the drug. ", "Intrapapillary injections were previously administrated for drugs targeting of interleukin‐1 and tumor necrosis factor activity in experimental periodontitis in primates.[142](#prd12269-bib-0142){ref-type=\"ref\"} Diseases like osteoarthritis are also being approached by using drugs that are formulated in the form of a gel, such as OLT1177, rather than systemic administration.", "\n\nIn this section we will discuss clinical and preclinical studies evaluating different strategies that target inflammasomes as a therapeutic approach. ", "We will not include pathways involved in priming of inflammasomes, which would include multiple PRRs and signaling pathways. ", "Although there is broad evidence that lipoxins and resolvins broadly decrease inflammation in diseases (including periodontal disease), the data suggest that they mostly affect the inflammasomes at the priming stage[143](#prd12269-bib-0143){ref-type=\"ref\"}, [144](#prd12269-bib-0144){ref-type=\"ref\"} and, therefore, will not be discussed in this review. ", "Therapeutic inhibition or suppression of the inflammasome can be targeted by three strategies:\n\nInhibiting the upstream intracellular signaling pathwaysBlocking inflammasome componentsInhibiting inflammasome‐mediated cytokines (interleukin‐1β and interleukin‐18)\n\n6.1. ", "Inhibiting the upstream intracellular signaling pathways {#prd12269-sec-0019}\n-------------------------------------------------------------\n\nThere are multiple upstream signals that can lead to NLRP3 inflammasome activation, including K^+^, Ca^2+^ and Cl^−^ flux, lysosomal disruption, mitochondrial damage and release of reactive oxygen species. ", "Most pathways converge on mitochondrial stress and, with the exception of viral activation, also leads to the release of reactive oxygen species. ", "The relevance of oxidative parameters in periodontal disease has been previously proposed, with periodontal disease associated with decreased saliva antioxidants and increased oxidative damage.[145](#prd12269-bib-0145){ref-type=\"ref\"}, [146](#prd12269-bib-0146){ref-type=\"ref\"}, [147](#prd12269-bib-0147){ref-type=\"ref\"} Therefore, we will discuss current trials using drugs that decrease the production of reactive oxygen species and further inflammasome activation. ", "Reactive oxygen species produced in the cell (potentially by mitochondria) are known as direct or indirect activators of the NLRP3 inflammasome.", "\n\nAllopurinol (Zyloprim/Aloprim®) is one of the drugs discovered in the Burroughs Wellcome program that started in the 1940s that led to the 1988 Nobel Prize in Physiology and Medicine award to Gertrude B. Elion and George H. Hitchings, shared with James W. Black, for \"discoveries of important principles for drug treatment\".[148](#prd12269-bib-0148){ref-type=\"ref\"} Allopurinol is the prototypical xanthine oxidase inhibitor that has been in the market for decades and is considered a standard treatment of hyperuricemia associated with treating gout (a form of arthritis that is NLRP3 inflammasome dependent[149](#prd12269-bib-0149){ref-type=\"ref\"}) and kidney stones.[148](#prd12269-bib-0148){ref-type=\"ref\"} The drug is being tested for treating individuals with type 2 diabetes and has reached phase III trials after promising results in experimental diabetes murine models (Table [2](#prd12269-tbl-0002){ref-type=\"table\"}).", "\n\n###### \n\nDrugs inhibiting inflammasome components\n\n Direct inhibitor Condition tested Inhibition mechanism Inflammasome component Clinical status ClinicalTrials.", "Gov References\n ----------------------------------------- -------------------------------------------------------------- --------------------------------------------------------------------------------------- ------------------------- ---------------------------------------------------------------------------------------------------- ------------------------------------------------------------- -------------------------------------------\n Allopurinol (Zyloprim) Diabetes mellitus (type 2) Inhibition of xanthine oxidase, reduction of uric acid Reactive oxygen species Approved for treatment of gout and kidney stonesDiabetic neuropathy phase III testing NCT02533648 NCT00430248 [174](#prd12269-bib-0174){ref-type=\"ref\"}\n SS‐31 (Elamipretide, Bendavia, MTP‐131) Heart failure, primary mitochondrial disease, Barth syndrome Stabilization of cardiolipin (mitochondrial membrane component) Reactive oxygen species Approved for treatment of gout and kidney stones;Heart failure phase I testingPMD phase II testing NCT02814097 NCT02976038 NCT03098797 NCT03323749 NCT02388464 [151](#prd12269-bib-0151){ref-type=\"ref\"}\n Nicotinamide riboside (NR) Atherosclerosis, diabetes, Coronary artery disease Activation of SIRT3, blunting of NLRP3 response similar to what occurs during fasting Reactive oxygen species Available as dietary supplement;Phase II completed to evaluate effects on immune response NCT02812238 [175](#prd12269-bib-0175){ref-type=\"ref\"}\n\nJohn Wiley & Sons, Ltd\n\nAnother antioxidant drug being evaluated in clinical trials is being tested for the treatment of several inflammatory conditions by stabilizing a phospholipid that is exclusively expressed in the inner mitochondrial membrane, named cardiolipin. ", "The therapeutic drug SS‐31 (Elamipretide, Bendavia, MTP‐131) is member of the Szeto‐Schiller (SS) peptides that selectively targets and stabilizes cardiolipin in the inner mitochondrial membrane. ", "This stabilization prevents excessive reactive oxygen species production and preserves the electron carrying function of cytochrome c. The drug currently shows benefits on treating highly complex diseases that share a pathogenesis of bioenergetics failure as mitochondrial dysfunctions result in insufficient energy to maintain cell function (Table [2](#prd12269-tbl-0002){ref-type=\"table\"}).[150](#prd12269-bib-0150){ref-type=\"ref\"}, [151](#prd12269-bib-0151){ref-type=\"ref\"} No preclinical or clinical studies evaluating these drugs were identified in the periodontal field.", "\n\n6.2. ", "Blocking inflammasome components {#prd12269-sec-0020}\n-------------------------------------\n\n### 6.2.1. ", "Caspase‐1 {#prd12269-sec-0021}\n\nCaspase‐1 activation precedes interleukin‐1β and interleukin‐18 release after inflammasome activation. ", "Three drugs targeting caspase‐1, Emricasan, VX‐740 (Pralnacasan) and VX‐765, have been tested in humans.[52](#prd12269-bib-0052){ref-type=\"ref\"}, [152](#prd12269-bib-0152){ref-type=\"ref\"} The most developed caspase‐1 inhibitor for therapeutic use is VX‐765, a reversible inhibitor of caspase‐1 that is metabolized by plasma esterases into its active form.[153](#prd12269-bib-0153){ref-type=\"ref\"} VX‐765 has been used for treating psoriasis and epilepsy, reaching phase II clinical trials (Table [3](#prd12269-tbl-0003){ref-type=\"table\"}).[154](#prd12269-bib-0154){ref-type=\"ref\"}\n\n###### \n\nDrugs blocking inflammasome components\n\n Direct inhibitor Condition tested Inhibition mechanism Inflammasome component Clinical status ClinicalTrials.", "Gov References\n ----------------------- -------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------- ------------------------ -------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------- --------------------------------------------------------------------------------------\n VX‐765 Psoriasis, epilepsy Inhibition of caspase‐1 Caspase‐1 Psoriasis phase II testing completedAlveolar bone loss inhibition in experimental periodontitis NCT00205465 NCT01048255 NCT01501383 [176](#prd12269-bib-0176){ref-type=\"ref\"}\n Ibrutinib (Imbruvica) Mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom\\'s macroglobulinemia Inhibitor of Bruton\\'s tyrosine kinase (BTK) (inhibits ASC phosphorylation) NLRP3 Approved for treatment of B cell cancersChronic graft‐vs‐host disease phase I testingAlveolar bone loss inhibition in experimental periodontitis NCT01578707 NCT03604692 [156](#prd12269-bib-0156){ref-type=\"ref\"}, [157](#prd12269-bib-0157){ref-type=\"ref\"}\n IDN‐6556 Emricasan Diabetes, nonalcoholic steatohepatitis Pan‐caspase inhibitor; prevents excessive apoptosis Caspase‐1 \"Fast‐track\" status for development of nonalcoholic steatohepatitis cirrhosisDiabetes phase II tested NCT01653899 NCT03205345 [177](#prd12269-bib-0177){ref-type=\"ref\"}\n Colchicine (Colcrys) Gout, familial Mediterranean fever, Behcet\\'s disease Blockage of tubulin assembly, inhibition of NLRP3 and interleukin‐1β processing and release NLRP3 and pyrin Approved for treatment of gout and familial Mediterranean fever NCT02145589 NCT00506883 [159](#prd12269-bib-0159){ref-type=\"ref\"}\n OLT‐1177 Dapansutrile Heart failure, osteoarthritis, Schnitzler syndrome Prevents oligomerization, inhibiting NLRP3‐ASC interaction, and NLRP3‐caspase‐1 interaction NLRP3 Heart failure phase I testingPhase II for Schnitzler syndrome NCT03595371 NCT03534297 NCT01768975 [178](#prd12269-bib-0178){ref-type=\"ref\"}\n\nJohn Wiley & Sons, Ltd\n\nIn order to gain a greater understanding of the effect of caspase‐1 inhibition in the periodontal host response, we administrated the caspase‐1 inhibitor VX‐765 using a protocol previously shown to decrease bone loss in murine osteoarthritis.[155](#prd12269-bib-0155){ref-type=\"ref\"} Male mice received daily oral dosages of 100 mg/kg of VX‐765 for 11 days, with the drug administration starting 1 day prior to the ligature placement and bone loss was monitored after 10 days. ", "Our micro‐computed tomography results show that caspase‐1 inhibition significantly decreased \\~50% of alveolar bone loss that is normally observed in this model of disease (Figure [8](#prd12269-fig-0008){ref-type=\"fig\"}). ", "The preliminary result further supports the concept of manipulation of inflammasome components to treat periodontitis.", "\n\n{ref-type=\"ref\"} A‐C, Mean representative images of each group showing alveolar bone loss at 9 days postligature placement. ", "D, Measurements taken from the alveolar bone crest (ABC) to the cementum‐enamel junction (CEJ) show significant inhibition of alveolar bone loss as compared with vehicle control. *", "\\*P *\\<* *.05, *\\*\\*\\*P *\\<* *.001](PRD-82-93-g008){#prd12269-fig-0008}\n\n### 6.2.2. ", "Bruton\\'s tyrosine kinase {#prd12269-sec-0022}\n\nBruton\\'s tyrosine kinase (BTK) is a nonreceptor tyrosine kinase, most prominently known for its indispensable role during B cell development. ", "During the activation of the NLRP3 inflammasome, BTK has been shown to interact with NLRP3 and ASC.[156](#prd12269-bib-0156){ref-type=\"ref\"} The interaction of BTK with ASC is crucial for ASC oligomerization during NLRP3 inflammasome activation. ", "Although it is not clear whether BTK directly phosphorylates ASC, the kinase activity of BTK is essential for ASC oligomerization and NLRP3 inflammasome activation. ", "The BTK inhibitor ibrutinib (PCI‐32765, Imbruvica) is a Food and Drug Administration‐approved drug for the treatment of a number of B cell cancers, including mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström\\'s macroglobulinemia and marginal zone lymphoma (Table [3](#prd12269-tbl-0003){ref-type=\"table\"}). ", "It is an orally available, selective inhibitor of BTK that inhibits the signaling of B cell chemotaxis and is mostly known for its antitumor and antimetastatic efficacy. ", "In addition to the treatment of different B cell cancers, it is currently being tested to treat chronic graft‐vs‐host disease (Table [3](#prd12269-tbl-0003){ref-type=\"table\"}). ", "Inhibition of BTK by pharmacological or genetic means severely impairs activation of the NLRP3 inflammasome. ", "BTK inhibitor efficiently suppresses infarct volume growth and neurological damage in a brain ischemia/reperfusion model in mice.[156](#prd12269-bib-0156){ref-type=\"ref\"}\n\nRecently, another BTK inhibitor, acalabrutinib (ACP‐196), has been evaluated for its potential to prevent alveolar bone loss in experimental periodontitis.[157](#prd12269-bib-0157){ref-type=\"ref\"} In this study, mice that received intragingival injections of *P. gingivalis*‐derived lipopolysaccharide were also given intraperitoneal injection of acalabrutinib (0.5 mg/kg on days 1, 4 and 7 postligature placement). ", "The results showed that BTK inhibitor ACP‐196 altered osteoclastogenesis and significantly decreased alveolar bone loss by approximately 50% compared with controls. ", "Although the role of inflammasomes was not explored in this study, it is possible that the effect of BTK initiated upstream by binding to NLRP3 and later affecting osteoclastogenesis.[65](#prd12269-bib-0065){ref-type=\"ref\"} The study suggests that inhibition of BTK is a plausible treatment for bone loss during periodontal disease development.", "\n\n### 6.2.3. ", "NLRP3 and pyrin inflammasomes {#prd12269-sec-0023}\n\nNLRP3 and pyrin inflammasomes are proposed to recognize perturbations in cellular homeostasis, which is a unique feature when compared with other well‐characterized inflammasomes that recognize PAMPs and DAMPs directly (like AIM2, IFI16). ", "NLRP3 components are one of the main targets currently being evaluated to treat a range of diseases in clinical trials, including heart failure, osteoarthritis, leukemia, psoriasis, diabetes and nonalcoholic steatohepatitis (Table [3](#prd12269-tbl-0003){ref-type=\"table\"}).[52](#prd12269-bib-0052){ref-type=\"ref\"}\n\nColchicine is a therapeutic agent used to treat diseases for over 3000 years that has been Food and Drug Administration approved to treat gout (a form of arthritis) in the USA since 2009.[158](#prd12269-bib-0158){ref-type=\"ref\"} Colchicine has been studied for its anti‐inflammatory, antioxidant, antimitotic and bone‐protective effects. ", "The primary mechanism of action of colchicine is tubulin disruption, which blocks microtubule assembly and impacts several innate immune pathways, including NLRP3 and pyrin‐inflammasome activation.[54](#prd12269-bib-0054){ref-type=\"ref\"}, [159](#prd12269-bib-0159){ref-type=\"ref\"}, [160](#prd12269-bib-0160){ref-type=\"ref\"} The spatial arrangement and relocalization of NLRP3 and pyrin inflammasome components during activation is driven by microtubulin dynamics.[90](#prd12269-bib-0090){ref-type=\"ref\"}, [91](#prd12269-bib-0091){ref-type=\"ref\"} Colchicine is used in the treatment of the inflammasome‐mediated diseases familial Mediterranean fever[160](#prd12269-bib-0160){ref-type=\"ref\"}, [161](#prd12269-bib-0161){ref-type=\"ref\"} and gout,[162](#prd12269-bib-0162){ref-type=\"ref\"} as well as cardiac disease (Table [3](#prd12269-tbl-0003){ref-type=\"table\"}).[163](#prd12269-bib-0163){ref-type=\"ref\"} The effects of colchicine as a therapeutic agent were recently evaluated in experimental periodontitis.[164](#prd12269-bib-0164){ref-type=\"ref\"} Preliminary evidence indicates that colchicine inhibited ligature‐induced periodontitis in rats at both dosages tested (intraperitoneal injections, 30 and 100 μg/kg/d) when compared with vehicle control in an 11‐day time course experiment.