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Kim, an 18 year old slut, lets her older boss use her as a sex toy to try and secure a pay rise.Tags: Ma/Fa, Reluctant, Coercion, Oral Sex, Anal Sex, Sex Toys, ExhibitionismSex Contents: Much SexPosted:2002-04-14
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Description: Eva Notty, Jada Stevens, Nikki Benz and Romi Rain are fucking in front of a crowd in this sexy orgy and their asses and tits are jiggling as they are giving this sexy performance. All of the people here look really happy.
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Sultan's Special Forces The Sultan's Special Force (SSF) — Arabic: قوات السلطان الخاصة, transliterated: Qawat al-Sultaniya al-Khasah is a separate force branch within the Sultan's Armed Forces (SAF) and although equipped to carry out land defense operations, it is not part of the Royal Army of Oman. The SSF was created based on the lessons learned in a successful (if not lengthy) prosecution of a counter insurgency campaign in the Dhofar'. However, it was the time, effort and special tactics needed to achieve the victory that convinced the Sultan that he needed his own domestic special purpose force. There has been and remains a clear and constant relationship between the SSF and the Palace Office, a government ministry which oversees all aspects of the Sultanate's security and the forces became The ninth strongest force in the world in 2013. History of the Force During the Dhofar Insurgency of the 1960s and 1970s Sutan Qaboos bin Said al Said became very reliant on British Forces to improve the expertise of his fledgling armed forces battling to defeat Communist insurgents in the south of the country. He became particularly reliant on members of the Special Air Service (SAS) who formed training teams. After the successful conclusion of the Dhofar War Sultan Qaboos decided to develop his own Omani SF capability. He did so relying heavily on retired British personnel (many from the SAS) and during the latter part of the 20th Century the SSF developed. The SSF was developed from the most able of the Dhofari Firqat forces that were trained by the SAS. The SSF's badge includes a representation of the compact Dhofari leather shield (also used on the SAF's Firqat Forces badge) and wings similar to the SAS parachute qualification badge. In 1985 the Sultan authorized a medal to recognise the service of SSF personnel; known as the Special Service Medal of the Sultan's Special Forces (Midal al-Khidmat al-Khasat Qawat al-Sultaniya al-Khasat). Brigadier Tony Hunter-Choat OBE (formerly UK SAS) was the last British commander of the SSF (retiring in 1997) the post then filled by an Omani officer. Organisation The SSF is split geographically into two units with operational elements based in the Muscat capital area and in Dhofar Mountains to the north of Salalah. The SSF is trained, equipped and exercised in Counter-terrorism (CT) skills; and one of the SSF's elite CT units is called Cobra based in the north and south of the country, and one Cobra team works closely with the Royal Oman Police. In the late 1990s the SSF were also involved in patrolling and observation duties in the Sultanate's Oryx Sanctuary, that was at the time suffering from a great deal of poaching. The SSF has limited responsibilities in counter smuggling and border patrolling. Base locations Headquarters SSF at Al Azaiba; the main HQ building is at Latitude/Longitude 23.588366N, 58.344137E the (SSF clinic is marked on mapping) There are staff married quarters and villas at the SSF complex at Al Azaiba The main base for the SSF's northern units is a substantial modern barracks associated with Muaskar Al Samoud, with an extensive training facility and ranges next to the village of Halban near Seeb; the HQ building is at Latitude/Longitude 23.619486N, 58.037970E The main base for the SSF's southern units was developed on a former SAS-Firqat training base near Zeek in the Dhofar Jebel, at Sharbithat this extensive base is at Latitude/Longitude 17.275175N, 54.126446E An operational base exists at Haima in the Al Wusta region with a focus on the Sultanate's Western border with Saudi Arabia. Equipment The SSF are equipped with a range of light infantry and assault weapons, equipment and vehicles, including: A range of modern conventional and suppressed assault small arms Advanced and compact night vision aids Various grenades Sniper weapons and special camouflage uniforms Body armor and special protective clothing Modified Toyota Land Cruiser patrol and assault vehicles Humvee desert patrol vehicles equipped with a range of support weapons (e.g. heavy machine guns and missiles) Mercedes G300 cdi 6x6 (high mobility troop and load carrying vehicles) Inshore fast assault boats Stealth assault swimmer diving equipment Fighting in built up area, breaching aids EMPL heavy recovery vehicles. The Force has adopted modern military combat survival methods, as illustrated by the SSF's ration packs. See also Sultan of Oman's Armed Forces Omani Civil War (1963-76) History of the Special Air Service Special Operations Command Central References Category:Military of Oman Category:Counter-terrorist organizations
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The incidence of cisplatin nephrotoxicity post hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery. Cisplatin is commonly used in hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of peritoneal carcinomatosis. Little is known about the nephrotoxic effects of cisplatin use in HIPEC. To report the incidence of nephrotoxicity post-HIPEC using cisplatin 50 mg/m(2) plus doxorubicin 15 mg/m(2). The incidence of hypomagnesemia was investigated as a secondary endpoint. This is a retrospective study evaluating patients who received cisplatin with doxorubicin during HIPEC. RIFLE classification was used to assess the development of nephrotoxicity. Variables, such as comorbidities and nephrotoxic medications were obtained. Renal function parameters were also collected, including serum creatinine levels and serum magnesium levels at baseline and at days 3, 7 and 30 after HIPEC. Perioperative urine output (UO) was also recorded. Fifty-three patients were identified. Based on the RIFLE classification, two patients (3.7%) developed acute kidney injury (AKI) following HIPEC with cisplatin. One patient met criteria for renal failure and progressed to chronic renal failure. The other patient had renal injury. Comparable mean creatinine levels were observed at baseline and on day 30 following HIPEC (p > 0.05). The incidence of hypomagnesemia increased to 24.5% by day 7 (p = 0.041) and 30.1% by day 30 (p < 0.001) following HIPEC. Low intraoperative UO, angiotensin II receptor antagonist use and hypertension were associated with development of AKI (p < 0.05). Nephrotoxicity can complicate HIPEC with cisplatin therapy and that permanent renal dysfunction may rarely occur. More attention to be directed toward monitoring magnesium levels after cisplatin use with HIPEC.
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Feeding via nasogastric tube or percutaneous endoscopic gastrostomy. A comparison. When a patient needs enteral feeding, there are two methods to administer the nutrition. The method most used is the nasogastric tube (NGT), although in the literature little is published about the advantages and complications of the NGT. The second method is percutaneous endoscopic gastrostomy (PEG). A prospective randomized trial was started, and so far 90 patients have entered the study (46 NGT and 44 PEG). In four patients it was not possible to insert the NGT, and in three patients it was impossible to place the PEG. In both groups 6.5% aspiration was found. Nasal decubitus and swallowing problems were seen in 13% and 17%, respectively, in the NGT group. Intraperitoneal bleeding and abdominal pain were found in 2% and 11%, respectively, in the PEG group. Fixation of the patients was needed in 7% of the PEG and 22% in the NGT group. In eight patients in the NGT group the feeding had to be stopped owing to problems; in none of the PEG group was this necessary. The nursing staff awarded marks to each patient on a scale of 5 for the convenience of care (very good, 1; very bad, 5). This resulted in a mean score of 2.6 in the NGT and 2.0 in the PEG group. The score given by the patients was 2.3 in the NGT and 1.8 in the PEG group. There seems to be a clear preference for the PEG as a method for enteral nutrition.
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“Without board approval, commissioned and installed a life-size mural depicting himself and now hung inside the Koret Foundation’s new headquarters in San Francisco at a cost to the Foundation of $80,000.” I’ll tell you, this one allegation should prolly make you never even consider starting up any kind of foundation. And what’s the response – a general denial about how all the charges are “bogus” and an ad hominem attack against the widow of Koret? Spokesmodel Nate Ballard could try to explain the painting / mural – like he could say how it didn’t cost $80k or how it was authorized, but he chooses not to. OK fine. Hey is it “erratic” to want to invite non-poor non-Jewish Willie Brown in to the Koret Foundation? Probably. But there’s a lot of erraticism going on on these charitable boards – that’s no reason for a dismissal. All right, have at it Koret Foundation. Let’s hope the fund will be in better shape and be used for better purposes after all this gets hashed out. SAN FRANCISCO, Oct. 8, 2014 /PRNewswire/ — The widow of Koret Foundation founder Joseph Koret has filed suit against Koret Foundation Board President Tad Taube, accusing him and the Foundation’s Board of Directors of conflicts of interest in funding pet projects that include conservative causes in the United States and charities in his native country of Poland. The suit filed October 7, 2014 in San Francisco Superior Court by Mrs. Koret alleges that under Taube’s direction the board has ignored the priorities established by her late husband to help the poor and assist Jewish causes in the Bay Area and Israel. Instead, her suit claims, the Koret board is using foundation funds to promote programs closely affiliated with individual board members and is purposely confusing the public by putting signage that prominently features Taube’s name alongside the Koret Foundation name on buildings and grants for which the Koret Foundation is the principal funder. “Defendants’ duty of loyalty to the Foundation has been corrupted by these directors’ close affiliations with many of the Foundation’s recent grants, resulting in tens of millions of dollars distributed due to self-interest,” according to the lawsuit.
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797.45K 71% He fucked my ass at my best friends house! sukisukigirl takes ANAL creampie 16:24 HD
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Intraesophageal perfusion of acid increases the bronchomotor response to methacholine and to isocapnic hyperventilation in asthmatic subjects. Gastroesophageal reflux (GER) has been shown to be more frequent in people with asthma, but the mechanism by which it might aggravate asthmatic symptoms remains unclear. We compared the effects on maximal expiratory flow at 50% of VC (MEF50) of esophageal perfusion of hydrochloric acid (HCl) and of normal saline (NaCl) in 12 asthmatic subjects chosen at random. In all subjects, HCl perfusion did not change MEF50 but potentiated the bronchoconstriction induced by isocapnic hyperventilation of dry air (maximal decrease in MEF50 = 44 +/- 7% with HCl versus 22 +/- 5% with NaCl; p less than 0.001) or methacholine (provocative dose producing a 20% decrease in FEV1 = 349 +/- 99 micrograms with HCl versus 496 +/- 119 micrograms with NaCl; p less than 0.01). Seven of the asthmatic subjects were found to have GER on esophageal pH monitoring. In these subjects, HCl alone decreased MEF50 slightly but significantly (-17.5 +/- 5.5%; p less than 0.05), possibly reflecting the higher degree of basal bronchial hyperreactivity observed in this group. Thus, perfusion of acid into the distal esophagus caused slight but significant bronchoconstriction in asthmatic subjects with GER and increased the bronchoconstriction produced by isocapnic hyperventilation and by methacholine in asthmatic subjects without regard for the presence of GER.
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What's Garcinia Cambogia Extract? What's Garcinia Cambogia Extract? Are you wondering whether The Apple Patch Diet Business Program is legitimate? Prior to you select to function for them, you should first comprehend what their company is all about, and how and when you will be paid commissions for promoting their goods. This article will explain what the apple patch diet plan is all about, what tools you can anticipate to obtain when you join their business plan, and how much you can anticipate to make. Garcinia Cambogia Name In Tamil However, not to be concerned, the claims are false. In a study printed in the Journal of the American Dietetic Association, 2.five grams of Chitosan had been taken by twelve women and 12 males over a period of 12 times. Although some fat absorption was achieved in the males, it was insignificant, which means it would take 7 months for men at this dosage to attain one pound of body fat loss. The women achieved zero fat absorption. 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STREAMWOOD – The Batavia girls basketball team survived a scare from host Streamwood on Saturday to clinch a share of the Upstate Eight Conference River title, knocking off the Sabres, 46-45. Security image: Note:the e-mail sent will contain information, such as your IP address (216.157.74.230), for purposes of tracking abuse. Use of this software to spam or harass individuals can and may result in penalties punishable by law.
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The methylenetetrahydrofolate reductase (MTHFR) 677C-->T mutation and cardiovascular risk--A case of ischemic stroke and acute myocardial infarction. The authors report the case of a 39-year-old male patient who had an ischemic stroke (complete infarction of right anterior cerebral circulation) and an acute myocardial infarction during the same year. Molecular study revealed he was homozygous for the 677C-->T mutation in the gene coding for methylenetetrahydrofolate reductase, a key enzyme of folate metabolism; deficiency of this enzyme is associated with increased cardiovascular risk and neurological lesions. Some considerations are put forward about hyperhomocysteinemia and the MTHFR 677C-->T mutation as cardiovascular risk factors.
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Fatima al-Batayahiyyah Fāțima bint Ibrahim ibn Mahmūd al-Bațā'ihiyya also known as Fatima al-Batayahiyyah was a Muslim scholar of hadith in the 8th century. Biography Fatima al-Batayahiyyah taught Sahih Bukhari in Damascus. She was known as one of the greatest scholars of that period, demonstrated especially during the Hajj when leading male scholars of the day flocked from afar to hear her speak in person. When she had become old, she moved to Madinah and taught her students for days in the Prophet’s mosque itself. Whenever she tired, she would rest her head on the Muhammad's grave and continue to teach her students. This tradition is contrasted with the practice today, where people are not allowed view Muhammad's resting place. References Category:8th-century Muslim scholars of Islam
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Q: Example of a restriction of sheaf not being a sheaf Let $\mathscr{F}$ be a sheaf on $X$, and $Y\subset X$ a subset. Define a presheaf $\mathscr{F}|_Y$ on $Y$ via the direct limit $$\mathscr{F}|_Y(V):=\lim_{V\subset U}\mathscr{F}(U),$$ where $V$ is an open subset of $Y$, and $U$ is an open subset of $X$. Clearly $\mathscr{F}|_Y$ is a sheaf if $Y$ is an open subset of $X$. But I can't think of an example where $\mathscr{F}|_Y$ is not a sheaf. Can anyone think of an example? A: $\DeclareMathOperator{\sh}{Sh}$ Edit: The question originally asked about $F|_Y(V)=\varinjlim_{U\subset V}F(U)$, and my answer reflects this. It now looks like the OP is asking out the inverse image functor. I claim that $F|_Y$ is the wrong thing to look at. In general, if $f:Y\to X$ is a continuous map between topological spaces (eg. the an embedding $Y\subset X$) then there is a natural functor $f_*:\sh(Y)\to\sh(X)$ given by $$ (f_* F)(U) = F(f^{-1}(U)) $$ In your case ($f:Y\to X$ is the embedding $Y\subset X$) one has $(f_* F)(V) = F(V\cap Y)$. Now, this functor isn't in the direction that you're looking for, but $f_*$ has a left adjoint $f^*:\sh(X)\to\sh(Y)$, which is characterized by the universal property $$ \hom_{\sh(Y)}(f^* F,G) = \hom_{\sh(X)}(F, f_* G) $$ for $F\in\sh(X)$, $G\in\sh(Y)$. (Note: in algebraic geometry one often writes $f^{-1}$ instead of $f^*$, but I'm just talking about sheaves of sets here.) Anyways, $f^* F$ is defined as follows: $$ (f^* F)(V) = \varinjlim_{U\supset f(V)} F(U) $$ So in your case ($Y\subset X$) one has $$ (f^* F)(V) = \varinjlim_{U\supset V} F(U) $$ which is very different than $\varinjlim_{U\subset V} F(U)$. For example, if $V$ has empty interior, than your definition yields $F|_Y(V) = *$ for all $V$. Edit: Georges pointed out that I was overly hasty: my definition of $f^* F$ yields a presheaf, the sheafification of which is the "actual" $f^* F$. Anyways, here is an example of an inclusion $f:Y\to X$ and a sheaf $F$ on $X$ for which $f^{pre}F:V\mapsto\varinjlim_{U\supset f(V)} F(U)$ is not a sheaf. Let $Y=\mathbb{R}$ with the discrete topology, $X=\mathbb{R}$ with the usual topology, and $f:Y\to X$ be the identity map. Then it is easy to see that if $F\in\sh(X)$ is the "sheaf of continuous functions," then $f^{pre} F$ is not a sheaf.
