gebhart/patrepeval huggingface dataset:
Purification and Characterization of Mouse Soluble Receptor for Advanced Glycation End Products (sRAGE) (2004)

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface proteins that has been implicated as a progression factor in a number of pathologic conditions from chronic inflammation to cancer to Alzheimer's disease. In such conditions, RAGE acts to facilitate pathogenic processes. Its secreted isoform, soluble RAGE or sRAGE, has the ability to prevent RAGE signaling by acting as a decoy. sRAGE has been used successfully in animal models of a range of diseases to antagonize RAGE-mediated pathologic processes. In humans, sRAGE results from alternative splicing of RAGE mRNA. This study was aimed to determine whether the same holds true for mouse sRAGE and, in addition, to biochemically characterize mouse sRAGE. The biochemical characteristics examined include glycosylation and disulfide patterns. In addition, sRAGE was found to bind heparin, which may mediate its distribution in the extracellular matrix and cell surfaces of tissues. Finally, our data indicated that sRAGE in the mouse is likely produced by carboxyl-terminal truncation, in contrast to the alternative splicing mechanism reported in humans.
An integrin receptor on normal and thrombasthenic platelets that binds thrombospondin [see comments] (1989)

The members of the integrin family of membrane glycoprotein heterodimer complexes function as cell surface receptors for adhesive proteins. We report here on the identification of two integrins on the surface of human platelets that bind to thrombospondin. When platelet membrane proteins are radiolabeled with 125I-lactoperoxidase, solubilized in n-octylglucoside, (Boehringer Mannheim Biochemicals, Indianapolis, IN), and applied to a column of thrombospondin-Sepharose, both complexes are bound to the column and specifically eluted with the peptide GRGDSP. One of these integrins, glycoprotein (GP) IIb-IIIa, appears to bind relatively weakly. The second integrin shares the same beta subunit (beta 3 or GPIIIa), but has a distinct alpha subunit that comigrates with the alpha subunit (alpha v) of the vitronectin receptor (VnR) on endothelial cells and reacts with a monoclonal antibody, LM142, which was raised against an integrin from M21 melanoma cells. The alpha v beta 3 integrin is present on a variety of cell types and appears to act as a receptor for thrombospondin on endothelial and smooth muscle cells. On endothelial and M21 melanoma cells this receptor is also involved in adhesion to fibrinogen, vitronectin, and von Willebrand factor (vWF). The alpha v beta 3 integrin is present at approximately equal levels on normal and thrombasthenic platelets, whereas levels of GPIIb-IIIa are greatly reduced on thrombasthenic platelets. The alpha v beta 3 integrin on thrombasthenic platelets also binds to thrombospondin-Sepharose and can be eluted with the peptide GRGDSP. These data indicate that the alpha v beta 3 integrin on platelets, endothelial cells, and smooth muscle cells functions as an Arg-Gly-Asp (RGD)-dependent receptor for thrombospondin.
The Size and Phenotype of Virus-Specific T Cell Populations Is Determined by Repetitive Antigenic Stimulation and Environmental Cytokines (2004)

Based on the expression of the TNFR SFP CD27, two Ag-primed CD8(+) T cell subsets can be discerned in the circulation of healthy individuals: CD27(+) T cells that produce a variety of cytokines but do not display immediate cytolytic activity; and cytotoxic CD27(-) T cells, which secrete only IFN-gamma and TNF-alpha. The mechanism that controls the generation of these different phenotypes is unknown. We show that CMV reactivation not only increases the number of virus-specific T cells but also induces their transition from a CD27(+) to a CD27(-) phenotype. In support of a relation between pool size and phenotype in a cohort of latently infected individuals, the number of Ag-specific CD27(-) CD8(+) T cells was found to be linearly related to the total number of CMV-specific CD8(+) T cells. In vitro studies revealed that the acquisition of the CD27(-) phenotype on CMV-specific T cells depended on the interaction of CD27 with its cellular ligand, CD70. Expression of CD70 was proportional to the amount of antigenic stimulation and blocked by the CD4(+) T cell-derived cytokine IL-21. Thus, induction of CD70, which may vary in distinct viral infections, appears to be a key factor in determining the size and phenotype of the CMV-specific T cell population in latently infected individuals.
Characterization of the Antibody Response to the Receptor Binding Domain of Botulinum Neurotoxin Serotypes A and E (2005)