[164](#prd12269-bib-0164){ref-type=\"ref\"} Among the cytokines evaluated, gingival tissue interleukin‐1β levels significantly decreased to half during colchicine treatment (\\~800 pg/mL in periodontitis and \\~400 pg/mL at baseline and after providing both dosages of colchicine). ", "The data indicate a general decrease in inflammation via the administration of colchicine that could be, in part, due to NLRP3 and/or pyrin inflammasomes.", "\n\n6.3. ", "Inhibiting inflammasome‐mediated cytokines {#prd12269-sec-0024}\n-----------------------------------------------\n\n### 6.3.1. ", "Interleukin‐1β {#prd12269-sec-0025}\n\nInterleukin‐1β is the most potent proinflammatory cytokine released by activation of inflammasomes and is implicated as the effector molecule in many inflammasome‐driven diseases.[52](#prd12269-bib-0052){ref-type=\"ref\"}, [165](#prd12269-bib-0165){ref-type=\"ref\"} Global inhibition of interleukin‐1β is currently used in the clinical setting by either a monoclonal antibody targeting interleukin‐1β (canakinumab), by a modified interleukin‐1β receptor antagonist (anakinra) or by a soluble decoy receptor (rilonacept). ", "These approved drugs are being used to treat rheumatoid arthritis,[166](#prd12269-bib-0166){ref-type=\"ref\"} atherosclerotic disease[167](#prd12269-bib-0167){ref-type=\"ref\"} and diabetes,[168](#prd12269-bib-0168){ref-type=\"ref\"} with promising results (Table [4](#prd12269-tbl-0004){ref-type=\"table\"}). ", "Among the therapeutic interventions, the CANTOS trial, with 10 061 individuals, recently demonstrated that individuals receiving 150 mg of canakinumab subcutaneously every 3 months had a significant lower rate of recurrent cardiovascular events than placebo.[167](#prd12269-bib-0167){ref-type=\"ref\"} It is important to note that these drugs are shown to moderately increase the risk of infection and there are currently no specific prevention strategies being recommended.[169](#prd12269-bib-0169){ref-type=\"ref\"} It is speculated that further understanding of the inflammasomes will allow targeting of other components more specific to different inflammasomes that could be less immune‐suppressive than a global interleukin‐1 therapy.[52](#prd12269-bib-0052){ref-type=\"ref\"} However, the CANTOS trials were received with enthusiasm in the medical field, given that many treatments have proven to be unsuccessful in treating coronary disease. ", "It is important to note that canakinumab was associated with a small but statistically significant risk of fatal infection but still had no effect on all‐cause mortality. ", "Of interest, a prespecified analysis demonstrated a reduction in the incidence of lung cancer in the pooled canakinumab population (*P* = .0001 for trend across groups) and a reduction in lung cancer‐related mortality (*P* = .0002). ", "Therefore, the CANTOS trial can be acknowledged as a landmark trial for its bold achievement in translating state of the art biology to the bed side to examine the true importance of inhibiting interleukin‐1β in diseased individuals. ", "The results of the trial may act as a strong stimulus to trial other safer, more widely available, less expensive therapies capable of inhibiting the inflammasome.[170](#prd12269-bib-0170){ref-type=\"ref\"}\n\n###### \n\nDrugs inhibiting final products of inflammasomes\n\n Direct inhibitor Condition tested Inhibition mechanism Inflammasome component Clinical status ClinicalTrials.", "Gov References\n --------------------------------- ----------------------------------------------------------------------- ------------------------------------------------------------------------------------------- -------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------- --------------------------------------------------------------------------------------\n Canakinumab, ACZ885 (ILARIS) RA, atherosclerosis Monoclonal antibody targeting interleukin‐1β Interleukin‐1β Approved for treatment of cryopyrin‐associated periodic syndromes and systemic juvenile idiopathic arthritis;Rheumatoid arthritis phase II testing terminatedAtherosclerosis phase II completed NCT00505089 [167](#prd12269-bib-0167){ref-type=\"ref\"}, [179](#prd12269-bib-0179){ref-type=\"ref\"}\n Rilonacept IL‐1 trap (Arcalyst) Cryopyrin‐associated periodic syndromes, familial Mediterranean fever Binds and neutralizes interleukin‐1 Interleukin‐1 Cryopyrin‐associated periodic syndromes phase II testing completedFamilial Mediterranean fever phase II testing completed NCT00288704 NCT01045772 NCT00582907 [180](#prd12269-bib-0180){ref-type=\"ref\"}\n Anakinra (Kineret) Rheumatoid arthritis, familial Mediterranean fever Blocks interleukin‐1 binding via competitive inhibition of interleukin‐1 type I receptors Interleukin‐1 receptor Approved for treatment of rheumatoid arthritisFamilial Mediterranean fever phase III testing completed NCT01705756 [181](#prd12269-bib-0181){ref-type=\"ref\"}\n GSK1070806 (anti‐IL‐18) Diabetes mellitus (type 2), Behcet\\'s disease Neutralization of interleukin‐18 Downstream Th1 cytokines, including interleukin‐1β; serum interleukin‐18 Diabetes mellitus (type 2, phase II completed, no effect observed)Behcet\\'s disease phase II testing NCT01035645 NCT03522662 NCT01648153 [171](#prd12269-bib-0171){ref-type=\"ref\"}\n\nJohn Wiley & Sons, Ltd\n\nIn primate experimental periodontitis, a combined treatment to block interleukin‐1 and tumor necrosis factor activity demonstrated a significant 50% reduction of levels of radiographic bone loss over that found in control sites.[142](#prd12269-bib-0142){ref-type=\"ref\"} The regimen provided was a three times per week intrapapillary injections of soluble human recombinant interleukin‐1 receptor consisting of the extracellular domain of the type I receptor and a fusion protein consisting of the extracellular domain of TNFR‐2 linked to the Fc portion of a human IgG1 over a 6‐week period. ", "The result suggests both interleukin‐1β and tumor necrosis factor‐α as potential target treatments for periodontal disease. ", "Therefore, targeting other inflammasome components prior to interleukin‐1β secretion may provide alternative paths for modulating the periodontal host response.", "\n\n### 6.3.2. ", "Interleukin‐18 {#prd12269-sec-0026}\n\nThe relevance of interleukin‐18 in disease pathogenesis is less explored compared with interleukin‐1β, translating into fewer trials evaluating interleukin‐18 blockade as a strategy for therapy. ", "A small sample study in diabetes concluded that although the usage of GSK1070806, an anti‐interleukin‐18 monoclonal antibody, was well tolerated, inhibition of interleukin‐18 did not lead to any improvements in glucose control.[171](#prd12269-bib-0171){ref-type=\"ref\"} Evaluation of therapeutics targeting interleukin‐18 for treating periodontal disease still requires further biological justification.", "\n\nAdditional inflammasome inhibitors targeting reactive oxygen species, caspase‐1, NLRP3 and pyrin are under clinical trials for treating several diseases (Tables [2](#prd12269-tbl-0002){ref-type=\"table\"}, [3](#prd12269-tbl-0003){ref-type=\"table\"}, [4](#prd12269-tbl-0004){ref-type=\"table\"}). ", "The data we evaluated support a role for inflammasomes in periodontal disease. ", "Therefore, testing of their therapeutic efficacy in periodontal disease is merited.", "\n\n7. ", "SUMMARY AND CONCLUSIONS {#prd12269-sec-0027}\n==========================\n\nThe literature supports that inflammasomes have a central role for microbe and damage sensing within the innate immune system and, as such, manipulation of its components is shown to be therapeutically beneficial. ", "Aberrant inflammasome activation is observed in diseased tissues derived from clinical and preclinical studies. ", "In autoinflammatory diseases such as Crohn\\'s disease and Behcet disease, genetic variations alter the protein function by auto‐activating or lowering the threshold for activation of inflammasomes that appears to affect clearance of pathogens and the integrity of the epithelial/mucosal barrier that normally protects the host. ", "Interestingly, the highlighted loci associated with a periodontal phenotype in a recent genome‐wide association study analysis included genes associated with immune response and epithelial barrier function.[107](#prd12269-bib-0107){ref-type=\"ref\"} In inflammatory diseases, such as atherosclerosis, diabetes and obesity, there is a chronic stimulus that primes and induces inflammasome activation. ", "The involvement of inflammasome components in periodontal health and subtypes of disease are in the early stages of exploration. ", "Are components shown to be expressed highly in diseased tissues the ones that will affect disease development in therapeutic approaches? ", "Is there an inflammasome pathway that can hamper periodontal disease development in patients? ", "Are there subtypes of periodontal disease that require different inflammasome targeting? ", "The data currently indicate that several inflammasome components are expressed at higher levels in saliva, gingival crevicular fluid and periodontal tissues. ", "Individuals with autoinflammatory disease may have different biological pathways that lead to periodontal disease. ", "It is unknown if the biological pathways that lead to aberrant inflammasome activation in chronic diseases also affect the periodontal host response. ", "There is strong impetus for further clarification of the role of inflammasome pathways as targets for treating periodontal disease.", "\n\nThis review was supported by the University of North Carolina at Chapel Hill and through grant K01DE027087 by the National Institute of Dental and Craniofacial Research (National Institutes of Health) awarded to J.T.M, K99DE027086 (NIDCR) awarded to S.Z. and through grant KL2TR002490 awarded to K.V.S. We would also like to thank Ms. Alexandra Gunn for help with designing the figures used in this manuscript and Dr Tom Van Dyke for revising this manuscript. ", "The Dental Atherosclerosis Risk in Communities (ARIC) study is carried out as a collaborative study supported by the National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HSN268201100012C) and grants (R01HL087641, R01HL59367, R01HL086694); the National Human Genome Research Institute (contract U01HG004402); the National Institutes of Health (NIH; contract HHSN268200625226C); the National Institute of Environmental Health Sciences (grant P30ES010126); and the National Institute of Dental and Craniofacial Research (grants R01DE11551, R01DE021418). ", "Infrastructure was partially supported by a component of the NIH and NIH Roadmap for Medical Research (grant UL1RR025005).", "\n" ]

{ "pile_set_name": "PubMed Central" }

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[ "/*\n This program is free software: you can redistribute it and/or modify\n it under the terms of the GNU General Public License as published by\n the Free Software Foundation, either version 3 of the License, or\n (at your option) any later version.", "\n\n This program is distributed in the hope that it will be useful,\n but WITHOUT ANY WARRANTY; without even the implied warranty of\n MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. ", " See the\n GNU General Public License for more details.", "\n\n You should have received a copy of the GNU General Public License\n along with this program. ", " If not, see <http://www.gnu.org/licenses/>.", "\n */\n#pragma once\n\nclass Empty::OpticalFlow : public AP_HAL::OpticalFlow {\npublic:\n void init() { }\n bool read(Data_Frame& frame) { return false; }\n void push_gyro(float gyro_x, float gyro_y, float dt) { };\n void push_gyro_bias(float gyro_bias_x, float gyro_bias_y) { }\n};\n" ]

{ "pile_set_name": "Github" }

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[ " NOT PRECEDENTIAL\n\n UNITED STATES COURT OF APPEALS\n FOR THE THIRD CIRCUIT\n _____________\n\n No. ", "18-3607\n _____________\n\n UNITED STATES OF AMERICA\n\n v.\n\n LEE SOKALSKY,\n Appellant\n\n\n On Appeal from the United States District Court\n for the Middle District of Pennsylvania\n District Court No. ", "3-15-cr-00040-001\n District Judge: The Honorable Robert D. Mariani\n\n Submitted Pursuant to Third Circuit L.A.R. 34.1(a)\n March 6, 2020\n\n Before: SMITH, Chief Judge, HARDIMAN, and KRAUSE, Circuit Judges\n\n (Filed: March 9, 2020)\n _____________________\n\n OPINION*\n _____________________\n\nSMITH, Chief Judge.", "\n\n\n\n\n*\n This disposition is not an opinion of the full Court and pursuant to I.O.P. 5.7 does\nnot constitute binding precedent.", "\n\f Lee Sokalsky pleaded guilty to four counts of bank robbery by force,\n\nviolence or intimidation in violation of 18 U.S.C. § 2113(a). ", "The presentence\n\ninvestigation report classified Sokalsky as a career offender under United States\n\nSentencing Guideline (U.S.S.G.) § 4B1.1. ", "Sokalsky objected to the career offender\n\nclassification, arguing that the § 2113(a) offense did not constitute a crime of\n\nviolence as defined in U.S.S.G. § 4B1.2(a). ", "The District Court disagreed and\n\nsentenced Sokalsky to 151 months of incarceration on each count to run\n\nconcurrently. ", "This timely appeal followed. ", "1 We will affirm.", "\n\n The only issue on appeal is whether bank robbery by intimidation under\n\n§ 2113(a) categorically constitutes a crime of violence. ", "We exercise plenary\n\nreview of a district court’s decision that a conviction qualifies as a crime of\n\nviolence under U.S.S.G. § 4B1.2(a). ", "United States v. Wilson, 880 F.3d 80, 83 (3d\n\nCir. ", "2018).", "\n\n Sokalsky acknowledges that in Wilson, we “join[ed] our sister circuits in\n\nholding that bank robbery by intimidation, as set forth in [18 U.S.C.] § 2113(a),\n\ncategorically qualifies as a crime of violence under [U.S.S.G.] § 4B1.2(a)’s\n\n‘elements’ clause.” ", "Id. at 88. ", "Nonetheless, he asserts that Wilson “was wrongly\n\ndecided.” ", "Appellant’s Br. ", "12. ", "Wilson is binding on this panel. ", "See 3d Cir. ", "I.O.P.\n\n\n1\n The United States District Court for the Middle District of Pennsylvania had\njurisdiction pursuant to 18 U.S.C. § 3231. ", "This Court has jurisdiction pursuant to\n28 U.S.C. § 1291 and 18 U.S.C. § 3742(a).", "\n 2\n\f9.1 (2018). ", "Accordingly, we conclude that the District Court did not err by\n\napplying § 4B1.1’s career-offender enhancement in this case. ", "We will affirm.", "\n\n\n\n\n 3\n\f" ]