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Q: What's wrong with click handling of my buttons inside a reusable layout? I have a reusable layout with a back button. I want to handle click event of my back button from BaseActivity. I set the onClick of the button to "headerClickHandler" and I have a method with this name in BaseActivity but When I click the button, an error says there is no headerClickHandler. What's wrong? this is my Header.xml: <?xml version="1.0" encoding="utf-8"?> <RelativeLayout xmlns:android="http://schemas.android.com/apk/res/android" android:layout_width="match_parent" android:layout_height="match_parent" > <TextView android:id="@+id/txtHeading" android:text="@string/general_title" android:layout_alignParentTop="true" android:layout_alignParentRight="true" android:layout_height="30dp" android:layout_width="200dp"/> <Button android:id="@+id/btnBack" android:layout_alignParentTop="true" android:layout_alignParentLeft="true" android:layout_height="30dp" android:layout_width="100dp" android:background="@color/red_hover" android:text="@string/return_value" android:onClick="headerClickHandler" /> </RelativeLayout> This is My BaseActivity: public class BaseActivity extends Activity { public void headerClickHandler(View v) { switch (v.getId()) { case R.id.btnBack: Toast.makeText(this, "TEST", Toast.LENGTH_LONG).show(); break; default: break; } } } this is my activity: public class PersonnelInfo extends BaseActivity { @Override protected void onCreate(Bundle savedInstanceState) { super.onCreate(savedInstanceState); setContentView(R.layout.activity_personnel_info); } @Override public boolean onCreateOptionsMenu(Menu menu) { getMenuInflater().inflate(R.menu.personnel_info, menu); return true; } } A: Remove android:onClick="headerClickHandler" from xml In base activity: public class BaseActivity extends Activity { public OnClickListener headerClickHandler = new OnClickListener() { public void onClick(View v) { switch (v.getId()) { case R.id.btnBack: Toast.makeText(BaseActivity.this, "TEST", Toast.LENGTH_LONG).show(); break; default: break; } } }; } In derive activity: Button btnBack = (Button) findViewById(R.id.btnBack); btnBack.setOnClickListener(headerClickHandler);
{ "pile_set_name": "StackExchange" }
0
Chemogenetic analysis of human protein methyltransferases. A survey of the human genome was performed to understand the constituency of protein methyltransferases (both protein arginine and lysine methyltransferases) and the relatedness of their catalytic domains. We identified 51 protein lysine methyltransferase proteins based on similarity to the canonical Drosophila Su(var)3-9, enhancer of zeste (E(z)), and trithorax (trx) domain. Disruptor of telomeric silencing-1-like, a known protein lysine methyltransferase, did not fit within the protein lysine methyltransferase family, but did group with the protein arginine methyltransferases, along with 44 other proteins, including the METTL and NOP2/Sun domain family proteins. We show that a representative METTL, METTL11A, demonstrates catalytic activity as a histone methyltransferase. We also solved the co-crystal structures of disruptor of telomeric silencing-1-like with S-adenosylmethionine and S-adenosylhomocysteine bound in its active site. The conformation of both ligands is virtually identical to that found in known protein arginine methyltransferases, METTL and NOP2/Sun domain family proteins and is distinct from that seen in the Drosophila Su(var)3-9, enhancer of zeste (E(z)), and trithorax (trx) domain protein lysine methyltransferases. We have developed biochemical assays for 11 members of the protein methyltransferase target class and have profiled the affinity of three ligands for these enzymes: the common methyl-donating substrate S-adenosylmethionine; the common reaction product S-adenosylhomocysteine; and the natural product sinefungin. The affinity of each of these ligands is mapped onto the family trees of the protein lysine methyltransferases and protein arginine methyltransferases to reveal patterns of ligand recognition by these enzymes.
{ "pile_set_name": "PubMed Abstracts" }
0
The present invention relates to a semiconductor device formed of an insulating tape that has an electrically conductive wiring provided to electrically connect a semiconductor chip and external terminals, and particularly to a ball grid array (BGA) type semiconductor device with its external terminals made of spherical solder balls. A BGA type semiconductor device suitable for multiple pins, small size and high-speed operation has been practically used in order to increase the mounting density of semiconductor devices. The BGA type semiconductor device has solder bumps disposed as its external terminals in a two-dimensional array on the surface of the semiconductor device. In the BGA type semiconductor device, a member called an interposer is also used that has a conductive wiring formed on and/or within its surface in order to electrically connect the semiconductor chip and the external terminals. The interposer is used in a form of a printed wiring board of which the base material is a glass/epoxy resin, or in another form of an insulating tape having a conductive wiring on the surface of a base made of polyimide or the like. A semiconductor device using the insulating tape with conductive wiring formed is described in xe2x80x9cHigh Connection Reliability Cleared by Structure-Improved CSPxe2x80x9d, Nikkei Microdevice, February, 1998, pp. 48-55. In a conventional BGA semiconductor device as illustrated in FIG. 10, an insulating tape 2 as an interposer is used that has a conductive wiring 4, bonding pads 3, lands 5 and an insulating film 6. A semiconductor chip 1 has its lower side 1b mounted on a semiconductor chip mounting surface 2a of the insulating tape 2 with an adhesive member 8. The bonding pads 3 formed on the semiconductor chip mounting surface 2a of the insulating tape 2 are respectively located within openings 12 that are formed in the insulating film 6. The bonding pads and electrodes formed on the upper surface, 1a of the semiconductor chip 1, though not shown are electrically connected by bonding metal fine wires 7 to those pads and electrodes, respectively. A sealing member, or mold 9 is provided on the chip mounting surface 2a side of the insulating tape 2, sealing the semiconductor chip 1 and the metal fine wires 7. The external terminals, 10 are provided on the mounted side 2b of the insulating tape 2, and bonded to the lands 5 within openings 11 of tape 2. The semiconductor chip 1 and external terminals 10 are electrically connected through the metal fine wires 7, bonding pads 3, conductive wiring 4 and lands 5. In the conventional semiconductor device shown in FIG. 10, the semiconductor chip 1 is made of a material of silicon (Si) of which the linear expansion coefficient is about 2xcx9c3xc3x9710xe2x88x926/xc2x0 C. The insulating tape 2 is made of a base material such as polyimide resin or glass/epoxy resin of which the linear expansion coefficient is about 10xc3x9710xe2x88x926/xc2x0 C. The sealing mold 9 is chiefly epoxy resin with silica particles filled, and has a linear expansion coefficient of about 8xcx9c14xc3x9710xe2x88x926/xc2x0 C. The semiconductor device is usually mounted through the external terminals 10 on a printed wiring board or substrate that is made of a base material of a glass/epoxy resin (for example, FR-4) of which the linear expansion coefficient is about 15xcx9c16xc3x9710xe2x88x926/xc2x0 C. The linear expansion coefficient of whole the conventional semiconductor device is close to that of the semiconductor chip 1 because the proportion of the semiconductor chip 1 within the whole semiconductor device is large. When the semiconductor device mounted on the printed wiring board undergoes a temperature cycle test for reliability, or experiences a temperature change, a distortion is caused at the external terminals 10 made of chiefly a solder material (such as Pbxe2x80x94Sn based eutectic solder or Snxe2x80x94Agxe2x80x94Cu based solder) due to the linear expansion coefficient difference between the semiconductor device and the printed wiring board. In the conventional semiconductor device shown in FIG. 10, only one side, or the chip mounting side 2a, of the insulating tape 2 is sealed with the sealing mold 9. Therefore, when the temperature is decreased, the semiconductor device is deformed to curve, causing a distortion at the external terminals 10 due to the contraction of the sealing mold 9. The distortion due to the warp is super-imposed on the distortion that is caused by the linear expansion coefficient difference of the semiconductor device to the printed wiring board, thus further increasing the distortion at the external terminals. When the external terminals 10 are greatly distorted and subjected to repetitive temperature changes, they are cracked and finally broken down. The distortion due to the above factors becomes the largest at the external terminal 10a that is bonded to the land 5a close to the edge of the semiconductor chip 1 of which the linear expansion coefficient is the smallest in the semiconductor device. The breakdown will be most probably caused from this portion. Particularly when the land 5a close to the edge of the semiconductor chip 1 is disposed to extend across the side edge of the semiconductor chip 1 as shown in FIG. 10, a large distortion is caused thereat as will be apparent from the following reason. Although the distortion at such a part of the external terminal 10a as located right under the semiconductor chip 1 can be alleviated by the deformation of the adhesive member 8 that is elastic, the other portion over which there is no semiconductor chip 1 is restricted by the sealing agent 9 and thus cannot be freely deformed. Therefore, a large distortion is concentrated at the end of the external terminal 10a that is located outside the side edge f the semiconductor chip 1, causing it to break down with high probability. When the linear expansion coefficient of the sealing agent 9 is not so large, the external terminal 10b located at the edge of the semiconductor device is sometimes distorted greatly, thus broken down with some probability as is similar to the external terminal 10a close to the edge of the semiconductor chip 1. Occurrence of breakdown of the external terminal 10 will result in electrical disconnection, and therefore the semiconductor device does not properly operate, thus the reliability of the semiconductor device being remarkably reduced. Accordingly, it is an object of the invention to provide a semiconductor device of particularly BGA type capable of preventing/suppressing the external terminals from being broken down, or having high reliability. The above object can be achieved by the semiconductor device having, for example, such structures of (A)xcx9c(H) as described below. (A) A structure having a first insulating member, external terminals provided on a main surface of the first insulating member, a semiconductor chip provided on the opposite side to the side of the first insulating member on which the external terminals are provided, a conductive member for electrically connecting the semiconductor chip and the external terminals, and a sealing member provided on the opposite side to the side of the first insulating member on which the external terminals are provided, wherein a second insulating member is interposed between the semiconductor chip and the first insulating member, and the outer edge of the second insulating member extends from the outer edge of the semiconductor chip. (B) A structure having a first insulating member, external terminals provided on a main surface of the first insulating member, a semiconductor chip provided on the opposite side to the side of the first insulating member on which the external terminals are provided, a conductive member for electrically connecting the semiconductor chip and the external terminals, and a sealing member provided on the opposite side to the side of the first insulating member on which the external terminals are provided, wherein a second insulating member is interposed between the semiconductor chip and the first insulating member, and the outer edge of the second insulating member extends to a location corresponding to the outer edge of the external terminal that is located outside the outer edge of the semiconductor chip and nearest to the semiconductor chip side. (C) A structure having an insulating tape including a plurality of bonding pads and lands and a conductive wiring for electrically connecting the bonding pads and the lands, a semiconductor chip, a conductive member for electrically connecting the semiconductor chip and the bonding pads, an adhesive member that is adhesive to the semiconductor chip and provided on the semiconductor chip mounting side of the insulating tape except at least the bonded area of the bonding pads with the conductive member, a sealing member for sealing the surroundings of the semiconductor chip and the conductive member, and external terminals bonded to the lands. The adhesive member is originally used for mounting the semiconductor chip on the surface of the insulating tape, and therefore usually provided only on the underside of the semiconductor chip. The adhesive member is made of epoxy based resin or polyimide based resin, and these materials are usually more flexible than the insulating tape material. This adhesive member is provided not only on the underside of the semiconductor chip but also on the semiconductor chip mounting side of the insulating tape except the bonding pad region, so that the distortion caused at the external terminals due to the linear expansion coefficient difference between the semiconductor chip and the printed wiring board or substrate can be alleviated by the deformation of the flexible adhesive member. In addition, since the amount of warp of the semiconductor device due to the contraction of the sealing member can be decreased, the distortion caused at the external terminals due to the warp can be reduced. Moreover, in order to make full use of the flexible property of the adhesive member, it is desirable to make the elastic coefficient of the adhesive member smaller than that of the insulating tape. When the elastic coefficient of the adhesive member is small, the adhesive member itself can be easily deformed to absorb the deformation caused at the external terminals. Thus, the distortion at the external terminals can be reduced more. The elastic coefficient (longitudinal modulus of elasticity) of the insulating tape is about 3000xcx9c9000 MPa. The elastic coefficient of the material of the adhesive member is smaller than that, but it is actually about 1000 MPa. (D) A structure having an insulating tape including a plurality of bonding pads and lands and a conductive wiring for electrically connecting the bonding pads and the lands, a semiconductor chip, a conductive member for electrically connecting the semiconductor chip and the bonding pads, an adhesive member for gluing the semiconductor chip to the semiconductor chip mounting side of the insulating tape, a sealing member for sealing the surroundings of the semiconductor chip and the conductive member, and external terminals bonded to the lands that are located on both the outside and inside of the edge of the semiconductor chip, wherein the adhesive member is provided to cover to a region including at least the lands located outside the edge of the semiconductor chip. When the lands bonded to the external terminals are provided outside and inside the edge of the semiconductor chip, the adhesive member, which itself is used for mounting the semiconductor chip on the insulating tape surface, is usually provided to cover only the lands located inside the edge of the semiconductor chip, or on the underside of the chip. Since the adhesive member that is more flexible than the insulating tape is provided not only to cover the lands located on the underside of the semiconductor chip but also the lands located on the outside of the edge of the semiconductor chip, the distortion caused at the external terminals due to the linear expansion coefficient difference between the semiconductor device and the printed wiring board can be alleviated by the deformation of the flexible adhesive member. In addition, since the amount of warp of the semiconductor device due to the contraction of the sealing member can be decreased, the distortion caused at the external terminals due to the warp can be reduced. Moreover, in order to make full use of the flexible property of the adhesive member, it is desirable to make the elastic coefficient of the adhesive member smaller than that of the insulating tape. (E) A structure having an insulating tape including a plurality of bonding pads and lands and a conductive wiring for electrically connecting the bonding pads and the lands, a semiconductor chip, a conductive member for electrically connecting the semiconductor chip and the bonding pads, an adhesive member for gluing the semiconductor chip to the semiconductor chip mounting side of the insulating tape, a sealing member for sealing the surroundings of the semiconductor chip and the conductive member, and external terminals bonded to the lands that are located on the outside of the edge of the semiconductor chip, wherein the adhesive member is provided to cover to a region including at least the lands located outside the edge of the semiconductor chip. When the lands bonded to the external terminals are provided outside the edge of the semiconductor chip, the adhesive member, which itself is used for mounting the semiconductor chip on the insulating tape surface, is usually provided only on the underside of the semiconductor chip but not to cover at least the lands located outside the edge of the semiconductor chip. The adhesive member that is more flexible than the insulating tape material is provided to cover to the region including the lands located outside the edge of the semiconductor chip, so that the distortion caused at the external terminals due to the linear expansion coefficient difference between the semiconductor device and the printed wiring board can be alleviated by the deformation of the flexible adhesive member. In addition, since the amount of warp of the semiconductor device due to the contraction of the sealing member can be decreased, the distortion caused at the external terminals due to the warp can be decreased. Moreover, in order to make full use of the flexible property of the adhesive member, it is desirable to make the elastic coefficient of the adhesive member smaller than that of the insulating tape. Also, it is desired that the adhesive member be made of a film-shaped material. There is a method of mounting the semiconductor chip on the surface of the insulating tape, in which the adhesive member is previously provided on the semiconductor chip mounting area of the insulating tape and then the semiconductor chip is bonded through the adhesive member. In this case, the adhesive member is provided by applying a liquid material or a film-shaped material. In order to make effective use of the distortion reducing effect of the adhesive member, it is necessary that the adhesive member be made of a low-elasticity material, and assure a certain useful thickness. This is because the distortion caused at the external terminals due to the linear expansion coefficient difference between the semiconductor device and the printed wiring board is chiefly shearing strain. The adhesive member according to the application of a liquid material is provided by means of screen printing or potting. However, these means are difficult in controlling the thickness of the adhesive member, and make the manufacturing process complicated. The adhesive member according to the application of a film-shaped material provides an approximately uniform film thickness, and thus the thickness of the adhesive member after the bonding can be easily controlled. The semiconductor device can also be produced in the same way as in the prior art. The film-shaped adhesive member can be made equal to the thickness of the insulating tape, or to about 50xcx9c80 xcexcm after the bonding of the semiconductor chip. Therefore, the adhesive member can be satisfactorily deformed to effectively reduce the distortion at the external terminals. (F) A structure having an insulating tape having a plurality of bonding pads and lands and a conductive wiring for electrically connecting the bonding pads and the lands, a semiconductor chip, a conductive member for electrically connecting the semiconductor chip and the bonding pads, an adhesive member for gluing the semiconductor chip to the semiconductor chip mounting side of the insulating tape, a sealing member for sealing the surroundings of the semiconductor chip and the conductive member, and external terminals bonded to the lands, wherein the adhesive member is provided to cover to a region including the lands that are located outside the edge of the semiconductor chip and at least close to the edge of the semiconductor chip. When the conventional semiconductor device shown in FIG. 10 is mounted on a printed wiring board or substrate, the largest distortion is caused at the external terminal 10a close to the edge of the semiconductor chip that has the smallest linear expansion coefficient among the other parts of the semiconductor device. In other words, this external terminal 10a most probably breaks down. Thus, the flexible adhesive member is provided to cover to the region including the lands located close to and outside the edge of the semiconductor chip, so that the distortion caused at the external terminal bonded to this land can be alleviated by the deformation of the flexible adhesive member. (G) A structure having an insulating tape having a plurality of bonding pads and lands and a conductive wiring for electrically connecting the bonding pads and the lands, a semiconductor chip, a conductive member for electrically connecting the semiconductor chip and the bonding pads, an adhesive member for gluing the semiconductor chip to the semiconductor chip mounting side of the insulating tape, a sealing member for sealing the surroundings of the semiconductor chip and the conductive member, and external terminals bonded to the lands that are located on both the outside and inside of the edge of the semiconductor chip, wherein a member with a lower elastic coefficient than the insulating tape is provided on the semiconductor chip mounting side of the insulating tape and to cover the lands located outside the projected plane of the semiconductor chips (H) A ball grid array type structure having an insulating tape having a plurality of bonding pads and lands and a conductive wiring for electrically connecting the bonding pads and the lands, a semiconductor chip, a conductive member for electrically connecting the semiconductor chip and the bonding pads, an adhesive member for gluing the semiconductor chip to the semiconductor chip mounting side of the insulating tape, a sealing member for sealing the surroundings of the semiconductor chip and the conductive member, and external terminals bonded to the lands located outside the edge of the semiconductor chip, wherein a member with a lower elastic coefficient than the insulating tape is provided on the semiconductor chip mounting side of the insulating tape and to cover the lands located outside the projected plane of the semiconductor chip. Since the flexible low-elasticity member is provided to cover the lands that are located outside the projected plane of the semiconductor chip, the distortion caused at the external terminals due to the linear expansion coefficient difference between the semiconductor device and the printed wiring board can be alleviated by the deformation of the flexible low-elasticity member. In addition, since the amount of warp of the semiconductor chip due to the contraction of the sealing member can be decreased, the distortion caused at the external terminals due to the warp can be reduced. Since the lands located inside the projected plane of the semiconductor chip are covered by the flexible adhesive member, the distortion caused at the external terminals bonded to the lands inside the edge can be reduced by the distortion alleviating action of the deformed adhesive member. Furthermore, in order to make full use of the flexible property of the adhesive member and low-elasticity member, it is desired that the elastic coefficients of both materials be smaller than that of the insulating tape. When the adhesive member and low-elasticity member have small elastic coefficients, these members themselves can be easily deformed. Thus, since the deformations of the external terminals can be easily absorbed by the deformations of the adhesive member and low-elasticity member, the distortion caused at the external terminals can be further reduced. The inventors of the present invention application examined by finite element method how the solder material of which the external terminals are made is distorted when the semiconductor device of the following structure is mounted on a printed circuit board or substrate, and when the ambient temperature is changed from 125xc2x0 C. to xe2x88x9255xc2x0 C. The result was that when the adhesive member was provided inside the projected plane of the semiconductor chip, or beneath the chip, the external terminals close to the edge of the semiconductor chip were distorted 1.5%, while when the adhesive member was provided on both the outside and inside of the projected plane of the semiconductor chip, these external terminals were distorted as low as 1.1%. The specifications of the semiconductor chip used for the analysis are given below. Size of semiconductor device: 13 mmxc3x9713 mm Size of semiconductor chip: 8.8 mmxc3x978.8 mm Number of external terminals: 176 Distance between external terminals: 0.8 mm
{ "pile_set_name": "USPTO Backgrounds" }
0
Kurdish journalist Sarkawt Shamsulddin was arrested by security forces in Sulaimaniya on Wednesday while leaving the office of the Kurdistan Parliament in the city. He was taken to an unknown location and has not been heard from since. Shamsulddin, the Washington, DC bureau chief for NRT TV, was in Kurdistan covering recent protests against government corruption and economic mismanagement. He had posted on Twitter and Facebook about the arrests of Newey Nwe leader Shaswar Abdulwahid and Gorran MP Rabun Maroof, the deaths of protestors at the hands of KRG security forces in Rania, and the shutdown of NRT TV. His last message, posted hours before he was arrested, read: “PUK Security forces are running after protesters and others, including me. #Freedom4Shaswar #Freedom4Rabwn.” Prior to his arrest, security forces raided the offices of NRT TV in Sulaimaniya, shutting the station’s broadcasting and websites down and destroying broadcasting equipment. The channel’s offices have been attacked before, including in both October and August of this year. While the government was not directly involved in those attacks, activists allege that they were undertaken with tacit government support. Critical reporting under KDP and PUK rule has long carried steep risks. While the Kurdistan Press Law guarantees many protections for journalists, those who report on corruption and authoritarianism within the regional government have faced threats and violence. In 2016 alone, Wedat Ali Hussein and Shukri Zaynadin were killed under mysterious circumstances. During the lead-up to the referendum, reporters who criticized the process were singled out as “traitors” and “mercenaries” in pro-government media, and were targeted online. Shamsulddin was among those who faced such attacks. The U.S. Embassy in Baghdad has issued a statement in response to the attacks on NRT, saying that: “The United States supports freedom of expression in Iraq as a key component of the country’s democratic foundation, as enshrined in the Iraqi Constitution. We are concerned by recent actions to curb the operations of some media outlets through force or intimidation, specifically yesterday’s raid by Kurdistan Regional Government security forces of the NRT offices in Sulaimaniyah.” Yet while U.S. weapons given to the KRG to fight ISIS are used against protestors on the streets of Kurdistan and while the previous murders of journalists have cause little international outrage, these are empty words. U.S. support for the Kurdistan Regional Government came with few political conditions. The immediate military needs of the war against the Islamic State took priority over criticism of President Massoud Barzani’s extending his term, the closing of the regional parliament, or the failure to pay public sector salaries. World powers enabled the conditions that led to the protests and supported the leaders who have responded to dissent with crackdowns and arrests. It is unlikely that international pressure to the extent that is needed will occur to push the KRG in the opposite direction. Instead, the KRG must get out of the way of the will of its people. An organizer for the Sulaimaniya protests issued a statement on behalf of the demonstrators, claiming that “if those in power had any political principles, they would resign and prepare their testimony for when they are brought before the courts to answer for their responsibility for all of the tragedy, poverty and destruction that they have brought upon the people.” This view is evidently common among the thousands of demonstrators who have risked their lives in the streets and the journalists and activists who argue for democracy despite government threats. The necessary systemic changes in South Kurdistan will not occur at the hands of any political elites, and the parties in power cannot stop these changes by arresting critical voices. All who respect democracy should call for the freedom of all journalists and politicians in the KRG, and for a true democratic solution to the region’s problems.