Clostridium botulinum neurotoxins (BoNTs) are the most toxic proteins for humans. The current clostridial-derived vaccines against BoNT intoxication have limitations including production and accessibility. Conditions were established to express the soluble receptor binding domain (heavy-chain receptor [HCR]) of BoNT serotypes A and E in Escherichia coli. Sera isolated from mice and rabbits immunized with recombinant HCR/A1 (rHCR/A1) from the classical type A-Hall strain (ATCC 3502) (BoNT/A1) and rHCR/E from BoNT serotype E Beluga (BoNT/E(B)) neutralized the homologous serotype of BoNT but displayed differences in cross-recognition and cross-protection. Enzyme-linked immunosorbent assay and Western blotting showed that alpha-rHCR/A1 recognized epitopes within the C terminus of the HCR/A and HCR/E, while alpha-rHCR/E recognized epitopes within the N terminus or interface between the N and C termini of the HCR proteins. alpha-rHCR/E(B) sera possessed detectable neutralizing capacity for BoNT/A1, while alpha-rHCR/A1 did not neutralize BoNT/E. rHCR/A was an effective immunogen against BoNT/A1 and the Kyoto F infant strain (BoNT/A2), but not BoNT serotype E Alaska (BoNT/E(A)), while rHCR/E(B) neutralized BoNT/E(A), and under hyperimmunization conditions protected against BoNT/A1 and BoNT/A2. The protection elicited by rHCR/A1 to BoNT/A1 and BoNT/A2 and by rHCR/E(B) to BoNT/E(A) indicate that immunization with receptor binding domains elicit protection within sub-serotypes of BoNT. The protection elicited by hyperimmunization with rHCR/E against BoNT/A suggests the presence of common neutralizing epitopes between the serotypes E and A. These results show that a receptor binding domain subunit vaccine protects against serotype variants of BoNTs.
Modulation of T-Cell Activation in an Experimental Model of Mammary Carcinoma. (1998)

One of the major goals of tumor immunotherapy is the induction of tumor-specific T cell responses that will be effective at eradicating disseminated tumors. The studies described in this update take advantage of our current knowledge of T cell activation and inhibitory signals. Using a transplantable mammary carcinoma, we demonstrated that blockade of inhibitory signals mediated by CTLA-4 using a monoclonal antibody synergizes with a cell-based vaccine to promote regression of the unmanipulated tumor in a T cell-dependent mechanism. Our recent studies have taken the information gained using this model and applied it to two models of primary carcinogenesis. Using an N-methyl- N-nitrosourea-induced model of mammary carcinogenesis, we have observed that active rejection of a genetically-modified tumor line induces protection against tumor development whereas vaccination in combination with anti-CTLA-4 did not confer similar immunity. In addition, using a transgenic model of prostate cancer, we have demonstrated that vaccination with a genetically-modified tumor line in combination with anti-CTLA-4 reduces tumor incidence, prolongs survival, and induces a strong intraprostatic inflammatory response. These results are discussed in the context of the goals of the proposal and additional experiments to be performed in the final year are described.
Inactivation of Calpain I and Calpain II by Specificity-Oriented Tripeptidyl Chloromethyl Ketones1 (1986)

Three new tripeptidyl chloromethyl ketones, Leu-Leu-XCH2Cl, with X representing Phe, Tyr, or Lys, were synthesized and their potencies to inactivate calpains I and II were compared. They were designed to fulfil the specificity requirement of calpains established recently. When compared in terms of the dose for 50% inactivation, Leu-Leu-PheCH2Cl was the strongest inactivator, being 500-600 times more effective than tosyl-PheCH2Cl and 5-14 times more than N-[N-(L-3-trans-carboxyoxiran-2-carbonyl)-L-leucyl]agmatine (E-64). The potency toward calpain, either I or II, decreased in the order Phe greater than Tyr greater than Lys derivatives greater than E-64, whereas that toward papain was E-64 greater than Lys greater than Phe greater than Tyr derivatives. From the determined kinetic parameters, the Phe derivative was 18.3 and 16.6 times more effective than E-64 on calpains I and II, respectively. Likewise, the rate of the alkylation reaction by these chloromethyl ketones with calpain I was 2-4 times greater than that with calpain II. Leu-Leu-PheCH2Cl and its N-dansylated product should be useful for highly selective affinity labeling of calpains I and II.
CATALOGUE OF THE SHORTHAND BOOKS IN THE LIBRARY OF SAMUEL PEPYS (2009)

