niryuu/sni-each-converted huggingface dataset:
The VISTA-16 trial of varespladib, a secretory phospholipase A2 (sPLA2) inhibitor, in patients with an acute coronary syndrome was terminated prematurely owing to futility and a signal towards harm. Despite these discouraging results, therapies that target inflammation to modify pathways in atherogenesis remain an area of active investigation.
Output: Which enzyme is inhibited by Varespladib?
In US, the potato is one of the most widely consumed crops. French fries are commonly found in typical American fast-food burger joints and cafeterias. French fries were introduced to the US when Thomas Jefferson served them in the White House during his presidency from 1801 t0 1809. Potato chips are popular with consumers as well. The humble potato is more than just a kind of food. In many ways it's part of the American pop culture. Let's take a look at some pop culture potatoes. Mashed Potato dance The Mashed Potato dance is a craze that began in 1962. The name of the dance came from the song it accompanies, Mashed Potato Time, performed by American R&B singer Dee Dee Sharp. The move vaguely resembles that of the Twist dance style, by Sharp's fellow Philadelphian, Chubby Checker. Hot Potato! Hot Potato! is an action puzzle video game released in 2001. In the game the player must drive a bus and clear the road of alien potato beings. The potato beings are either red or blue; when two like-colored potatoes touch each other, they disappear. .Over the years, Hot Potato! has received mostly positive reception from critics. Mr. Potato Head Mr. Potato Head is an American toy invented by George Lerner in 1949. The toy consists of a plastic potato model and a variety of plastic parts like hands, feet, ears and mouths. In 1952, Mr. Potato Head became the first toy advertised on television. This commercial revolutionized marketing and caused a boom that solidified this toy's place in American pop culture.
Output: Which is the newest to the American pop culture?
Liu Rushi (Chinese: ; pinyin: Liu Rushi; Wade--Giles: Liu Ju-shih; 1618--1664), also known as Liu Shi, Liu Yin and Yang Yin, was a Chinese courtesan and poet in the late Ming dynasty who married Qian Qianyi at the age of 25.
Output: What is Liu Rushi's spouse's name?
We show that overexpression of Polo-like kinase 4 (Plk4) in human cells induces centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole. This provided an opportunity for dissecting centriole assembly and characterizing assembly intermediates. Critical components were identified and ordered into an assembly pathway through siRNA and localized through immunoelectron microscopy. Plk4, hSas-6, CPAP, Cep135, gamma-tubulin, and CP110 were required at different stages of procentriole formation and in association with different centriolar structures. Remarkably, hSas-6 associated only transiently with nascent procentrioles, whereas Cep135 and CPAP formed a core structure within the proximal lumen of both parental and nascent centrioles. Finally, CP110 was recruited early and then associated with the growing distal tips, indicating that centrioles elongate through insertion of alpha-/beta-tubulin underneath a CP110 cap. Collectively, these data afford a comprehensive view of the assembly pathway underlying centriole biogenesis in human cells.
Output: Where in the cell do we find the protein Cep135?
In neurodegenerative diseases, it remains unclear why certain brain regions are selectively vulnerable to protein aggregation. In transgenic mice expressing human A53T -synuclein, the brainstem and spinal cord develop the most prominent -synuclein inclusions which correlate with age-dependent motor dysfunction. Herein we present the novel finding that this selective aggregation is in part dependent on the inability of chaperone-mediated autophagy (CMA) to effectively degrade -synuclein in these brain regions. Lysosomal assays revealed that CMA activity was significantly decreased in aggregation-prone regions compared to the remainder of the brain. Previously, CMA activity has been shown to be proportional to levels of the CMA receptor Lamp-2a. Using antibodies, brain tissue from Lamp-2a null mice, enzymatic deglycosylation, and mass spectrometry, we identified Lamp2a as a novel 72kDa glycoprotein in the mouse brain. Examination of Lamp-2a levels revealed differences in expression across brain regions. The brainstem and the spinal cord had a more than three-fold greater levels of Lamp-2a as compared to regions less vulnerable to aggregation and exhibited a selective upregulation of Lamp-2a during development of -synuclein inclusions. Despite this dynamic response of Lamp-2a, the levels of substrates bound to the brain lysosomes as well as the rates of substrate uptake and degradation were not proportional to the levels of Lamp-2a. These regional differences in CMA activity and Lamp-2a expression were found in both non-transgenic mice as well as A53T -syn mice. Therefore, these are inherent variations and not a transgene-specific effect. However, differences in CMA activity may render select brain regions vulnerable to homeostatic dysfunction in the presence of stressors such as overexpression of human A53T -syn. Collectively, the data provide a potential mechanism to explain the dichotomy of vulnerability or resistance that underlies brain regions during aggregate formation in neurodegenerative disease.
Output: Which is the receptor for substrates of Chaperone Mediated Autophagy?
Civic Choice (Italian: Scelta Civica, SC) is a centrist and liberal political party in Italy founded by Mario Monti.
Output: Who led Civic Choice?