{ "pile_set_name": "OpenWebText2" }
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Serotonin and schizophrenia: correlations between serotonergic activity and schizophrenic motor behavior. Increased serotonergic activity in animals has been associated with a variety of stereotyped motor behaviors. In addition, serotonin facilitates brainstem, reticular, and spinal motor neuronal activity implicated in the expression of these behaviors. This report presents positive correlations between both peripheral (platelet serotonin levels) and central (cerebrospinal concentrations of 5-hydroxy-indoleacetic acid) measures of serotonin metabolism and the symptom of peculiar or unusual mannerisms and posturing in schizophrenic patients. The findings are discussed in light of the animal behavioral correlates of increased serotonergic activity and the stereotyped affectomotor behavior seen in some schizophrenic patients.
{ "pile_set_name": "PubMed Abstracts" }
0
Q: JIRA Rest API Close Issue Using JSON I am trying to write a method that will allow users to close a JIRA issue using json. Here is the url I am using: ../jira/rest/api/latest/issue/MyProj-524/transitions Here is my json string: { "update" : {"comment": [{"add": {"body":"Fixed"}}]}, "fields" : { "resolution" : {"id":"10000","name":"Done" }}, transition": {"id": "6"}} I get a 400 exception (Bad Request) and status of ProtocolError. According to the documentation 400 will be returned if there is no transition specified. Also when I query the JIRA server from my browser with ..:8090/jira/rest/api/latest/issue/MyProj-524/transitions I get the following: {"expand":"transitions","transitions":[{"id":"5","name":"Resolve Issue","to":{"self":"/jira/rest/api/2/status/5","description":"A resolution has been taken, and it is awaiting verification by reporter. From here issues are either reopened, or are closed.","iconUrl":"..8090/jira/images/icons/statuses/resolved.png","name":"Resolved","id":"5","statusCategory":{"self":"...8090/jira/rest/api/2/statuscategory/3","id":3,"key":"done","colorName":"green","name":"Done"}}},{"id":"2","name":"Close Issue","to":{"self":".:8090/jira/rest/api/2/status/6","description":"The issue is considered finished, the resolution is correct. Issues which are closed can be reopened.","iconUrl":"..8090/jira/images/icons/statuses/closed.png","name":"Closed","id":"6","statusCategory":{"self":"8090/jira/rest/api/2/statuscategory/3","id":3,"key":"done","colorName":"green","name":"Done"}}}]} So it appears there are available transitions. We are using the "Classic Default Workflow" that contains: Open, Resolved, Closed, Reopened, and In Progress. The current status of the ticket is: Open. A: Are you sure you're using the correct transitions id? Did you check against .../jira/rest/api/latest/issue/MyProj-524/transitions?expand=transition.fields Your id should match the transition you want to convert to. In my case (using the standard transitions that come with the Jira cloud, my ID is 31 (for "Done") You might also want to confirm that your workflow allows for taking an issue from Open to Closed. You can view this as a diagram from Admin > Issues > Workflows > Assigned schemes > View as a diagram There are some more suggestions here: https://answers.atlassian.com/questions/86247/how-can-i-close-an-issue-via-a-rest-api-call
{ "pile_set_name": "StackExchange" }
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0.020124
Diagnostic delay in breast disease: a system analysis of a public urban hospital. To analyze the diagnostic process in 146 women referred to a breast clinic in an urban setting between January 1, 1994, and December 31, 1996. We devised the "diagnostic delay index (DDI)," defined as the time between the medical system's awareness of a diagnostic need and the completion of the diagnostic process. The time awaiting breast clinic consultation and the diagnostic events experienced--including clinic visits, imaging studies, and biopsies--were recorded. We stratified patients in 2 pathways (palpable masses and mammogram-identified lesions) and by benign or malignant outcome. Patients in pathways 1 (n = 85) and 2 (n=61) had a mean (+/-SD) DDI of 68.4 (+/-46.9) days and 71.9 (+/-35.2) days, respectively. Patients in both pathways who had a malignant outcome had a significantly lower DDI than those who had a benign outcome (47.5+/-30.9 days vs 78.6+/-42.6) (P<.001); this advantage was most pronounced in patients with palpable lumps. The average patient waited more than 3 weeks for both an initial clinic consultation and operating room access. Quartile analysis of the DDI revealed statistically significant differences in clinic access time, number of visits, diagnostic events per visit, and operating room access time. Regression analysis demonstrates the relationship between DDI and measured process variables: DDI= -21.11+0.09 age+1.86 pathway-12.18 outcome+1.08 clinic access+11.91 visits+0.94 operating room access (R2=61.5%). In a public hospital, diagnostic delay is related to inadequate access to surgical consultation and a delay in operating room access. Regression analysis demonstrates the relationships between these components of system diagnostic delay and suggests strategies for reducing the DDI.
{ "pile_set_name": "PubMed Abstracts" }
0
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Armen Ra Armen Ra is a Persian-Armenian artist, self-taught thereminist, production designer, director, and performer. Musical career Career (2010-2013) Ra began studying the theremin in 2001, debuting with the orchestral group Antony & the Johnsons in New York City. Ra has played at the United Nations, Wiener Konzerthaus Mozartsaal Vienna, CBGBs, Knitting Factory, La MaMa E.T.C., Joe's Pub, Boulder Museum of Modern Art, Lincoln Center, The Gershwin Hotel, B.B. King Museum, and Dietch Projects. He has performed and recorded with various bands and on many projects (including a collaboration with British recording artist Marc Almond (of Soft Cell), on the song "My Madness & I" from his 2010 release Varieté). His debut solo CD Plays the Theremin (released on Bowl & Fork Records in 2010) showcases many classical Armenian laments and folk songs. Ra performed on the Sharon Needles album PG-13 on band Ministry's cover track "Everyday Is Halloween". Career (2014-present) In recent years, Ra has appeared in the following works: Armen plays on the Current 93 album entitled HoneySuckle Æons. He appears in multiple songs on this 2011 release. Armen plays on the debut album of Sharon Needles. The songs “Everyday Is Halloween” and “This Club Is a Haunted House” were released in 2013. In 2014, he played the theremin for Voltaire's album Raised by Bats. In 2015, he released Theremin Classique, a collection of European arias. Armen's recording of “Dle Yaman” was used for the video of designer Michael Schmidt’s 3-D gown in 2015. He was featured on Selena Gomez’s Revival on the track “Me and My Girls” in 2016 He was featured on Gwen Stefani’s album on the track “Naughty” in 2016. He was featured on track 11 "Supernatural" of BØRNS' Blue Madonna Appearances in Media He has a cameo appearance in the film Party Monster. Other appearances in media include: Cameo as a desk clerk in Tomorrow Always Comes in 2006. Music for the short film Connect in 2010. Guest judge on the Logo Network show The Arrangement. Opener for Nick Cave & The Bad Seeds's Grinderman on their 2010 tour. Production designer for the 2012 horror movie Excision. Release of the documentary When My Sorrow Died: The Legend of Armen Ra & the Theremin. Music for the movie Hara Kiri in 2016. Promotional videos for electropop artist BØRNS, entitled "The Search for the Lost Sounds" and "The Faded Heart Sessions". References External links Official Website Armen Ra at a benefit concert on April 4 at the Angel Orensanz Center in New York Category:Living people Category:LGBT artists from Iran Category:LGBT musicians from the United States Category:American male musicians Category:American musicians Category:American musicians of Armenian descent Category:American drag queens Category:Iranian Armenian people Category:Iranian emigrants to the United States Category:People from Tehran Category:1969 births
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What I learned from Pinkie at the P.O. Daphne SimpkinsCHICAGO TRIBUNE Two days before the Postal Service officials started saying out loud on TV what they have been whispering to each other -- we need to cut back on service one day a week -- I was visiting the post office, and buying my Valentine stamps from Pinkie who works there. She is a lovely woman whose tempo of doing business suits mine. If there is a line of customers, I often let other people move in front of me so that I can have an unhurried visit with Pinkie. While waiting, I visit with others, wondering only why there isn't a separate line for military families who want to ship packages to service people overseas. They should have premium access to Pinkie; mothers with children too. But that's about it -- about all the reform at the post office I would propose. The rest of us can wait to mail our missives or bundles because when you are old enough to run errands you know that waiting is a part of accomplishing most tasks -- of simply living. Sometimes a timeout is a healthy event. Or instructive. I do not mind waiting at the post office. I liked meeting that muscular, energetic man who explained that, yes, he was a physical fitness coach. "You're not ever going to really want to push yourself to a point of discomfort in exercise, but you have to be in charge of yourself. You are the boss of you." I've walked many a mile in the park on those words. Coach was not the only memorable man I've met there. I like the older guys who wear Old Spice and plaid flannel shirts. When they see me dressed for exercise, they encourage me automatically: "Keep it up young lady. (I'm 54.) Exercise is good for you." I would send them all Valentines if I could, but I don't know any of their names -- just who they are: smiling older men who are at peace with themselves and have seen a lifetime of change and are not afraid. They are the boss of themselves. Nor do I know the name of the handsome man who comes to the post office and also runs in my park where I walk. He calls out three mornings a week, "Hello, my Sister," and I reply, "Hello, my Brother!" If I ask "How are you?," he bellows, "Blessed by the Lord!" I asked him once if he was a preacher, but he isn't. I don't know what he does for a living, but I know who he is. He is everyone's brother. At the post office, Pinkie is his sister. Mine, too. I watched Pinkie the other day when a customer realized with a start that she had forgotten her wallet and was momentarily panicked about how to pay for her stamps. I was just about to step over and slip her $5 (she looked good for it), but Pinkie smiled and with a little wave of her hand stopped me. She urged the woman: "Get your wallet from the car. Everything is all right here." And then in a glance and with a smile that soothed a line of people who were inclined to pulse from the habit of pushing we inhaled Pinkie's smile of reassurance that everything was all right. Pinkie had enough time; so did we. The lady returned quickly, paid for her stamps, and the line of customers moved up, none of us the worse for wear because life had slowed down for a spell. In fact, we swapped ideas about plumbing repairs and traded the names of handymen, and suddenly it was our turn to do business. I bought my stamps and told Pinkie, "Seeing you is always a pleasure," and she said, "Oh, Girl, how you do go on." I do go on -- here and there, listening in on the serious-sounding discussions of serious people who are considering important choices about business operations that will have a domino effect on people and the economy. Who can understand it all? If the post office takes a day off, my Netflix movies will come a day later. Fliers will come a day later. Bills will come a day later, and I will pay them. Birthday cards and Valentines will be welcome whenever they arrive. And the people who are old enough to drive themselves to the post office when it is open will take their places in the line and wait for Pinkie -- or someone like her without grumbling because if you are old enough to drive, you are old enough to understand that grumbling isn't the same thing as problem-solving. Like the men in plaid shirts, I understand that troubles come, change is inevitable, and sometimes a brother or a sister has to go find a forgotten wallet. If anyone in charge of making that decision about closing the post office for a day asks me what I think about it, I will remember that I am the boss of me, smile in honor of Pinkie (pray for her job security), and reply, "Do what you need to do. I know how to wait." ---------- Daphne Simpkins lives in Montgomery, Ala., and is the author of the memoir "The Long Good Night."