4¾ × 2½ in., 24mo, pp. (256) letterpress, Roman and italic letter. With headlines, no numbers to pages. Sign. A12, B6, ❡6, A–G12, H6, I12, K2. Shorthand characters inserted in MS. S.T.C. 3743.
Bacillus thuringiensis var israelensis crystal δ-endotoxin: effects on insect and mammalian cells in vitro and in vivo (1983)

Bacillus thuringiensis var israelensis parasporal crystal delta-endotoxin was purified by ultracentrifugation on a discontinuous sucrose gradient. Native delta-endotoxin crystals showed no detectable toxicity in the vitro and in vivo systems that are described. By contrast alkali-solubilized crystal delta-endotoxin caused rapid cytological and cytopathological changes in Aedes albopictus, Choristoneura fumiferana 63 CF1, Spodoptera frugiperda and Trichoplusia ni cell lines as observed by phase-contrast microscopy and vital staining. Mouse fibroblasts, primary pig lymphocytes and three mouse epithelial carcinoma cell types showed a similar response to the alkali-soluble crystal delta-endotoxin. In addition the soluble crystal delta-endotoxin protein caused haemolysis of rat, mouse, sheep, horse and human erythrocytes. Intravenous administration of the alkali-soluble crystal delta-endotoxin to Balb. c mice at a dose rate of 15-30 micrograms of protein per gram body weight resulted in rapid paralysis followed by death within 12h. Subcutaneous inoculation of 15-30 micrograms of protein per gram body weight resulted in death of suckling mice in 2-3 h. The alkali-solubilized crystal delta-endotoxin was not toxic however, when administered per os. A comparison is made with a similar alkali-soluble fraction from the parasporal crystal delta-endotoxin of B. thuringiensis var kurstaki. With the exception of the Lepidopteran cell line, Choristoneura fumiferana 63 CF1, this soluble crystal delta-endotoxin protein showed no in vitro or in vivo toxicity, and no haemolytic activity.
Dental Plaque, Platelets, and Cardiovascular Diseases (1998)

Cardiovascular diseases, including atherosclerosis and myocardial ischemia, occur as a result of a complex set of genetic and environmental factors. During periodontitis, dental plaque microorganisms may disseminate through the blood to infect the vascular endothelium and contribute to the occurrence of atherosclerosis and risk of myocardial ischemia and infarction. Myocardial ischemia and infarction are often preceded by acute thromboembolic events. In an in vitro model of thrombosis, certain dental plaque bacteria induce platelets to aggregate. Aggregation of platelets is induced by the platelet aggregation-associated protein [PAAPJ expressed on plaque bacteria, including Streptococcus sanguis and Porphyromonas gingivalis. Intravenous infusion of S. sanguis into rabbits has been shown previously to cause changes in the electrocardiogram (ECG), heart rate, blood pressure, and cardiac contractility. These changes are consistent with the occurrence of myocardial infarction. The ECG changes are now shown to begin within 30 seconds after infusion of PAAP+ S. sanguis, followed by alterations in blood pressure and respiratory rate. These changes occurred intermittently over a 30-minute period and changed within one heartbeat to a normal pattern and suddenly back to abnormal. Intermittent ECG abnormalities were seen in 13 of 15 rabbits, including left axis deviation, ST-segment depression, preventricular contractions, alternans, and bigemnia. Dose-dependent thrombocytopenia, accumulation of 111Indium-labeled platelets in the lungs, and tachypnea also occurred. No changes occurred with the PAAp- strain. The data indicated that PAPP+ S. sanguis interacts with circulating platelets, inducing thromboemboli to cause the pulmonary and cardiac abnormalities. During periodontitis, therefore, PAAP+ S. sanguis and P. gingivalis bacteremia may contribute to the chance of acute thromboembolic events.
Ophthalmic adhesives: a materials chemistry perspective (2008)

Recent advances in the field of ophthalmology include adhesives for the treatment of surgical and trauma-induced ocular wounds. Employed as surgical adhesives for more than forty years, cyanoacrylate and fibrin currently approved as general surgical adhesives remain contraindicated for ophthalmic use. Researchers have developed new adhesive systems based on protein tissue solder and hydrogels to improve upon sutures, used in current practice. We have reviewed these new adhesives and found them to be efficacious in closing many ocular wound types. Based on our findings in the laboratory and those reported in the literature, we summarize current ophthalmic adhesive research, provide insight into the effects of molecular composition, structure, and functionality on adhesive performance, and suggest testing protocols for the design of an ideal ophthlamic adhesive.
Single-Molecule, Motion-Based DNA Sequencing Using RNA Polymerase (2006)