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[ "/*\n * Copyright (c) 2005, 2014, Oracle and/or its affiliates. ", "All rights reserved.", "\n * DO NOT ALTER OR REMOVE COPYRIGHT NOTICES OR THIS FILE HEADER.", "\n *\n * This code is free software; you can redistribute it and/or modify it\n * under the terms of the GNU General Public License version 2 only, as\n * published by the Free Software Foundation. ", " Oracle designates this\n * particular file as subject to the \"Classpath\" exception as provided\n * by Oracle in the LICENSE file that accompanied this code.", "\n *\n * This code is distributed in the hope that it will be useful, but WITHOUT\n * ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or\n * FITNESS FOR A PARTICULAR PURPOSE. ", " See the GNU General Public License\n * version 2 for more details (a copy is included in the LICENSE file that\n * accompanied this code).", "\n *\n * You should have received a copy of the GNU General Public License version\n * 2 along with this work; if not, write to the Free Software Foundation,\n * Inc., 51 Franklin St, Fifth Floor, Boston, MA 02110-1301 USA.", "\n *\n * Please contact Oracle, 500 Oracle Parkway, Redwood Shores, CA 94065 USA\n * or visit www.oracle.com if you need additional information or have any\n * questions.", "\n */\n/*\n * $Id: PGPData.java,v 1.4 2005/05/10 16:35:35 mullan Exp $\n */\npackage javax.xml.crypto.dsig.keyinfo;\n\nimport java.util.", "Collections;\nimport java.util.", "List;\nimport javax.xml.crypto.", "XMLStructure;\n\n/**\n * A representation of the XML <code>PGPData</code> element as defined in\n * the <a href=\"http://www.w3.org/TR/xmldsig-core/\">\n * W3C Recommendation for XML-Signature Syntax and Processing</a>. ", "A\n * <code>PGPData</code> object is used to convey information related to\n * PGP public key pairs and signatures on such keys. ", "The XML Schema Definition\n * is defined as:\n *\n * <pre>\n * &lt;element name=\"PGPData\" type=\"ds:PGPDataType\"/&gt;\n * &lt;complexType name=\"PGPDataType\"&gt;\n * &lt;choice&gt;\n * &lt;sequence&gt;\n * &lt;element name=\"PGPKeyID\" type=\"base64Binary\"/&gt;\n * &lt;element name=\"PGPKeyPacket\" type=\"base64Binary\" minOccurs=\"0\"/&gt;\n * &lt;any namespace=\"##other\" processContents=\"lax\" minOccurs=\"0\"\n * maxOccurs=\"unbounded\"/&gt;\n * &lt;/sequence&gt;\n * &lt;sequence&gt;\n * &lt;element name=\"PGPKeyPacket\" type=\"base64Binary\"/&gt;\n * &lt;any namespace=\"##other\" processContents=\"lax\" minOccurs=\"0\"\n * maxOccurs=\"unbounded\"/&gt;\n * &lt;/sequence&gt;\n * &lt;/choice&gt;\n * &lt;/complexType&gt;\n * </pre>\n *\n * A <code>PGPData</code> instance may be created by invoking one of the\n * {@link KeyInfoFactory#newPGPData newPGPData} methods of the {@link\n * KeyInfoFactory} class, and passing it\n * <code>byte</code> arrays representing the contents of the PGP public key\n * identifier and/or PGP key material packet, and an optional list of\n * elements from an external namespace.", "\n *\n * @author Sean Mullan\n * @author JSR 105 Expert Group\n * @since 1.6\n * @see KeyInfoFactory#newPGPData(byte[])\n * @see KeyInfoFactory#newPGPData(byte[], byte[], List)\n * @see KeyInfoFactory#newPGPData(byte[], List)\n */\npublic interface PGPData extends XMLStructure {\n\n /**\n * URI identifying the PGPData KeyInfo type:\n * http://www.w3.org/2000/09/xmldsig#PGPData. ", "This can be specified as the\n * value of the <code>type</code> parameter of the {@link RetrievalMethod}\n * class to describe a remote <code>PGPData</code> structure.", "\n */\n final static String TYPE = \"http://www.w3.org/2000/09/xmldsig#PGPData\";\n\n /**\n * Returns the PGP public key identifier of this <code>PGPData</code> as\n * defined in <a href=\"http://www.ietf.org/rfc/rfc2440.txt\">RFC 2440</a>,\n * section 11.2.", "\n *\n * @return the PGP public key identifier (may be <code>null</code> if\n * not specified). ", "Each invocation of this method returns a new clone\n * to protect against subsequent modification.", "\n */\n byte[] getKeyId();\n\n /**\n * Returns the PGP key material packet of this <code>PGPData</code> as\n * defined in <a href=\"http://www.ietf.org/rfc/rfc2440.txt\">RFC 2440</a>,\n * section 5.5.", "\n *\n * @return the PGP key material packet (may be <code>null</code> if not\n * specified). ", "Each invocation of this method returns a new clone to\n * protect against subsequent modification.", "\n */\n byte[] getKeyPacket();\n\n /**\n * Returns an {@link Collections#unmodifiableList unmodifiable list}\n * of {@link XMLStructure}s representing elements from an external\n * namespace.", "\n *\n * @return an unmodifiable list of <code>XMLStructure</code>s (may be\n * empty, but never <code>null</code>)\n */\n List<XMLStructure> getExternalElements();\n}\n" ]

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[ "Q:\n\nfind: match to column, other than row\n\nI'm working through some reference/match logic and was wondering if anyone had an idea on how to go about this. ", "I've whipped up a tool like this in excel and a limited one in pi, but it would be nice to use r instead so I can tie it into a few other functions I have. ", "\nThere's a dataframe with three columns: 'table_name', 'columnfriendlyname', and 'iskey'. ", "\nWithin 'columnfriendlyname' includes the labels for regular field names, the names of foreign keys, and the names of primary keys. ", "\nWhat the table is supposed to to (hopefully), is append tags into the iskey, using the the nomenclature of the databases labels (found in columnfriendlyname). ", "\nThe logic goes: \n\nif in row, columnfriendlyname=table_name, then: is_key\n<-\"primary_key\"\nif out of row, columnfriendlyname=table_name, then: is_key\n<-\"foreign_key\"\nif no match at all columnfriendlyname!=table_name, then: is_key <-\"non_key\"\n\nI created a conditional insert based on the logic in this question here: R conditional lapply?", "\nand so far it works great for primary keys:\nprime<- (dict_data_raw$columnfriendlyname==dict_data_raw$table_name)==TRUE\ndict_data_raw$iskey[prime] <-\"Primary_key\"\n\nBut now I need to figure out == table_name, but !", "= table_name in row. ", "\nEdit: A sample of the data follows, if it helps to clarify:\n table_name columnfriendlyname is_key\n1 address address primary_key\n2 address entity foreign_key\n3 address zip non_key\n4 matter matter primary_key\n5 matter address foreign_key\n6 matter mattertype non_key\n7 entity entity primary_key\n8 entity address foreign_key\n9 entity dob non_key\n\nThanks for any help!", "\n\nA:\n\nYou could use a loop that uses ifelse like this:\nfor (x in 1:nrow(dict_data_raw)){\n dict_data_raw$iskey[x] <- ifelse(dict_data_raw$columnfriendlyname[x] == dict_data_raw$table_name[x], \"primary_key\", ifelse(dict_data_raw$columnfriendlyname[x] %in% dict_data_raw$table_name, \"foreign_key\", \"non_key\"))\n}\n\nOne row after another, it checks with the first ifelse if the value of columnfriendlyname is equal to table_name, writting \"primary_key\" if it is and, if it is not, checking with a second ifelse if the value in columnfriendlyname is within all the values in table_name. ", "If it is, writes \"foreign_key\", if it isn´t, writes \"non_key\".", "\nifelse checks if a condition is true or false and gives one value or another depending on that. ", "A second ifelse can be nested on the false value to solve your question.", "\nHope it helps!", "\n\n" ]

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[ "---\nauthor:\n- |\n A. Martínez Torres[^1], $\\,\\,$E. Oset[^2]\\\n \\\n \\\ntitle: 'Study of the $\\gamma d\\to K^{+}K^{-}np$ reaction and an alternative explanation for the “$\\Theta^{+}(1540)$ pentaquark” peak'\n---\n\nIntroduction\n============\n\nThe discovery of a peak in the $\\gamma \\, ^{12}C \\to K^+ K^- X$ reaction in the $K^+n$ invariant mass spectrum, which was identified as a signal for a pentaquark of positive strangeness, the $\\Theta^+$ [@nakaone], created a turmoil in the Hadron Physics Community and stimulated many theoretical and experimental works. ", "A large number of experiments were conducted, many of which found also the signal, but gradually other experiments were performed that did not produce the expected peak. ", "The number of theoretical works stimulated by this finding in the following years was of the order of one thousand and, whether they could or could not find a justification for the $\\Theta^+$ state, they gave collectively a big push towards the understanding of the hadronic spectra. ", "A comprehensive review of these developments was done after some time in [@hicks], were one can see the relevant literature on the subject. ", "More recently a new experiment was done at LEPS on a deuteron target, and with more statistics, and a clear peak was observed around 1526 MeV in the $K^+n$ invariant mass distribution [@nakatwo]. ", "While quite some evidence is given for the existence of the peak in [@nakatwo], it is not ruled out that it could be a consequence of the peculiar dynamics of the process, with the experimental set up and the cuts applied to see the peak, rather than the signal of a genuine new resonance. ", "The fact that the same reaction measured at CLASS with ten times more statistics and complete kinematics fails to see the $\\Theta^{+}$ peak [@kinnon], is certainly an incentive to search for some alternative explanation of the peak observed at LEPS. ", "A first thought comes to our mind: in the reaction of [@nakatwo], $\\gamma ~d \\to ~K^+ K^- ~n ~p $, the main contribution comes from $\\phi$ production, which is removed by particular cuts done in the $K^+ K^-$ invariant mass in [@nakatwo]. ", "This, together with the fact that the particles are detected in the forward direction could lead to some unwanted structure in the mass distribution of $K^+ ~n$. It should not be overlooked the fact that in [@nakatwo] only the $K^+$ and the $ K^-$ are detected, but not the $p$ and the $n$. The reconstruction of the $K^+ ~n$ invariant mass is done using a prescription to eliminate as much as possible the effects of Fermi motion and to have the $p$ as a spectator. ", "We shall show in the present paper that the prescription works to show peaks coming from genuine resonances, but also creates a distorted spectrum. ", "On the other hand, the procedure does not work in the reverse direction, and if a peak appears it is not necessarily an evidence of the presence of a resonance.", "\n\nThere is another issue which requires attention. ", "The experiment is done in deuterium, since one is interested in having the $K^+ ~n$ invariant mass. ", "This means one necessarily will have rescattering of the produced kaons. ", "Hence, assuming that a $\\phi$ is created and one of the kaons rescatters from a second nucleon, the rescattered kaon changes energy and direction and the reconstructed $K^+ K^-$ invariant mass does no longer match the original $\\phi$ from where the two kaons came from. ", "Since the $\\phi$ production counts for the largest part of the cross section in the experiment of [@nakatwo], it could be that this part of the amplitude accounts for a relatively sizable part of the total amplitude and through interference with the one body processes leads to a some kind of signal which might be misidentified in the analysis.", "\n\nThere are, thus, some reasons that make us think that some peak could be produced, not tied to the existence of a resonance but to this peculiar combination of dynamics, multiple scattering and cuts. ", "The present paper presents a thorough simulation of the physical process, using a theoretical model that accounts for $\\phi$ production and rescattering of the kaons. ", "The production of the $\\Lambda(1520)$ is also considered and the procedure to filter events with a nucleon as spectator is tested with this resonance. ", "The rescattering part versus the one body part of the amplitude is done accurately, using realistic deuteron wave functions and amplitudes for $K N \\to KN$ and $\\bar{K} N \\to \\bar{K}N$ constructed using chiral unitary dynamics.", "\n\nThe results obtained show that a peak around 1530 MeV for the invariant mass of the $K^+ n$ pair appears, even with large statistics, without having any $\\Theta^+$ term in the amplitude. ", "The peak obtained is broad. ", "However, with the statistics of the experiment of [@nakatwo], fluctuations appear often which can produce a narrower peak in that region, very similar to that obtained in [@nakatwo]. ", "We also show that it is possible, after some strength appears in that region with a predetermined set up, to obtain a sharper peak by changing a bit this set up. ", "All these findings give us strong reasons to think that the peak seen in [@nakatwo] obeys to this combination of facts related to the experimental set up and is not a signal for a new resonance.", "\n\nThe work proceeds as follows. ", "In section \\[forma\\] we explain the formalism to calculate the cross section for the process $\\gamma d\\to K^{+}K^{-}np$ with detail and the model to take into account the $\\phi$ and $\\Lambda(1520)$ productions. ", "In section \\[penphi\\] we show the $K^{+}n$ invariant mass distribution obtained with the same set up than at LEPS . ", "In section \\[in1520\\] we show the results that we obtain when we introduce the $\\Lambda(1520)$, in section \\[resca\\] the rescattering contribution and in section \\[sta1\\] we make a statistical analysis and compare with the results of LEPS, after which we draw our conclusions.", "\n\nFormalism {#forma}\n=========\n\nWhen trying to simulate the $\\gamma d\\to K^{+}K^{-}np$ reaction one must consider the basic features learned from the experiment in [@nakatwo]. ", "The most important contribution comes from $\\phi$ production, the elementary reaction $\\gamma p\\to \\phi p$ and $\\gamma n\\to \\phi n$. We will implement this $\\phi$ production in our simulation through a minimal model which incorporates the basic structure of $K^{+}K^{-}$ production correlated by the $\\phi$ propagator. ", "We will also take into account empirical information from [@nakaphi], from where one induces similar $\\phi$ cross section production from proton or neutron targets.", "\n\nAnother element in the dynamics of the $\\gamma d\\to K^{+}K^{-}np$ reaction is the production of the $\\Lambda(1520)$. Although its contribution to the process is small compared to that of $\\phi$ production, we will take advantage of it to test the method used in [@nakatwo] to eliminate Fermi motion in the reaction on deuteron.", "\n\nAn important ingredient in our approach is the rescattering that unavoidably occurs in the reaction in deuteron. ", "Indeed, consider a first step of $\\gamma p\\to \\phi p\\to K^{+}K^{-}p$ and then a rescattering of the $K^{+}$ or the $K^{-}$ with the neutron. ", "This double scattering step can be evaluated theoretically, and its ratio to the first step $\\gamma p\\to\\phi p$ can be calculated rather reliably. ", "This is so since uncertainties in the elementary $\\phi$ production model cancel in the ratio and the rest roughly requires the knowledge of the deuteron wave function and the scattering amplitude of $K^{+}$ ($K^{-}$) with the nucleons, which one has rather under control from studies of the $\\bar{K}N$ and $KN$ interaction using unitary chiral dynamics [@ramos; @bennhold; @meissner; @meissner2; @magas; @felipe].", "\n\n![(", "Color online) Diagrammatic representation of the model for the $\\gamma d\\to K^{+}K^{-}np$ reaction.