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Q: Laravel 5.4 How to get all relations if user is an admin E.G. $user->relatedModel (without parentheses) returns the entire RelatedModel collection if the user is an admin or the typical filtered collection if they are not. I am trying to alter a number of user relationships so that if the logged in user is an admin, then they can see all models in that relationship without having to write the same conditions every time I need to use it, and without creating all the relationships in the property_user table for every admin on every related model that I need this on. There is an answer here which explains fairly clearly what I want to achieve https://stackoverflow.com/a/34910225/1080341 which is exactly the idea I am looking for except that when I try this in Laravel 5.4 it throws an exception when the user is an admin. Relationship method must return an object of type Illuminate\Database\Eloquent\Relations\Relation If the user is a standard user the relationship returns the appropriate filtered collection. Here is the code example from that answer public function properties() { if ($this->isAdmin()) { return Property::query(); } elseif ($this->isManager() || $this->isBroker()) { return $this->belongsToMany('App\Property'); } return null; } This is already a large site with many relationship calls already written so I do not wish to have to refactor all those code instances when I believe I can simply modify the relationship definition. How can I return a relationship from this function that includes all models when the user is an admin, and keep it so the use of $user->properties around the site will not need to be modified? [2018-06-02 12:58:23] local.ERROR: LogicException: Relationship method must return an object of type Illuminate\Database\Eloquent\Relations\Relation in /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Database/Eloquent/Concerns/HasAttributes.php:403 Stack trace: #0 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Database/Eloquent/Concerns/HasAttributes.php(386): Illuminate\Database\Eloquent\Model->getRelationshipFromMethod('sites') #1 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Database/Eloquent/Concerns/HasAttributes.php(316): Illuminate\Database\Eloquent\Model->getRelationValue('sites') #2 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Database/Eloquent/Model.php(1279): Illuminate\Database\Eloquent\Model->getAttribute('sites') #3 /home/vagrant/Leadgen/app/Http/Controllers/Backend/SiteController.php(29): Illuminate\Database\Eloquent\Model->__get('sites') #4 [internal function]: App\Http\Controllers\Backend\SiteController->index(Object(Illuminate\Http\Request)) #5 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Controller.php(55): call_user_func_array(Array, Array) #6 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php(44): Illuminate\Routing\Controller->callAction('index', Array) #7 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Route.php(203): Illuminate\Routing\ControllerDispatcher->dispatch(Object(Illuminate\Routing\Route), Object(App\Http\Controllers\Backend\SiteController), 'index') #8 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Route.php(160): Illuminate\Routing\Route->runController() #9 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Router.php(572): Illuminate\Routing\Route->run() #10 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(30): Illuminate\Routing\Router->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #11 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php(41): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #12 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\Routing\Middleware\SubstituteBindings->handle(Object(Illuminate\Http\Request), Object(Closure)) #13 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #14 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Auth/Middleware/Authenticate.php(43): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #15 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\Auth\Middleware\Authenticate->handle(Object(Illuminate\Http\Request), Object(Closure)) #16 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #17 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php(65): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #18 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\Foundation\Http\Middleware\VerifyCsrfToken->handle(Object(Illuminate\Http\Request), Object(Closure)) #19 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #20 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/View/Middleware/ShareErrorsFromSession.php(49): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #21 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\View\Middleware\ShareErrorsFromSession->handle(Object(Illuminate\Http\Request), Object(Closure)) #22 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #23 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Session/Middleware/StartSession.php(64): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #24 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\Session\Middleware\StartSession->handle(Object(Illuminate\Http\Request), Object(Closure)) #25 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #26 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Cookie/Middleware/AddQueuedCookiesToResponse.php(37): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #27 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\Cookie\Middleware\AddQueuedCookiesToResponse->handle(Object(Illuminate\Http\Request), Object(Closure)) #28 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #29 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Cookie/Middleware/EncryptCookies.php(59): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #30 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\Cookie\Middleware\EncryptCookies->handle(Object(Illuminate\Http\Request), Object(Closure)) #31 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #32 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(102): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #33 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Router.php(574): Illuminate\Pipeline\Pipeline->then(Object(Closure)) #34 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Router.php(533): Illuminate\Routing\Router->runRouteWithinStack(Object(Illuminate\Routing\Route), Object(Illuminate\Http\Request)) #35 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Router.php(511): Illuminate\Routing\Router->dispatchToRoute(Object(Illuminate\Http\Request)) #36 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Foundation/Http/Kernel.php(176): Illuminate\Routing\Router->dispatch(Object(Illuminate\Http\Request)) #37 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(30): Illuminate\Foundation\Http\Kernel->Illuminate\Foundation\Http\{closure}(Object(Illuminate\Http\Request)) #38 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/TransformsRequest.php(30): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #39 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\Foundation\Http\Middleware\TransformsRequest->handle(Object(Illuminate\Http\Request), Object(Closure)) #40 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #41 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/TransformsRequest.php(30): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #42 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\Foundation\Http\Middleware\TransformsRequest->handle(Object(Illuminate\Http\Request), Object(Closure)) #43 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #44 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/ValidatePostSize.php(27): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #45 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\Foundation\Http\Middleware\ValidatePostSize->handle(Object(Illuminate\Http\Request), Object(Closure)) #46 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #47 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/CheckForMaintenanceMode.php(46): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #48 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(148): Illuminate\Foundation\Http\Middleware\CheckForMaintenanceMode->handle(Object(Illuminate\Http\Request), Object(Closure)) #49 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Routing/Pipeline.php(53): Illuminate\Pipeline\Pipeline->Illuminate\Pipeline\{closure}(Object(Illuminate\Http\Request)) #50 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php(102): Illuminate\Routing\Pipeline->Illuminate\Routing\{closure}(Object(Illuminate\Http\Request)) #51 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Foundation/Http/Kernel.php(151): Illuminate\Pipeline\Pipeline->then(Object(Closure)) #52 /home/vagrant/Leadgen/vendor/laravel/framework/src/Illuminate/Foundation/Http/Kernel.php(116): Illuminate\Foundation\Http\Kernel->sendRequestThroughRouter(Object(Illuminate\Http\Request)) #53 /home/vagrant/Leadgen/public/index.php(53): Illuminate\Foundation\Http\Kernel->handle(Object(Illuminate A: Since it isn't a real relationship, you can't access it as one. Use this: $sites = $user->sites()->get(); If you want to access it as a property and don't need the query object (e.g. to add other constraints), you can use an accessor: public function getPropertiesAttribute() { if ($this->isAdmin()) { return Property::all(); } elseif ($this->isManager() || $this->isBroker()) { return $this->belongsToMany('App\Property')->get(); } return null; } A dirty hack: public function sites() { if ($this->isAdmin()) { return $this->hasMany('App\Site', 'id')->orWhereRaw(1); } return $this->belongsToMany('App\Site'); }
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Q: Iterator providing a "view" of its current element The design issue I'm currently solving is to iterate over some region of memory and on each such iteration retrieve from that memory some meta-data the client is interested in. I see 2 solutions currently: I. struct queue; struct queue_element_view{ int id; char *description; }; //0 - if ok, -1 - if end of queue reached int next(struct queue*); //0 - if ok, -1 - if end of queue reached int current_element_view(struct queue*, struct queue_element_view *); So the queue opaque struct can be traversed via next function and since the queue elements are platform dependent and I want to keep the library cross platform I provided a platform-independent struct queue_element_view that is sensible on all platforms. Drawback: If client writes code like this: struct queue *queue_ptr = // struct queue_element_view current_out; current_element_view(queue_ptr, &current_out); //current_out now contains current's element meta data next(queue_ptr); //current_out now may contain unspecified data //since queue's current element changed. So calling to next after calling to current_element_view clobbers the current_out. II. struct queue; struct queue_element_view; struct queue_element_view *allocate_view(void); int * get_id(struct queue_element_view *); char * get_description(struct queue_element_view *); //0 - if ok, -1 - if end of queue reached int next(struct queue*); //0 - if ok, -1 - if end of queue reached int current_element_view(struct queue*, struct queue_element_view *); In this case we have allocated struct queue_element_view and current_element_view copies data to the object pointed to by struct queue_element_view * so next does not clobber the data. Drawbacks: It involves a function additional call to simply retrieve int and char * fields It makes testing public api more complicated. So I'm kind of confused which one would be preferrable/readable? Probably there is another alternative? A: Alternative I The perceived problem with alternative (I) is apparently that calling next() will cause data previously copied into a struct queue_element_view to become invalid, as a result of next() (possibly) deallocating memory. Solution: make sure next() does not do that. This may mean that you have to make a copy of the description string to put in the view, instead of just giving the client a copy of the original pointer itself. In this case it may be helpful to provide a function for releasing any internal allocations reflected in a struct queue_element_view, maybe something like this: void queue_element_view_clean(struct queue_element_view *view) { free(view->description); } This relieves the client from having to know details of what needs to be cleaned up, and how, and what doesn't. They can then retain the data as long as they want, cleaning it up when they decide they are done with it. That a call to next() will mean that they are no longer the data for the current element of the iteration is a feature, not a bug -- why would it make sense to interfere with clients retaining data from previous iterations if they want to do so? Alternative II The perceived problems revolve around accesses to the members of the view going through functions. It's unclear how this solves the perceived problem with alternative I. Although it could be part of a solution for that problem, I see no reason to think it a necessary part. Solution: use alternative I. Seriously. If you're going to make copies of the data as needed for the view to persist appropriately when next() is called, then I don't see how you gain anything by making the view structure opaque. Overall Your two alternatives seem oddly flipped. It would make sense to me to use accessor functions if you wanted to avoid having a separate view structure or copying data. The functions would return data pertaining to the current element of the iteration - no separate view structure involved. You would then have the alternative of making the accessors provide copies of the data for which the caller takes responsibility, or making it a caller responsibility to copy any data they want to retain when the iterator is stepped forward. On the other hand, if you provide a separate structure for an element view then it seems odd that you would do so in a way that allows it to become invalid when the iterator is advanced. The separate view object seems a natural way to go for allowing the view data to be preserved as long as the caller wants it. Any way around, yes, some kind of responsibility is placed on the caller. This is natural -- there is no free lunch. Document clearly what those responsibilities are, and try to design the overall API in a way that feels consistent with respect to what kinds of responsibility are placed on the user, under what circumstances, and how those responsibilities are to be discharged.
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Predictors of Clostridioides difficile recurrence across a national cohort of veterans in outpatient, acute, and long-term care settings. The greatest challenge in treating Clostridioides difficile infection (CDI) is disease recurrence, which occurs in about 20% of patients, usually within 30 days of treatment cessation. We sought to identify independent predictors of first recurrence among a national cohort of veterans with CDI. We conducted a case-control study among acute and long-term care Veterans Affairs (VA) inpatients and outpatients with a first CDI episode (positive stool sample for C. difficile toxin[s] and receipt of at least 2 days of CDI treatment) between 2010 and 2014. Cases experienced first recurrence within 30 days from the end of treatment. Controls were those without first recurrence matched 4:1 to cases on year, facility, and severity. Multivariable conditional logistic regression was used to identify predictors of first recurrence. We identified 32 predictors of first recurrence among 974 cases and 3,896 matched controls. Significant predictors included medication use prior to (probiotics, fluoroquinolones, laxatives, third- or fourth-generation cephalosporins), during (first- or second-generation cephalosporins, penicillin/amoxicillin/ampicillin, third- and fourth-generation cephalosporins), and after CDI treatment (probiotics, any antibiotic, proton pump inhibitors [PPIs], and immunosuppressants). Other predictors included current biliary tract disease, malaise/fatigue, cellulitis/abscess, solid organ cancer, medical history of HIV, multiple myeloma, abdominal pain, and ulcerative colitis. In a large national cohort of outpatient and acute and long-term care inpatients, treatment with certain antibiotics, PPIs, immunosuppressants, and underlying disease were among the most important risk factors for first CDI recurrence.
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Dunno what intruded on this shot. It adds to the radness. So yeah this dude's a legend. Someone that always has ur back is good for your well-being 🤘🏻📷🦂@gerhardtctz . #olympusmjuii#kodakcolorplus200#35mmfilm “I'm not afraid to compete. It's just the opposite. Don't you see that? I'm afraid I will compete — that's what scares me. That's why I quit the Theatre Department. Just because I'm so horribly conditioned to accept everybody else's values, and just because I like applause and people to rave about me, doesn't make it right. I'm ashamed of it. I'm sick of it. I'm sick of not having the courage to be an absolute nobody. I'm sick of myself and everybody else that wants to make some kind of a splash.” -J.D. Salinger, Franny and Zooey. Fucking greatest book ever. #mood Shooting film has made me appreciate even more what digital has to offer. Iso 12800 on digital, that’s insane. You have no limits, no boundaries with digital. You can shoot even where there’s no light practically. Modern cameras has become like computers or night vision devices. I made this photo on film with literally no light on the room. Iso 400 hand held probably at about 1/2 second. I have a nice hand pulse tho. Do what you can with iso 400 even on the lowest light. That’s awesome 🔥 || Leica M6 and 35 summícron, with Tri X 400.
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Prasophyllum niphopedium Prasophyllum niphopedium, commonly known as the marsh leek orchid, is a species of orchid endemic to a small area in Victoria. It has a single tubular leaf and up to twenty greenish flowers with reddish markings. It is only known from five population on grassy alpine plains with the total number of individual plants less than five hundred. Description Prasophyllum niphopedium is a terrestrial, perennial, deciduous, herb with an underground tuber and a single tube-shaped leaf up to long and wide at the base. Between ten and twenty faintly scented flowers are loosely arranged along flowering stem long which reaches to a height of . The flowers are lightly scented, greenish with pink or reddish markings and as with others in the genus, are inverted so that the labellum is above the column rather than below it. The ovary is oval-shaped and long. The dorsal sepal is egg-shaped and long and the lateral sepals are a similar length but linear to lance-shaped and are free, or mostly free from each other. The petals are linear to lance-shaped, and curve forwards. The labellum is trowel-shaped, pink, long and turns sharply upwards near its middle. There is a brown or green, short, channelled and wrinkled callus in the centre of the labellum. Flowering occurs from December to February. Taxonomy and naming Prasophyllum niphopedium was first formally described in 2000 by David Jones and the description was published in The Orchadian from a specimen collected in the Cobberas Range. Distribution and habitat The marsh leek orchid grows on snow plains in grassy alpine heath, usually near watercourses in the Cobberas Range and Benambra area. The number of plants fluctuates between two hundred and five hundred in five populations. Conservation Prasophyllum niphopedium is listed as "Endangered" under the Victorian Flora and Fauna Guarantee Act 1988 but is not listed under the Commonwealth Government Environment Protection and Biodiversity Conservation Act 1999 (EPBC) Act. The main threats to the species are soil disturbance and grazing by feral horses and cattle and inappropriate fire regimes. References External links niphopedium Category:Flora of Victoria (Australia) Category:Endemic orchids of Australia Category:Plants described in 2000
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This invention relates to an optically irreversible circuit device for use in optical communication, optical measurement and other similar fields.
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Q: Overriding the CSS in the style tag I have the following HTML and CSS which is generated by the jQuery Mobile Framework. I have NO control on the generated HTML. I can only style them. <div class="ui-popup-container slideup in ui-popup-active" id="productSummaryOverlay-popup" tabindex="0" style="max-width: 1201px; top: 0px; left: 17px;"> I want to ignore or remove everything in the style attribute as it is making it impossible to go full screen and it is also giving a margin which I do not want. How can I ignore the style attribute? A: use !important at the end of the line: #productSummaryOverlay-popup { max-width: none !important; top: auto !important; left: auto !important; }
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Q: How to take first row from this list of text? I have a list of columns containing text but I just to fetch first upper row from this list. How to do that? #include <stdio.h> int main() { FILE *fr; char c; fr = fopen("prog.txt", "r"); while( c != EOF) { c = fgetc(fr); /* read from file*/ printf("%c",c); /* display on screen*/ } fclose(fr); return 0; } A: Your stop condition is EOF, everything will be read to the end of the file, what you need is to read till newline character is found, furthermore EOF (-1) should be compared with int type. You'll need something like: #include <stdio.h> #include <stdlib.h> int main() { FILE *fr; int c; if(!(fr = fopen("prog.txt", "r"))){ //check file opening perror("File error"); return EXIT_FAILURE; } while ((c = fgetc(fr)) != EOF && c != '\n') { printf("%c",c); /* display on screen*/ } fclose(fr); return EXIT_SUCCESS; } This is respecting your code reading the line char by char, you also have the library functions that allow you to read whole line, like fgets() for a portable piece of code, or getline() if you are not on Windows, alternatively download a portable version, and, of course you can make your own like this one or this one.
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Interpretative consequences of adopting the Global Lungs 2012 reference equations for spirometry for children and adolescents. To determine the interpretative consequences of adopting the Global Lungs 2012 (GLI-2012) spirometric prediction equations in a pediatric hospital population. Spirometric records from 2,192 white boys and 1,842 white girls, and 412 and 334 African-American boys and girls, respectively, aged 6.0-18.0 years, treated mainly for asthma, cystic fibrosis, cough, and dyspnoea. Predicted values and lower limits of normal were calculated for FEV1, FVC, and FEV1/FVC, using prediction equations from GLI-2012, Hankinson, Knudson, Polgar, Wang, and Zapletal. Obstruction was defined as FEV1/FVC < LLN, a restrictive pattern as FEV1/FVC > LLN and FVC < LLN. There was good agreement for predicted values for FEV1, FVC, and FEV1/FVC from GLI-2012, Hankinson and Wang equations within ethnic groups. A near normal FEV1 but above normal FVC contributed to a low FEV1/FVC, particularly in African-Americans. Polgar, Knudson, and Zapletal predicteds produced disparate results. A restrictive pattern occurred in 2.2-11.2% of cases, with no statistical difference between GLI-2012 and Hankinson. Transition from Hankinson and Wang equations to GLI-2012 leads to grossly similar prevalence rates of abnormally low values for FEV1, FVC, and FEV1/FVC, unlike equations from Knudson, Polgar, and Zapletal.