A new canal with a port in Furth, the Rhine-Main-Danube Canal, was completed in 1992, creating a navigable connection from the Rhine delta in Rotterdam to the Danube Delta on the Black Sea.
Output: What body of water was Fürth next to?
The mammalian target of rapamycin (mTOR) has been suggested as a target for radiosensitization. Given that radiotherapy is a primary treatment modality for glioblastoma (GBM) and that mTOR is often dysregulated in GBM, the goal of this study was to determine the effects of AZD2014, a dual mTORC1/2 inhibitor, on the radiosensitivity of GBM stem-like cells (GSCs). mTORC1 and mTORC2 activities were defined by immunoblot analysis. The effects of this mTOR inhibitor on the in vitro radiosensitivity of GSCs were determined using a clonogenic assay. DNA double strand breaks were evaluated according to H2AX foci. Orthotopic xenografts initiated from GSCs were used to define the in vivo response to AZD2014 and radiation. Exposure of GSCs to AZD2014 resulted in the inhibition of mTORC1 and 2 activities. Based on clonogenic survival analysis, addition of AZD2014 to culture media 1 hour before irradiation enhanced the radiosensitivity of CD133+ and CD15+ GSC cell lines. Whereas AZD2014 treatment had no effect on the initial level of H2AX foci, the dispersal of radiation-induced H2AX foci was significantly delayed. Finally, the combination of AZD2014 and radiation delivered to mice bearing GSC-initiated orthotopic xenografts significantly prolonged survival as compared with the individual treatments. These data indicate that AZD2014 enhances the radiosensitivity of GSCs both in vitro and under orthotopic in vivo conditions and suggest that this effect involves an inhibition of DNA repair. Moreover, these results suggest that this dual mTORC1/2 inhibitor may be a radiosensitizer applicable to GBM therapy.
Output: What does mTOR stands for?
Neurofibromatosis type 1 (NF1) is a common genetic disease caused by haploinsufficiency of the NF1 tumor-suppressor gene. Different pathogenetic mechanisms have been identified, with the majority (95%) causing intragenic lesions. Single or multiexon NF1 copy number changes occur in about 2% of patients, but little is known about the molecular mechanisms behind these intragenic deletions. We report here on the molecular characterization of a novel NF1 multiexonic deletion. The application of a multidisciplinary approach including multiplex ligation-dependent probe amplification, allelic segregation analysis, and fluorescent in situ hybridization allowed us to map the breakpoints in IVS27b and IVS48. Furthermore, the breakpoint junction was characterized by sequencing. Using bioinformatic analysis, we identified some recombinogenic motifs in close proximity to the centromeric and telomeric breakpoints and predicted the presence of a mutated messenger ribonucleic acid, which was deleted between exons 28 and 48 and encodes a neurofibromin that lacks some domains essential for its function. Through reverse transcriptase-polymerase chain reaction, the expression of the mutated allele was verified, showing the junction between exons 27b and 49 and, as expected, was not subjected to nonsense-mediated decay. Multiexonic deletions represent 2% of NF1 mutations, and until now, the breakpoint has been identified in only a few cases. The fine characterization of multiexonic deletions broadens the mutational repertoire of the NF1 gene, allowing for the identification of different pathogenetic mechanisms causing NF1.
Output: Which is the gene mutated in type 1 neurofibromatosis?
The SWR1 complex replaces the canonical histone H2A with the variant H2A.Z (Htz1 in yeast) at specific chromatin regions. This dynamic alteration in nucleosome structure provides a molecular mechanism to regulate transcription, gene silencing, chromosome segregation and DNA repair. Here we show that genetic instability, sensitivity to drugs impairing different cellular processes and genome-wide transcriptional misregulation in htz1Delta can be partially or totally suppressed if SWR1 is not formed (swr1Delta), if it forms but cannot bind to chromatin (swc2Delta) or if it binds to chromatin but lacks histone replacement activity (swc5Delta and the ATPase-dead swr1-K727G). These results suggest that in htz1Delta the nucleosome remodelling activity of SWR1 affects chromatin integrity because of an attempt to replace H2A with Htz1 in the absence of the latter. This would impair transcription and, either directly or indirectly, other cellular processes. Specifically, we show that in htz1Delta, the SWR1 complex causes an accumulation of recombinogenic DNA damage by a mechanism dependent on phosphorylation of H2A at Ser129, a modification that occurs in response to DNA damage, suggesting that the SWR1 complex impairs the repair of spontaneous DNA damage in htz1Delta. In addition, SWR1 causes DSBs sensitivity in htz1Delta; consistently, in the absence of Htz1 the SWR1 complex bound near an endonuclease HO-induced DSB at the mating-type (MAT) locus impairs DSB-induced checkpoint activation. Our results support a stepwise mechanism for the replacement of H2A with Htz1 and demonstrate that a tight control of this mechanism is essential to regulate chromatin dynamics but also to prevent the deleterious consequences of an incomplete nucleosome remodelling.
Output: Which protein mediates the replacement of H2A by H2A.Z in the yeast Saccharomyces cerevisiae?