[]{data-label=\"model\"}](diagrams.eps){width=\"\\textwidth\"}\n\nThe consideration of the rescattering is important in principle in this simulation. ", "Indeed, the $\\phi$ production takes the largest strength of the $\\gamma p\\to K^{+} K^{-}p$ reaction in the energy region of LEPS. ", "Yet, with the cuts of LEPS one removes this contribution, that would show up as a large background on the $K^{+}n$ spectrum precluding the observation of some smaller signal. ", "However, if one has $\\phi$ production and rescattering of one of the kaons, this latter kaon will change energy and direction upon rescattering, such that when the cut on the $K^{+}K^{-}$ invariant mass is implemented, these events are not removed. ", "The kinematics of these events coming from a primary $\\phi$ production is very peculiar, such that it is not unlikely that they could lead to some peak in the $K^{+}n$ invariant mass distribution which could be misidentified as a signal of some resonance.", "\n\nThe model that we take is depicted diagrammatically in Fig. ", "\\[model\\]. ", "We have there $\\phi$ production on the $p$ plus the same with rescattering of the $K^{+}$ or the $K^{-}$. Similarly we also have $\\phi$ production on the neutron plus the same with rescattering of the $K^{+}$ or the $K^{-}$. In the case of $\\gamma p\\to K^{+}K^{-}p$ we also can have the $K^{-}p$ making the $\\Lambda(1520)$, which we will also take into account. ", "The technical details follow in the next subsections.", "\n\nThe impulse approximation\n-------------------------\n\nIn order to calculate the cross section for the process $\\gamma d\\to K^{+}K^{-}np$ we need to determine the $S$ matrix or $T$ matrix for this reaction. ", "Let us consider the first diagram in Fig. ", "\\[model\\], corresponding to the impulse approximation, and let us evaluate its contribution to the $S$ matrix. ", "Considering plane waves for the wave functions of the incident photon and the particles in the final state, the $S$-matrix for the diagram of Fig. ", "\\[model\\]a can be expressed as $$\\begin{aligned}\nS^{(a)}&=\\int d^{4}x_{1}\\frac{1}{(\\sqrt{V})^{4}}\\mathcal{N}_{p}\\mathcal{N}_{K^{+}}\\mathcal{N}_{K^{-}}\\mathcal{N}_{\\gamma}e^{i(p_{p}+q+q^{\\prime}-k)x_{1}}\\nonumber\\\\\n&\\quad\\times(-it^{(a)}_{\\gamma p\\to K^{+}K^{-}p})\\mathcal{N}_{1} e^{-ip^{0}_{1}x^{0}_{1}}\\varphi_{1}(\\vec{x}_{1})\\int d^{3}x_{2}\\frac{1}{\\sqrt{V}}\\mathcal{N}_{n}e^{-i\\vec{p}_{n}\\vec{x}_{2}}\\mathcal{N}_{2}\\varphi_{2}(\\vec{x}_{2})\\label{Sa_a}\\end{aligned}$$ where $\\varphi_{i}$ ($i=1,2$) are the wave functions of the nucleons in the deuteron, $p^{0}_{1}$ is the energy of the proton inside the deuteron, $p_{p}$, $p_{n}$, $q$, $q^{\\prime}$ correspond to the four momentum of the proton, neutron, $K^{+}$ and $K^{-}$ of the final state, respectively, and $k$ to the four momentum of the incident photon. ", "The normalization factor $\\mathcal{N}_{i}$ is given by $\\mathcal{N}_{i}=\\sqrt{M_{i}/E_{i}}$ for baryons and $\\mathcal{N}_{i}=1/\\sqrt{2\\omega_{i}}$ for mesons. ", "The plane waves are normalized inside a box with a volume $V$.\n\nThe calculation of $S^{(a)}$ requires the evaluation of the integrals in the $x_{1}$ and $x_{2}$ variables. ", "In order to perform the integration in $x_{1}$ we separate the temporal and the spatial components and write $$\\begin{aligned}\n\\int d^{4}x_{1}e^{i(p_{p}+q+q^{\\prime}-k)x_{1}}e^{-ip^{0}_{1}x^{0}_{1}}=\\int dx^{0}_{1}e^{i(p^{0}_{p}+q^{0}+{q^{\\prime}}^{0}-k^{0}-p^{0}_{1})x^{0}_{1}}\\int d^{3}x_{1}e^{-i(\\vec{p}_{p}+\\vec{q}+\\vec{q}^{\\,\\prime}-\\vec{k})\\vec{x}_{1}}.\\nonumber\\end{aligned}$$ The integration over the time component $x^{0}_{1}$ gives the delta function for the energy conservation $$\\begin{aligned}\n\\int dx^{0}_{1}e^{i(p^{0}_{p}+q^{0}+{q^{\\prime}}^{0}-k^{0}-p^{0}_{1})x^{0}_{1}}=2\\pi\\delta(k^{0}+p^{0}_{1}-p^{0}_{p}-q^{0}-{q^{\\prime}}^{0}).\\label{del}\\end{aligned}$$ In the impulse approximation the energy of the spectator, in this case the neutron, does not change, i.e., $p^{0}_{n}=p^{0}_{2}$, with $p^{0}_{2}$ the energy of the neutron inside the deuteron (omitting the small binding energy). ", "Therefore, we can write the $\\delta$ in Eq. (", "\\[del\\]) as $$\\begin{aligned}\n\\delta(k^{0}+p^{0}_{1}-p^{0}_{p}-q^{0}-{q^{\\prime}}^{0})=\\delta(k^{0}+p^{0}_{1}+p^{0}_{2}-p^{0}_{p}-p^{0}_{n}-q^{0}-{q^{\\prime}}^{0}).\\end{aligned}$$\n\nThe evaluation of the spatial integrals is done by making the usual transformation $$\\begin{aligned}\n\\vec{R}&=\\frac{1}{2}(\\vec{x}_{1}+\\vec{x}_{2})\\nonumber\\\\\n\\vec{r}&=\\vec{x}_{1}-\\vec{x}_{2}\\label{CM}\\end{aligned}$$ with $\\vec{R}$ being the center of mass position of the $p n$ system (assuming an average mass for the proton and the neutron) and $\\vec{r}$ the relative coordinate between $\\vec{x}_{1}$ and $\\vec{x}_{2}$. In this way, the term\n\n$$\\begin{aligned}\n\\int d^{3}x_{1}\\int d^{3}x_{2}e^{-i(\\vec{p}_{p}+\\vec{q}+\\vec{q}^{\\,\\prime}-\\vec{k})\\vec{x}_{1}}e^{-i\\vec{p}_{n}\\vec{x}_{2}}\\mathcal{N}_{1}\\mathcal{N}_{2}\\varphi_{1}(\\vec{x}_{1})\\varphi_{2}(\\vec{x}_{2})\\end{aligned}$$\n\npresent in Eq. (", "\\[Sa\\_a\\]) can be written as $$\\begin{aligned}\n\\int d^{3}R \\,e^{-i(\\vec{p}_{p}+\\vec{q}+\\vec{q}^{\\,\\prime}-\\vec{k}-\\vec{p}_{d}+\\vec{p}_{n})\\vec{R}}\\int d^{3}r e^{-\\frac{i}{2}(\\vec{p}_{p}+\\vec{q}+\\vec{q}^{\\,\\prime}-\\vec{k}-\\vec{p}_{n})\\vec{r}}\\frac{1}{\\sqrt{V}}\\mathcal{N}_{d}\\varphi(\\vec{r})\\label{intr}\\end{aligned}$$ where we have introduce the deuteron wave function $\\varphi(\\vec{r})$ for the relative motion $$\\begin{aligned}\n\\mathcal{N}_{1}\\mathcal{N}_{2}\\varphi_{1}(\\vec{x}_{1})\\varphi_{2}(\\vec{x}_{2})\\to\\frac{1}{\\sqrt{V}}\\mathcal{N}_{d}e^{i\\vec{p}_{d}\\vec{R}}\\varphi(\\vec{r})\\end{aligned}$$ with $\\vec{p}_{d}$ the momentum of the deuteron. ", "The deuteron wave function is normalized as $$\\begin{aligned}\n\\int d^{3}r |\\varphi(\\vec{r})|^{2}=1.\\end{aligned}$$ We only consider the s-wave component of the deuteron wave function, which in the rest frame of the deuteron can be parametrized as [@deuteron] $$\\begin{aligned}\n \\varphi(\\vec{r})=\\sum_{i=1}^{11}\\frac{C_{i}}{r}exp(-m_{i}r).\\end{aligned}$$ The coefficients $C_{i}$ and $m_{i}$ can be found in [@deuteron2]. ", "The integration over $\\vec{r}$ in Eq. (", "\\[intr\\]) results into the Fourier transformation of the deuteron wave function, while the integration over $\\vec{R}$ generates the delta function of the total momentum conservation\n\n$$\\begin{aligned}\n\\int d^{3}r\\,e^{\\frac{i}{2}(\\vec{k}+\\vec{p}_{n}-\\vec{p}_{p}-\\vec{q}-\\vec{q}^{\\,\\prime})\\vec{r}}\\varphi(\\vec{r})=\\tilde{\\varphi}\\Bigg(\\frac{\\vec{k}+\\vec{p}_{n}-\\vec{p}_{p}-\\vec{q}-\\vec{q}^{\\,\\prime}}{2}\\Bigg)\\nonumber\\\\\n\\int d^{3}R\\,e^{-i(\\vec{p}_{p}+\\vec{q}+\\vec{q}^{\\,\\prime}-\\vec{k}-\\vec{p}_{d}+\\vec{p}_{n})\\vec{R}}=(2\\pi)^{3}\\delta^{3}(\\vec{p}_{p}+\\vec{q}+\\vec{q}^{\\,\\prime}-\\vec{k}-\\vec{p}_{d}+\\vec{p}_{n}).\\end{aligned}$$\n\nTaking the deuteron energy as the sum of the energies of the nucleons, i.e., $p^{0}_{d}=p^{0}_{1}+p^{0}_{2}$, we have, collecting the previous results, $$\\begin{aligned}\nS^{(a)}&=-i\\frac{1}{V^{3}}\\mathcal{N}_{d}\\mathcal{N}_{\\gamma}\\mathcal{N}_{p}\\mathcal{N}_{n}\\mathcal{N}_{K^{+}}\\mathcal{N}_{K^{-}}(2\\pi)^{4}\\delta(p^{0}_{d}+k^{0}-p^{0}_{p}-p^{0}_{n}-q^{0}-{q^{0}}^{\\prime})\\nonumber\\\\\n&\\quad\\times\\delta^{3}(\\vec{p}_{p}+\\vec{p}_{n}+\\vec{q}+\\vec{q}^{\\,\\prime}-\\vec{k}-\\vec{p}_{d})\\tilde{\\varphi}\\Bigg(\\frac{\\vec{k}+\\vec{p}_{n}-\\vec{p}_{p}-\\vec{q}-\\vec{q}^{\\,\\prime}}{2}\\Bigg)\\label{Sa_b}\n\\nonumber\\\\\n&\\quad\\times t^{(a)}_{\\gamma p\\to K^{+}K^{-}p}.\\end{aligned}$$ Using the momentum conservation law for the reaction $\\gamma d\\to K^{+}K^{-}np$ $$\\begin{aligned}\n\\vec{k}+\\vec{p}_{d}=\\vec{q}+\\vec{q}^{\\,\\prime}+\\vec{p}_{p}+\\vec{p}_{n}\\label{conser}\\end{aligned}$$ the argument of the $\\tilde{\\varphi}$ function in Eq. (", "\\[Sa\\_b\\]) can be put as $$\\begin{aligned}\n\\tilde{\\varphi}\\Bigg(\\frac{\\vec{k}+\\vec{p}_{n}-\\vec{p}_{p}-\\vec{q}-\\vec{q}^{\\,\\prime}}{2}\\Bigg)=\\tilde{\\varphi}\\Bigg(\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}\\Bigg).\\end{aligned}$$ and, therefore, Eq. (", "\\[Sa\\_b\\]) reads as $$\\begin{aligned}\nS^{(a)}&=-i\\frac{1}{V^{3}}\\mathcal{N}_{d}\\mathcal{N}_{\\gamma}\\mathcal{N}_{p}\\mathcal{N}_{n}\\mathcal{N}_{K^{+}}\\mathcal{N}_{K^{-}}(2\\pi)^{4}\\delta^{4}(k+p_{d}-p_{p}-p_{n}-q-q^{\\,\\prime})\\nonumber\\\\\n&\\quad\\times\\tilde{\\varphi}\\Bigg(\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}\\Bigg)\n t^{(a)}_{\\gamma p\\to K^{+}K^{-}p}\n \\end{aligned}$$ Calling $$\\begin{aligned}\n \\mathcal{A}=\\frac{1}{V^{3}}\\Bigg(\\prod_{i}\\mathcal{N}_{i}\\Bigg)(2\\pi)^{4}\\delta^{4}(k+p_{d}-p_{p}-p_{n}-q-q^{\\,\\prime})\\label{A}\\end{aligned}$$ we arrive to $$\\begin{aligned}\nS^{(a)}=-i \\mathcal{A}\\tilde{\\varphi}\\Bigg(\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}\\Bigg)\n t^{(a)}_{\\gamma p\\to K^{+}K^{-}p}.\\end{aligned}$$ Similarly, it is straight forward to show that $$\\begin{aligned}\nS^{(b)}&=-i\\mathcal{A}\\tilde{\\varphi}\\Bigg(\\frac{\\vec{p}_{d}}{2}-\\vec{p}_{p}\\Bigg)\n t^{(b)}_{\\gamma n\\to K^{+}K^{-}n}.\\end{aligned}$$\n\nThe rescattering terms\n----------------------\n\nLet us consider now the diagrams where a kaon rescatters with one of the nucleons of the deuteron as shown in Figs. ", "\\[model\\]c-\\[model\\]f. ", "Analogously to the single scattering diagrams evaluated in the previous section, the $S$ matrix contribution for the diagram Fig. ", "\\[model\\]c is given by $$\\begin{aligned}\nS^{(c)}&=\\int d^{4}x_{1}\\int d^{4}x_{2}\\Bigg(\\prod_{i}\\mathcal{N}_{i}\\Bigg)\\frac{1}{(\\sqrt{V})^{5}}e^{iq x_{1}}e^{iq^{\\prime}x_{2}}e^{ip_{p}x_{1}}e^{ip_{n}x_{2}}\\nonumber\\\\\n&\\quad\\times\\int\\frac{d^{4}q_{ex}}{(2\\pi)^{4}}\\frac{i e^{iq_{ex}(x_{1}-x_{2})}}{q^{2}_{ex}-m_{K}^{2}+i\\epsilon}e^{-ikx_{1}}e^{-ip^{0}_{1}x^{0}_{1}}\\varphi_{1}(\\vec{x}_{1})e^{-ip^{0}_{2}x^{0}_{2}}\\varphi_{2}(\\vec{x}_{2})\\nonumber\\\\\n&\\quad\\times(-i t^{(c)}_{\\gamma p\\to K^{+}K^{-}p})(-i t^{(c)}_{K^{-}n\\to K^{-}n})\\label{Sc}\\end{aligned}$$ Separating the temporal and the spatial part in the integration over the variables $x_{1}$ and $x_{2}$, we have, for the temporal part, $$\\begin{aligned}\n\\int d x^{0}_{1}e^{i(q^{0}+p^{0}_{p}+q^{0}_{ex}-k^{0}-p^{0}_{1})x^{0}_{1}}&=(2\\pi)\\delta(k^{0}+p^{0}_{1}-q^{0}-p^{0}_{p}-q^{0}_{ex})\\label{exp1}\\\\\n\\int d x^{0}_{2}e^{i({q^{\\prime}}^{0}+p^{0}_{n}-q^{0}_{ex}-p^{0}_{2})x^{0}_{2}}&=(2\\pi)\\delta(q^{0}_{ex}+p^{0}_{2}-{q^{\\prime}}^{0}-p^{0}_{n})\\label{exp2}\\end{aligned}$$ Considering $p^{0}_{d}=p^{0}_{1}+p^{0}_{2}$ and using Eqs. (", "\\[exp1\\]), (\\[exp2\\]), Eq. (", "\\[Sc\\]) can be written as $$\\begin{aligned}\nS^{(c)}&=-i\\Bigg(\\prod_{i}\\mathcal{N}_{i}\\Bigg)\\frac{1}{(\\sqrt{V})^{5}}\\int\\frac{d^{3}q_{ex}}{(2\\pi)^{2}}\\delta(k^{0}+p^{0}_{d}-q^{0}-{q^{\\prime}}^{0}-p^{0}_{p}-p^{0}_{n})\\nonumber\\\\\n&\\quad\\times\\int d^{3}x_{1}e^{-i(\\vec{q}+\\vec{p}_{p}+\\vec{q}_{ex}-\\vec{k})\\vec{x}_{1}}\\varphi_{1}(\\vec{x}_{1})\\int d^{3}x_{2}e^{-i(\\vec{q}^{\\,\\prime}+\\vec{p}_{n}-\\vec{q}_{ex})\\vec{x}_{2}}\\varphi_{2}(\\vec{x}_{2})\\nonumber\\\\\n&\\quad\\times t^{(c)}_{\\gamma p\\to K^{+}K^{-}p}t^{(c)}_{K^{-}n\\to K^{-}n}\\frac{1}{(q^{0}_{ex})^{2}-(\\vec{q}_{ex})^{2}-m^{2}_{K}+i\\epsilon}\\Bigg |_{q^{0}_{ex}=k^{0}+p^{0}_{1}-q^{0}-p^{0}_{p}}\\label{Sc_a}\\end{aligned}$$ where we have made use of Eq. (", "\\[exp1\\]) in order to determine the value for $q^{0}_{ex}$. Writing Eq. (", "\\[Sc\\_a\\]) as a function of the $\\vec{R}$ and $\\vec{r}$ coordinates defined in Eq. (", "\\[CM\\]) we have $$\\begin{aligned}\nS^{(c)}&=-i\\Bigg(\\prod_{j}\\mathcal{N}_{j}\\Bigg)\\frac{1}{(\\sqrt{V})^{6}}\\int \\frac{d^{3}q_{ex}}{(2\\pi)^{2}}\\delta(k^{0}+p^{0}_{d}-q^{0}-{q^{\\prime}}^{0}-p^{0}_{p}-p^{0}_{n})\\nonumber\\\\\n&\\quad\\times\\int d^{3}R \\,e^{-i(\\vec{q}+\\vec{q}^{\\,\\prime}+\\vec{p}_{p}+\\vec{p}_{n}-\\vec{k}-\\vec{p}_{d})\\vec{R}}\\int d^{3}r e^{-\\frac{i}{2}(\\vec{q}+\\vec{p}_{p}+2\\vec{q}_{ex}-\\vec{k}-\\vec{q}^{\\,\\prime}-\\vec{p}_{n})\\vec{r}}\\varphi(\\vec{r})\\nonumber\\\\\n&\\quad\\times t^{(c)}_{\\gamma p\\to K^{+}K^{-}p}t^{(c)}_{K^{-}n\\to K^{-}n}\\frac{1}{(q^{0}_{ex})^{2}-(\\vec{q}_{ex})^{2}-m^{2}_{K}+i\\epsilon}\\Bigg |_{q^{0}_{ex}=k^{0}+p^{0}_{1}-q^{0}-p^{0}_{p}}\\label{Sc_b}\\end{aligned}$$ with $j$ an index running over the final $p$, $n$, $K^{+}$, $K^{-}$ and the initial photon and deuteron. ", "The integration over $\\vec{R}$ generates a delta function for the momentum conservation and the integration over $\\vec{r}$ the corresponding Fourier transformation of the deuteron wave function $\\varphi(\\vec{r})$. Taking into account this fact, Eq. (", "\\[Sc\\_b\\]) can be expressed as $$\\begin{aligned}\nS^{(c)}&=-i\\Bigg(\\prod_{j}\\mathcal{N}_{j}\\Bigg)\\frac{1}{(\\sqrt{V})^{6}}(2\\pi)^{4}\\delta^{4}(k+p_{d}-p_{p}-p_{n}-q-q^{\\,\\prime})\\nonumber\\\\\n&\\quad\\times\\int\\frac{d^{3}q_{ex}}{(2\\pi)^{3}}\\tilde{\\varphi}\\Bigg(\\vec{q}^{\\,\\prime}+\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}-\\vec{q}_{ex}\\Bigg)\nt^{(c)}_{\\gamma p\\to K^{+}K^{-}p}t^{(c)}_{K^{-}n\\to K^{-}n}\\nonumber\\\\\n&\\quad\\times\\frac{1}{(q^{0}_{ex})^{2}-(\\vec{q}_{ex})^{2}-m^{2}_{K}+i\\epsilon}\\Bigg |_{q^{0}_{ex}=k^{0}+p^{0}_{1}-q^{0}-p^{0}_{p}}\\label{Sc_c}\\end{aligned}$$ where we have used Eq. (", "\\[conser\\]) for the argument of $\\tilde{\\varphi}$. In terms of Eq. (", "\\[A\\]), Eq. (", "\\[Sc\\_c\\]) reads like $$\\begin{aligned}\nS^{(c)}&=-i\\mathcal{A}\\int\\frac{d^{3}q_{ex}}{(2\\pi)^{3}}\\tilde{\\varphi}\\Bigg(\\vec{q}^{\\,\\prime}+\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}-\\vec{q}_{ex}\\Bigg)\nt^{(c)}_{\\gamma p\\to K^{+}K^{-}p}t^{(c)}_{K^{-}n\\to K^{-}n}\\nonumber\\\\\n&\\quad\\times\\frac{1}{(q^{0}_{ex})^{2}-(\\vec{q}_{ex})^{2}-m^{2}_{K}+i\\epsilon}\\Bigg |_{q^{0}_{ex}=k^{0}+p^{0}_{1}-q^{0}-p^{0}_{p}}.\\label{Sc_d}\\end{aligned}$$\n\nProceeding in a similar way, it is possible to find the contribution for the remaining diagrams of Fig. ", "\\[model\\], which we just write bellow $$\\begin{aligned}\nS^{(d)}&=-i\\mathcal{A}\\int\\frac{d^{3}q_{ex}}{(2\\pi)^{3}}\\tilde{\\varphi}\\Bigg(-\\vec{q}^{\\,\\prime}-\\vec{p}_{p}+\\frac{\\vec{p}_{d}}{2}+\\vec{q}_{ex}\\Bigg),\nt^{(d)}_{\\gamma n\\to K^{+}K^{-}n}t^{(d)}_{K^{-}p\\to K^{-}p}\\nonumber\\\\\n&\\quad\\times\\frac{1}{(q^{0}_{ex})^{2}-(\\vec{q}_{ex})^{2}-m^{2}_{K}+i\\epsilon}\\Bigg |_{q^{0}_{ex}=k^{0}+p^{0}_{2}-q^{0}-p^{0}_{n}}\\label{Sd}\\\\\nS^{(e)}&=-i\\mathcal{A}\\int\\frac{d^{3}q_{ex}}{(2\\pi)^{3}}\\tilde{\\varphi}\\Bigg(\\vec{q}+\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}-\\vec{q}_{ex}\\Bigg)\nt^{(e)}_{\\gamma p\\to K^{+}K^{-}p}t^{(e)}_{K^{+}n\\to K^{+}n}\\nonumber\\\\\n&\\quad\\times\\frac{1}{(q^{0}_{ex})^{2}-(\\vec{q}_{ex})^{2}-m^{2}_{K}+i\\epsilon}\\Bigg |_{q^{0}_{ex}=k^{0}+p^{0}_{1}-{q^{\\,\\prime}}^{0}-p^{0}_{p}},\\label{Se}\\\\\nS^{(f)}&=-i\\mathcal{A}\\int\\frac{d^{3}q_{ex}}{(2\\pi)^{3}}\\tilde{\\varphi}\\Bigg(-\\vec{q}-\\vec{p}_{p}+\\frac{\\vec{p}_{d}}{2}+\\vec{q}_{ex}\\Bigg)\nt^{(f)}_{\\gamma n\\to K^{+}K^{-}n}t^{(f)}_{K^{+}p\\to K^{+}p}\\nonumber\\\\\n&\\quad\\times\\frac{1}{(q^{0}_{ex})^{2}-(\\vec{q}_{ex})^{2}-m^{2}_{K}+i\\epsilon}\\Bigg |_{q^{0}_{ex}=k^{0}+p^{0}_{2}-{q^{\\,\\prime}}^{0}-p^{0}_{n}}.\\label{Sf}\\end{aligned}$$\n\nThe total $S$ matrix will be given by the sum of the contribution of the different diagrams $$\\begin{aligned}\nS=1+\\sum_{i=a}^{f}S_{i}\\end{aligned}$$ and the total T matrix is obtained using the relationship $$\\begin{aligned}\nS=1-i\\mathcal{A}\\,T.\\label{ST}\\end{aligned}$$\n\nBasic model for $\\phi$ production and the $\\bar{K}N$, $KN$ amplitudes\n---------------------------------------------------------------------\n\nAs shown in the former subsections, the calculation of the $S$ matrix involves the evaluation of the amplitudes for the processes $\\gamma N \\to \\phi N\\to K^{+}K^{-} N$, where N represents a nucleon, i.e., $N=$ $n$, $p$, and $\\bar{K} N\\to \\bar{K}N$, $K N\\to KN$. In order to determine the amplitude for the process $\\gamma N\\to \\phi N\\to K^{+}K^{-}N$, we are going to assume a minimal structure which satisfies gauge invariance. ", "Let us first consider the process $\\gamma N\\to \\phi N$ (Fig. ", "\\[phiprod\\]) .", "\n\n![", "Diagrammatic representation for the process $\\gamma p\\to \\phi p$.