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Q: Use round or floor depending the number after the comma What would be the solution to have: 7.1 => 7 7.5 => 7 7.8 => 8 So I need to round number or floor depending on the number after the comma. How to do that? Thanks. A: You should be able to use the constant, PHP_ROUND_HALF_DOWN, to have the round function round down when it is half way. echo round(7.1, 0, PHP_ROUND_HALF_DOWN) . "\n"; echo round(7.5, 0, PHP_ROUND_HALF_DOWN) . "\n"; echo round(7.8, 0, PHP_ROUND_HALF_DOWN) . "\n"; Output: 7 7 8 From the manual: Round val down to precision decimal places towards zero, when it is half way there. Making 1.5 into 1 and -1.5 into -1. PHP Demo: https://eval.in/427706
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Photo of the Philadelphia Police Department’s fake “Google Maps” vehicle by Matt Blaze (Twitter) Yesterday we told you about the suspicious SUV in Pennsylvania that had a license plate reader mounted on the front and a Google Maps sticker on the side. The Pennsylvania State Police told us that it wasn’t their vehicle, despite the fact that it had a PSP placard in the window. We now know that it was actually the city of Philadelphia’s SUV. Motherboard talked with the Philadelphia Police Department over email, which released this statement: We have been informed that this unmarked vehicle belongs to the police department; however, the placing of any particular decal on the vehicle was not approved through any chain of command. With that being said, once this was brought to our attention, it was ordered that the decals be removed immediately. Motherboard talked with an expert who claimed that it’s “highly illegal to have Google’s markings on there,” which we suspected yesterday. Whoever owned the vehicle, it clearly wasn’t an official Google project. The sticker simply looked too handmade. The Philly Police say that they’re starting an inquiry into the matter. One has to guess that some genius in the PD thought that it would make the vehicle less visible, but that plan obviously backfired. It will certainly be interesting to see how far up the chain of command this idiotic idea went. We’ll update you when we get more details. [Motherboard]
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Florida and California When it’s time to get away with the family for some fun and sun, Canadian families are thinking more and more of California and Florida. These States are easy to get to and offer a wide variety of things to see and do to keep kids entertained and parents inspired. Our readers’ poll showed that time at the beach is the number one family favourite followed closely by taking a cruise. Cultural/educational events scored well, followed by road trips. (Surprisingly, theme parks, camping and hiking scored very low in our poll.) Whatever you choose to do for the family vacation, California and Florida have a lot to offer. Sharing these great States with your family will be a rewarding and memorable experience. Beyond Disney The Disney resorts rank as the top attractions for families in America. These expansive properties comprise many theme parks, accommodation, restaurants and shops with a variety of entertainment for all ages. See our Planning article from our May issue for details on visiting the Disney parks with tips and recommendations by Ensemble agent Janice Robertson. In this edition of Spotlight, we’re focusing on family-friendly things to see and do beyond the famous theme parks of Florida and California. Outstanding Beaches Florida is surrounded by water on three sides with long stretches of beaches along the Atlantic and Gulf of Mexico coasts. Some of the best beaches are just 90 minutes away from Orlando on the Gulf of Mexico where the St. Petersburg/Clearwater area boasts 35 miles of white-sand beaches and fun activities like dolphin-spotting, shelling, and Captain Memo’s Pirate Cruise. A one hour drive east of Orlando brings you to the Atlantic white sand beaches of the Space Coast and Cocoa Beach. California’s 450 beaches range from sandy to rocky with cooler sea temperatures than Florida (75F/23C in the summer). Beach playgrounds are popular with families at Santa Monica, Santa Barbara, Ventura and others where swing sets and playground equipment are set up along the sand. Board walks for cycling and roller blading are also popular. California is a leader in surf beaches including those at Malibu, Huntington Beach and Santa Cruz while the best beaches for sunbathing are located from San Diego to Santa Cruz. Aquariums A natural addition to any beach vacation is a visit to discover what lives beneath the waves. Florida The Florida Aquarium, Tampa Bay – One of the best in the country. Here you can swim with the fishes, watch the penguin promenade, celebrate the year of the frog and learn about coral reefs. Also an important centre for research and conservation. SeaWorld, Orlando – We’ve included this educational theme park since it made Parents Magazine top ten list of aquariums in the United States. The Penquin Encounter was chosen as the standout feature. Here you take a moving walkway for excellent views of these popular birds. Clearwater Marine Aquarium – This educational facility is dedicated to the rescue, rehabilitation and release of animals notably River Otters, Dolphins and Sea Turtles. On your visit, take the Sea Life Safari Eco-Boat Tour which runs three times a day. California Monterey Aquarium – Home to one of the most diverse marine ecosystems in the world and one of the U.S.A.’s top family attractions. 26 species of marine mammals live in the Monterey Bay National Marine Sanctuary, situated in a very scenic part of Northern California. San Francisco Aquarium of the Bay – Learn about the ecology and marine life of San Francisco Bay as you walk through 300 feet of under water tunnels. Walk with sharks, touch bat rays and learn about the conservation of San Francisco Bay. Situated on the Embarcadero, adjacent to Fisherman’s Wharf, near Pier 39, and close to the cruise ship pier The Aquarium of the Pacific, Long Beach – World class aquarium focusing on the wonders of the Pacific Ocean. Visit the interactive Shark Lagoon, hand feed lorikeet birds, join a Behind-the-Scenes tour and watch Monsters of the Abyss, a film with 3-D technology and digital animation that explores the deep ocean. Zoos Always a family favourite, you’ll find zoos dotted throughout these States. Here are some of the best. Florida Lowry Park Zoo,Tampa, Florida, has 1900+ animals and is considered one of the best in Florida. The Palm Beach Zoo at Dreher park, West Palm Beach, Florida, is a 23 acre zoological park with 1500+ animals in tropical habitats. Brevard Zoo, Melbourne, Florida, focuses on conservation and interactive educational experiences for kids and adults including animal feeding and wild encounters. A miniature train runs through part of the park. California San Diego Zoo, situated in Balboa Park, is a world famous for research and conservation. It is home to over 4,000 rare and endangered animals including the famous pandas. The Wild Animal Park is an expansive wildlife sanctuary that is home to more than 3,500 animals. The climate in San Diego is ideal for growing most of the plants these animals need. Los Angeles Zoo, situated in Griffith Park, the largest natural municipal park in the United States. 113 acres is devoted to the zoo which has 1,200 animals and is a leader in efforts to save the California Condor. San Francisco Zoo, situated on the Great Highway, next to the Pacific Ocean, is the largest zoo in Northern California with 1,000+ animals including a rare white tiger. The children’s zoo is specially geared for younger visitors. Cultural/Educational Family Activities Today’s museums, visitors centres and historic sights have become interactive and educational making it more fun for the whole family. Consider visiting these favourites. Florida Everglades National Park in Southern Florida – You’ll find saw grass marshes, mangrove forests and extensive wetlands. This natural area is perfect for eco tours, air boating, kayaking and canoeing. Guides lead tours, day and evening, to discover wildlife including flamingoes, alligators and even the Florida panther. Amelia Island – This barrier island in the northeast, near Jacksonville, has evolved into a family friendly destination. Families can enjoy quality time together on river cruises, nature centre programs, fly fishing, kayaking, hiking the self guided nature trails, horseback riding, exploring the wildlife on a Segway Personal Transporter Safari, and of course, spending time on the gorgeous beaches. Enjoy combing for seashells, hunting for shark teeth, or observing sea turtles in their natural habitat. Visit 19th century Fort Clinch where guides re-enact the stories of its history. In historic downtown Fernandina Beach, families can take a horse-drawn carriage ride while listening to an oral history of the city’s historic district. Many hotels offer programs and accommodations catered specifically to families and children. Kennedy Space Centre – Only 45 minutes away from Orlando, plan a full day to explore NASA’s launch headquarters, located on a huge island wildlife refuge. At the Visitor Complex you’ll find amazing exhibits and inspiring shows about the past, present and future of the space program. If visiting during a peak period it can be crowded, especially on a cold day. Best visited in non-peak periods. National Parks – Discover California’s natural beauty in the National Park Service areas found throughout the State. Here visitors find a wide variety of adventures from historical and cultural experiences to natural wonders. The National Park Service maintains a total of 23 different units in California including nine National Parks. See the Giant Redwoods at Redwood National Park, visit the Victorian home of John Muir, noted author and preservationist at the John Muir National Historic Site or see the cascading waterfalls of famous Yosemite National Park, one of the first wilderness parks in the United States. The legendary Queen Mary – Tour this historic liner, docked in Long Beach. On the Behind the Scenes Guided Tour or self guided tours, you’ll learn about the ship’s history as a transatlantic liner and World War II troopship. Visit the first-class swimming pool, a popular spot for ghost sightings which is part of the Ghosts & Legends show. Spend the night in an original First Class Stateroom or dine in one of the restaurants. The Sunday brunch is said to be the best in Southern California. *Applicable to all escorted tour or cruise bookings for two or more passengers valued at over $1000 per person before taxes and made through Grand Escapades with our preferred suppliers – Visa gift card will be made available following full payment of booking – One visa gift card per booking – cannot be combined with any other Grand Escapades promotion or discount – to qualify for gift card, client must provide promo-code VGC100 at the time of booking – Not valid in jurisdictions that deems it illegal – Offer may be withdrawn or modified at any time. – Visa, and the Visa design are trademarks of Visa International.
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At least at the over-the-counter retail level, product labeling is a necessary function of commerce. When labeling a product, it is mandatory that labeling be achieved in a way that the sales person is able to ascertain the product price, either visually or by using Universal Product Code (UPC) bars and appropriate bar "reading" equipment. Typically, computerized equipment capable of reading UPC bars also automatically adjusts inventory so that store personnel can quickly be apprised of the remaining stock, if any. And, preferably, it is also helpful if the label explains how to use the product. But many product labels bear no instruction for use. One problem associated with certain types of product labeling includes defacing of a product surface as a result of the means, e.g., high-bond adhesive, used to attach the label. Product defacing associated with labeling can be avoided through the use of a low-bond adhesive that allows for easy removal. Although the use of such easily removable labels overcomes problems dealing with product appearance, it creates a new problem in that such labels can be easily and surreptitiously changed using a label from another product. Such changing of labels is known as "price swapping" and is undertaken by unscrupulous purchasers for the purpose of obtaining a lower price. Another problem that arises in the labeling of certain products involves the need to include (or at least the desirability of including) operating instructions on the label. Certain products are packaged in a manner that does not allow for the inclusion of an operating manual or instruction sheet. Or the manufacturer simply elects to forego the expense (and resulting cost to the consumer) of elaborate packages containing instruction sheets or the like. When no packaging is included with the product and when operating instructions are desirable, the historic practice has been to apply an adhesive instructional label to the product outer surface. But such instructional labeling is attended by one of the disadvantages noted above, defacing or price-swapping, depending upon whether the label is permanent or readily removed. An improved method and display card for labeling products that overcomes shortcomings associated with current product labeling would be a distinct advance in the art.
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Heatpulse 8108 The Heatpulse® 8108 system is a single-wafer, cassette-to-cassette rapid thermal processor, capable of processing in inert or corrosive ambient. The system is built for the production environment. It is housed in a compact, through-the-wall frame (which can also be installed stand-alone, if desired). The AG Associates Heatpulse8108 rapid thermal anneal system contains a subsystem for each of the following:• Electronics (including a dedicated microprocessor)• Mass-flow-controlled gas handling• Cooling• ULPA filtration• Mechanical assembliesSoftware programs, called recipes, specify the details for each process. The AG Associates Heatpulse 8108 system includes a 3-1/2-inch floppy disk drive for process recipe storage. A three-axis industrial robot automates processing by transporting wafers into and out of the process chamber. It uses closed-loop feedback for precise motion control and accurate positioning.To provide cold-wall processing, water is circulated through the process-chamber walls. The quartz isolation tube is cooled with nitrogen or compressed air. The Heatpulse 8108 system is a versatile tool which can be useful for many applications, such as (but not limited to):• Silicon dielectric growth• Implant annealing• Glass re-flow• Silicide formation and annealing• Nitridation of metals• Contact alloying• Oxygen donor annihilation Temperature repeatability: + 3°C or better at 1150°C wafer to wafer. (Repetition specifications are based on a 100-wafer set.) Temperature uniformity: + 5°C across an 8-inch wafer at 1150°C. (This is a 1-sigma deviation from 100-angstrom oxide uniformity.) For a titanium silicidation process, no more than 1.5 percent increase to uniformity during the first anneal at 650 – 700°C. AG Associates Heatpulse 8108 Physical Dimensions Width Monitor-Fab-Wall configurations: 40 in. (102 cm) Monitor-Side-Panel configurations: 60 in. (152 cm) Depth 42 in. (107 cm) Height 82 in. (208 cm) Weight Monitor-Fab-Wall configurations: 1800 lbs (816 kg); Monitor-Side-Panel configurations: 1840 lbs (835 kg) Shipping weight Monitor-Fab-Wall configurations: 2000 lbs (907 kg); Monitor-Side-Panel configurations: 2040 lbs (925 kg) AG Associates Heatpulse 8108 Utility Requirements Power StandardWater Type Refer to the Heatpulse® 8108 Facilities Manual.(Recirculator) AG Associates Heatpulse 8108 Rapid Thermal Anneal equipment FEATURES: The AG Associates Heatpulse 8108 Rapid Thermal Annealing system contains many capabilities which provide significant advantages over conventional batch processing in the production of VLSI circuits. Cleanroom integrity, precise temperature control and measurement, software flexibility, and the physical structure of the system (designed for the production environment) are among these advantages. Contaminant-Free Processing The Heatpulse 8108 system is designed with the cleanroom environment in mind. The following are the key features which make this Heatpulse 8108 system contaminant-free: • Stainless-steel laminar flow processing floor and ULPA filter located in the processing area to reduce the number of particles in the environment. The walls of the processing area are also stainless steel.• Design which prevents particles from circulating around the wafer-handling area, which allows the front panel door to remain open during processing.• Easy service access available from rear and side panels.• Through-the-wall installation, which maintains cleanroom integrity.• No belts and pulleys (a large source of particle contamination) exist in the 8108 wafer-handling area.• Front touch-screen controller remotely mounted to further reduce particle attraction. Heating, Cooling, and Temperature Measurement The following lists the key features of 8108 heating, cooling, and temperature measurement:• High-intensity radiation which heats wafers for short periods of 1 to 600 seconds at precisely controlled temperatures in the 400-to-1200°C range.• Tungsten halogen lamps and cold process-chamber walls which allow fast wafer heating and cooling rates, respectively.• Lamps arranged in 2 banks of 14 lamps each, 1 bank above and the other below the process chamber. Upper lamps which run crosswise and lower lamps which run lengthwise. Thus, the upper and lower lamps are at right angles to each other for optimization of temperature control. In addition, 10-zone lamp control to enable further wafer uniformity.• The system delivers time and temperature profiles tailored to suit specific process requirements.• Pyrometer or thermocouple sensing (with DTC option) which offers precise closed-loop temperature control.• Open-loop intensity control (OLIC) option which offers accurate, repeatable temperature control. (This feature requires ±0.5 VAC at 208 VAC line voltage regulation to function accurately.)• Purge gas which flows through the process chamber and cooling gas (CDA) which flows around the isolation tube and lamps.• Water de-ionizing system for oven cooling water to minimize metal corrosion. Software The Heatpulse 8108 system features touch-screen operation which is easy to learn. Additional software features are listed below.• Menu screens which allow a process cycle to be easily defined and executed.• Status reports continually displayed on the screen as the system operates.• Self-diagnostic routine active whenever the system is on and terminates the cycle in progress if an abnormal condition is detected.• Access codes which provide security for the system, recipe programming, and diagnostic functions.• Highly flexible recipes and process procedures.• Simple and easy-to-use menu screens.• Touch-screen menus which eliminate the need for special commands.• Manual mode which allows engineers and service personnel to activate individual subassemblies and functions.• Discrete diagnostic routines, using a separate Diagnostic mode, are available.• Maintenance menu which allows you to customize messages by condition and date to appear on the GUI screen at a set time.• Thermal processing cycles which may be customized for unique processing requirements.• Custom recipes created by process engineers which may be saved on floppy diskette and executed by production line operators. Service Access The 8108 system has been built for fast servicing in the production environment which provides low mean time to repair (MTTR ). The features listed below reflect this purpose:• Optional menu screen available at the rear of the system, enabled through a key control switch.• Gas box specifically designed for easy access and maintenance.• Front access window closes to prevent cleanroom contamination during maintenance for through-the-wall installation.• Top window, which flips out of the way, enables easier wafer-handling area access. Wafer Handling, Control, and Accuracy 8108 wafer-handling system features include the following:• Consistent wafer-to-wafer process cycle repeatability• Optional send and receive cassette bases which swivel to accommodate loading and unloading by a cleanroom robot in a fully robotic environment• Antistatic Ion Bar in the laminar flow system which reduces electrostatic charges on wafer handling components.• Controlled ambient• Robotic transport of wafers in excess of 80 wafers per hour (in a null cycle without the flat-finder option)• A process-per-wafer (PPW) feature which enables you to program a different recipe for each wafer in a cassette. For pick-and-place operation, one recipe and be selected for each cassette, or up to 50 different recipes can be programmed when two 25-slot cassettes are used, or 52 recipes when two 26-slot cassettes are used Rapid Thermal Processing and Rapid Thermal Anneal Introduction Rapid thermal processing (or RTP) refers to a semiconductor manufacturing process which heats silicon wafers to high temperatures (up to 1200 C or greater) on a timescale of several seconds or less. The wafers must be brought down (temperature) slow enough however, so they do not break due to thermal shock..Such rapid heating rates are attained by high intensity lamps process. These processes are used for a wide variety of applications in semiconductor manufacturing including dopant activation, thermal oxidation, metal reflow and chemical vapor deposition.Rapid thermal anneal (RTA) is a process used in semiconductor device fabrication which consists of heating a single wafer at a time in order to affect its electrical properties. Unique heat treatments are designed for different effects. Wafers can be heated in order to activate dopants, change film-to-film or film-to-wafer substrate interfaces, densify deposited films, change states of grown films, repair damage from ion implantation, move dopants or drive dopants from one film into another or from a film into the wafer substrate. Rapid thermal anneals are performed by equipment that heats a single wafer at a time using lamp based heating that a wafer is brought near. Unlike furnace anneals they are short in duration, processing each wafer in several minutes. Rapid thermal anneal is a subset of processes called Rapid Thermal Process (RTP).Rapid thermal processing (or RTP) refers to a semiconductor manufacturing process which heats silicon wafers to high temperatures (up to 1200 C or greater) on a timescale of several seconds or less. The wafers must be brought down (temperature) slow enough however, so they do not break due to thermal shock..Such rapid heating rates are attained by high intensity lamps process. These processes are used for a wide variety of applications in semiconductor manufacturing including dopant activation, thermal oxidation, metal reflow and chemical vapor deposition.Rapid thermal anneal (RTA) is a process used in semiconductor device fabrication which consists of heating a single wafer at a time in order to affect its electrical properties. Unique heat treatments are designed for different effects. Wafers can be heated in order to activate dopants, change film-to-film or film-to-wafer substrate interfaces, densify deposited films, change states of grown films, repair damage from ion implantation, move dopants or drive dopants from one film into another or from a film into the wafer substrate. Rapid thermal anneals are performed by equipment that heats a single wafer at a time using lamp based heating that a wafer is brought near. Unlike furnace anneals they are short in duration, processing each wafer in several minutes. Rapid thermal anneal is a subset of processes called Rapid Thermal Process (RTP).Rapid thermal processing (RTP) provides a way to rapidly heat wafers to an elevated temperature to perform relatively short processes, typically less than 1-2 minutes long. Over the years, RTP has become essential to the manufacture of advanced semiconductors, where it is used for oxidation, annealing, silicide formation and deposition.An RTP system heats wafers singly, using radiant energy sources controlled by a pyrometer that measures the wafer’s temperature. Previous thermal processing was based on batch furnaces, where a large batch of wafers is heated in a tube. Batch furnaces are still widely used, but are more appropriate for relatively long processes of more than 10 minutes.RTP is a flexible technology that provides fast heating and cooling to process temperatures of ~200-1250??C with ramp rates typically 20-200??C/sec, combined with excellent gas ambient control, allowing the creation of sophisticated multistage processes within one processing recipe. This capability to process at elevated temperatures for short time periods is crucial because advanced semiconductor fabrication requires thermal budget minimization to restrict dopant diffusion. Replacement of the slower batch processes with RTP also enables some device makers to greatly reduce manufacturing cycle time, an especially valuable benefit during yield ramps and where cycle-time minimization has economic value.RTP systems use a variety of heating configurations, energy sources and temperature control methods. The most widespread approach involves heating the wafer using banks of tungsten-halogen lamps because these provide a convenient, efficient and fast-reacting thermal source that is easily controlled. In a typical RTP system , the wafer is heated by two banks of linear lamps ?a one above and one below it. The lamps are further subdivided into groups or zones that can be individually programmed with various powers to maximize temperature uniformity. In RTP, the energy sources face the wafer surfaces rather than heating its edge, as happens in a batch furnace. Thus, RTP systems can process large wafers without compromising process uniformity or ramp rates. RTP systems frequently incorporate the capability to rotate the wafer for better uniformity.An important RTP application is the activation of ion-implanted dopants to form ultrashallow junctions. This requires fast ramp and cooling capabilities because the wafer must be heated to ~1050??C to anneal out ion implantation damage and activate the implanted dopant species. However, the time at temperature must be reduced to minimize diffusion. This has led to the spike-anneal approach, where the wafer is ramped to a high temperature and then cooled immediately.Another indispensable RTP application is in the formation of silicides. In this process, metal films react with the silicon on source/drain and gate regions to form silicides. In advanced logic processes, the metal is usually cobalt, but nickel is being explored for the 65 nm node. Silicide formation processes are usually performed at <500??C, and wafers must be kept in a very pure gas ambient because metal films can be sensitive to oxidation. RTP systems are ideal, because they have small chamber volumes easily purged with high-purity gas, creating a very clean environment.RTP is also increasingly important in oxidation applications, where the capability to use short process times at high temperatures and a wide variety of gas ambients provides excellent quality films and superior process control. RTP-grown oxides are often used for gate dielectrics, tunnel oxides and shallow-trench isolation liners. The use of steam in the gas ambient has opened new RTP applications. One of special interest for advanced DRAM technology is the use of a hydrogen-rich steam ambient for selective oxidation of gate stacks that include tungsten.Recently, RTP-like processing has found applications in another rapidly growing field ?a solar cell fabrication. RTP-like processing, in which an increase in the temperature of the semiconductor sample is produced by the absorption of the optical flux, is now used for a host of solar cell fabrication steps, ncluding phosphorus diffusion for N/P junction formation and impurity gettering, hydrogen diffusion for impurity and defect passivation, and formation of screen-printed contacts using Ag-ink for the front and Al-ink for back contacts, respectively.Some solar cell companies have successfully applied our advanced Rapid Thermal Processing (RTP) technology to its process for creating highly efficient and durable CIGS solar cells. This eliminates a key process bottleneck found in many state-of-the-art process implementations and enables the use of low-cost substrates in ways that were not considered possible before.In Rapid Thermal Processing, a layer is heated for a very brief period only in a highly controlled way. For instance, RTP techniques can flash-heat a layer for just several picoseconds and put energy just into the top several nanometers of a layer in a highly controlled way — while leaving the rest of the layer unaffected.RTP has a secondary benefit of reducing the energy payback time of their solar cells to less than two months (for the full panel). By comparison, a typical silicon solar panel has an energy payback time of around three years, and a typical vacuum-deposited thin-film cell has one of 1-2 years. The energy payback time is the time that a solar panel has to be used in order to generate the amount of energy that it required to be produced.