Jozef Cyrek (born 13 September 1904 in Bysina; d. 2 September 1940 at Auschwitz) was a Polish writer and Roman Catholic clergyman, member of the Society of Jesus involved in the religious publishing industry, who shortly after the Nazi invasion of Poland was arrested by the Gestapo, imprisoned at several places of detention, and lastly deported to the Auschwitz concentration camp where he was murdered.
Output: To which religious order did Józef Cyrek belong?
Cyclosporine mediates its immunosuppressive effect by preventing the synthesis of lymphokine mRNA during the process of T lymphocyte activation. Although the detailed molecular mechanism by which CsA achieves this effect is unknown, two proteins have been identified as putative intracellular CsA-receptor proteins. One of these, calmodulin, is an important Ca++-binding protein and enzyme cofactor and the other, cyclophilin, is a novel protein that is reported to have protein kinase activity. In this study the CsA-binding capacity of both these proteins has been assessed using CsA-coated ELISA plates and CsA-affinity gel matrices. CsA binding was shown by cyclophilin whereas no CsA-calmodulin binding could be detected under identical conditions. However, it was not possible to demonstrate any cyclophilin-associated protein kinase activity. Jurkat cells were probed for the presence of CsA-binding proteins using the CsA-affinity gel matrix; a 17 KD protein, most probably cyclophilin, was identified as the major CsA-binding protein. In addition, a previously unidentified CsA-binding 45 KD phosphoprotein was precipitated from 32P-labeled Jurkat cells. These results would support cyclophilin as the major, if not only, intracellular receptor protein for CsA. However, the relationship between binding of CsA to cyclophilin and/or the 45 KD phosphoprotein and the immunosuppressive effects of CsA is still unknown.
Output: Which is the receptor for the immunosuppressive drug cyclosporin A (CsA)?
Judge and the Forest (Bulgarian: , translit. Sledovatelyat i gorata) is a 1975 Bulgarian drama film directed by Rangel Vulchanov.
Output: The year that Judge and the Forest was made was what?
Malformation of cortical development (MCD) is a well-known cause of drug-resistant epilepsy and focal cortical dysplasia (FCD) is the most common neuropathological finding in surgical specimens from drug-resistant epilepsy patients. Palmini's classification proposed in 2004 is now widely used to categorize FCD. Recently, however, Blumcke et al. recommended a new system for classifying FCD in 2011. We applied the new classification system in practical diagnosis of a sample of 117 patients who underwent neurosurgical operations due to drug-resistant epilepsy at Severance Hospital in Seoul, Korea. Among 117 cases, a total of 16 cases were shifted to other FCD subtypes under the new classification system. Five cases were reclassified to type IIIa and five cases were categorized as dual pathology. The other six cases were changed within the type I category. The most remarkable changes in the new classification system are the advent of dual pathology and FCD type III. Thus, it will be very important for pathologists and clinicians to discriminate between these new categories. More large-scale research needs to be conducted to elucidate the clinical influence of the alterations within the classification of type I disease. Although the new FCD classification system has several advantages compared to the former, the correlation with clinical characteristics is not yet clear.
Output: Which disorder is rated by Palmini classification?
HD 114837 is a star in the constellation Centaurus.
Output: The star HD 114837 is part of the constellation known as what?
The British Museum Description: The British Museum is a museum in London, which is one of the world's greatest museums of human history and culture. Its collections, which number more than 13 million objects, are amongst the largest and most comprehensive in the world and originate from all continents, illustrating and documenting the story of human culture from its beginning to the present. The British Museum was established in 1753, largely based on the collections of the physician and scientist Sir Hans Sloane. The museum first opened to the public on 15 January 1759 in Montagu House in Bloomsbury, on the site of the current museum building. Its expansion over the following two and a half centuries was largely a result of an expanding British colonial footprint and has resulted in the creation of several branch institutions. Until 1997, when the British Library (previously centered on the Round Reading Room)moved to a new site, the British Museum housed both a national museum of antiquities and a national library in the same building. The museum is a non-departmental public body sponsored by the Department for Culture, Media and Sport. Since 2002 the director of the museum has been Neil MacGregor. Admission and opening hours: The museum is open every day from 10am to 6pm (Fridays 10am to 5:30pm)and it charges no admission fee, except for loan exhibitions. How to get there: By train: 7:00-18:30 every day. By Underground: 8:00-18:30 every day. By bus: 7:30-18:30 every day. By coach: 7:00--19:30 every day. Nearest underground stations: Tottenham Court Road (500m) Holborn (500m) Russell Square (800m)
Output: You are at the Museum at seven in the evening and you want to go back to Oxford. Which means of transportation will you choose?
Peter Coutts was educated at the University of Melbourne in electrical engineering but was later a post-graduate student in the School of General Studies at the Australian National University.
Output: Which college or university is related with Peter Coutts?