We present a method for sequencing DNA that relies on the motion of single RNA polymerase molecules. When a given nucleotide species limits the rate of transcription, polymerase molecules pause at positions corresponding to the rare base. An ultrastable optical trapping apparatus capable of base pair resolution was used to monitor transcription under limiting amounts of each of the four nucleotide species. From the aligned patterns of pauses recorded from as few as four molecules, we determined the DNA sequence. This proof of principle demonstrates that the motion of a processive nucleic acid enzyme may be used to extract sequence information directly from DNA.
Inhibition of Erythroid Progenitor Cells by Anti-Kell Antibodies in Fetal Alloimmune Anemia (1998)

Anti-Kell antibodies specifically inhibit the growth of Kell-positive erythroid burst-forming units and colony-forming units, a finding that supports the hypothesis that these antibodies cause fetal anemia by suppressing erythropoiesis at the progenitor-cell level.
Gene Therapy Death Prompts Review of Adenovirus Vector (1999)

For the past 3 months, one-third of the 250 faculty and staff members connected with the University of Pennsylvania's Institute for Human Gene Therapy have been studying a single case. They've been trying to understand why Jesse Gelsinger, a relatively fit 18-year-old with an inherited enzyme deficiency, died on 17 September, 4 days after doctors at Penn injected a genetically altered virus into his liver.
Biophysical and biological activity of a synthetic 8.7-kDa hydrophobic pulmonary surfactant protein SP-B. (1990)

We have synthesized pulmonary surfactant apoprotein SP-B peptides by solid-phase chemistry and demonstrated their ability to enhance the surface-active properties of synthetic lipid mixtures. The synthetic peptides were reactive with antiserum generated against the native bovine surfactant peptide. Both peptides conferred surfactant-like properties to synthetic lipid mixtures as assessed by a Wilhelmy balance and pulsating bubble surfactometer. Likewise, mixtures of synthetic SP-B peptides and lipid restored compliance of isolated surfactant-deficient rat lungs. This work demonstrates the utility of SP-B as a functional component of pulmonary surfactant mixtures for treatment of respiratory distress syndrome or other disorders characterized by surfactant deficiency.
Dynamic Imaging of Cerebral Blood Flow Using Laser Speckle (2001)

A method for dynamic, high-resolution cerebral blood flow (CBF) imaging is presented in this article. By illuminating the cortex with laser light and imaging the resulting speckle pattern, relative CBF images with tens of microns spatial and millisecond temporal resolution are obtained. The regional CBF changes measured with the speckle technique are validated through direct comparison with conventional laser-Doppler measurements. Using this method, dynamic images of the relative CBF changes during focal cerebral ischemia and cortical spreading depression were obtained along with electrophysiologic recordings. Upon middle cerebral artery (MCA) occlusion, the speckle technique yielded high-resolution images of the residual CBF gradient encompassing the ischemic core, penumbra, oligemic, and normally perfused tissues over a 6 x 4 mm cortical area. Successive speckle images demonstrated a further decrease in residual CBF indicating an expansion of the ischemic zone with finely delineated borders. Dynamic CBF images during cortical spreading depression revealed a 2 to 3 mm area of increased CBF (160% to 250%) that propagated with a velocity of 2 to 3 mm/min. This technique is easy to implement and can be used to monitor the spatial and temporal evolution of CBF changes with high resolution in studies of cerebral pathophysiology.
A complex array of double-stranded and single-stranded DNA-binding proteins mediates induction of the ovalbumin gene by steroid hormones (1993)

The transcriptional induction of the chicken ovalbumin gene by steroid hormones is abolished by inhibitors of protein synthesis such as cycloheximide, suggesting that a labile protein mediates this process. A steroid-dependent regulatory element (SDRE) has been identified in the 5'-flanking region of the gene between -900 and -780 that is required for induction by steroids. Additional transfection experiments limit the 5'-border of the SDRE to the region between -892 and -864. To investigate whether any of the proteins binding to the SDRE are affected by estrogen or cycloheximide, protein binding was investigated using DNase I and exonuclease III footprinting and gel mobility shift assays. These experiments demonstrate that labile proteins bind to the sequences between -900 and -860 and between -810 and -820. Four oviduct nuclear proteins, including one of the labile proteins, binding to the SDRE prefer single-stranded DNA (ssDNA) in a sequence-specific manner. The binding activity of three of these ssDNA-binding proteins is increased in oviduct nuclear protein extracts from estrogen-treated chicks. These data suggest that induction of the ovalbumin gene is mediated by a complex collection of ssDNA- and double-stranded DNA-binding proteins whose activities are in turn regulated by their short half-lives or by estrogen.
Fast Monte-Carlo algorithms for finding low-rank approximations (2002)