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Share photos on WhatsApp? You should be careful. There is a new bug in the service that may lead to strangers viewing the photos that you shared with your contacts. Graham Cluley, a UK-based security researcher said, the privacy flaw appeared with WhatsApp's newly-introduced web interface. "17-year-old security researcher Indrajeet Bhuyan has discovered a privacy hole in WhatsApp that could expose your account's profile photo to complete strangers, even if you have set it to be viewable to Contacts Only," Cluley wrote on his blog . "Sure, it's not the most serious privacy breach that has ever occurred, but that's missing the point. The expectation (of users) is that WhatsApp will only allow their photos to be viewable by those who the user has approved." WhatsApp Web, which was released recently, allows WhatsApp users to access the service in a browser. However, it is not a true web service. Even if a user wants to use WhatsApp on the web, he or she needs a smartphone with WhatsApp on it. "Today, for the first time, millions of you will have the ability to use WhatsApp on your web browser. Our web client is simply an extension of your phone: the web browser mirrors conversations and messages from your mobile device -- this means all of your messages still live on your phone," WhatsApp had said. Bhuyan demonstrated the bug in the following video that he posted on YouTube. Read Also: How to enable WhatsApp on the web Read Also: 7 tips to stay safe on WhatsApp
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Q: How to Input Multiple Columns Under One Primary Key? Using Microsoft Visual Web Developer and MSSQL as the database, is there a way to insert multiple values under one primary key? Just like the common systems used in grocery stores(eg. 7-11)? Thanks in advance. A: You can never do that for Primary Keys are unique with each other what you can do is to insert multiple values under one type/brand/dealer. For Example: INSERT INTO Product(PKID,Name,Quantity,Dealer) VALUES (NEWID(),'Product1','100','CompanyX') INSERT INTO Product(PKID,Name,Quantity,Dealer) VALUES (NEWID(),'Product2','121','CompanyX') INSERT INTO Product(PKID,Name,Quantity,Dealer) VALUES (NEWID(),'Product3','200','CompanyY') INSERT INTO Product(PKID,Name,Quantity,Dealer) VALUES (NEWID(),'Product4','50','CompanyY') INSERT INTO Product(PKID,Name,Quantity,Dealer) VALUES (NEWID(),'Product5','53','CompanyY') Result: +---------------------------------------------------------------+ | PKID | Name |Quantity| Dealer| +---------------------------------------------------------------+ |E04B64F7-8B84-465A-91F3-635DBDA242B0|Product1| 100|CompanyX| |49BB0054-A654-4877-B991-8300F660B72A|Product2| 121|CompanyX| |1DBE1BBF-89AF-482B-9BB7-DC2B1AA2932E|Product3| 200|CompanyY| |6EC8A994-7D40-40C0-B390-2761857EF42B|Product4| 50|CompanyY| |5DFFB38E-C564-4DDF-946A-08C47DFC044F|Product5| 53|CompanyY| +---------------------------------------------------------------+ In this case, you added multiple values under one dealer.
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Introduction ============ During primary T cell--dependent immune responses, somatic mutation of Ig V region genes in germinal center B cells generates variants expressing Ig with altered affinity for antigen [1](#R1){ref-type="bib"} [2](#R2){ref-type="bib"} [3](#R3){ref-type="bib"}. Variants with improved affinity are positively selected so as to eventually comprise the majority of the antigen-specific memory and antibody-forming cell (AFC) B cell populations [4](#R4){ref-type="bib"} [5](#R5){ref-type="bib"} [6](#R6){ref-type="bib"} [7](#R7){ref-type="bib"}. The increasing frequency of high-affinity B cells within these two populations is referred to as affinity maturation, a phenomenon originally observed in the improvement in the average affinity of serum antibodies [8](#R8){ref-type="bib"}. Although both memory B cells [2](#R2){ref-type="bib"} [3](#R3){ref-type="bib"} and high-affinity AFCs located in the bone marrow [5](#R5){ref-type="bib"} [6](#R6){ref-type="bib"} [9](#R9){ref-type="bib"} originate in the germinal center, the mechanism underlying the recruitment and maintenance of high-affinity germinal center variants into these populations remains obscure. Although it is generally regarded that memory B cells require antigen for their continued survival [10](#R10){ref-type="bib"}, the means by which bone marrow AFCs are selected and maintained is less clear. A number of reports indicate that once in the bone marrow, these AFCs are unresponsive to antigen [9](#R9){ref-type="bib"} [11](#R11){ref-type="bib"} [12](#R12){ref-type="bib"}, arguing against antigen-dependent selection in the bone marrow. This is consistent with the downregulation of surface Ig on AFCs as they mature [5](#R5){ref-type="bib"}. Takahashi and colleagues have proposed that, after the cells leave the germinal center, selection for high-affinity bone marrow AFCs continues in an antigen-dependent manner [6](#R6){ref-type="bib"} [13](#R13){ref-type="bib"}. If selection of memory B cells and bone marrow AFCs utilizes similar criteria, it would follow that circumstances that alter selection of one cell type would affect the other in the same manner. Differences in outcome, however, would indicate differences in selection criteria. In this study, we have assessed the relative contribution of cell survival mechanisms regulated by BCL-2 in the affinity maturation of antigen-specific memory B cell and AFC compartments. This was done by analysis of the immune response in *bcl*-2--transgenic mice in which, to a large degree, B cell survival is independent of B cell antigen receptor (BCR)-mediated stimuli [14](#R14){ref-type="bib"} [15](#R15){ref-type="bib"} [16](#R16){ref-type="bib"}. A previous analysis of the immune response of these transgenic mice revealed an amplification of both the antigen-specific germinal center/memory and splenic AFC compartments [5](#R5){ref-type="bib"}, although affinity maturation among the memory and bone marrow AFC compartments was not measured. Although other groups have examined aspects of immunity in *bcl*-2--transgenic mice [17](#R17){ref-type="bib"} [18](#R18){ref-type="bib"}, the effects of blocking cell death in this way on affinity maturation in the memory and AFC compartments has yet to be assessed. Our results lead us to conclude that constitutive expression of the *bcl*-2 cell survival gene distorts selection of the memory B cell compartment while leaving the proportion of high-affinity cells in the bone marrow AFC compartment essentially unchanged. B cells with no affinity-enhancing V~H~ gene somatic mutations persist in abnormally large numbers in the germinal center/memory B cell pathway of the transgenic mice. Similarly, low-affinity AFCs persist in the spleens of these mice. The preferential appearance of high-affinity AFCs in the bone marrow, however, is not altered despite an overall increase in the number of AFCs in both the spleen and bone marrow. The ability of a *bcl*-2 transgene to alter the composition of the memory population but not that of the bone marrow AFCs implies that fundamental differences exist in the manner in which germinal center B cells are selected and/or maintained in these compartments. The basis of this difference is discussed. Materials and Methods ===================== Mice and Immunization. ---------------------- Hemizygous transgenic mice of the Eμ-*bcl*-2-36 strain [19](#R19){ref-type="bib"}, backcrossed with inbred C57BL/6 mice for more than 15 generations, were provided by Drs. A.W. Harris and S. Cory (The Walter and Eliza Hall Institute). Transgene-bearing mice were identified as described [19](#R19){ref-type="bib"}. Nontransgenic littermates were used as controls throughout. In most experiments, mice were immunized by intraperitoneal injection of 100 μg of alum-precipitated NP (\[4-hydroxy-3-nitrophenyl\]acetyl) conjugated to keyhole limpet hemocyanin (KLH) (NP/KLH conjugation ratio 17:1), prepared as described previously [20](#R20){ref-type="bib"}. For the bromodeoxyuridine (BrdU) incorporation experiments, mice were immunized subcutaneously at the base of the tail with 100 μg of alum-precipitated NP~17~--KLH. Immunofluorescent Staining, Flow Cytometric Analysis, and Cell Sorting. ----------------------------------------------------------------------- NP-specific memory B cells, defined as IgM^−^IgD^−^ IgG1^+^CD38^+^ and NP binding, were resolved from other splenocytes as previously described [21](#R21){ref-type="bib"}. The so-called "dump" channel comprised biotin conjugates of the rat mAbs 281.2 (antisyndecan), 331.12 (anti-IgM), and 11-26C (anti-IgD), all revealed with streptavidin--PE (Caltag Labs.), plus propidium iodide to exclude AFCs, naive B cells, and dead cells, respectively, from the analysis. Antigen-specific B cells were identified by simultaneously binding NP coupled to allophycocyanin and Texas Red--conjugated goat anti--mouse IgG1 (Southern Biotechnology Associates). CD38 expression levels, used to resolve NP-specific germinal center (CD38^−^) and memory (CD38^+^) B cells [21](#R21){ref-type="bib"}, were determined using FITC-conjugated NIMR5/18 (a gift from Dr. M. Howard, DNAX Research Institute, Palo Alto, CA). Cells were sorted with a dual laser FACStar^PLUS™^ (Becton Dickinson) and an associated automated cell deposition unit (ACDU). Cell Culture. ------------- Cells were sorted into flat-bottomed 96-well plates using the ACDU and cultured in 200 μl of RPMI culture medium supplemented with 50 μM 2-ME, 10% FCS, IL-4, IL-5, and an optimal concentration of CD40 ligand (CD40L) expressed from a baculovirus construct (a gift from Dr. P. Hodgkin, Centenary Institute, Sydney, Australia). After 7 d, culture supernatants were assayed for high-affinity and total anti-NP IgG1 as described below. Purified NP-specific monoclonal IgG1 was used as a standard. ELISA and ELISPOT Assays. ------------------------- Total and high-affinity NP-specific IgG1 was detected by ELISA using 96-well plates (Costar Corp.) coated with NP~13~-- and NP~2~--BSA, respectively, as described [20](#R20){ref-type="bib"}. ELISPOT assays to enumerate AFCs were performed by titrating bone marrow or spleen cells into replicate wells of 96-well cellulose ester--based plates (Millipore Corp.) coated with NP~13~-- or NP~2~--BSA, followed by 16-h culture in RPMI containing 50 μM 2-ME and 10% FCS. Plates were washed, and bound NP-specific IgG1 was revealed with goat anti--mouse IgG1 conjugated to horseradish peroxidase (Southern Biotechnology Associates), visualized by the addition of 3-aminoethyl carbazole. Spots, each representing a single AFC, were counted using a dissecting microscope. V~H~ Gene Sequence Analysis of NP-specific B Cells. --------------------------------------------------- Sequences of V~H~186.2 genes were obtained from single NP-specific memory B cells as described [5](#R5){ref-type="bib"}. Two rounds of PCR were performed on cDNA derived from single B cells using nested primers specific for Cγ1 [22](#R22){ref-type="bib"}, together with a single proximal 5′ primer for the J558 V~H~ gene family [23](#R23){ref-type="bib"}. Products with bands of the expected size were purified and sequenced, with V~H~186.2-containing sequences positively identified at this stage. The efficiency of each step in this procedure is shown in [Table](#T1){ref-type="table"}. The improved efficiency of cDNA synthesis from *bcl*-2--transgenic single B cells (80 vs. 40%) is presumably due to the enhanced viability of these cells during the ex vivo manipulations. The entire PCR product was sequenced, and the region encoding amino acids 10--96 was compared in detail with the germline V~H~186.2 sequence [24](#R24){ref-type="bib"}. No clonal repeats were found, as assessed by comparison of complementarity determining region (CDR)3 sequences. BrdU Incorporation and Detection. --------------------------------- To identify proliferating cells within LN germinal centers, mice immunized 14 d previously were injected with a single dose of BrdU (100 μg per gram body weight; Sigma Chemical Co.) dissolved in 0.007 N NaOH in normal saline. After 6 h, the mice were killed, and LNs were fixed in Bouin\'s fluid and processed for paraffin embedding. Immunostaining was performed as described [25](#R25){ref-type="bib"}. In brief, sections of LN were treated with xylene to remove paraffin and rehydrated in solutions with graded ethanol concentrations. Excessive aldehydes in the fixed sections were quenched by incubation in 0.2 M glycine for 30 min. Sections were then treated for 30 min with 0.3% hydrogen peroxide to block endogenous peroxidase, followed by a 30-min incubation in 10% normal mouse serum to block nonspecific binding sites. All antibody incubation steps were for 30 min, followed by washings with PBS/1% BSA. To make BrdU accessible to antibody, sections were pretreated with 1.4 N HCl for 2 h, followed by staining with rat anti-BrdU antibody (Sera-Lab Ltd.). Bound antibody was detected by the secondary reagent, biotinylated MAR 18.5 (mouse anti--rat Igκ). The sections were then incubated for 30 min in avidin--peroxidase complex (ABC Elite kit; Vector Labs., Inc.), followed by detection with diaminobenzidene in 0.07% hydrogen peroxide as the substrate. Sections were counterstained with hematoxylin, dehydrated in alcohol and xylene, and mounted in DPX. All germinal centers in two nonsequential sections from each of two LNs from each control and *bcl*-2--transgenic animal were scored and the percentage of BrdU-containing cells within each germinal center calculated. The average BrdU^+^ percentage from all individual germinal centers was then calculated for each mouse. TUNEL Staining. --------------- LN sections, initially treated as above, were incubated with proteinase K (20 μg/ml) for 15 min and then washed three times in PBS. Endogenous peroxidases were blocked by incubating the sections with 0.3% hydrogen peroxide in methanol for 5 min, followed by washing. Sections were then incubated for 60 min in a humidified incubator with terminal deoxynucleotidyltransferase (TdT; Promega Corp.) in the presence of biotinylated dUTP (Pharmacia). Incorporated biotinylated dUTP was revealed with avidin--peroxidase complex (ABC Elite kit; Vector Labs., Inc.), followed by detection with diaminobenzidene in 0.07% hydrogen peroxide as the substrate. Sections were counterstained with hematoxylin, dehydrated in alcohol and xylene, and mounted in DPX. TUNEL^+^ clusters within germinal centers were scored from two nonsequential sections from each of two LNs per mouse. Thus, a total of 12 sections were analyzed for each genotype. Sections were photographed using a Zeiss Axiaphot (Carl Zeiss, Inc.) with Kodak 64T film at the degrees of magnification indicated. Results ======= bcl-2 Promotes the Accumulation of Memory B Cells with Few Ig V Gene Mutations. ------------------------------------------------------------------------------- To investigate the role of apoptotic pathways blocked by BCL-2 in B cell selection in the germinal center, we examined this process in mice expressing a *bcl*-2 transgene. We have shown previously that a *bcl*-2 transgene expressed in the B cell lineage increases the cellularity of the germinal center/memory compartment by 10- to 20-fold [20](#R20){ref-type="bib"}. We sought to determine the nature of the B cell expansion with respect to cell subset composition and affinity-enhancing V~H~ gene mutations to gain insight into selection in the germinal center. To evaluate which population of B cells was expanded in the transgenic mice, we determined CD38 expression on antigen-specific IgG1^+^ B cells late in the primary immune response. Germinal center B cells can be resolved from naive and memory B cells by reduced levels of CD38 [21](#R21){ref-type="bib"}. Mice were immunized by intraperitoneal injection of 100 μg of alum-precipitated NP--KLH, and 42 d later they were examined for the frequency of isotype-switched NP-binding B cells. Approximately 50% of NP-binding IgG1^+^ B cells in the spleens of control mice were CD38^+^, whereas the remainder retained the CD38^lo^ germinal center B cell phenotype. More than 80% of NP^+^IgG1^+^ B cells in the *bcl*-2--transgenic mice had the CD38^+^ memory phenotype ([Fig. 1](#F1){ref-type="fig"} A). That the expanded CD38^+^ antigen-specific B cell population in the spleens of *bcl*-2--transgenic mice actually constituted the memory population and was not due to altered CD38 regulation in the transgenic B cells was confirmed by the following observations. First, these B cells bound low levels of peanut agglutinin and did not have the light scatter characteristics of blast cells (data not shown). Second, germinal center B cells within the mesenteric LNs of *bcl*-2--transgenic mice reduced CD38 expression to the same extent as control mice ([Fig. 1](#F1){ref-type="fig"} B), indicating that CD38 expression is regulated appropriately in these mice. We next compared the distribution of V~H~ gene somatic mutations in purified NP-binding B cells from transgenic and control mice. To ensure that the same B cell populations were compared, we focused on the antigen-specific CD38^+^ subset. Single IgG1^+^ NP-specific CD38^+^ B cells were sorted from the spleens of *bcl*-2--transgenic and control mice immunized 42 d previously. IgG~1~ rearrangements involving the V~H~186.2 gene segment were amplified by PCR from cDNA templates and sequenced. Analysis of these sequences from *bcl*-2 mice revealed a number of