Mowat-Wilson syndrome (MWS) is characterized by severe mental retardation with seizures, specific facial dysmorphism, Hirschsprung disease, anomalies of the corpus callosum, and genitourinary and cardiac malformations. The cause of MWS is a de novo mutation in the ZEB2 gene. This report describes a Turkish boy who was clinically diagnosed with MWS and had his diagnosis confirmed by molecular analysis of the ZEB2 gene. The investigation identified a heterozygous complex rearrangement in exon 8 of ZEB2, specifically a 48-nucleotide deletion and a 44-nucleotide insertion that caused a frameshift. MWS is a relatively newly identified disorder, and even MWS patients without Hirschsprung disease can be diagnosed easily based on clinical findings alone.
Output: Which gene is responsible for the development of the Mowat-Wilson syndrome?
Isova is a ruined Frankish monastery in the Peloponnese, Greece, which was built after the Fourth Crusade and inhabited by Cistercian monks.
Output: To which religious order did Isova belong?
Phosphorylation of cytoplasmic polyadenylation element binding protein (CPEB) regulates protein synthesis in hippocampal dendrites. CPEB binds the 3' untranslated region (UTR) of cytoplasmic mRNAs and, when phosphorylated, initiates mRNA polyadenylation and translation. We report that, of the protein kinases activated in the hippocampus during synaptic plasticity, calcium/calmodulin-dependent protein kinase II (CaMKII) robustly phosphorylated the regulatory site (threonine 171) in CPEB in vitro. In postsynaptic density fractions or hippocampal neurons, CPEB phosphorylation increased when CaMKII was activated. These increases in CPEB phosphorylation were attenuated by a specific peptide inhibitor of CaMKII and by the general CaM-kinase inhibitor KN-93. Inhibitors of protein phosphatase 1 increased basal CPEB phosphorylation in neurons; this was also attenuated by a CaM-kinase inhibitor. To determine whether CaM-kinase activity regulates CPEB-dependent mRNA translation, hippocampal neurons were transfected with luciferase fused to a 3' UTR containing CPE-binding elements. Depolarization of neurons stimulated synthesis of luciferase; this was abrogated by inhibitors of protein synthesis, mRNA polyadenylation, and CaMKII. These results demonstrate that CPEB phosphorylation and translation are regulated by CaMKII activity and provide a possible mechanism for how dendritic protein synthesis in the hippocampus may be stimulated during synaptic plasticity.
Output: Which kinase is inhibited by the small molecule KN-93?
The War of the Spanish Succession was a European conflict of the early 18th century, triggered by the death of the childless Charles II of Spain in November 1700. His closest heirs were members of the Austrian Habsburg and French Bourbon families; acquisition of an undivided Spanish Empire or Monarchy by either threatened the European balance of power. Charles left his throne to Louis XIV's grandson Philip who was proclaimed King of Spain on 16 November 1700. Disputes over the separation of the Spanish and French crowns, division of territories and commercial rights led to war in 1701 between the Bourbons of France and Spain and the Grand Alliance, whose candidate was Archduke Charles, younger son of Habsburg Emperor Leopold. By 1710, fighting was deadlocked; Allied victories in Italy and the Low Countries had driven the French back to their borders but they could not achieve a decisive breakthrough while Philip was secure in Spain. When Archduke Charles succeeded his brother Joseph I as Emperor in 1711, Britain effectively withdrew, forcing its Allies to make peace and leading to the 1713 Treaty of Utrecht, followed in 1714 with Rastatt and Baden. Philip was confirmed as King of Spain and renounced the French throne; Spain retained the bulk of its pre-war territories outside Europe with their European territories divided between Austria, Britain and Savoy. Longer term impacts included Britain's emergence as the leading maritime and commercial power, the beginning of the decline of the Dutch Republic, the creation of a centralised Spanish state and the acceleration of the break-up of the Holy Roman Empire.
Output: Who was Emperor first, Archduke Charles or his brother Joseph I?
Imatinib mesylate (STI571, Glivec, Gleevec) is a powerful inhibitor of the tyrosine kinase activity of Bcr-Abl, the oncoprotein responsible for chronic myeloid leukemia (CML). The drug shows great efficacy in chronic phase, but is less effective in maintaining hematologic remissions in blast crisis patients. Our group has previously described several cell lines made resistant to imatinib. We now examine the question of cross-resistance to other chemotherapeutic drugs used in CML. Four paired imatinib-sensitive/resistant CML cell lines were assessed by caspase-3 and MTS assays for their proliferative response to cytosine arabinoside (Ara-C), daunorubicin (DNR), homoharringtonine (HHT) and hydroxyurea (HU), either alone or in combination with imatinib. Primary blasts from advanced-stage CML patients refractory to imatinib therapy were studied by semi-solid media clonogenic assays. We found that these drugs are generally capable of major inhibition of proliferation of the CML cell lines, although differential responses to DNR and HHT were noted between some sensitive and resistant cell line pairs, implying that resistance to imatinib may confer a growth advantage under such conditions. The four drugs were also effective in preventing the formation of progenitor cell colonies from CML patients both before treatment with imatinib, and after relapse on the drug. Isobolographic analysis implied that these drugs will generally combine well with imatinib, and in some cases will be synergistic. We conclude that Ara-C, DNR or HHT, either alone or in combination with imatinib, are likely to be the best therapeutic alternatives in the management of patients who become resistant to imatinib monotherapy.