[]{data-label=\"phiprod\"}](phiprod.eps){width=\"50.00000%\"}\n\nThe amplitude which describes this process must be a function depending on the four momentum of the photon, $k$, and the $\\phi$, $p_{\\phi}$, and their respective polarization vectors, $\\epsilon_{\\gamma}$ and $\\epsilon_{\\phi}$. Imposing gauge invariance, this amplitude must be of the form $$\\begin{aligned}\nt_{\\gamma N\\to \\phi N}\\sim(\\epsilon_{\\gamma}\\epsilon_{\\phi}k\\cdot p_{\\phi}-p_{\\phi}\\epsilon_{\\gamma} k\\epsilon_{\\phi}).\\label{coulomb}\\end{aligned}$$ If we work in the Coulomb gauge for the photons, $p_{\\phi}\\epsilon_{\\gamma}=-\\vec{p}_{\\phi}\\vec{\\epsilon}_{\\gamma}$, and considering $k\\cdot p_{\\phi}\\sim k^{0} M_{\\phi}$, we can neglect the second term in Eq. (", "\\[coulomb\\]) as far as $|\\vec{p}_{\\phi}|<< M_{\\phi}$. The particular structure of this amplitude is not essential in order to see the effects that the cuts of [@nakatwo] can produce in the $M_{K^{+}n}$ invariant mass distribution. ", "Since we will evaluate the cross section in a reduced range of the photon energy, $k^{0}$, we can further assume this to be constant and thus $$\\begin{aligned}\nt_{\\gamma N\\to \\phi N}=\\tilde{a}_{N}\\epsilon_{\\gamma}\\epsilon_{\\phi}\\end{aligned}$$ where $\\tilde{a}_{N}$ is considered as a parameter which determine the magnitude of the amplitude for this process.", "\n\n![", "Diagrammatic representation for the reaction $\\gamma p\\to\\phi p\\to K^{+}K^{-}p$.[]{data-label=\"phiprodpropa\"}](phiprodpropa.eps){width=\"70.00000%\"}\n\nOnce the $\\phi$ is produced, it can decay into a $K^{+}K^{-}$ pair as shown in Fig. ", "\\[phiprodpropa\\]. ", "Therefore, naming $k_{1}$ and $k_{2}$ the four momentum of the $K^{+}$ and $K^{-}$, respectively, coming from the $\\phi$ decay, we can describe the process $\\gamma N\\to \\phi N\\to K^{+}K^{-}N$ by means of the amplitude\n\n$$\\begin{aligned}\nt_{\\gamma N\\to K^{+}K^{-} N}=\\tilde{a}_{N}\\epsilon^{\\mu}_{\\gamma}{\\epsilon_{\\mu\\,\\phi}}\\frac{1}{p^{2}_{\\phi}-M^{2}_{\\phi}+iM_{\\phi}\\Gamma_{\\phi}}g\\epsilon^{\\nu}_{\\phi}(k_{1}-k_{2})_{\\nu}\\end{aligned}$$\n\nwith $\\Gamma_{\\phi}$ the width of the $\\phi$ and $g$ the $\\phi K^{+}K^{-}$ coupling. ", "Summing over the polarizations of the $\\phi$, $\\lambda_{\\phi}$, and using that $$\\begin{aligned}\n\\sum_{\\lambda_{\\phi}}\\epsilon^{\\mu}_{\\phi}\\epsilon^{\\nu}_{\\phi}=-g^{\\mu\\nu}+\\frac{p^{\\mu}_{\\phi}p^{\\nu}_{\\phi}}{M^{2}_{\\phi}}\\end{aligned}$$ we have $$\\begin{aligned}\nt_{\\gamma N\\to K^{+}K^{-} N}=a_{N}\\frac{1}{(k_{1}+k_{2})^{2}-M^{2}_{\\phi}+iM_{\\phi}\\Gamma_{\\phi}}\\epsilon^{\\mu}_{\\gamma}(k_{1}-k_{2})_{\\mu}\\label{ampli2}\\end{aligned}$$ where $a_{N}=\\tilde{a}_{N}g$ and we have used that $p_{\\phi}=k_{1}+k_{2}$ and taken an average mass for the kaons, i.e., $k^{2}_{1}=k^{2}_{2}=m^{2}_{K}$.\n\nIn the Coulomb gauge, Eq. (", "\\[ampli2\\]) reads as $$\\begin{aligned}\nt_{\\gamma N\\to K^{+}K^{-} N}\\equiv\\vec{t}_{\\gamma N\\to K^{+}K^{-} N}\\vec{\\epsilon}_{\\gamma}\\end{aligned}$$ with $$\\begin{aligned}\n\\vec{t}_{\\gamma N\\to K^{+}K^{-} N}\\equiv -a_{N}\\frac{1}{(k_{1}+k_{2})^{2}-M^{2}_{\\phi}+iM_{\\phi}\\Gamma_{\\phi}}(\\vec{k}_{1}-\n\\vec{k}_{2})\\end{aligned}$$ and this is the expression which we use in order to describe the process $\\gamma N\\to \\phi N\\to K^{+}K^{-}N$. Note that the values of $\\vec{k}_{1}$ and $\\vec{k}_{2}$ depend on the diagram under evaluation.", "\n\nFor the one body process $k_{1}$, $k_{2}$ correspond to external variables which are known in the integration over phase space. ", "The two body contributions are relatively smaller, even when the $\\phi$ cut is done, as will be shown in section \\[resca\\]. ", "There one of the momentum is an external momentum while the other one corresponds to $\\vec{q}_{ex}$, an integration variable, which we approximate in the matrix element by its value for $\\vec{p}_{1}=\\vec{p}_{2}=0$ in the laboratory frame, where the deuteron wave function in momentum space has its largest value. ", "In this form, the amplitude $t_{\\gamma N\\to K^{+}K^{-}N}$ can be taken out of the integrals in Eqs. (", "\\[Sc\\_d\\])-(\\[Sf\\]).", "\n\nThe $t$-matrix for the $\\bar{K}N$ and $K N$ interactions are calculated by solving the Bethe-Salpeter equation in a coupled channels approach, taking as potential the lowest order chiral amplitude as done in [@ramos; @bennhold; @felipe]. ", "For the $\\bar{K}N$ system and coupled channels, the scattering amplitude calculated with this approach reproduces the total cross section of $K^{-}p$ to all channels, and gives rise to two $\\Lambda(1405)$ states as dynamical generated resonances in the meson-baryon interaction [@meissner; @meissner2], which can be seen in the invariant mass distribution of $\\pi\\Sigma$ in different reactions [@meissner; @jido]. ", "The $t$ matrices for the processes $\\bar{K}N\\to \\bar{K}N$ and $KN\\to KN$ depend on the invariant mass of the interacting particles, which are given by the following expressions according to the diagrams of Fig. ", "\\[model\\] considered\n\n$$\\begin{aligned}\ns^{(c)}&=(p_{n}+q^{\\,\\prime})^{2}=M^{2}_{n}+m^{2}_{K}+2p^{0}_{n}{{q}^{\\,\\prime}}^{0}-2\\vec{p}_{n}\\vec{q}^{\\,\\prime},\\nonumber\\\\\ns^{(d)}&=(p_{p}+q^{\\,\\prime})^{2}=M^{2}_{p}+m^{2}_{K}+2p^{0}_{p}{{q}^{\\,\\prime}}^{0}-2\\vec{p}_{p}\\vec{q}^{\\,\\prime},\\nonumber\\\\\ns^{(e)}&=(p_{n}+q)^{2}=M^{2}_{n}+m^{2}_{K}+2p^{0}_{n}{q}^{0}-2\\vec{p}_{n}\\vec{q},\\\\\ns^{(f)}&=(p_{p}+q)^{2}=M^{2}_{p}+m^{2}_{K}+2p^{0}_{p}{q}^{0}-2\\vec{p}_{p}\\vec{q}.\\nonumber\\end{aligned}$$\n\nSince these invariant masses are defined in terms of external variables, the $\\bar{K}N$ and $KN$ amplitudes can be taken out of the integrals in Eqs. (", "\\[Sc\\_d\\])-(\\[Sf\\]).", "\n\nIn these way we can define the following function $$\\begin{aligned}\n\\phi(q^{0}_{ex},\\vec{Q})=\\int \\frac{d^{3}q_{ex}}{(2\\pi)^{3}}\\tilde{\\varphi}(\\vec{Q}-\\vec{q}_{ex})\\frac{1}{(q^{0}_{ex})^{2}-(\\vec{q}_{ex})^{2}-m^{2}_{K}+i\\epsilon}\\end{aligned}$$ which depends upon $q^{0}_{ex}$ and $\\vec{Q}^{2}$, such that from Eqs. (", "\\[Sc\\_d\\])-(\\[Sf\\]) and Eq. (", "\\[ST\\]) we can write the $T$ matrix from the different diagrams in Fig. ", "\\[model\\] as $$\\begin{aligned}\nT^{(a)}&=\\tilde{\\varphi}\\Bigg(\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}\\Bigg)\n \\vec{t}^{\\,\\,(a)}_{\\gamma p\\to K^{+}K^{-}p}\\vec{\\epsilon}_{\\gamma}\\equiv \\overrightarrow{T}^{(a)}\\vec{\\epsilon}_{\\gamma},\n\\nonumber\\\\\nT^{(b)}&=\\tilde{\\varphi}\\Bigg(\\frac{\\vec{p}_{d}}{2}-\\vec{p}_{p}\\Bigg)\n\\vec{t}^{\\,\\,(b)}_{\\gamma n\\to K^{+}K^{-}n}\\vec{\\epsilon}_{\\gamma} \\equiv \\overrightarrow{T}^{(b)}\\vec{\\epsilon}_{\\gamma},\n\\nonumber\\\\\nT^{(c)}&=\\phi\\Bigg(k^{0}+p^{0}_{1}-q^{0}-p^{0}_{p},\\vec{q}^{\\,\\prime}+\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}\\Bigg)\\vec{t}^{\\,\\,(c)}_{\\gamma p\\to K^{+}K^{-}p} t^{(c)}_{K^{-}n\\to K^{-}n}\\vec{\\epsilon}_{\\gamma} \\equiv \\overrightarrow{T}^{(c)}\\vec{\\epsilon}_{\\gamma}\\label{Ti},\\\\\nT^{(d)}&=\\phi\\Bigg(k^{0}+p^{0}_{2}-q^{0}-p^{0}_{n},\\vec{q}^{\\,\\prime} +\\vec{p}_{p}-\\frac{\\vec{p}_{d}}{2}\\Bigg)\\vec{t}^{\\,\\,(d)}_{\\gamma n\\to K^{+}K^{-}n} t^{(d)}_{K^{-}p\\to K^{-}p}\\vec{\\epsilon}_{\\gamma} \\equiv \\overrightarrow{T}^{(d)}\\vec{\\epsilon}_{\\gamma},\\nonumber\\\\\nT^{(e)}&=\\phi\\Bigg(k^{0}+p^{0}_{1}-{q^{\\,\\prime}}^{0}-p^{0}_{p},\\vec{q}+\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}\\Bigg)\\vec{t}^{\\,\\,(e)}_{\\gamma p\\to K^{+}K^{-}p} t^{(e)}_{K^{+}n\\to K^{+}n}\\vec{\\epsilon}_{\\gamma} \\equiv \\overrightarrow{T}^{(e)}\\vec{\\epsilon}_{\\gamma},\\nonumber\\\\\nT^{(f)}&=\\phi\\Bigg(k^{0}+p^{0}_{2}-{q^{\\,\\prime}}^{0}-p^{0}_{n},\\vec{q}+\\vec{p}_{p}-\\frac{\\vec{p}_{d}}{2}\\Bigg)\\vec{t}^{\\,\\,(f)}_{\\gamma n\\to K^{+}K^{-}n} t^{(f)}_{K^{+}p\\to K^{+}p}\\vec{\\epsilon}_{\\gamma} \\equiv \\overrightarrow{T}^{(f)}\\vec{\\epsilon}_{\\gamma}.\\nonumber\\end{aligned}$$ The total $T$ matrix will be given by the sum of $T^{(i)}$, $i=a,b,\\dots,f$. We have then from the different terms in Eqs. (", "\\[Ti\\]) $$\\begin{aligned}\nT\\equiv\\overrightarrow{T}\\vec{\\epsilon}_{\\gamma}\\end{aligned}$$ where $$\\begin{aligned}\n\\overrightarrow{T}=\\sum_{i=a}^{f}\\overrightarrow{T}^{(i)}.\\end{aligned}$$\n\nEvaluation of the cross section\n-------------------------------\n\nIn order to calculate the total cross section for the process $\\gamma p\\to K^{+}K^{-}pn$ we are going to work in the center of mass system, where we denote the variables with a tilde. ", "In this frame, the cross section will be given by\n\n$$\\begin{aligned}\n\\sigma&=\\frac{M_{d}}{s-M_{d}^{2}}\\int\\frac{d^{3}\\tilde{p}_{n}}{(2\\pi)^{3}}\\int\\frac{d^{3}\\tilde{q}}{(2\\pi)^{3}}\\int\\frac{d^{3}\\tilde{q}^{\\,\\prime}}{(2\\pi)^{3}}\\int\\frac{d^{3}\\tilde{p}_{p}}{(2\\pi)^{3}}\\frac{1}{2\\tilde{\\omega}(\\vec{\\tilde{q}}\\,\\,)}\\frac{1}{2\\tilde{\\omega}^{\\,\\prime}(\\vec{\\tilde{q}}^{\\,\\prime})}\\frac{M_{p}}{\\tilde{E}_{p}(\\vec{\\tilde{p}}_{p})}\\frac{M_{n}}{\\tilde{E}_{n}(\\vec{\\tilde{p}}_{n})}\\nonumber\\\\\n&\\quad\\times (2\\pi)^{4}\\delta^{4}(\\tilde{k}+\\tilde{p}_{d}-\\tilde{p}_{p}-\\tilde{p}_{n}-\\tilde{q}-\\tilde{q}^{\\,\\prime})\\overline{\\sum_{\\lambda}}\n|T|^{2}\\end{aligned}$$\n\nwith $M_{d}$ the deuteron mass, $\\tilde{\\omega}(\\vec{\\tilde{q}}\\,\\,)=\\sqrt{\\vec{\\tilde{q}}^{\\,\\,2}+m^{2}_{K}}$, $\\tilde{\\omega}^{\\,\\prime}(\\vec{\\tilde{q}}^{\\,\\prime})=\\sqrt{(\\vec{\\tilde{q}}^{\\,\\prime})^{2}+m^{2}_{K}}$, $\\tilde{E}_{p}(\\vec{\\tilde{p}}_{p})=\\sqrt{(\\vec{\\tilde{p}}_{p})^{2}+M^{2}_{N}}$ and $\\tilde{E}_{n}(\\vec{\\tilde{p}}_{p})=\\sqrt{(\\vec{\\tilde{p}}_{n})^{2}+M^{2}_{N}}$. We are using an average mass for the proton and neutron, i.e., $M_{p}=M_{n}=M_{N}$ where $M_{N}=(M_{p}+M_{n})/2$. Since the momentum of the neutron is not measured at LEPS, we can use the delta of Dirac to remove the integration in this variable. ", "In this way we have $$\\begin{aligned}\n\\sigma&=\\frac{M_{d}}{s-M_{d}^{2}}\\int\\frac{d^{3}\\tilde{q}}{(2\\pi)^{3}}\\int\\frac{d^{3}\\tilde{q}^{\\,\\prime}}{(2\\pi)^{3}}\\int\\frac{d^{3}\\tilde{p}_{p}}{(2\\pi)^{3}}\\frac{1}{2\\tilde{\\omega}(\\vec{\\tilde{q}}\\,\\,)}\\frac{1}{2\\tilde{\\omega}^{\\,\\prime}(\\vec{\\tilde{q}}^{\\,\\prime})}\\frac{M_{p}}{\\tilde{E}_{p}(\\vec{\\tilde{p}}_{p})}\\frac{M_{n}}{\\tilde{E}_{n}(-\\vec{\\tilde{p}}_{p}-\\vec{\\tilde{q}}-\\vec{\\tilde{q}}^{\\,\\prime})}\\nonumber\\\\\n&\\quad\\times(2\\pi)\\delta(\\sqrt{s}-\\tilde{\\omega}(\\vec{\\tilde{q}}\\,\\,)-\\tilde{\\omega}^{\\,\\prime}(\\vec{\\tilde{q}}^{\\,\\prime})-\\tilde{E}_{p}(\\vec{\\tilde{p}}_{p})-\\tilde{E}_{n}(-\\vec{\\tilde{p}}_{p}-\\vec{\\tilde{q}}-\\vec{\\tilde{q}}^{\\,\\prime}))\\overline{\\sum_{\\lambda}}|T|^{2}\\label{delta}\\end{aligned}$$ where we have used that in the center of mass frame $\\vec{\\tilde{k}}+\\vec{\\tilde{p}}_{d}=0$. The $\\delta$ function is used to integrate over the angle between $\\vec{\\tilde{p}}_{p}$ and $\\vec{\\tilde{q}}+\\vec{\\tilde{q}}^{\\,\\prime}$ which is then given by $$\\begin{aligned}\ncos \\tilde{\\theta}_{0}\\equiv\\frac{1}{2|\\vec{\\tilde{p}}_{p}|\\cdot |\\vec{\\tilde{q}}+\\vec{\\tilde{q}}^{\\,\\prime}|}\\Bigg[\n(\\sqrt{s}-\\tilde{\\omega}(\\vec{\\tilde{q}}\\,\\,)-\\tilde{\\omega}^{\\,\\prime}(\\vec{\\tilde{q}}^{\\,\\prime})-\\tilde{E}_{p}(\\vec{\\tilde{p}}_{p}))^{2}-M^{2}_{N}-(\\vec{\\tilde{p}}_{p})^{2}-(\\vec{\\tilde{q}}+\\vec{\\tilde{q}}^{\\,\\prime})^{2}\\Bigg]\\nonumber\\end{aligned}$$ and the remaining integrals give now the cross section, which can be written as $$\\begin{aligned}\n\\sigma&=\\frac{M_{d}M_{n}M_{p}}{s-M_{d}^{2}}\\frac{1}{4(2\\pi)^{2}}\\int \\frac{d^{3}\\tilde{q}}{(2\\pi)^{3}\\tilde{\\omega}(\\vec{\\tilde{q}}\\,\\,)}\\int \\frac{d^{3}\\tilde{q}^{\\,\\prime}}{(2\\pi)^{3}\\tilde{\\omega}^{\\,\\prime}(\\vec{\\tilde{q}}^{\\,\\prime})}\\int d\\tilde{E}_{p}\\int d\\tilde{\\phi}\\frac{1}{| \\vec{\\tilde{q}}+\\vec{\\tilde{q}}^{\\,\\prime}|}\\overline{\\sum_{\\lambda}}|T|^{2}\\nonumber\\\\\n&\\quad\\times\\Theta(1-cos^{2}\\tilde{\\theta}_{0})\\Theta(\\sqrt{s}-\\tilde{\\omega}(\\vec{\\tilde{q}}\\,\\,)-\\tilde{\\omega}^{\\,\\prime}(\\vec{\\tilde{q}}^{\\,\\prime})-\\tilde{E}_{p}(\\vec{\\tilde{p}}_{p}))\\label{cross}\\end{aligned}$$ where the $\\Theta$ function guaranties that $|cos\\tilde{\\theta}_{0}|\\leqslant 1$ and $\\sqrt{s}-\\tilde{\\omega}(\\vec{\\tilde{q}}\\,\\,)-\\tilde{\\omega}^{\\,\\prime}(\\vec{\\tilde{q}}^{\\,\\prime})-\\tilde{E}_{p}(\\vec{\\tilde{p}}_{p})>0$, as it should be. ", "In the Coulomb gauge, the element $$\\begin{aligned}\n\\overline{\\sum_{\\lambda}}|T|^{2}\\end{aligned}$$ can be written using the sum over photon polarizations $$\\begin{aligned}\n{\\sum_{\\lambda}} {\\epsilon}^{\\,\\,i}_{\\gamma}{\\epsilon}^{\\,\\,j}_{\\gamma}=\\delta_{ij}-\\frac{k_{i}k_{j}}{\\vec{k}^{2}}\\label{eps}\\end{aligned}$$ as $$\\begin{aligned}\n\\overline{\\sum_{\\lambda}}|T|^{2}=\\frac{1}{2}\\Bigg[\\overrightarrow{T}\\cdot\\overrightarrow{T}-\\frac{(\\vec{k}\\cdot\\overrightarrow{T})^{2}}{\\vec{k}^{2}}\\Bigg].\\end{aligned}$$ Although Eq. (", "\\[cross\\]) corresponds to the cross section calculated in the center of mass frame, $\\overline{\\displaystyle{\\sum_{\\lambda}}}|T|^{2}$ is an invariant and can be calculated in any colinear frame. ", "For this reason, for convenience, it is simpler to obtain it in the frame where the deuteron is at rest, i.e., $\\vec{p}_{d}=0$. For this purpose, we have to make a boost from the center of mass frame to a frame which is moving with a speed $$\\begin{aligned}\n\\vec{v}=\\frac{\\vec{k}+\\vec{p}_{d}}{k^{0}+M_{d}}=\\frac{\\vec{k}}{k^{0}+M_{d}},\\end{aligned}$$ with $\\vec{k}$, $k^{0}$ variables of the photon in the laboratory frame, according to the following relation [@pedro] $$\\begin{aligned}\n\\vec{p}_{i}=\\Bigg[\\Bigg(\\frac{k^{0}+M_{d}}{\\sqrt{s}}-1\\Bigg)\\frac{\\vec{\\tilde{p}}_{i}\\cdot\\vec{k}}{\\vec{k}^{2}}+\\frac{\\tilde{p}^{0}_{i}}{\\sqrt{s}}\\Bigg]\\vec{k}+\\vec{\\tilde{p}}_{i}\\end{aligned}$$ with $\\vec{\\tilde{p}}$ an arbitrary vector in the center of mass frame and $\\vec{p}$ the expression of this vector in the frame where the deuteron is at rest.", "\n\nThe integrals in Eq. (", "\\[cross\\]) are done using the Monte Carlo method, which is particularly suited to implement the experimental cuts.", "\n\n$\\Lambda(1520)$ production {#1520}\n--------------------------\n\nA detailed model for $\\Lambda(1520)$ production, which reproduces fairly well the data, is available in [@sibirtsev]. ", "In this work the Drell mechanism with $K^+$ and $K^-$ exchange is used to study the $\\gamma p \\to K^+ K^- p$ reaction, and the production of the $\\Lambda(1520)$ is taken into account by a new term where the resonance is excited by means of $K^*$ exchange. ", "Another phenomenological analysis is done in [@roca] where the $\\Lambda(1520)$ resonance is assumed to be dynamically generated in coupled channels. ", "Here we follow a more empirical approach, since we are interested only about the shape of the $K^-p$ distribution and the strength of the $\\Lambda(1520)$ production is fitted to the data. ", "We assume that the $\\Lambda(1520)$ does not interfere with the $\\phi$ production mechanism, and we consider a minimal structure for $\\gamma p\\to K^{+}\\Lambda(1520)\\to K^{+}K^{-}p$ compatible with the quantum numbers of the $\\Lambda(1520)$ ($J^{P}=3/2^{-}$) and the D-wave character [@roca] $$\\begin{aligned}\nt_{\\Lambda}=b_{\\Lambda}(\\vec{\\sigma}\\times\\vec{q})\\vec{\\epsilon}\\,\\mathcal{D}_{\\Lambda}\\label{lamb}\\end{aligned}$$ with $$\\begin{aligned}\n\\mathcal{D}_{\\Lambda}=\\frac{1}{M_{K^{-}p}-M_{\\Lambda(1520)}+i\\frac{\\Gamma_{\\Lambda(1520)}}{2}}\\end{aligned}$$ the $\\Lambda(1520)$ propagator, $M_{\\Lambda(1520)}$ and $\\Gamma_{\\Lambda(1520)}$ the mass and the width, respectively, of the $\\Lambda(1520)$ resonance, $b_{\\Lambda}$ a parameter, $\\vec{\\sigma}$ the Pauli matrices, and $M_{K^{-}p}$ the $K^{-}p$ invariant mass. ", "In this way $$\\begin{aligned}\n|t_{\\Lambda}|^{2}=|b_{\\Lambda}|^{2}|\\mathcal{D}_{\\Lambda}|^{2}\\epsilon_{ijk}\\sigma_{j}q_{k}\\epsilon_{i}\\epsilon_{lmn}\\sigma_{m}q_{n}\\epsilon_{l}\\label{tl}\\end{aligned}$$ Using Eq. (", "\\[eps\\]), in the Coulomb gauge we find $$\\begin{aligned}\n\\overline{\\sum_{\\lambda_{\\gamma},s}}|t_{\\Lambda}|^{2}=\\frac{1}{2}|b_{\\Lambda}|^{2}|\\mathcal{D}_{\\Lambda}|^{2}\\Bigg[\\vec{q}^{\\,\\,2}+\\frac{(\\vec{k}\\cdot\\vec{q})^{2}}{\\vec{k}^{2}}\\Bigg].