differences in the pattern of somatic mutation seen in the equivalent control B cell population ([Table](#T1){ref-type="table"} and [Fig. 2](#F2){ref-type="fig"} A). First, 25% of the V~H~186.2 sequences from *bcl*-2--transgenic cells contained zero mutations, compared with 4% in controls. Second, 36% of V~H~186.2 gene sequences from *bcl*-2--transgenic mice contained either one or two mutations and lacked the affinity-enhancing tryptophan→leucine exchange at amino acid 33. The equivalent group comprised 16% of control sequences. Thus, some 60% of memory phenotype B cells in the *bcl*-2--transgenic mice showed no evidence of affinity maturation of their V~H~ gene sequences, compared with only 20% in controls. The affinity-enhancing exchange at V~H~ position 33 was present in 13% of *bcl*-2--transgenic memory B cells, compared with 64% in control mice ([Table](#T1){ref-type="table"} and [Fig. 2](#F2){ref-type="fig"}), which indicated that BCL-2 did not prevent the appearance of high-affinity cells. The cumulative distribution of somatic mutations in the V~H~ gene sequences is depicted in [Fig. 2](#F2){ref-type="fig"} B. It should also be noted that the proportion of recovered PCR products using the V~H~186.2 gene segment was the same in antigen-specific B cells from both types of mice. That is, there was no bias toward related V~H~ genes in the *bcl*-2--transgenic memory B cells. Finally, when V~H~ genes were sequenced from populations of IgG1^+^ antigen-specific B cells irrespective of their CD38 levels (i.e., all B220^+^IgG1^+^ NP-binding cells) from both *bcl*-2 and control mice, the observed pattern of mutations was very similar to that observed when CD38 was used as a marker (not shown). From these results, it should follow that NP-specific Ig produced by the memory B cell population of *bcl*-2--transgenic mice should correlate with a lower degree of affinity maturation than Ig produced by the equivalent population from control mice. To determine whether this was the case, IgM^−^IgD^−^CD38^+^IgG1^+^ NP-binding B cells were sorted from spleens of *bcl*-2--transgenic and control mice at day 42 after immunization and stimulated in vitro with CD40L plus cytokines. The fraction of total NP-specific IgG1 able to bind to NP~2~-conjugated plate coats from *bcl*-2--transgenic mice was 30%, compared with 100% in control cultures. This confirms a lower representation of high-affinity B cells in the *bcl*-2 memory B cell population. Collectively, these data demonstrate the persistence of excessive numbers of low-affinity B cells in the memory populations of *bcl*-2--transgenic mice. Transgenic expression of *bcl*-2 therefore results in the persistence of cells with a memory phenotype and a pattern of V~H~ gene mutations suggesting low affinity, an observation confirmed by measurement of the affinity of antibody produced by these same cells after sorting and culture in vitro. These results indicate that constitutive expression of BCL-2 allows for and may even enhance the differentiation of germinal center cells into memory cells, despite their being of low affinity. bcl-2 Inhibits Apoptosis and Proliferation in Germinal Centers to Varying Degrees. ---------------------------------------------------------------------------------- BCL-2, defined as an inhibitor of apoptosis [26](#R26){ref-type="bib"}, is also able to delay entry of mitogen-stimulated lymphocytes into the cell cycle [27](#R27){ref-type="bib"} [28](#R28){ref-type="bib"} [29](#R29){ref-type="bib"}. To better define the basis of the effect of constitutive *bcl*-2 expression on selection of antigen-specific B cells, we sought to quantify the extent of apoptosis and proliferation in the germinal centers of *bcl*-2--transgenic mice. For these experiments, mice were immunized at the base of the tail, and 14 d later the paraaortic LNs were taken, fixed in paraformaldehyde, and sectioned. Paraaortic LNs were chosen because without deliberate immunization, this tissue contained no germinal centers and we could therefore be certain that all of the germinal centers that developed had developed in a synchronized manner. Sections from immunized and unimmunized transgenic and control animals were stained using the TUNEL (TdT-mediated dUTP-biotin nick-end labeling) technique to reveal the frequency of apoptotic cells ([Fig. 3](#F3){ref-type="fig"}). The results show that BCL-2 reduced apoptosis by a factor of ∼10-fold ([Table](#T2){ref-type="table"}). This implies that the major form of cell death in germinal centers is due to apoptotic pathways that can be blocked by BCL-2 and that BCL-2--insensitive pathways of apoptosis, such as those activated by death receptors, play only a minor role [30](#R30){ref-type="bib"} [31](#R31){ref-type="bib"}. The frequency of proliferating cells in LN germinal centers of *bcl*-2--transgenic and control mice was determined by scoring the number of cells per germinal center that had incorporated BrdU during a 6-h pulse. Histological sections were first scored for the frequency and size of germinal centers, and no significant difference was observed between *bcl*-2--transgenic mice and controls ([Table](#T3){ref-type="table"}). The similarity in germinal center size and frequency in the two strains implies that the additional antigen-specific B cells that accumulate during the immune response in the *bcl*-2--transgenic mice reside in a postgerminal center compartment. This is consistent with the increased frequency of B cells with a memory phenotype defined above ([Fig. 1](#F1){ref-type="fig"}). The fraction of cells synthesizing DNA during the 6-h pulse differed somewhat between the two groups, with transgenic mice showing a decrease of ∼25% ([Table](#T3){ref-type="table"}). As the size distribution of germinal centers in the two strains was the same ([Table](#T3){ref-type="table"}), the decrease in the proportion of BrdU-labeled germinal center cells in the *bcl*-2--transgenic mice is equivalent to a reduced number of proliferating cells. Thus, constitutive *bcl*-2 expression does not affect germinal center formation but does reduce both apoptosis and proliferation within the germinal center, although the effect on the former is much greater. High-Affinity AFCs Are Selectively Recruited into the Bone Marrow of bcl-2--transgenic Mice. -------------------------------------------------------------------------------------------- Having observed an enhanced preservation of low-affinity B cells within the memory compartment of *bcl*-2--transgenic mice, we next examined whether the AFC compartments in the spleen and bone marrow were similarly affected. We measured the frequency of high-affinity NP-specific IgG1 AFCs in spleens and bone marrow of *bcl*-2--transgenic and control animals ([Table](#T4){ref-type="table"}). At day 42 after immunization, the average frequency of NP-specific IgG1 AFCs in the spleens of control mice was 1.5 per 10^5^ splenocytes, of which 90% were high affinity, as determined by binding to the low conjugation plate coat, NP~2~--BSA. The frequency of antigen-specific IgG1 AFCs in the bone marrow of control animals at day 42 was 5 per 10^5^ cells, of which 80% were high affinity, a proportion not significantly different from that in the spleens of the same animals ([Table](#T4){ref-type="table"}). Thus, in control mice at this time after primary immunization, the vast majority of antigen-specific AFCs secreted high-affinity antibody, irrespective of their location. The situation in *bcl*-2--transgenic animals differed in two respects: first, the frequency of NP-specific IgG1 AFC was higher, and second, the degree of affinity maturation differed between the tissues examined ([Table](#T4){ref-type="table"}). The frequency of NP-specific IgG1 AFCs in the spleens of *bcl*-2--transgenic mice was ∼50-fold higher than in controls---corresponding to a 150-fold increase in absolute numbers---but only 30% of these AFC secreted high-affinity antibody ([Table](#T4){ref-type="table"}). This result confirms the preservation of splenic AFCs in *bcl*-2--transgenic mice [19](#R19){ref-type="bib"} [20](#R20){ref-type="bib"} and demonstrates that most of these cells secrete low-affinity Ig. Although the frequency of NP-specific IgG1 AFCs in the bone marrow of *bcl*-2--transgenic mice was approximately threefold higher than in controls, the proportion of AFCs secreting high-affinity antibody was close to normal at 70%. Importantly, the degree of affinity maturation amongst the bone marrow AFCs of *bcl*-2--transgenic mice differed significantly from that in the spleen of these mice ([Table](#T4){ref-type="table"}). That high-affinity cells accumulate normally in the bone marrow AFC compartment of *bcl*-2--transgenic mice but fail to do so in either the memory or splenic AFC compartments demonstrates a significant difference in the selective processes operating to establish and/or maintain these populations of antigen-specific B cells. Discussion ========== It is widely accepted that both the memory B cell and high-affinity AFC populations are recruited in the germinal center on the basis of their affinity for antigen [2](#R2){ref-type="bib"} [3](#R3){ref-type="bib"} [5](#R5){ref-type="bib"} [6](#R6){ref-type="bib"}. Although little is known regarding the molecular signals underpinning germinal center activity, a model to explain affinity maturation in the germinal center [2](#R2){ref-type="bib"} [3](#R3){ref-type="bib"} [32](#R32){ref-type="bib"} [33](#R33){ref-type="bib"} may be summarized as follows. Somatic hypermutation of Ig V genes randomizes the affinity for antigen of B cells within germinal centers. Some variants will have their affinity increased, some left unchanged, and others decreased. As germinal center B cells require an antigen-dependent signal for their continued survival and participation in the processes of affinity maturation, those with improved affinity will have a competitive advantage in accessing antigen, localized in the germinal center as immune complexes on follicular dendritic cells. Such high-affinity B cells will therefore preferentially survive and thus will come to dominate the germinal center and, eventually, the memory population. Germinal center B cells that fail to receive antigen-dependent survival signals will undergo apoptosis, reinforcing the ascendancy of the high-affinity variants. In such a model, preventing the death of low-affinity variants should distort the process of affinity maturation. This model of germinal center activity in the generation of B cell memory is well supported by data from our current analysis of *bcl*-2--transgenic mice. By blocking apoptosis in the germinal center, a population of low-affinity B cells has been preserved inappropriately, and these cells have assumed the phenotype of memory B cells ([Fig. 1](#F1){ref-type="fig"}). This result implies that cell survival is a key determinant for entry into the memory B cell compartment. Thus, a constitutive cell survival signal has uncoupled affinity maturation in the germinal center from entry into the memory B cell compartment. This provides the first direct evidence that formation of a normally selected memory B cell compartment requires apoptosis in the germinal center. A model of survival-dependent differentiation, however, does not explain the formation of the high-affinity bone marrow AFC compartment. Transgenic *bcl*-2 clearly promoted the survival of AFCs, as demonstrated by the 50-fold increase in antigen-specific IgG1 AFCs in the spleen and threefold increase in bone marrow AFCs ([Table](#T4){ref-type="table"}). Recruitment and persistence of AFCs in the bone marrow, however, was not random, as the fraction of such cells secreting high-affinity antibody remained the same as in controls ([Table](#T4){ref-type="table"}). That is, germinal center--derived cells were recruited into the bone marrow AFC compartment on the basis of affinity and not solely on their potential to survive. Thus, the ability of BCL-2 to distort affinity maturation of memory B cells but not bone marrow AFCs reveals a fundamental difference in the means by which these populations are formed (or possibly maintained) from germinal center precursors. One explanation of how transgenic *bcl*-2 alters the composition of the memory B cell population but not that of bone marrow AFCs is that the differentiation of germinal center B cells is determined by the strength of the BCR interaction with antigen. B cells that bind antigen avidly will have a greater degree of receptor occupancy and cross-link more of their surface Ig than B cells with low-affinity Ig. This strength of signal could then be translated into commitment to differentiate into an AFC at the high end of the spectrum, survival in the germinal center at a central level, or apoptosis at the low end of the spectrum. Thus, differentiation into an AFC requires a particular threshold of signal strength to be reached, a signal that cannot be provided by BCL-2. Current data do not allow determination of where or over what time frame this BCR signal would be delivered, although recent data suggest a period of postgerminal center selection in bone marrow AFC formation [6](#R6){ref-type="bib"}. Indeed, an extended period of selection may distinguish the developmental pathway of bone marrow AFCs from that of the splenic foci, which are very sensitive to *bcl*-2 ([Table](#T4){ref-type="table"}). The proposed model of the germinal center ([Fig. 4](#F4){ref-type="fig"}) accounts for several aspects of germinal center activity: (a) the early appearance of sparsely mutated, high-affinity AFCs in the bone marrow [5](#R5){ref-type="bib"} and their corresponding absence from the germinal center [34](#R34){ref-type="bib"}; (b) the particular ability of BCL-2 to rescue low-affinity B cells in the germinal center; and (c) the continued improvement of AFC affinity during the first weeks of the response [5](#R5){ref-type="bib"} [6](#R6){ref-type="bib"}. This last observation would reflect the continued heightening of the affinity threshold necessary to enter the AFC population caused by germinal center--derived B cells having to compete with increasing titers of high-affinity serum Ig. Such competition would also require B cells within the germinal center to improve their affinity for antigen to receive a signal of sufficient strength to ensure their survival. The affinity of the memory B cell population would therefore be improved but would lag behind that of the cells destined to become bone marrow AFCs. The concept of lymphocyte differentiation being influenced by the degree of receptor occupancy has been proposed to explain early stages of the B cell response to both self- and foreign antigen [35](#R35){ref-type="bib"} [36](#R36){ref-type="bib"}. Regulating differentiation by the same mechanism in the germinal center would obviate the need for unique signaling pathways for different developmental stages. A prediction of this model is that mutations that alter the threshold of BCR-mediated activation should have an inverse effect on affinity maturation. Thus, mice with hyperresponsive B cells should show diminished affinity maturation, whereas those with hyporesponsive B cells should show more stringent selection. This principle may, for example, underlie the poor survival in germinal centers of B cells rendered hyporesponsive by ablation of CD21 [37](#R37){ref-type="bib"} and CD19 [38](#R38){ref-type="bib"}. A definitive answer requires a more detailed analysis of affinity maturation in these mice. A fundamental question remaining to be answered is, What changes occur to allow the germinal center output to shift from AFC production to that of memory B cell production? The memory B cell population is formed over a longer period than the bone marrow AFC population [21](#R21){ref-type="bib"} [39](#R39){ref-type="bib"} [40](#R40){ref-type="bib"}, although analysis of V gene somatic mutation indicates that the bulk of the memory population is generated late in the response [4](#R4){ref-type="bib"} [5](#R5){ref-type="bib"} [41](#R41){ref-type="bib"}. As this corresponds to the period of the response when titers of antibody are highest, it may be that B cell Fc receptors are of prime importance. Cross-linking FcγRIIb with the BCR inhibits B cell proliferation [42](#R42){ref-type="bib"} and differentiation into AFCs [43](#R43){ref-type="bib"} and may thus trigger germinal center B cells to assume a memory phenotype. Interestingly, in the absence of FcγRII, antibody production is elevated in response to immunization [44](#R44){ref-type="bib"}, consistent with FcγRII being involved in cessation of AFC production. Our analysis of the immune response of *bcl*-2--transgenic mice is not the first to address the impact of apoptosis on affinity maturation. Transgenic mice expressing in their B cells the *bcl*-2 homologue *bcl*-xL have been similarly analyzed [13](#R13){ref-type="bib"}. Despite the similarity of mechanism by which these two antiapoptotic genes block cell death [45](#R45){ref-type="bib"}, some differences are evident in the results obtained. First, *bcl*-xL mice show no increase in the frequency or longevity of AFCs in either the spleen or bone marrow compared with *bcl*-2 mice in which both of these compartments are amplified, raising the question of whether the *bcl*-xL transgene is expressed in terminally differentiated B cells. Second, *bcl*-xL mice show reduced affinity maturation of both serum Ig and bone marrow AFCs [13](#R13){ref-type="bib"}, again unlike *bcl*-2 mice ([Table](#T4){ref-type="table"} and