gebhart/patrepeval huggingface dataset:
Coupling of a Signal Response Domain in IκBα to Multiple Pathways for NF-κB Activation (1995)

The eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli.
Semantics modeling based image retrieval system using neural networks (2005)

Semantics based image retrieval techniques show a promising direction to the development of CBIR systems. To design such systems, semantics modeling is one of the most difficult tasks. This paper aims to develop a semantics modeling approach using neural networks. In our work, a neural network is utilized to memorize the semantic patterns within the images. An intelligent image retrieval system is designed based on this model. User's relevance feedback is used for enhancing the retrieval performance. Experimental results from the prototype system demonstrate the effectiveness of the proposed approach.
Increased frequencies of CD8+ T lymphocytes recognizing wild‐type p53‐derived epitopes in peripheral blood correlate with presence of epitope loss tumor variants in patients with hepatocellular carcinoma (2006)

Wild-type (WT) sequence p53 peptides are attractive candidates for broadly applicable cancer vaccines. The aim of this study was to evaluate the potential of a WT p53-based immunotherapeutic approach for patients with hepatocellular carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients. Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay. Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells. HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls. Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells. Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system. Our results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC. These findings may have important implications for the future development of cancer vaccines.
Annexin V as a probe of aminophospholipid exposure and platelet membrane vesiculation: a flow cytometry study showing a role for free sulfhydryl groups (1993)

Annexin V, a protein with a high affinity and a strict specificity for aminophospholipids at physiologic calcium concentrations, was used to probe platelet activation and the development of procoagulant activity. Platelet secretion was studied in parallel using VH10, a murine monoclonal antibody specific for GMP-140, an alpha-granule membrane glycoprotein. Both proteins were labeled with fluorescein isothiocyanate and platelet activation was assessed by flow cytometry. Microparticles, which are shed from the platelet surface and also support procoagulant activity, were distinguished from platelets according to their associated light scattering signal. The relative ability of different inducers to trigger exposure of the procoagulant surface and microparticle formation was: ionophore A23187 > thrombin plus collagen > collagen > thrombin. The density of aminophospholipid on microparticles was higher than on remnant platelets. Platelet activation by these agonists was accompanied by GMP-140 exposure, both on platelets and microparticles. Here, thrombin was the most efficient agonist. The mechanisms responsible for the above processes were investigated using E-64-d, a specific membrane-permeable inhibitor of Ca(2+)-activated protease (calpain); tetracaine, an activator of calpain; and N-ethylmaleimide and diamide, two sulfhydryl-reactive agents. These agents were added to platelets alone or before stimulation by agonists. Calpain activity was assessed by the hydrolysis of cytoskeletal proteins as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Results showed that calpain activity is not essential for aminophospholipid translocation or for secretion. In contrast, although sulfhydryl-reactive agents alone can trigger procoagulant activity, they inhibit microvesicle formation and platelet secretion induced by the above agonists, suggesting that different mechanisms account for these phenomena. The use of annexin V in flow cytometry is a rapid method to assess procoagulant activity in platelets and the loss of phospholipid asymmetry in cell membranes.
Syntheses of 1α, 2α-and 1β, 2β-Epithio-A-nor-5α-androstan-17β-ol and Related Compounds. (1967)

17β-Hydroxy-A-nor-5α-androstan-1α, 2α-episulfide (XXIIIa) and -1β, 2β-episulfide (XIa) were prepared from 17β-acetoxy-A-nor-5α-androstan-2-one (Ib) via the corresponding epoxides (XXa) and (IXa) as intermediates.
Theoretical Analysis of Diamond Mechanosynthesis. Part III. Positional C 2 Deposition on Diamond C(110) Surfac eUsin gSi/Ge/Sn-Base dDime rPlacemen tTools (2006)

Theoretical Analysis of Diamond Mechanosynthesis. Part III. Positional C2 Deposition on Diamond C(110) Surface Using Si/Ge/Sn-Based Dimer Placement Tools Jingping Peng,1 Robert A. Freitas, Jr.,2 ∗ Ralph C. Merkle,3 James R. Von Ehr,1 John N. Randall,1 and George D. Skidmore1 1Zyvex Corporation, 1321 North Plano Road, Richardson, TX 75081, USA 2Institute for Molecular Manufacturing, Suite 354, Palo Alto, CA 94301, USA 3Georgia Institute of Technology, Atlanta, GA 30332, USA
Death Receptor Agonists as a Targeted Therapy for Cancer (2010)