Output: What tyrosine kinase, involved in a Philadelphia- chromosome positive chronic myelogenous leukemia, is the target of Imatinib (Gleevec)?
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Despite significant progresses in the last decades, the origin of this cancer remains unclear and no efficient therapy exists. PDAC does not arise de novo: three remarkable different types of pancreatic lesions can evolve towards pancreatic cancer. These precursor lesions include: Pancreatic intraepithelial neoplasia (PanIN) that are microscopic lesions of the pancreas, Intraductal Papillary Mucinous Neoplasms (IPMN) and Mucinous Cystic Neoplasms (MCN) that are both macroscopic lesions. However, the cellular origin of these lesions is still a matter of debate. Classically, neoplasm initiation or progression is driven by several genetic and epigenetic alterations. The aim of this review is to assemble the current information on genetic mutations and epigenetic disorders that affect genes during pancreatic carcinogenesis. We will further discuss the interest of the genetic and epigenetic alterations for the diagnosis and prognosis of PDAC. Large genetic alterations (chromosomal deletion/amplification) and single point mutations are well described for carcinogenesis inducers. Mutations classically occur within key regions of the genome. Consequences are various and include activation of mitogenic pathways or silencing of apoptotic processes. Alterations of K-RAS, P16 and DPC4 genes are frequently observed in PDAC samples and have been described to arise gradually during carcinogenesis. DNA methylation is an epigenetic process involved in imprinting and X chromosome inactivation. Alteration of DNA methylation patterns leads to deregulation of gene expression, in the absence of mutation. Both genetic and epigenetic events influence genes and non-coding RNA expression, with dramatic effects on proliferation, survival and invasion. Besides improvement in our fundamental understanding of PDAC development, highlighting the molecular alterations that occur in pancreatic carcinogenesis could provide new clinical tools for early diagnosis of PDAC and the molecular basis for the development of new effective therapies.
Output: Which is the molecular mechanism underlying K-ras alterations in carcinomas?
An annoying problem for humans, who like to boast about all the distant planets and moons we have explored, is that we've never taken a good look right under our noses. The inside of the earth is relatively close, but how can we get there? The deepest oil well enters a mere six miles into the crust (the center of the earth is about 4,000 miles deeper). Russian scientists dug the deepest hole in Siberia, but bottomed out at about 7.5 miles below the surface. The Mohole project, a U.S. plan in the 1950s, called for drilling a hole 25 miles down to the boundary between the hard rocks of the crust and the soft mantle . Sadly the project involved government supporting. It gets harder and harder to drill deep into the earth because rocks get softer and softer. Hard but easily broken at the surface, rocks become plastic at depth, and the pressure caused by the weight of the overlaying crust --- about 52,800 pounds per square inch at a depth of ten miles, makes further drilling impossible. What little we know about the inside of the earth (like the fact that there's a crust, a mantle, and a core) comes from indirect evidence, such as the analysis of earthquakes. So maybe it's time for a thorough new method to explore the earth's inside. Scientist David Stevenson says we should forget about drilling holes. Instead, we should open a crack . Stevenson suggests digging a crack about a half mile long, a yard wide, and a half mile deep (not with a shovel) but with an explosion on the scale of a nuclear bomb. Next, he'd pour a few hundred thousand tons of molten iron into the crack, along with a robot. The iron, thicker than the surrounding crust, would move downward at about 16 feet per second, carrying the robot with it and opening the crack deeper and deeper. The iron mass would drop for about a week and 2,000 miles to the outer edge of the earth core, the robot sending out data to the surface. Stevenson compares his idea to space exploration. "We're going somewhere we haven't been before,"he says. "In all possibility, there will be surprises." This idea can probably be put in the drawer marked with Isn't Going To Happen. The robot would have to survive temperatures that would melt pretty much anything. But Stevenson's idea may inspire a new look at an old problem. Great things can come from what seems like impossible ideas.
Output: How deep have we gone into the earth until now?
DNA damage is preferentially repaired in the transcribed strand of many active genes. Although the concept of DNA repair coupled with transcription has been widely accepted, its mechanisms remain elusive. We recently reported that in Chinese hamster ovary cells while ultraviolet light-induced cyclobutane pyrimidine dimers (CPDs) are preferentially repaired in the transcribed strand of dihydrofolate reductase gene, CPDs are efficiently repaired in both strands of adenine phosphoribosyltransferase (APRT) locus, in either a transcribed or nontranscribed APRT gene (1). These results suggested that the transcription dependence of repair may depend on genomic context. To test this hypothesis, we constructed transfectant cell lines containing a single, actively transcribed APRT gene, integrated at different genomic sites. Mapping of CPD repair in the integrated APRT genes in three transfectant cell lines revealed two distinct repair patterns, either preferential repair of CPDs in the transcribed strand or very poor repair in both strands. Similar kinetics of micrococcal nuclease digestion were seen for all three transfectant APRT gene domains and endogenous APRT locus. Our results suggest that both the efficiency and strand-specificity of repair of an actively transcribed gene are profoundly affected by genomic context but do not reflect changes in first order nucleosomal structure.