In several applications, the data consists of an m/spl times/n matrix A and it is of interest to find an approximation D of a specified rank k to A where, k is much smaller than m and n. Traditional methods like the Singular Value Decomposition (SVD) help us find the "best" such approximation. However, these methods take time polynomial in m, n which is often too prohibitive. In this paper, we develop an algorithm which is qualitatively faster provided we may sample the entries of the matrix according to a natural probability distribution. Indeed, in the applications such sampling is possible. Our main result is that we can find the description of a matrix D* of rank at most k so that /spl par/A-D*/spl par//sub F//spl les/min/D,rank(D)/spl les/k/spl par/A-D/spl par//sub F/+/spl epsiv//spl par/A/spl par//sub F/ holds with probability at least 1-/spl delta/. (For any matrix M, /spl par/M/spl par//sub F//sup 2/ denotes the sum of the squares of all the entries of M.) The algorithm takes time polynomial in k, 1//spl epsiv/, log(1//spl delta/) only, independent of m, n.
Projection Methods: Swiss Army Knives for Solving Feasibility and Best Approximation Problems with Halfspaces (2015)

We model a problem motivated by road design as a feasibility problem. Projections onto the constraint sets are obtained, and projection methods for solving the feasibility problem are studied. We present results of numerical experiments which demonstrate the efficacy of projection methods even for challenging nonconvex problems.
Roles of NAD (P) H-Quinone Oxidoreductase 1 (NQO1) On Cancer Progression and Chemoresistance (2017)

NAD(P)H-Quinone Oxidoreductase 1 (NQO1), originally referred to as DT-diaphorase, is a xenobiotic metabolizing/antioxidant enzyme that detoxifies chemical stressors, providing cytoprotection in normal tissues. NQO1 catalyzes obligatory two-electron reduction of several endogenous and environmental quinones to hydroquinone that are ready for further conjugation and excretion. The enzyme requires NADH or NADPH as an electron donor for enzymatic activity. High-level of NQO1 expression has however, been correlated with numerous human malignancies, suggesting its role in cancer progression and chemoresistance. This adaptation renders the cancer cells to survive in relatively high oxidative stress condition compared to normal cells, as well as protects cancer cells from toxic action of chemotherapeutic agents. Inhibitors of NQO1 enzyme have been found to improve anticancer activities of conventional chemotherapeutic agents. The review provides a perspective on a molecular basis of NQO1-mediated cancer cells progression and the suppression and possible strategy to improve chemosensitivity and to overcome chemoresistance of NQO1 inhibitors when used in combination with chemotherapeutic drugs.
Negotiating Silence in American Classrooms: Three Chinese Cases (2002)

A common observation about Chinese students in American classrooms is their silence, which has been speculated on by many second-language acquisition researchers as the result of the students' lacking communicative competence compatible to their native-English-speaking counterparts. By focusing on three students from mainland China as part of a larger investigation of Asian students' classroom communication patterns in US universities, this paper explores in depth the complexities of silence, and the cultural interpretations of silence in various social contexts. Multiple functions of silence in terms of linkage, affecting, revelational, judgemental, and activating functions are explored across the three cases. This paper further investigates how Chinese students construct their identities through silence, and how they can reconstruct their identities by negotiating silence in American classrooms and by developing adaptive cultural transformation competence in the target culture.
Long-term follow-up of meniscectomy in athletes. A prospective longitudinal study (1987)

We report the results of a prospective longitudinal study of 147 athletes who had had a meniscectomy for an isolated meniscus injury. The patients were reviewed in detail after median periods of 4.5 years and 14.5 years and the results analysed. The frequency of complaints related to the operation increased from 53% at 4.5 years to 67% at 14.5 years, while demonstrable knee instability increased from 10% to 36%. The incidence of radiographic changes of degeneration rose from 40% to 89% and at late review 8% of patients had definite osteoarthritis by the criteria of Ahlbäck (1968). In consequence 46% had given up or reduced their sporting activity, and 6.5% had changed their occupation. Radiographic deterioration started after the 4.5-year review in 49% of the patients and was more frequent after lateral than medial meniscectomy.