Apoptosis is integral to normal, physiologic processes that regulate cell number and results in the removal of unnecessary or damaged cells. Apoptosis is frequently dysregulated in human cancers, and recent advancements in our understanding of the regulation of programmed cell death pathways has led to the development of novel agents to reactivate apoptosis in malignant cells. The activation of cell surface death receptors by tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) and death receptor agonists represent an attractive therapeutic strategy to promote apoptosis of tumor cells through the activation of the extrinsic pathway. The observation that Apo2L/TRAIL can eliminate tumor cells preferentially over normal cells has resulted in several potential therapeutics that exploit the extrinsic pathway, in particular, the soluble recombinant human (rh)Apo2L/TRAIL protein and agonist monoclonal antibodies that target death receptors 4 or 5. Many of these agents are currently being evaluated in phase 1 or 2 trials, either as a single agent or in combination with cytotoxic chemotherapy or other targeted agents. The opportunities and challenges associated with the development of death receptor agonists as cancer therapeutics, the status of ongoing clinical evaluations, and the progress toward identifying predictive biomarkers for patient selection and pharmacodynamic markers of response are reviewed.
A Randomized Phase III Study of Doxorubicin Versus Cisplatin/Interferon α-2b/Doxorubicin/Fluorouracil (PIAF) Combination Chemotherapy for Unresectable Hepatocellular Carcinoma (2005)

Although patients on PIAF had a higher overall response rate and better survival than patients on doxorubicin, the differences were not statistically significant. PIAF was also associated with increased treatment-related toxicity. The prognosis of patients with unresectable HCC remains poor.
The Omptins ofYersinia pestisandSalmonella entericaCleave the Reactive Center Loop of Plasminogen Activator Inhibitor 1 (2010)

Plasminogen activator inhibitor 1 (PAI-1) is a serine protease inhibitor (serpin) and a key molecule that regulates fibrinolysis by inactivating human plasminogen activators. Here we show that two important human pathogens, the plague bacterium Yersinia pestis and the enteropathogen Salmonella enterica serovar Typhimurium, inactivate PAI-1 by cleaving the R346-M347 bait peptide bond in the reactive center loop. No cleavage of PAI-1 was detected with Yersinia pseudotuberculosis, an oral/fecal pathogen from which Y. pestis has evolved, or with Escherichia coli. The cleavage and inactivation of PAI-1 were mediated by the outer membrane proteases plasminogen activator Pla of Y. pestis and PgtE protease of S. enterica, which belong to the omptin family of transmembrane endopeptidases identified in Gram-negative bacteria. Cleavage of PAI-1 was also detected with the omptins Epo of Erwinia pyrifoliae and Kop of Klebsiella pneumoniae, which both belong to the same omptin subfamily as Pla and PgtE, whereas no cleavage of PAI-1 was detected with omptins of Shigella flexneri or E. coli or the Yersinia chromosomal omptins, which belong to other omptin subfamilies. The results reveal a novel serpinolytic mechanism by which enterobacterial species expressing omptins of the Pla subfamily bypass normal control of host proteolysis.
The validity of the family history screen for assessing family history of mental disorders (2008)

There is a need to collect psychiatric family history information quickly and economically (e.g., for genome-wide studies and primary care practice). We sought to evaluate the validity of family history reports using a brief screening instrument, the Family History Screen (FHS). We assessed the validity of parents' reports of seven psychiatric disorders in their adult children probands from the Dunedin Study (n = 959, 52% male), using the proband's diagnosis as the criterion outcome. We also investigated whether there were informant characteristics that enhanced accuracy of reporting or were associated with reporting biases. Using reports from multiple informants, we obtained sensitivities ranging from 31.7% (alcohol dependence) to 60.0% (conduct disorder) and specificities ranging from 76.0% (major depressive episode) to 97.1% (suicide attempt). There was little evidence that any informant characteristics enhanced accuracy of reporting. However, three reporting biases were found: the probability of reporting disorder in the proband was greater for informants with versus without a disorder, for female versus male informants, and for younger versus older informants. We conclude that the FHS is as valid as other family history instruments (e.g., the FH-RDC, FISC), and its brief administration time makes it a cost-effective method for collecting family history data. To avoid biasing results, researchers who aim to compare groups in terms of their family history should ensure that the informants reporting on these groups do not differ in terms of age, sex or personal history of disorder.
Natural Antibiotic Function of a Human Gastric Mucin Against Helicobacter pylori Infection (2004)

Helicobacter pylori infects the stomachs of nearly a half the human population, yet most infected individuals remain asymptomatic, which suggests that there is a host defense against this bacterium. Because H. pylori is rarely found in deeper portions of the gastric mucosa, where O-glycans are expressed that have terminal alpha1,4-linked N-acetylglucosamine, we tested whether these O-glycans might affect H. pylori growth. Here, we report that these O-glycans have antimicrobial activity against H. pylori, inhibiting its biosynthesis of cholesteryl-alpha-D-glucopyranoside, a major cell wall component. Thus, the unique O-glycans in gastric mucin appeared to function as a natural antibiotic, protecting the host from H. pylori infection.
Exploration at the Edge: Reassessing the Fate of Sir John Franklin's Last Arctic Expedition (2008)