\\end{aligned}$$ We can add a background to this amplitude of the form $\\frac{1}{2}|c_{\\Lambda}|^{2}$, with $c_{\\Lambda}$ being a parameter, and, then, substitute in Eq. (", "\\[cross\\]) $$\\begin{aligned}\n\\overline{\\sum_{\\lambda}}|T|^{2}\\to\\overline{\\sum_{\\lambda}}|T|^{2}+\\Bigg(\\frac{1}{2}|b_{\\Lambda}|^{2}|\\mathcal{D}_{\\Lambda}|^{2}\\Bigg[\\vec{q}^{\\,\\,2}+\\frac{(\\vec{k}\\cdot\\vec{q})^{2}}{\\vec{k}^{2}}\\Bigg]+\\frac{1}{2}|c_{\\Lambda}|^{2}\\Bigg)\\Bigg|\\tilde{\\varphi}\\Bigg(\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}\\Bigg)\\Bigg|^{2}.\\end{aligned}$$ Since in the energy region considered the term $$\\begin{aligned}\n\\vec{q}^{\\,\\,2}+\\frac{(\\vec{k}\\cdot\\vec{q})^{2}}{\\vec{k}^{2}}\\end{aligned}$$ does not change too much, we can take it as a constant and absorb it in the parameter $b_{\\Lambda}$. This mean that in our case $$\\begin{aligned}\n\\overline{\\sum_{\\lambda}}|T|^{2}\\to\\overline{\\sum_{\\lambda}}|T|^{2}+\\frac{1}{2}\\Bigg(|b_{\\Lambda}|^{2}|\\mathcal{D}_{\\Lambda}|^{2}+|c_{\\Lambda}|^{2}\\Bigg)\\Bigg|\\tilde{\\varphi}\\Bigg(\\vec{p}_{n}-\\frac{\\vec{p}_{d}}{2}\\Bigg)\\Bigg|^{2}\\label{eqtdos}.\\end{aligned}$$ We shall see that the results at LEPS can be reproduced with the $\\phi$ and $\\Lambda(1520)$ production, and there is no need for an extra background, represented by the $c_{\\Lambda}$ term in the former equation.", "\n\nThe $\\Lambda(1520)$ is dynamically generated in the $\\bar{K}N$ system and coupled channels [@roca]. ", "One can benefit from the study done in [@roca] to include the $\\Lambda(1520)$ production in the $t$ matrix for the process $K^{-}p\\to K^{-}p$ which appears in Fig. ", "\\[model\\]d. ", "Following [@roca] $$\\begin{aligned}\nt^{\\Lambda(1520)}_{\\bar{K}N\\to\\bar{K}N}&=t^{I=0}_{\\bar{K}N\\to\\bar{K}N}\\sum_{M}\\mathcal{C}\\Bigg(\\frac{1}{2},2,\\frac{3}{2}; m, M-m\\Bigg)Y_{2, m-M}(\\hat{p})\\nonumber\\\\\n&\\quad\\times\\mathcal{C}\\Bigg(\\frac{1}{2},2,\\frac{3}{2};m^{\\prime},M-m^{\\prime}\\Bigg)Y_{2,m^{\\prime}-M}(\\hat{p}^{\\prime})(-1)^{m^{\\prime}-m}4\\pi\\end{aligned}$$ with $\\vec{p}$, $\\vec{p}^{\\,\\prime}$ the initial and final momentum of the $K^{-}$, $t^{I=0}_{\\bar{K}N\\to\\bar{K}N}$ the $t$ matrix for the $\\bar{K}N$ system in isospin zero obtained solving the Bethe-Salpeter equations in a unitary chiral approach [@ramos; @bennhold], $\\mathcal{C}$ Clebsch-Gordan coefficients and $Y$ the spherical harmonics. ", "We take $\\hat{p}$ in the $z$ direction, and then, the only not zero spherical harmonic is $Y_{2,0}(\\hat{p})$. In LEPS they measure angles in the forward direction. ", "Then, taking $\\hat{p}$ and $\\hat{p}^{\\prime}$ in the forward direction $$\\begin{aligned}\nY_{2,0}(\\hat{p})=Y_{2,0}(\\hat{p}^{\\prime})=\\sqrt{\\frac{5}{4\\pi}}.\\end{aligned}$$ Let us consider $m=m^{\\prime}=1/2$. Since $\\mathcal{C}\\Bigg(\\frac{1}{2},2,\\frac{3}{2};\\frac{1}{2},0,\\frac{1}{2}\\Bigg)=\\sqrt{\\frac{2}{5}}$, we have that $$\\begin{aligned}\nt^{\\Lambda(1520)}_{\\bar{K}N\\to\\bar{K}N}=2t^{I=0}_{\\bar{K}N\\to\\bar{K}N}.\\end{aligned}$$ Using that $$\\begin{aligned}\n|\\bar{K}N, I=0\\rangle=\\frac{1}{\\sqrt{2}}|K^{-}p+\\bar{K}^{0}n\\rangle\\end{aligned}$$ we can determine the element $t^{\\Lambda(1520)}_{K^{-}p\\to K^{-}p}$ as $$\\begin{aligned}\nt^{\\Lambda(1520)}_{K^{-}p\\to K^{-}p}=\\frac{t^{I=0}_{\\bar{K}N\\to\\bar{K}N}}{2}=t^{I=0}_{\\bar{K}N\\to\\bar{K}N}\\end{aligned}$$ and close to the resonance, $t^{I=0}_{\\bar{K}N\\to\\bar{K}N}$ can be written like $$\\begin{aligned}\nt^{I=0}_{\\bar{K}N\\to\\bar{K}N}=\\frac{g^{2}_{\\bar{K}N}}{M_{K^{-}p}-M_{\\Lambda(1520)}+i\\frac{\\Gamma_{\\Lambda(1520}}{2}}\\end{aligned}$$ where $g_{\\bar{K}N}$ is the coupling of the $\\Lambda(1520)$ to the $\\bar{K}N$ channel, which according to [@roca] is -0.54. ", "This term must be added to the s-wave $K^{-}p\\to K^{-}p$ amplitude which appears in Eqs. (", "\\[Sd\\]). ", "We mention already here that including this term to the rescattering part induces corrections which provide a small contribution, thus, has negligible effects in the final results.", "\n\nSet up at LEPS {#MMSA}\n--------------\n\nThe LEPS detector is a forward magnetic spectrometer, therefore, it can only detect particles in the forward direction. ", "The angular coverage of the spectrometer is approximately $\\pm$ 20 and $\\pm$10 degrees in the horizontal and the vertical directions, respectively. ", "In our simulation we impose that the angle of the kaons in the final state with respect the incident photon is not bigger than 20 degrees.", "\n\nThe nucleons are not detected at LEPS, therefore, some prescription is required in order to estimate the momentum of the $p$ and $n$ in the reaction $\\gamma d \\to K^{+}K^{-}np$ and determine the invariant mass of $K^{-}p$ or $K^+ n$. This is done using the minimum momentum spectator approximation (MMSA). ", "The aim is to guarantee that a chosen nucleon is the closest possible to be a spectator in the reaction. ", "The chosen spectator nucleon is the proton if one evaluates the $K^{+}n$ invariant mass, or the neutron when the $K^{-}p$ invariant mass is evaluated. ", "For this purpose one defines the magnitude $$\\begin{aligned}\np_{pn}=p_{miss}=p_{\\gamma} +p_d - p_{K^+} -p_{K^-}\\end{aligned}$$ which corresponds to the four momentum of the outgoing $pn$ pair. ", "In the $pn$ center of mass frame, the momentum of a nucleon is given by $$\\begin{aligned}\n|\\vec{p}_{CM}| = \\frac{\\lambda^{1/2}(M^{2}_{pn},M^{2}_{p},M^{2}_{n})}{2M_{pn}}\\end{aligned}$$ Boosting back this momentum to the laboratory frame, we will have a minimum modulus for the momentum of the spectator nucleon when the momentum $\\vec{p}_{CM}$ for this nucleon goes in the direction opposite to $\\vec{p}_{miss}$. Thus, the minimum momentum, $p_{min}$, is given by $$\\begin{aligned}\n p_{min} = -|\\vec{p}_{CM}| \\cdot \\frac{E_{miss}}{M_{pn}} + E_{CM} \\cdot\\frac{|\\vec{p}_{miss}|}{M_{pn}}\\end{aligned}$$ where $E_{CM}=\\sqrt{|\\vec{p}_{CM}|^{2}+M^{2}_{N}}$ is the energy of the nucleon in the CM frame. ", "In this case, the momentum of the other nucleon will be in the direction of the missing momentum with a magnitude $$\\begin{aligned}\np_{res} = |\\vec{p}_{miss}| -p_{min} \\end{aligned}$$ In [@nakatwo] the $M_{K^+ n}$ invariant mass for the reaction $\\gamma d\\to K^{+}K^{-}np$ is evaluated assuming the proton to have a momentum $p_{min}$. Consequently, in this prescription, the momentum of the neutron in the final state will be $$\\begin{aligned}\n\\vec{p}_{n}=p_{res}\\cdot\\frac{\\vec{p}_{miss}}{|\\vec{p}_{miss}|}\\end{aligned}$$ which is used to calculate the $M_{K^{+}n}$ invariant mass for the reaction $\\gamma d\\to K^{+}K^{-}np$ in [@nakatwo]. ", "At LEPS only events which satisfy $|p_{min}|<$ 100 MeV are considered. ", "This condition is also implemented in our simulation of the process.", "\n\nIn order to remove the contribution from the $\\phi$ production at LEPS one considers events which satisfy that the invariant mass of the $K^{+}K^{-}$ pair is bigger than 1030 MeV and bigger than the value obtained from the following expression $$\\begin{aligned}\n1020\\, \\textrm{MeV} +0.09\\times (E^{eff}_{\\gamma}(\\textrm{MeV})-2000\\, \\textrm{MeV})\\end{aligned}$$ where $E^{eff}_{\\gamma}$ is defined as the effective photon energy $$\\begin{aligned}\nE^{eff}_{\\gamma}=\\frac{s_{K^{+}K^{-}n}-M^{2}_{n}}{2M_{n}}\\end{aligned}$$ with $s_{K^{+}K^{-}n}$ the square of the total center of mass energy for the $K^{+}K^{-}n$ system calculated using the MMSA approximation to determine the momentum of the neutron assuming the proton as spectator. ", "In [@nakatwo] only events for which $2000$ MeV $<E^{eff}_{\\gamma} $ $<2500$ MeV are considered, a condition which is also incorporated in our simulation. ", "This is the cut implemented when the invariant $K^{+}n$ mass is reconstructed. ", "When the $K^{-}p$ mass is reconstructed, the cut is the same but $E^{eff}_{\\gamma}$ is now evaluated with the MMSA prescription assuming the neutron as spectator. ", "These energies would correspond to the photon in a $\\gamma n$ ($\\gamma p$) reaction with the original $p$ ($n$) at rest.", "\n\nResults with $\\phi$ production {#penphi}\n==============================\n\nWe consider first the production of $\\phi$ on proton and neutron followed by rescattering and we look at the distribution of $d\\sigma/d M_{K^{+}n}$ which is obtained taking for the neutron the momentum provided by the MMSA prescription described in the former section.", "\n\nWe have made the integrals in Eq. (", "\\[cross\\]) using the Monte Carlo integration method with different seeds and with a statistics of 20 million points in the variables of Eq. (", "\\[cross\\]), such that we get about 66500 “good\" points in the integral over the phase space which pass all the tests of the cuts. ", "In order to take into account that the photon energies in the LEPS experiment run from 2 GeV to 2.4 GeV, we have generated 20 random energies in that range.", "\n\nIn Fig. ", "\\[penta\\] we show the first distribution obtained with the cuts of [@nakatwo] and using the MMSA prescription for the nucleon momenta as done in [@nakatwo]. ", "What we see in the figure is a pronounced peak around an invariant $K^{+}n$ mass of 1530 MeV, very similar to the peak observed in [@nakatwo], which was identified as a possible signature of the $\\Theta^{+}$ pentaquark. ", "However, the peak has appeared here as a consequence of the cuts and not as a signal of a resonance which is not present in our theoretical model.", "\n\n![(", "Color online) $M_{K^{+}n}$ invariant mass distribution with about 66500 “good” points.[]{data-label=\"penta\"}](Kpneu_2_1_1_Nakano.eps){width=\"70.00000%\"}\n\nOne may rightly ask oneself whether the peak obtained in Fig. ", "\\[penta\\] is a necessary peak coming from the LEPS cuts or it is a statistical fluctuation. ", "The answer comes from running with much more statistics, which we show below. ", "However, before showing these results let us mention that statistically we get a clear peak around this energy in about $1/3$ of the runs with different seeds, but in all of them there is some trace of extra strength in this region.", "\n\nSince one may argue that statistically it is more probable not to find a clear peak (about $2/3$ probability), we find opportune to make the following test. ", "Let us imagine that we had devised that a proper cut to see a possible signature of the $\\Theta^{+}$ would be to take 1030 MeV for the $\\phi$ cut and 100 MeV for the $p_{min}$ test. ", "The results with these cuts can be seen in Fig. ", "\\[pentades\\].", "\n\n![", "$M_{K^{+}n}$ invariant mass distribution with about 71000 “good” points and with the cuts $p_{min}<$100 MeV and $M_{K\\bar{K}}>$ 1030 MeV.[]{data-label=\"pentades\"}](Kpneu_2_1_1_Nakano_destroy.eps){width=\"70.00000%\"}\n\nA peak is still seen around $M_{K^{+}n}\\sim$ 1530 MeV, but of the same size as the statistical fluctuations that one observes in other parts of the spectrum. ", "If in an eventual experiment one might decide that a cut like the one applied for Fig. ", "\\[penta\\] is more appropriate to analyze the experiment, one would then find the peak around 1530 MeV of Fig. ", "\\[penta\\] and could see in it the signature of a new resonance.", "\n\nAfter these exercises one still would like to see what happens with large statistics. ", "We have made a run with 2000 millions points, out of which around 6420000 points are “good\" points passing the test of the LEPS cuts. ", "The results are shown in Fig. ", "\\[pentamore\\]. ", "We see that the narrow peak has disappeared in the 1530 MeV region, but a softer bump still remains. ", "A structure of this type in an eventual experimental spectrum could easily be interpreted as due to a resonance present in the reaction, but in our case it has been created by the cuts taken from the LEPS set up since we do not have any $K^{+}n$ resonance in the model.", "\n\n![(", "Color online) $M_{K^{+}n}$ invariant mass distribution calculated with $\\sim$ 6420000 “good” points with the same cuts as those made in [@nakatwo] at LEPS.[]{data-label=\"pentamore\"}](Kpneu_2_1_1_Nakano_more.eps){width=\"70.00000%\"}\n\nOne can visualize the comment made above by separating the mass spectrum of Fig. ", "\\[pentamore\\] into a smooth background and a “resonant\" signal as shown in Fig.\\[separa\\], as is usually done in many experimental analyses. ", "A structure with resonant shape around 1520 MeV and a width of about 85 MeV has been generated as a consequence of the cuts.", "\n\n![(", "Color online) $M_{K^{+}n}$ invariant mass distribution shown in Fig. ", "\\[pentamore\\], together with the result from the sum of two gaussian functions, one peaking at 1520 MeV with a width of 85 MeV and another one peaking at 1645 MeV with a width of 185 MeV.[]{data-label=\"separa\"}](Kpneu_2_1_1_Nakano_more_fit.eps){width=\"70.00000%\"}\n\nIn order to see the effects of the cuts we show in Fig. ", "\\[kplusn\\_nocut\\], \\[kplusn\\_anglecut\\], \\[kplusn\\_phicut\\_anglecut\\] the results for the distributions which we get by not putting any cut, only the angle cut, or the angle and a $\\phi$ cut, i.e., $M_{K^{+}K^{-}}>$ 1050 MeV, respectively. ", "In figures \\[kplusn\\_nocut\\], \\[kplusn\\_anglecut\\] and \\[kplusn\\_phicut\\_anglecut\\] the neutron momentum is the one provided in the Monte Carlo runs and is not evaluated according to the MMSA prescription as in the former figures. ", "What we observe is that the “resonant like” structure of Figs. ", "\\[pentamore\\], \\[separa\\] does not show up in any of the runs where the real momenta have been used. ", "Since the $\\phi$ cut used in [@nakatwo] is dependent on $p_{min}$ and the MMSA prescription is used for the kinematics of the nucleons, we must conclude that the combination of these two facts is responsible for the “resonant like” structure seen in Figs. ", "\\[pentamore\\], \\[separa\\].", "\n\n![(", "Color online) $M_{K^{+}n}$ invariant mass distribution obtained with $\\sim$ 41280000 “good” points without any cut.[]{data-label=\"kplusn_nocut\"}](Kpneu_nocuts_more2.eps){width=\"70.00000%\"}\n\n![(", "Color online) $M_{K^{+}n}$ invariant mass distribution calculated with $\\sim$ 23900000 “good” points with only the angular cut.