Output: Which gene strand is targeted by transcription-coupled repair (TCR)?
Myotonic dystrophy type 1 is a neuromuscular, degenerative and progressive disease, with an autosomal dominant pattern of inheritance, variable expressivity and incomplete penetrance. The genetic defect is an unstable mutation due to the expansion of the triplet CTG in the 3 unstranslated region at the DMPK gene on chromosome 19q13.3. The main objective was to study the intergenerational behavior of the DM1 mutation in order to evaluate the importance of this disease as a neurological problem that could be manageable by genetic counseling. The study involved 84 patients with clinical diagnosis of DM1 and their relatives, which were confirmed through molecular diagnosis using Southern blot and PCR. Data analysis reveals the size of the mutation presents a positive correlation with the severity of the symptoms and a negative correlation with the age of onset. Transmission of the DM1 mutation is sex and size dependent among the Costa Rican patients. There is an important increment in the size of the mutation between generations and there are no differences in mutation size respect to the transmitting sex. The worldwide intergenerational behavior of the DM1 mutation is similar in Costa Rica
Output: How is myotonic dystrophy inherited?
Net energy is the amount of useable energy available from a resource after subtracting the amount of energy needed to make the energy from that resource available. For example, every 5 barrels of oil that are made available for use require 1 barrel for extracting and refining the petroleum. What is the net energy from this process? About 4 barrels (5 barrels minus 1 barrel). What happens if the energy needed to extract and refine oil increases? Why might that happen? The energy cost of an energy resource increases when the easy deposits of that resource have already been consumed. For example, if all the nearshore petroleum in a region has been extracted, more costly drilling must take place further offshore (Figure 1.1). If the energy cost of obtaining energy increases, the resource will be used even faster. Offshore drilling is taking place in deeper water than before. It takes a lot of energy to build a deep drilling platform and to run it. The net-energy ratio demonstrates the difference between the amount of energy available in a resource and the amount of energy used to get it. If it takes 8 units of energy to make available 10 units of energy, then the net-energy ratio is 10/8 or 1.25. What does a net-energy ratio larger than 1 mean? What if the net-energy ratio is less than 1? A net-energy ratio larger than 1 means that there is a net gain in usable energy; a net-energy ratio smaller than one means there is an overall energy loss. Table 1.1 shows the net-energy ratios for some common energy sources. Energy Source Solar Energy Natural Gas Petroleum Coal-fired Electricity Net-energy Ratio 5.8 4.9 4.5 2.5-5.1 Notice from the table that solar energy yields much more net energy than other sources. This is because it takes very little energy to get usable solar energy. Sunshine is abundant and does not need to be found, extracted, or transported very far. The range for coal-fired electricity is because of the differing costs of transporting the coal. What does this suggest about using coal to generate electricity? The efficiency is greater in areas where the coal is locally mined and does not have to be transported great distances (Figure 1.2). Obtaining coal for energy takes a lot of energy. The coal must be located, extracted, refined, and transported. Because so much of the energy we use is from fossil fuels, we need to be especially concerned about using them efficiently. Sometimes our choices affect energy efficiency. For example, transportation by cars and airplanes is less energy-efficient than transportation by boats and trains.
Output: what is the amount of useable energy available from a resource after subtracting the amount of energy needed to make that energy available?
One of the major histopathological hallmarks of Alzheimer's disease (AD) is cerebral deposits of extracellular -amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP) and presenilin-1 (PS1) are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer's disease carrying different clinical APP/PS1 mutations, i.e. the 'London' (hAPPLon/PS1A246E) and 'Swedish' mutation variant (hAPPSwe/PS1E9) of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months (100 or 500 ng/kg/day, s.c.), or 7 month-old hAPPSwe/PS1E9 mice for 5 months (500 ng/kg/day, s.c.). In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1E9 mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPPLon/PS1A246E and hAPPSwe/PS1E9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.
Output: Which disease the London mutation involved in?
The European eel is a critically endangered species.
Output: What is the status of European eel?
Forbidden Paradise is a 1924 American silent drama film produced by Famous Players-Lasky and distributed by Paramount Pictures.
Output: What studio produced Forbidden Paradise?
-Synuclein (Syn), which forms amyloid fibrils, is linked to the neuronal pathology of Parkinson's disease, as it is the major fibrillar component of Lewy bodies, the inclusions that are characteristic of the disease. Oligomeric structures, common to many neurodegenerative disease-related proteins, may in fact be the primary toxic species, while the amyloid fibrils exist either as a less toxic dead-end species or even as a beneficial mechanism for clearing damaged proteins. To alter the progression of the aggregation and gain insights into the prefibrillar structures, we determined the effect of heme on Syn oligomerization by several different techniques, including native (nondenaturing) polyacrylamide gel electrophoresis, thioflavin T fluorescence, transmission electron microscopy, atomic force microscopy, circular dichroism, and membrane permeation using a calcein release assay. During aggregation, heme is able to bind the Syn in a specific fashion, stabilizing distinct oligomeric conformations and promoting the formation of Syn into annular structures, thereby delaying and/or inhibiting the fibrillation process. These results indicate that heme may play a regulatory role in the progression of Parkinson's disease; in addition, they provide insights into how the aggregation process may be altered, which may be applicable to the understanding of many neurodegenerative diseases.