reference 20). Third, there was an abnormal persistence of B cells containing noncanonical VDJ gene rearrangements in *bcl*-xL mice despite V186.2 rearrangements being normally mutated and selected [13](#R13){ref-type="bib"}. That is, the effect of the *bcl*-xL transgene appeared to be restricted to B cells bearing non-V~H~186.2 rearrangements. The effects of the *bcl*-2 transgene reported here, on the other hand, are distributed irrespective of V~H~ gene content, as there is no distortion of V~H~ gene usage in any of the compartments examined ([Table](#T1){ref-type="table"}). Thus, without knowing the full extent of *bcl*-xL transgene expression, we must assume that the differences in results obtained are due to the bcl-xL transgene not being expressed in all B cell compartments. This may also explain the variance observed between these two strains in a model system of self-, anti-self B cell tolerance [46](#R46){ref-type="bib"}. In summary, we have used *bcl*-2--transgenic mice to demonstrate that apoptosis of low-affinity germinal center B cells is necessary for the formation of a normally selected memory B cell population. Moreover, this increase in germinal center cell survival revealed marked differences in the nature of selection of memory B cells and bone marrow AFCs. Selection of the memory compartment was perturbed by constitutive *bcl*-2 expression in the germinal center, consistent with a model of selection where competition of B cells for an antigen-mediated survival signal is required for entry to the memory compartment. In contrast, the stringent selection of high-affinity bone marrow AFCs is not influenced by the *bcl*-2 transgene, consistent with a selective process requiring the germinal center B cell to exceed an "affinity threshold." We thank the WEHI Flow Cytometry facility for help with cell sorting and Drs. Alan Harris and Suzanne Cory for providing *bcl*-2--transgenic mice. This work was supported primarily by the National Health and Medical Research Council (NH & MRC), Canberra, Australia. Additional support was provided by the Wellcome Trust through a Biomedical Research Collaboration Grant (to K.G.C. Smith and D. Tarlinton), an MRC Career Establishment Grant (to K.G.C. Smith), and by grants and fellowships from the Dr. Josef Steiner Cancer Research Foundation (Bern, Switzerland), the Anti-Cancer Council of Victoria, the Cancer Research Institute (New York), and the Leukemia Society of America (New York) (to A. Strasser and L. O\'Reilly). *Abbreviations used in this paper:* AFC, antibody-forming cell; BCR, B cell antigen receptor; BrdU, bromodeoxyuridine; KLH, keyhole limpet hemocyanin; TUNEL, terminal deoxynucleotidyltransferase--mediated dUTP-biotin nick-end labeling. ###### Summary of V~H~186.2 Sequences from NP-specific IgG1^+^ B Cells at Day 42 after Immunization Control CD38^+^ *bcl*-2 CD38^+^ ------------------ ----------------- ----------------- Single cells 74 38 PCR^+^ 31 32 V~H~186.2^+^ 26 24 R/S ratio CDR1+2 4.0 2.9 FW1−3 2.7 1.8 Position 33 W→L 62% 13% Mutation average 4.6 2.7 Range 0--14 0--12 R/S ratio, ratio of replacement to silent mutations. ###### Apoptosis in the Germinal Centers of bcl-2--transgenic and Control Mice Mouse TUNEL^+^ clusters per germinal center in immunized mice ------- --------------------------------------------------------- ----------- 1 0.8 ± 1.7 8.2 ± 6.2 2 0.8 ± 1.0 8.1 ± 3.8 3 2.7 ± 2.1 9.7 ± 3.7 Mean 1.4 8.7 ###### Proliferation in the Germinal Centers of bcl-2--transgenic and Control Mice Mouse Percent BrdU^+^ cells per GC GC size (cells per germinal center) Total --------- ------- ------------------------------ ------------------------------------- ------- ----- ----- Control 1 41.6 ± 10.6 0 16 2 18 2 43.0 ± 13.6 1 21 6 28 3 35.9 ± 14.8 4 12 1 15 Mean 40.8 1.7 16.0 3.0 --- *bcl*-2 1 27.3 ± 11.3 3 17 3 23 2 19.2 ± 9.3 0 11 5 16 3 31.1 ± 13.7 3 18 11 32 Mean 27.2 2.0 15.3 6.3 --- GC, germinal center. ###### Frequency and Affinity of AFCs at Day 42 of the Primary Response Anti-NP IgG1 AFCs per 10^5^ Input Cells at Day 42 ----------- --------------------------------------------------- ------------- ------------ ----------- ------------- ------------ --------- Control 1.3 ± 1.1 1.4 ± 0.9 0.9 ± 0.04 7.9 ± 6.6 10.2 ± 9.3 0.8 ± 0.03 0.46 *bcl*-2 18.0 ± 9.0 64.8 ± 33.0 0.3 ± 0.01 21.3 ± 12 31.0 ± 17.0 0.7 ± 0.01 \<0.001 *P* value \<0.001 0.43 ###### Levels of CD38 on antigen-specific IgG1 B cells at day 42 of the primary response. (A) Spleens from mice immunized 42 d previously with 100 μg i.p. of NP--KLH were stained with the indicated antibodies and analyzed by flow cytometry. Viable cells having the phenotype IgM^−^IgD^−^ were electronically gated on (rectangle) and examined for expression of IgG1 and the ability to bind the immunizing hapten NP coupled to a fluorescent protein. Such double-positive cells were gated on (rectangle), and the level of CD38 was determined. This result is depicted as the solid histogram in this figure. Negative control staining was less than the fluorescence level marked by the dashed vertical line. The percentages of NP-binding IgG1^+^ cells expressing high levels of CD38 are indicated. Cells used in this experiment were pooled from three mice, and the data shown are representative of three experiments. (B) Germinal center cells in *bcl*-2--transgenic mice downregulate CD38. Mesenteric LN B cells were gated on by expression of CD45R. These cells were then examined for CD38 levels and binding of the lectin peanut agglutinin; such B cells are boxed. ![](JEM991706.f1a) ![](JEM991706.f1b) ###### Reduced frequency of V~H~ gene somatic mutations in NP-specific memory B cells from *bcl*-2--transgenic mice. The frequency of mutations in V~H~186.2 genes from single, antigen-specific CD38^+^IgG1^+^ B cells was determined by nucleotide sequencing. Single cells were sorted from a pooled spleen preparation from each mouse strain using the criteria depicted in [Fig. 1](#F1){ref-type="fig"}. All recovered sequences showed unique CDR3 junctions, indicating clonality. (B) Cumulative distribution of somatic mutations in control and *bcl*-2 NP-specific B cells. In both components of the figure, the number of sequences containing mutations giving rise to a tryptophan→leucine exchange at amino acid 33 (numbered according to reference 24) is depicted by the hatched segment of each column. Details of the sequences are summarized in [Table](#T1){ref-type="table"}. These sequence data are available from EMBL/GenBank/DDBJ under accession no. AF210258-AF210307. ![](JEM991706.f2a) ![](JEM991706.f2b) ![The frequency of apoptotic cells in germinal centers is reduced in *bcl*-2--transgenic mice. 2 wk after immunization, LNs were sectioned and stained for the presence of apoptotic cells using the TUNEL technique. An example of one such experiment using LNs from immunized and unimmunized control and *bcl*-2--transgenic mice is shown. Arrows indicate the location of germinal centers. No germinal centers were observed in the LNs of unimmunized mice. Magnification is 100, and one representative section is shown. Quantification of this data is presented in [Table](#T3){ref-type="table"}.](JEM991706.f3){#F3} ![Selection in the germinal center during the development of memory and AFCs in a primary immune response. A schematic representation of the forces acting to influence the outcome of the germinal center reaction during the primary immune response. Indicted are the fact that (a) high-affinity cells selectively become AFCs; (b) low-affinity cells apoptose, an event that can be blocked by BCL-2; and (c) intermediate affinity cells remain in the germinal center. As the response progresses, the affinity threshold for each differentiation pathway will increase as the cells compete with antibody in serum. It is predicted that this reaches a level where memory B cell production will be the favored outcome. This change may well involve FcγRII.](JEM991706.f4){#F4}
{ "pile_set_name": "PubMed Central" }
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1. Field of the Invention The present invention relates to an infrared sensor structured as a membrane and provided with an infrared detector generating an electric signal based on changes in temperature occurring at the time of receiving infrared rays, more particularly relates to an infrared sensor mounted by bonding with a mounting surface constituted by a sensor support using an adhesive. 2. Description of the Related Art As will be explained in detail later with reference to the drawings, when mounting an infrared sensor on a sensor support using an adhesive, the excess adhesive squeezed out from the bottom of the substrate of the infrared sensor creeps up along the inside walls of the inner cavity of the substrate below the membrane. If reaching the membrane, the temperature difference between the hot contacts and cold contacts of the thermocouples will become small and a drop in sensor sensitivity will be caused. In the semiconductor sensor disclosed in Japanese Unexamined Patent Publication (Kokai) No. 7-58134 as related art, to prevent this creep of the adhesive, as shown in the later drawings, an adhesive constituted by a die bonding paste is provided locally rather than over the entire bottom surface of the substrate. With this mounting method, however, it is necessary to control the coating positions and amounts of coating of the adhesive in the mounting step of the infrared sensor. This is troublesome.
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The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients. The incidence of posttransplant diabetes mellitus (PTDM) was compared in three groups of renal transplant recipients: nondiabetic patients who had been randomized between 1980 and 1983 to receive antilymphoblast globulin (ALG), azathioprine (AZA), and prednisone (P) (group 1) or cyclosporine (CsA) plus prednisone (group 2). Group 3 consisted of a more recent (1984-85) cohort who were given a combination of azathioprine, cyclosporine, and prednisone (+/- ALG). PTDM developed in 20 of 173 previously nondiabetic 18-55-year-old patients. Three of 47 patients (6.4%) in group 1, 4 of 58 patients (6.9%) in group 2, and 13 of 68 patients in group 3 (19.1%) developed PTDM. Thus in the two groups composing the concurrent prospective randomized trial (groups 1 and 2) the incidence of PTDM did not differ. The subsequent patients who were given a combination of ALG, azathioprine, cyclosporine, and prednisone developed a significantly greater incidence of PTDM even though the total dose of cyclosporine and prednisone were lower than in groups 1 and 2. PTDM usually occurred within two months of transplantation, and 11 of 17 patients who initially required insulin are still dependent upon exogenous insulin. The incidence of PTDM was not significantly affected by sex of the recipient, HLA-type, primary renal disease, rejection episodes, primary vs. secondary transplant, or prior splenectomy. The incidence of PTDM is greater in patients older than 45 (34.2% vs. 5.2%), and heavier than 70 kg (21.1% vs. 5.1%); in recipients of cadaveric allografts (15.7% vs. 4.6%); and in patients who were hospitalized for infections (22.4% vs. 4.7%). CsA levels tended to be higher in the group 2 and 3 patients who developed PTDM than in those who remained nondiabetic. One-year actuarial patient survival in those with PTDM was 83.3% vs. 98% (P less than .01) in the nondiabetic and graft survival was 77.1% vs. 87.1% (NS). The combination of Minnesota ALG, azathioprine, cyclosporine, and prednisone appears to predispose older, heavier recipients of cadaver allografts to the development of PTDM. The risk of PTDM must be weighed against the more usual results of improved patient and graft survival using this combination of immunosuppression.
{ "pile_set_name": "PubMed Abstracts" }
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import sklearn.neural_network as skl_nn from Orange.base import NNBase from Orange.classification import SklLearner __all__ = ["NNClassificationLearner"] class NIterCallbackMixin: orange_callback = None @property def n_iter_(self): return self.__orange_n_iter @n_iter_.setter def n_iter_(self, v): self.__orange_n_iter = v if self.orange_callback: self.orange_callback(v) class MLPClassifierWCallback(skl_nn.MLPClassifier, NIterCallbackMixin): pass class NNClassificationLearner(NNBase, SklLearner): __wraps__ = MLPClassifierWCallback def _initialize_wrapped(self): clf = SklLearner._initialize_wrapped(self) clf.orange_callback = getattr(self, "callback", None) return clf
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Indole-containing fractions of Brassica rapa inhibit inducible nitric oxide synthase and pro-inflammatory cytokine expression by inactivating nuclear factor-κB. In an attempt to identify bioactive natural products with anti-inflammatory activity, we evaluated the anti-inflammatory potential of the indole-containing fraction from the roots of Brassica rapa (IBR) (Family Brassicaceae) and the underlying mechanisms. Initially, we examined the inhibitory effect of IBR on the production of pro-inflammatory mediators in vitro and then evaluated its in vivo anti-inflammatory effects. IBR was found to concentration-dependently reduce the productions of nitric oxide, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced macrophages. Consistent with these findings, IBR suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS) at the protein level and of iNOS, TNF-α, and IL-6 at the mRNA level. Furthermore, IBR attenuated LPS-induced DNA-binding activities of nuclear factor-κB (NF-κB), and this was accompanied by a parallel reduction in the degradation and phosphorylation of inhibitory κBα and, consequently, by a reduction in the nuclear translocation of the p65 subunit of NF-κB. In addition, treatment with IBR inhibited carrageenan-induced paw edema in rats and acetic acid-induced writing response in mice. Taken together, our data suggest that the expressional inhibitions of iNOS, TNF-α, and IL-6 caused by an attenuation of NF-κB activation are responsible for the anti-inflammatory and antinociceptive activity of IBR.
{ "pile_set_name": "PubMed Abstracts" }
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The Blog The latest from OSF The Latest News Categories Summerland, B.C., Canada – Okanagan Specialty Fruits Inc. (OSF) introduced nonbrowning Arctic® apple fresh slices to a receptive foodservice industry at the Produce Marketing Association’s (PMA) recent Foodservice Show in Monterey, California. “It was exciting for us to exhibit at the PMA Foodservice show for the first time and to give attendees the opportunity to experience the orchard freshness of Arctic® Golden fresh slices,” said J.F. Gamelin, Director of Sales for OSF. “Arctic® apples’ nonbrowning trait offers a key benefit to the food service industry – including less prep, less waste and better taste.” Developed through bioengineering, Arctic® apples fresh slicesRead More Every year, one of the events the Arctic® apples team anticipates most is the preeminent produce industry event of the year – Produce Marketing Association’s Fresh Summit Convention & Expo – and this year was no exception! With our first nonbrowning variety, Arctic® Goldens, hitting stores in early November as fresh slices, the timing for this show couldn’t be better. We handed out hundreds of delicious apple slices to attendees, participated in the Fresh Ideas Showcase, showed off the packaging Arctic® Goldens will first hit stores in, and previewed our next variety projected to hit stores – Arctic® Granny! That’s farRead More Arctic® apple smoothies were a big hit at this year’s PMA Fresh Summit, and a packed trade show floor and excellent educational sessions showed why it’s the produce industry’s premier event. We were pretty hyped up for this year’s Fresh Summit since it’s the first time we’ve ever exhibited there, and the experience did not disappoint! Educational sessions emphasized causes we strongly believe in, such as reducing food waste in the produce industry and making fruits and veggies more accessible and appealing to children. The importance of embracing disruptive, innovative technology was also a consistent theme. Keynote speaker Mike WalshRead More
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School News RCC graduate returns to serve at West Point Middle School Georgiana Lee will tell you that she knew what she wanted to do with her career but was not sure how to get there. After two years at Rappahannock Community College, the Middlesex County native found her path and is back home. “I am more than excited to be coming home,” said Lee, who will soon begin at West Point Middle School as a counselor. “[Home] is definitely a place of comfort and peace, and a place where I have a lot of support from my old professors, family, and my teachers from high, middle and elementary school.” Lee’s journey from Middlesex to West Point might look like about a 15-minute drive, but it turns out that this trip took many years and hundreds of miles. She started her journey as a graduate from Middlesex High School. She then entered Rappahannock Community College. She says that as a first-in-her-family college student there was an adjustment period. Luckily for her, Lee had a team at RCC on her side every step of the way. Read the rest of this story in this week’s Southside Sentinel at newsstands throughout the county, or sign up here to receive a print and/or electronic pdf subscription.
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