[]{data-label=\"kplusn_anglecut\"}](Kpneu_0_1_1_Nakano_more.eps){width=\"70.00000%\"}\n\n![(", "Color online) $M_{K^{+}n}$ invariant mass distribution obtained with $\\sim$ 12700000 “good” events with the $\\phi$ cut $M_{K^{+}K^{-}}>$ 1050 MeV and the angular cut.[]{data-label=\"kplusn_phicut_anglecut\"}](Kpneu_1_1_1_Nakano_more.eps){width=\"70.00000%\"}\n\nIntroducing the $\\Lambda(1520)$ {#in1520}\n===============================\n\nNow we introduce in the amplitude $\\gamma d\\to K^{+}K^{-}np$ a term accounting for the production of the $\\Lambda(1520)$ as explained in section \\[1520\\]. ", "The different structure in the momenta of the final states for the $K^{+}\\Lambda(1520)$ and $\\phi p$ production suggest the incoherent sum of cross sections and we follow this option.", "\n\nWe find that adding the $\\Lambda(1520)$ production in the amount demanded by the LEPS experiment does not spoil the mass distribution found in Fig. ", "\\[penta\\], taking the same seed for the Monte Carlo integration. ", "This is shown in Fig. ", "\\[pentaLamb\\].", "\n\n![(", "Color online) $M_{K^{+}n}$ invariant mass distribution obtained with $\\sim$ 66500 “good” points, the same cuts as those made in [@nakatwo] at LEPS and with the $\\Lambda(1520)$ term.[]{data-label=\"pentaLamb\"}](Kpneu_2_1_1_Nakano_Lambda.eps){width=\"70.00000%\"}\n\nHowever, the introduction of the $\\Lambda(1520)$ production term serves us also another purpose. ", "Indeed, we can make a test to see how the prescription used at LEPS to identify resonances works in this case. ", "Since neither the final proton not the neutron are detected in the experiment, one must take some prescription to have the best guess for the neutron momentum in order to determine the $K^{+}n$ invariant mass of an event. ", "The prescription taken at LEPS relies on the concept of minimum momentum as we explained in section \\[MMSA\\].", "\n\n![(", "Color online) $M_{K^{-}p}$ invariant mass distributions with and without the $\\Lambda(1520)$ term and making the same cuts that at LEPS. ", "These distributions have been obtained with $\\sim$ 6420000 “good” points.[]{data-label=\"Lambda\"}](Lambda_1520.eps){width=\"70.00000%\"}\n\nIn Fig. ", "\\[Lambda\\] we show the results for the $K^{-}p$ invariant mass considering the same cuts as in LEPS. ", "We can see that, using the MMSA prescription to calculate the $K^{-}p$ invariant mass as described in section \\[MMSA\\], one gets a peak at the right mass coming from the $\\Lambda(1520)$, and the spectrum resembles much the spectrum found at LEPS. ", "In this case, if we remove the term of the $\\Lambda(1520)$ production in the $\\gamma p\\to K^{+}K^{-}p$ amplitude and plot the $K^{-}p$ invariant mass distribution we do not find the signal of the resonance, as can be seen in Fig. ", "\\[Lambda\\] (lower area of the spectrum). ", "It is interesting to note that, by reasons of symmetry, the spectrum obtained for the $K^- p$ invariant mass in the absence of any $\\Lambda(1520)$ term is basically the same as the one obtained for the $K^+ n$ invariant mass in Fig. ", "\\[pentamore\\], up to minor differences from the rescattering terms. ", "It is interesting to point out here that, should one have a statistical fluctuation around 1530 MeV as one has in Fig. ", "\\[penta\\], it would go unnoticed since it would be buried below the $\\Lambda(1520)$ peak, which has become wider than the natural width as a consequence of the MMSA prescription.", "\n\nFig. ", "\\[Lambda\\] shows, indeed, that the prescription to identify a resonance using the MMSA prescription works if the cross section for the production of this resonance is sufficiently large. ", "However, let us see what would happen if we actually measured the proton such that we can clearly determine the $K^{-}p$ distribution without using the MMSA prescription. ", "The results are seen in Fig. ", "\\[nocuts\\]. ", "We can see that the peak for the $\\Lambda(1520)$ is sharper than in Fig. ", "\\[Lambda\\]. ", "We also notice that the non $\\Lambda(1520)$ part of the spectrum (lower area in the figure) changes from one figure to the other. ", "This is telling us that the MMSA prescription can indeed be used to identify a resonance, but it also distorts the shape of the spectrum and could have some repercussions in the $K^+ n$ spectrum, as we have already seen. ", "We have checked that the contribution to the spectrum at large $K^{-}p$ invariant masses in Fig. ", "\\[nocuts\\] comes from $\\phi$ production on the neutron, where the proton is a spectator.", "\n\n![(", "Color online) $M_{K^{-}p}$ invariant mass distributions with and without the $\\Lambda(1520)$ term and making the angle cut and with $M_{K^{+}K^{-}}>$ 1050 MeV using the real $K^{-}$ and $p$ momenta. ", "These distributions have been calculated with $\\sim$ 12700000 “good” points.[]{data-label=\"nocuts\"}](Lambda_without_nakano_cuts.eps){width=\"70.00000%\"}\n\nBefore ending the section, we show in Fig. ", "\\[pentamore\\_Lambda\\] the equivalent of Fig. ", "\\[pentamore\\] using the MMSA prescription and the cuts done in [@nakatwo], but with the full model, i.e., including $\\phi$ and $\\Lambda(1520)$ production. ", "The results resemble those of Fig. ", "\\[pentamore\\] but the peak at higher invariant masses is a bit more pronounced. ", "This should be compared to Fig. ", "12 of [@nakatwo].", "\n\n![(", "Color online) $M_{K^{+}n}$ distribution calculated with the same cuts as those done in [@nakatwo] and including the $\\Lambda(1520)$ term for $\\sim$ 6420000 “good” points.[]{data-label=\"pentamore_Lambda\"}](Kpneu_2_1_1_Nakano_more_with_Lambda.eps){width=\"70.00000%\"}\n\nRescattering contribution {#resca}\n=========================\n\nIn Fig. ", "\\[single\\] we show the $M_{K^{+}n}$ distribution calculated with the MMSA prescription and the same cuts as those made in [@nakatwo] at LEPS obtained considering only the contribution from the single scattering, which corresponds to the diagrams Fig. ", "\\[model\\]a, \\[model\\]b, while in Fig. ", "\\[double\\] we show the result obtained taking into account only the rescattering diagrams of Fig. ", "\\[model\\].", "\n\n![(", "Color online) $M_{K^{+}n}$ invariant mass distribution with a statistic similar to the one in Fig. ", "\\[penta\\], including only the single scattering contribution and with the same cuts as those done in [@nakatwo] at LEPS.[]{data-label=\"single\"}](single.eps){width=\"70.00000%\"}\n\nAs one can see, the single scattering terms provide the dominant contribution, although the double scattering terms help in increasing a bit the magnitude and their contribution also shows some peak around 1520 MeV.\n\n![(", "Color online) $M_{K^{+}n}$ invariant mass distribution with a statistic similar to the one in Fig. ", "\\[penta\\], including only the rescattering contribution and with the same cuts as those done in [@nakatwo] at LEPS.[]{data-label=\"double\"}](double.eps){width=\"70.00000%\"}\n\nStatistical analysis and comparison with LEPS results {#sta1}\n=====================================================\n\nIn this section we address the question of statistics and error analysis. ", "In the first place we consider the error from the Monte Carlo simulation. ", "This is given by the standard formula\n\n$$\\begin{aligned}\n\\epsilon^{2}_{r}=\\frac{1}{\\displaystyle{\\sum_{j=1}^{N_{E}}n_{j}}}\\left\\{\\frac{\\displaystyle{\\Bigg(\\sum_{j=1}^{N_{E}}n_{j}\\Bigg)^{-1}\\sum_{j=1}^{N_{E}}\\sum_{i=1}^{n_{j}}V^{2}_{j}f^{2}}}{\\Bigg [\\Bigg(\\displaystyle{\\sum_{j=1}^{N_{E}}n_{j}\\Bigg)^{-1}}\\displaystyle{\\sum_{j=1}^{N_{E}}\\sum_{i=1}^{n_{j}}V_{j}f\\Bigg]^{2}}}-1\\right\\} \\label{formuguar}\\end{aligned}$$\n\nwhere $\\epsilon_{r}$ is the relative error for $d\\sigma/d M_{inv}$ in a bin of the invariant mass, $f$ is the integrand in the integral for the cross section (Eq. (", "\\[cross\\])) for the Monte Carlo points that fall inside a certain bin, $N_{E}$ the number of energies of the photon for which we calculate the distributions, $n_{j}$ the number of “good” events in one bin for each of these energies and $V_{j}$ the volume of the phase space for each photon energy.", "\n\nComing back to Fig. ", "\\[penta\\], we obtain using Eq. (", "\\[formuguar\\]) a relative error of $\\sim$ 20 % in the bins of invariant mass around 1530 MeV. This is an error that justifies the fluctuation seen in the figure.", "\n\nThe equivalence of $N$ integration points and $\\tilde{N}$ measured events in a experiment from the statistical point of view is not straightforward. ", "For this reason, we approach now a different procedure which is suited to generate events like in the experiment, which we call simulation run. ", "We use the Von Neumann rejection method to generate events. ", "This procedure works like a Quantum Mechanical experiment in which events are produced or not according to their probability. ", "The Von Neumann rejection method does that: it generates or not an event according to its probability measured with respect to the maximum probability, where the probability is given by the integrand of Eq. (", "\\[cross\\]).", "\n\nWe made ten Monte Carlo simulation runs, producing about 2500-3000 events in each of them, to simulate the statistics of the 2000 events in [@nakatwo]. ", "We can make a statistical analysis of these ten different sets of results. ", "The relative error is given by\n\n$$\\begin{aligned}\n{\\epsilon^{\\,\\prime}}^{2}_{r}=\\frac{(N^{\\,\\prime})^{-1}\\displaystyle{\\sum_{i=1}^{N^{\\,\\prime}}g^{2}_{i}}-\\Big[(N^{\\,\\prime})^{-1}\\displaystyle{\\sum_{i=1}^{N^{\\,\\prime}}g_{i}\\Big]^{2}}}{\\Big[(N^{\\,\\prime})^{-1}\\displaystyle{\\sum_{i=1}^{N^{\\,\\prime}}g_{i}\\Big]^{2}}}\\label{error}\\end{aligned}$$\n\nwhere $N^{\\prime}=10$ and now $g_{i}$ stands for the number of events falling inside a certain bin in each of the $i=1,...,N^{\\prime}$ samples.", "\n\nWe show in Figs. ", "\\[1\\]-\\[4\\] four of the ten sets obtained with the simulation. ", "We also take a different bin, 6.28 MeV, to facilitate the comparison with the data of [@nakatwo]. ", "The error obtained with Eq. (", "\\[error\\]) is of the order of 20 % for the bins around $M_{K^{+}n}=1530$ MeV. The runs required 1210 million Monte Carlo points. ", "We can see that in one of the runs we obtain a statistical fluctuation of about 20 counts over the peak at 1530 MeV of Fig. ", "\\[pentamore\\_Lambda\\], indicating that, with these errors, statistical fluctuations of about the magnitude of the $\\Theta^{+}$ peak seen in [@nakatwo] are possible. ", "These errors in the simulation are similar to those of Figs. ", "\\[penta\\], \\[pentaLamb\\] using the Monte Carlo integral method, where similar statistical fluctuations were also observed. ", "It is also interesting to note that, like in the integration method, with the simulation we also observe clear peaks around 1530 MeV in about $1/3$ of the runs, and accumulation of strength in that region in practically all of them.", "\n\n![(", "Color online) $M_{K^{+}n}$ distribution calculated with the MMSA prescription and the same cuts as those done in [@nakatwo] for 3098 events.[]{data-label=\"1\"}](KpneuVN_2_1_1_full_model_1.eps){width=\"55.00000%\"}\n\n![(", "Color online) $M_{K^{+}n}$ distribution obtained with the MMSA prescription and the same cuts as those done in [@nakatwo] for 2523 events and a different seed than for Fig. ", "\\[1\\] for the simulation run.[]{data-label=\"2\"}](KpneuVN_2_1_1_full_model_2.eps){width=\"55.00000%\"}\n\n![(", "Color online) $M_{K^{+}n}$ distribution calculated with the MMSA prescription and the same cuts as those done in [@nakatwo] for 2627 events and a different seed than for Figs. ", "\\[1\\], \\[2\\] for the simulation run.[]{data-label=\"3\"}](KpneuVN_2_1_1_full_model_3.eps){width=\"55.00000%\"}\n\n![(", "Color online) $M_{K^{+}n}$ distribution calculated with the MMSA prescription and the same cuts as those done in [@nakatwo] for 2502 events and a different seed than for Figs. ", "\\[1\\], \\[2\\], \\[3\\] for the simulation run.[]{data-label=\"4\"}](KpneuVN_2_1_1_full_model_4.eps){width=\"55.00000%\"}\n\n Figure “exact” reference $\\chi^{2}/d.o.f$\n -------------------- --------------------------------------- ------------------\n Fig. ", "\\[penta\\] Fig. ", "\\[pentamore\\] 1.50\n Fig. ", "\\[pentades\\] High statistic run with the same cuts 2.33\n Fig. ", "\\[pentaLamb\\] Fig. ", "\\[pentamore\\_Lambda\\] 1.65$^{\\,a}$\n Fig. ", "\\[1\\] Averaged ten Von Neumann runs 0.67\n Fig. ", "\\[2\\] Idem 1.81\n Fig. ", "\\[3\\] Idem 0.56\n Fig. ", "\\[4\\] Idem 1.00\n\n : Values of $\\chi^{2}/d.o.f$ for different figures in the paper. ", "$^{a}$Three points of the tail of the $M_{K^{+}n}$ distribution, around 1800-1850 MeV, of no relevance to the “$\\Theta^{+}$” peak have been omitted in this evaluation of $\\chi^{2}/d.o.f$.[]{data-label=\"t1\"}\n\nWe also can do another test of the statistical significance of our runs. ", "For this we can take advantage of the fact that we know the “exact\" curve from our large statistic integration, Fig. ", "\\[pentamore\\] for the $\\phi$ production model and Fig. ", "\\[pentamore\\_Lambda\\] for the full model, or the average of the ten Von Neumann runs, which is already practically equal to Fig. ", "\\[pentamore\\_Lambda\\]. ", "Then we can take the standard $\\chi^{2}$ function of any run with respect to the exact curve. ", "The $\\chi^{2}$ is defined as\n\n$$\\begin{aligned}\n \\chi^2= \\sum_{i}\\frac{(f_i -f_{i}^{exact})^2}{\\tilde{\\sigma}^2}\\end{aligned}$$\n\nwhere for $\\tilde{\\sigma}$ we take $\\sqrt{f_i}$. All the curves are normalized to the number of events in the LEPS experiment, 1967 events for the $K^{+}n$ invariant mass. ", "In Table \\[t1\\] we show the reduced $\\chi^2$ (we have divided the $\\chi^{2}$ by the number of degrees of freedom (d.o.f) which corresponds to the number of bins used) for the different figures that we have used in the discussion.", "\n\nWe can see that the $\\chi^{2}/d.o.f$ is between 0.56 and 1.81 for the Von Neumann runs. ", "The statistical significance of the results of Fig. ", "\\[penta\\], and particularly, Fig. ", "\\[pentaLamb\\], which is done with the full model, is similar to that of the Von Neumann runs. ", "The $\\chi^{2}/d.o.f$ for Fig. ", "\\[pentades\\] is a bit bigger than in the other cases. ", "This run was obtained using the same seed as in Fig. ", "\\[penta\\] (equivalent to having the same experiment) and making a different cut. ", "This figure is done with $\\phi$ production alone and not the full model, so the results are only indicative. ", "One can make a run with more points to have a smaller $\\chi^{2}/d.o.f$ but the results do not change qualitatively. ", "However, Fig. ", "\\[pentades\\] with the same seed as Fig. ", "\\[penta\\], a similar number of points, and a different cut is more significative because it gives a hint of what might happen in the experiment, having a different shape than Fig. ", "\\[penta\\] and producing larger fluctuations. ", "We do not have the experimental data for this cut and hence one cannot compare like in the other cases.", "\n\nAn interesting test that we can do to compare with the LEPS results is the distribution of $p_{min}$. This is done in Fig. ", "\\[pmin\\] using the full model, i.e, including $\\phi$ and $\\Lambda(1520)$ production. ", "We can see that we get one sharp peak around zero extending up to about -100 MeV to 100 MeV. The results are remarkably similar to those obtained in the LEPS experiment (see Fig. ", "4 of [@nakatwo]). ", "Now it is equally interesting to make a plot for the distribution of proton momenta in the real case. ", "In Fig. ", "\\[pl\\] we show the real distribution of the proton momentum component along the direction of $\\vec{p}_{miss}$. We find a peak similar to the one of $p_{min}$, and a second broad peak, around 500 MeV, corresponding to protons which in the CM frame of the $np$ final state go in the same direction of $\\vec{p}_{miss}$ rather than opposite to it, which is the situation that leads to $p_{min}$. In the LEPS analysis these latter events would be given a momentum $\\vec{p}_{min}$ and no transverse component to the direction of $\\vec{p}_{miss}$. This transverse component is also interesting to investigate. ", "In Fig. ", "\\[pt\\] we show the distribution for the modulus of the transverse proton momentum component, $\\vec{p}_{T}$. As we can see, the distribution peaks around 50 MeV and stretches up to about 200 MeV.