Output: Which is the primary protein component of Lewy bodies?
The International Union for Conservation of Nature (IUCN) has listed the Antilles catshark under Data Deficient, as there is little known of deepwater fishery activities within its range.
Output: What status on the endangered list is Antilles catshark?
Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor, has revolutionized the treatment of Bcr-Abl positive chronic myeloid leukemia and become the standard of care for this disease. The aim of this study was evaluation and analysis of cytogenetic response in different intervals and risk groups as well as finding association between pre-treatment characteristics and later probability of achievement of major cytogenetic response. We analyzed a total of 22 adult patients with newly diagnosed Philadelphia positive early chronic phase chronic myeloid leukemia treated at our institution from June 2006 to December 2009. The median follow-up time for patients during treatment with imatinib was 25.7 months (range, 12-42 months). A complete hematologic response was achieved in all of the analyzed patients within 6 months from the start of the treatment. The major cytogenetic response rate was 81.8%, and the complete cytogenetic response rate was 72.7%. The patients with low or moderate relative risk had the rate of complementary achieving major and complete cytogenetic response of 75-90%. A multivariate analysis identified the following independent prognostic factors for achieving major cytogenetic response: the absence of splenomegaly, white blood cell count less than 10 x 10(9)/L, the platelet count less than 450 x 10(9)/L, the presence of less than 5% of bone marrow blasts and basophils, the absence of blasts in peripheral blood, the presence of less than 7% of basophils in peripheral blood. Patients who early achieve complete and major cytogenetic response as well as those with low and moderate relative risk have a higher rate of achieving and maintaining complete cytogenetic response. There are also characteristics of patients before treatment that may indicate the treatment outcome.
Output: What tyrosine kinase, involved in a Philadelphia- chromosome positive chronic myelogenous leukemia, is the target of Imatinib (Gleevec)?
Once in a blue moon, there is one on New Year's Eve. Revelers ringing in 2010 will be treated to a so-called blue moon. According to popular definition, a blue moon is the second full moon in a month. But don't expect it to be blue - the name has nothing to do with the color of our closest celestial neighbor. A full moon occurred on December 2. It will appear again on Thursday in time for the New Year's countdown. The New Year's Eve blue moon will be visible in the United States, Canada, Europe, South America and Africa. For partygoers in Australia and Asia, the full moon does not show up until New Year's Day, making January a blue moon month for them. A full moon occurs every 29.5 days, and most years have 12. On average, an extra full moon in a month - a blue moon - occurs every 2.5 years. The last time there was a lunar double take was in May 2007. New Year's Eve blue moons are rarer, occurring every 19 years. The last time was in 1990; the next one won't come again until 2028. "Blue moons have no astronomical significance," said Greg Laughlin, an astronomer at the University of California. "'Blue moon' is just a name in the same sense as a 'hunter's moon'(a full moon in octorber) or a 'harvest moon,'" Laughlin said in an e-mail. The popular definition of blue moon came about after a writer for Sky & Telescope magazine in 1946 misinterpreted the Maine Farmer's Almanac and labeled a blue moon as the second full moon in a month. In fact, the almanac defined a blue moon as the third full moon in a season with four full moons.
Output: Which full moon should be called blue moon according to the original definition?
It does not come as a surprise that Dubai has a growing problem with tragic.The local rulers have explored all the conventional ways to get traffic moving again,including higher prices for parking,fuel and insurance.But at a recent conference in Hamburg,Hussain Lootah said that the city may adopt a more strict approach:setting an income level for vehicle ownership. Mr Lootah's approach is unlikely to be copied widely,but mayors of other big cities around the world are starting to think about taking severe actions of their own,including complete car bans in inner cities.But the efforts may not be enough to reduce traffic and pollution.The problems will only get worse:the number of vehicles sold globally each year will grow from around 80 million today to more than 100 million by the end of the decade,according to IHS Automotive.[] There are already a handful of car-free communities around the world.But these are typically small and often tourist destinations that seek to create a throwback in time,such as Sark Island,in the English Channel.The largest ear-free urban area is probably Venice,where it is impossible to build roads and bridges to link the more than 100 small islands the city sits on. Yet pedestrian malls and other car-free zones keep popping up in cities around the world.Some cities are considering ways to limit central city access to"green"machines,such as battery-electric vehicles.Hamburg is perhaps the furthest along. Such extreme plans may fly in a city such as Hamburg.But in many other cities the political resistance even to less far-reaching measures is hard to overcome.Michael Bloomberg,New York's former mayor,tried twice to introduce a jam charge for much of Manhattan,but his plans were rejected by state lawmakers.
Output: What made Michael Bloomberg's plans defeated?