\n\n![(", "Color online) $p_{min}$ distribution.[]{data-label=\"pmin\"}](p_min_Naka.eps){width=\"70.00000%\"}\n\n![(", "Color online) Distribution for the real proton momentum component along the $\\vec{p}_{miss}$ direction.[]{data-label=\"pl\"}](ppro_real.eps){width=\"70.00000%\"}\n\n![(", "Color online) Distribution for the modulus of the real transverse proton momentum component, $|\\vec{p}_{T}|$.[]{data-label=\"pt\"}](ppro_trans.eps){width=\"70.00000%\"}\n\nIt is easy to identify the sharp narrow peak of Fig. ", "\\[pl\\] with events where the proton is a spectator ($\\phi$ production on the neutron), while the broad peak would come from events of $\\Lambda(1520)$ or $\\phi$ production on the proton, where the neutron would be a spectator.", "\n\nA complement to the further discussion can be seen in Fig. ", "\\[Minvnaka\\_real\\], where we show a two dimensional plot for the correlation between the $K^{+}n$ invariant mass evaluated with the MMSA prescription and the real one. ", "The events for which the two magnitudes are evaluated have been generated using the Von Neumann rejection method. ", "We observe a relatively large dispersion of the points with respect to a diagonal line where the two invariant masses would be equal. ", "Actually, we see two blocks of points, one around the diagonal and another one to the right of the diagonal at large $K^{+}n$ invariant masses. ", "It is easy to identify the first block with the mechanism where the proton is a spectator while the second block corresponds to events where the neutron is the spectator. ", "In order to visualize this assertion, we run again the simulation removing the $\\Lambda(1520)$ and $\\phi$ production on the proton and the double scattering. ", "We show the results in Fig. ", "\\[Minvnaka\\_real\\_singleterm\\]. ", "As we can see, now there is a very good correlation between the two invariant masses and the MMSA prescription should be a good tool to analyze a mechanism of this type. ", "Of course, in the actual reaction one has both contributions from $\\gamma$ scattering with the proton and the neutron and the realistic situation of the correlation between the two invariant masses is the one given in Fig. ", "\\[Minvnaka\\_real\\].", "\n\n![(", "Color online) $M_{K^{+}n}$ calculated using the MMSA prescription versus $M_{K^{+}n}$ obtained with the real momentum for the nucleons and the full model, i.e., $\\phi$ production on the nucleons and $\\Lambda(1520)$ production on the proton.[]{data-label=\"Minvnaka_real\"}](Minv_Kpneu_with_MMSA_and_real.eps){width=\"50.00000%\"}\n\n![(", "Color online) $M_{K^{+}n}$ calculated using the MMSA prescription versus $M_{K^{+}n}$ obtained with the real momentum for the nucleons omitting the double scattering, $\\phi$ production on the proton and $\\Lambda(1520)$ production on the proton.[]{data-label=\"Minvnaka_real_singleterm\"}](Minv_Kpneu_with_MMSA_and_real_singleterm.eps){width=\"50.00000%\"}\n\nThe simulation runs, which require a large number of Monte Carlo points to get a few thousand of events, are suited to the actual experiment, and one should admit the same errors in the experiment of [@nakatwo] as we have found here. ", "Also one should be ready to admit the possibility to have in the experiment the same statistical fluctuations over the peak of the large statistic distribution generated with the MMSA prescription.", "\n\nThere is one further element in favor of the former argumentation of the statistical fluctuations. ", "In Fig. ", "10(a) of [@nakatwo] we see in the spectrum of the $M_{K^- p}$ a peak of about 20 events per bin around 1650 MeV. This peak is assumed in [@nakatwo] to be a statistical fluctuation, since in Fig. ", "16 of [@nakatwo], making a cut $M_{K^+ K^-}>$ 1500 MeV, the peak disappears. ", "Then one should note that the peak in $M_{K^+ n}$ seen at LEPS around 1526 MeV, when subtracted from the “real\" large statistics spectrum of our Fig. ", "\\[pentamore\\_Lambda\\], corresponds also to about 20 events per bin ( see Fig. ", "12 of [@nakatwo]). ", "The justification of the peak in the $M_{K^- p}$ spectrum as a statistical fluctuation has as a consequence the acceptance that the peak in the $M_{K^+ n}$ can equally be a statistical fluctuation. ", "The large statistics calculation done here is important in this respect because it establishes the starting point from where to count the fluctuation. ", "Since one already starts from a “resonant like\" structure around 1530 MeV, the diversion of the data of LEPS over this realistic spectrum is smaller than one might assume by inspection of Fig. ", "12 of [@nakatwo] alone.", "\n\nConclusions\n===========\n\nWe have made a simulation of the $\\gamma d\\to K^{+}K^{-}np$ reaction using a theoretical model that accounts for $\\phi$ and $\\Lambda(1520)$ production, the two visible resonance structures in the reaction of LEPS [@nakatwo]. ", "The model takes into account rescattering of one of the kaons with the second nucleon in the deuteron.", "\n\nA Monte Carlo simulation of the reaction was done and distributions of $K^{+}n$ and $K^{-}p$ invariant masses were reconstructed. ", "One of the elements in the LEPS analysis was the consideration of a $p_{min}$ of the nucleons, by means of which one could minimize the effect of Fermi motion of the nucleons in the deuteron and make an educated guess for the final, undetected neutron or proton momentum (MMSA prescription). ", "We could see that the procedure allows to recognize a resonance if it is present in the theoretical amplitude. ", "However, we also saw that the MMSA procedure, together with the cuts to eliminate the $\\phi$ contribution, lead to a “resonant like\" structure around 1530 MeV in the $K^{+}n$ mass distribution, which we could show with a large statistics run. ", "Since the peak seen at LEPS is narrower than this “resonant like\" structure, we made a thorough statistical analysis of the process to see if a statistical fluctuation could be responsible for it. ", "For this purpose we made several simulation runs using the Von Neumann rejection method to generate events weighted by their probability of production, much as a Quantum Mechanical experiment does. ", "The statistical study of these runs with a similar number of events as in the experiment [@nakatwo] provided the intrinsic error. ", "These runs showed that a fluctuation over the peak generated by the MMSA prescription and the LEPS cuts around 1530 MeV was possible, with a similar size as the peak seen in [@nakatwo]. ", "On the other hand, in the $M_{K^- p}$ spectrum of [@nakatwo] there is a peak around 1650 MeV which was assumed to be a statistical fluctuation since it disappeared making a slightly different $\\phi$ cut. ", "Then, using the spectrum obtained with high statistics Monte Carlo runs we could see that the peak in $M_{K^+ n}$ in [@nakatwo] over this realistic spectrum has the same strength as the peak in $M_{K^- p}$, which was assumed to be a fluctuation in [@nakatwo]. ", "The parallel study done at LEPS of the $M_{K^- p}$ spectrum has thus served to set a scale for the statistical fluctuations in the LEPS experiment, in such a way that one can accept the $M_{K^+ n}$ peak as a statistical fluctuation like the one admitted in [@nakatwo] for the peak in the $M_{K^- p}$ spectrum which has the same strength.", "\n\nAnother point worth making is that we could see in our Monte Carlo runs that for a same seed (equivalent to having a unique experiment) and different $\\phi$ cuts, the $M_{K^{+}n}$ spectra changes appreciably, to the point that for some cuts the peak around 1530 MeV looks more prominent than for others. ", "This means that, in principle, it is possible to convert an original fluctuation into one more pronounced by suitable changes in the cuts, which should be considered as a warning when analyzing this type of experiments. ", "In fact, as mentioned above, the use of a $\\phi$ cut $M_{K^{+}K^{-}}>$ 1050 MeV does not lead to a peak around $M_{K^{-}p}\\sim 1650$ MeV in the experiment of [@nakatwo], while the main $\\phi$ cut used in [@nakatwo] gives rise to a peak at this value of the $M_{K^{-}p}$ invariant mass.", "\n\nAcknowledgments {#acknowledgments .unnumbered}\n===============\n\nThis work is partly supported by the DGICYT contract FIS2006-03438, the Generalitat Valenciana in the program Prometeo and the EU Integrated Infrastructure Initiative Hadron Physics Project under Grant Agreement n.227431. ", "One of the authors (A. M. 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[ "Tracer Talk\n\nSchools, churches, theaters, concert venues. ", "These are all places that you should feel secure and safe. ", "But as seen in recent tragic events in Las Vegas; Sutherland Springs, Texas; Aurora, Colorado; Newtown, Connecticut – that isn’t always the case.", "\n\nNo product can prevent these tragedies, but Shot Tracer® can help law enforcement and emergency services be alerted sooner to minimize the victim count.", "\n\nShot Tracer Eagle is a unique gunshot detection sensor. ", "The Eagle can operate in three configurations:\n\nAdapted to your existing alarm panel using contact closures without any additional hardware,\n\nStandalone utilizing the Shot Tracer IP alert notification system over cellular, or\n\nAdded to your existing IP based alarm system using JSON or CID formatted data.", "\n\nOther products require you to have their system first, then you can add their sensors. ", "This means that Shot Tracer can be a single standalone sensor where nothing more than power is needed to operate. ", "Other gunshot alert companies require you to buy their system and install their server hardware and software before adding any sensors. ", "The Shot Tracer difference equates to monetary savings, increased reliability, no single points of failure and a much easier integration.", "\n\nDo you want to try one of our sensors? ", "All you need is the sensor – and you’re ready.", "\n\nStart out the new year right with a security product that is markedly more affordable and easier to integrate than other products and keep your customers, friends and family safe." ]

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[ "El vicepresidente de la UDI, Gustavo Hasbún emplazó al diputado y ex presidente gremialista, Patricio Melero a que evalúe su gestión cuando estuvo a la cabeza de la colectividad entre 2012 y 2014, argumentando que fue la peor gestión que ha tenido el partido.", "\n\nEsto, en respuesta a la solicitud de Melero de realizar un consejo directivo ampliado, para evaluar la continuidad de la directiva, encabezada por el diputado Ernesto Silva.", "\n\nLee también: Melero pide evaluación de directiva UDI durante consejo ampliado del partido\n\nHasbún afirmó que hay que ser bastante cuidadoso con las declaraciones que se dan, ya que a la actual directiva le tocó asumir los errores de la anterior. ", "En esa línea, el legislador dijo que si bien el Caso Penta explotó este año, las irregularidades vienen de la gestión de Patricio Melero.", "\n\nEl parlamentario fue más allá y dijo que la gestión de Melero ha sido la peor que ha tenido la UDI, en donde también se tuvo la peor derrota electoral, siendo que se tenía el mejor escenario, argumentando que eran gobierno, tenían buenos candidatos y no existía el tema Penta.", "\n\nLa arista política del Caso Penta sigue trayendo divisiones internas al interior de la UDI y críticas desde su partido aliado, Renovación Nacional. ", "A esto se sumó el rechazo histórico de la ciudadanía, reflejado en la última encuesta Adimark.", "\n\nEn este escenario el vicepresidente de la UDI, Gustavo Hasbún salió a respaldar la gestión de la actual directiva. ", "El parlamentario emplazó al diputado y ex presidente gremialista, Patricio Melero a que evalúe la gestión que tuvo cuando estuvo a la cabeza de la colectividad entre 2012 y 2014, argumentando que fue la peor gestión que ha tenido el partido.", "\n\nEsto en respuesta a la solicitud de Melero de realizar un consejo directivo ampliado, para evaluar la continuidad de la directiva, encabezada por el diputado Ernesto Silva.", "\n\nHasbún afirmó que hay que ser bastante cuidadoso con las declaraciones que se dan, ya que a la actual directiva le tocó asumir los errores de la anterior. ", "En esa línea, el legislador dijo que si bien el Caso Penta explotó este año, las irregularidades vienen de la gestión de Patricio Melero.", "\n\nEl parlamentario fue más allá y dijo que la gestión de Melero ha sido la peor que ha tenido la UDI, en donde también se tuvo la peor derrota electoral, siendo que se tenía el mejor escenario, argumentando que eran gobierno, tenían buenos candidatos y no existía el tema penta, y que fue debido a la falta de liderazgo del ex líder.", "\n\nEn tanto, la senadora también de la UDI, Jacqueline Van Rysselberghe dijo que efectivamente se debe hacer un consejo directivo ampliado como lo planteó Melero, pero no para evaluar la continuidad de la directiva, sino que para apelar a la unidad del sector.", "\n\nUna posición más neutra tuvo el jefe de bancada de la colectividad, Felipe Ward quien dijo la directiva es la que debe determinar si hacer un consejo directivo ampliado o no. ", "Ward afirmó que hay que evitar hacer declaraciones sobre la continuidad de la actual mesa.", "\n\nLos cuestionamientos no sólo vienen del interior de la UDI, sino también de su partido aliado, quien había evitado las confrontaciones. ", "El senador Manuel José Ossandón emplazó al gremialismo a asumir responsabilidades institucionales. ", "Además, dijo que los militantes que están involucrados en el caso Penta, deberían dar un paso al costado.", "\n\nEl vicepresidente de RN, Luis Mayol le quitó el peso a las críticas del senador Ossandón. ", "Mayol afirmó que corresponden a opiniones y que en RN no han tomado ninguna determinación de decirle a la UDI qué es lo que deben hacer.", "\n\nMientras que en Renovación Nacional insistieron en que han sido acarreados por el caso Penta, en la UDI calificaron de injustas las palabras de su partido aliado, argumentando que el financiamiento de la política es un problema que afecta a todos." ]

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