Selenocysteine is incorporated into proteins via "recoding" of UGA from a stop codon to a sense codon, a process that requires specific secondary structures in the 3' untranslated region, termed selenocysteine incorporation sequence (SECIS) elements, and the protein factors that they recruit. Whereas most selenoprotein mRNAs contain a single UGA codon and a single SECIS element, selenoprotein P genes encode multiple UGAs and two SECIS elements. We have identified evolutionary adaptations in selenoprotein P genes that contribute to the efficiency of incorporating multiple selenocysteine residues in this protein. The first is a conserved, inefficiently decoded UGA codon in the N-terminal region, which appears to serve both as a checkpoint for the presence of factors required for selenocysteine incorporation and as a "bottleneck," slowing down the progress of elongating ribosomes. The second adaptation involves the presence of introns downstream of this inefficiently decoded UGA which confer the potential for nonsense-mediated decay when factors required for selenocysteine incorporation are limiting. Third, the two SECIS elements in selenoprotein P mRNA function with differing efficiencies, affecting both the rate and the efficiency of decoding different UGAs. The implications for how these factors contribute to the decoding of multiple selenocysteine residues are discussed.
Output: Which is the human selenoprotein that contains several Se-Cys residues?
Scelsi Morning is a 2003 album by Marc Ribot released on Tzadik Records.
Output: What is the name of Scelsi Morning's record label?
South Asia heatwave kills nearly 100 DHAKA - A heat wave sweeping India, Bangladesh and Nepal has killed nearly 100 people over the past two weeks, officials said on June 3, 2005. A third of the people died in northern Bangladesh, mostly women and children from dehydration , heat stroke and diarrhoea . "We are getting reports of several deaths due to heat wave and related diseases almost every day," an official said, as temperatures touched 43degC . The weather office in Dhaka said the hot weather will persist for another week until the monsoon rains which are normally due by the middle of June. Severe heat conditions in the southern Indian have killed at least 55 people, officials in the two states said. While temperatures have fallen from a high of 45degC in Andhra Pradesh to around 40degC, giving a respite to people, they are still on the rise in Orissa with Talcher town registering 48.5deg C, a weather official said. At least five people have died in prefix = st1 /Nepalfrom extreme heat, the government said.
Output: Which place is the hottest in the early June, 2005?
In chronic lymphocytic leukemia (CLL) signals from the B cell receptor (BCR) play a major role in disease development and progression. In this light, new therapies that specifically target signaling molecules downstream of the BCR continue to be developed. While first studies on the selective small molecule inhibitor of Bruton's tyrosine kinase (Btk), Ibrutinib (PCI-32765), demonstrated that Btk inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior, these studies however did not address whether Btk-mediated signaling is involved in the process of CLL leukemogenesis. To investigate the requirement of Btk signaling for CLL development, we modulated Btk expression in the IgH.ET CLL mouse model, which is based on sporadic expression of the simian oncovirus SV40 T-antigen in mature B cells. To this end, we crossed IgH.ET mice on a Btk-deficient background or introduced a human Btk transgene (CD19-hBtk). Here we show that Btk deficiency fully abrogates CLL formation in IgH.ET mice, and that leukemias formed in Btk haplo-insufficient mice selectively expressed the wild-type Btk allele on their active X chromosome. Conversely, Btk overexpression accelerated CLL onset, increased mortality, and was associated with selection of non-stereotypical BCRs into CLL clones. Taken together, these data show that Btk expression represents an absolute prerequisite for CLL development and that Btk mediated signaling enhances leukemogenesis in mice. We therefore conclude that in CLL Btk expression levels set the threshold for malignant transformation.
Output: What is the name of Bruton's tyrosine kinase inhibitor that can be used for treatment of chronic lymphocytic leukemia?
Luane is a bed ridden hypochondriac, a black widow who has sat for years in the center of a web of telephone lines. Her poison tongue spreads gossip and innuendos about the various denizens of the town. Years ago Luane's dead father scams $10,000 from Pete but dies before he can spend "the sugar". The money is never recovered and Pete strongly suspects Luane of holding out on him. Business at The Pavilion bar is down so Pete and Rags decide that the best way to get The Pavilion off the skids is to turn it into a strip joint. Pete "discovers" streetwalker Dannie Lee and convinces her to strip. Meanwhile, drug pusher Bobbie scams Ralph out of his maintenance job at the Park and gets Myra hooked on horse. It all hits the fan when Luane's husband Ralph falls for Dannie Lee and Pete finds out Myra's on the needle.
Output: What is the name of the nightclub?
Transmembrane protein 53, or TMEM53, is a protein that is encoded on chromosome 1 in humans.
Output: Which chromosone can you find Transmembrane protein 53?
Andrey Atanasov (Bulgarian: ; born 9 April 1987) is a Bulgarian footballer who currently plays as a forward for Greek side Acharnaikos.
Output: What was Andrey Atanasov specialty in their profesisonal sport?
Mary Jo Kopechne (/kopkni/; July 26, 1940 -- July 18, 1969) was an American teacher, secretary, and political campaign specialist who died in a car accident at Chappaquiddick Island on July 18, 1969, while a passenger in a car being driven by longtime U.S. Senator Ted Kennedy.
Output: Was the death of Mary Jo Kopechne an accident or suicide?