Few historical figures can claim to have had so many of the Earth's topographical features named after them as Sir John Franklin. Thomas Jefferson and Benjamin Franklin may dominate the place names of the United States of America, but the reach of Sir John Franklin's name is truly global, from the Arctic in the north to Australia and Antarctica in the south. The names of a river, an island, a fort, a strait, a cape, a bay, a sound, a point, a lake, a national park, a town, a village, two mountains and a mountain range memorialise the achievements of the Royal Navy explorer. In only one place has he failed to be commemorated: on the Moon. No fewer than six nineteenth-century polar explorers including Francis Crozier, Franklin's second-in-command on his final journey have features of the Moon named after them, but Sir John's name was rejected in the 1860s, no doubt because a crater already commemorated his namesake, Benjamin.&#13;\n&#13;\nDespite Sir John Franklin's undoubted impact on the world's atlas, today he is remembered, if at all, only for his ultimately disastrous Arctic expedition in search of the final section of a navigable North - West Passage. Currently, many historians do not hold Franklin in high esteem, especially those based in North America and influenced by the disciplines of anthropology and ethnography. He has been criticised for his inflexibility, his cultural myopia and his ethnocentrism; he is parodied as 'the man who ate his boots' to prevent starvation and much is made of a comment by the American Dr. Richard King in 1845 that he had sailed to the Arctic 'to become the nucleus of an iceberg'. Yet, like Henry Hudson and James Cook before him and Robert Falcon Scott after, Franklin belongs in a pantheon of British maritime heroes who died, in extremis, on missions of exploration that helped to create and define the modern world. Perhaps paradoxically and like other explorers, he not only helped to open up the world but also, by his surveying so much of the North American coastline, helped to define and delimit it. Reserved, good-natured, dutiful but unlucky, Franklin was an unlikely but genuinely heroic figure whose reputation has not survived the passing of his era and its replacement by one which focuses on the dark underside of western imperial expansion rather than on its achievements. Modern explanations of the mystery of Franklin's last expedition need to be considered within this context. This article reviews the recent interpretations of Franklin and reassesses the evidence relating to his final expedition. It concludes that the lampooning of Franklin is unwarranted and that most of the mystery surrounding the crews' fate has now been satisfactorily explained.
Accurate Vibration Analysis of Simply Supported Rhombic Plates by Considering Stress Singularities (1995)

This is the first known work which explicitly considers the bending stress singularities that occur in the two opposite, obtuse corner angles of simply supported rhombic plates undergoing free, transverse vibration. The importance of these singularities increases as the rhombic plate becomes highly skewed (i.e., the obtuse angles increase). The analysis is carried out by the Ritz method using a hybrid set consisting of two types of displacement functions, e.g., (1) algebraic polynomials and (2) corner functions accounting for the singularities in the obtuse corners. It is shown that the corner functions accelerate the convergence of solution, and that these functions are required if accurate solutions are to be obtained for highly skewed plates. Accurate nondimensional frequencies and normalized contours of the vibratory transverse displacement are presented for simply supported rhombic plates with skew angles ranging to 75 deg. (i.e., obtuse angles of 165 deg.). Frequency and mode shapes of isosceles and right triangular plates with all edges simply supported are also available from the data presented.
Differential expression of monocyte CD163 in single – and dual‐asthmatic responders during allergen‐induced bronchoconstriction (2006)

Both pro-inflammatory and anti-inflammatory responses to allergen challenge are uniquely expressed among SR and DR.
The contribution of the toxicity of a glycerol–egg yolk–citrate cryopreservative to the decline in human sperm motility during cryopreservation (1992)

Summary. The contribution of the toxicity of glycerol–egg yolk–citrate (GEYC) cryopreservative medium to the loss of function of human spermatozoa during cryopreservation was determined by investigating the effect of mixing semen with the medium on sperm motility. The percentage of progressively motile spermatozoa, velocity (μm s−1) and lateral head displacement (μm) (mean ± sem, n = 28) were 55 ± 4·1, 47 ± 2·7, 4·4 ± 0·2 and 32 ± 3·8, 40 ± 2·5, 3·6 ± 0·25 and 15 ± 2·5, 28 ± 1·1, 2·8 ± 0·15 in suspensions of washed spermatozoa prepared from fresh, GEYC-treated and frozen–thawed semen, respectively. The variables changed only slightly after incubation for 3 h. The toxicity of GEYC did not vary significantly between samples which survived the complete freeze–thaw cycle well or very poorly. The toxicity of GEYC is responsible for about 50% of the loss of progressively motile spermatozoa during the complete cryopreservation process, but has little effect on the quality of motility. Susceptibility to GEYC does not explain observed differences in the ability of semen samples to survive freezing. Keywords: cryopreservation; spermatozoa; motility; glycerol; donor insemination; human
Rationally designed capsid and transgene cassette of AAV6 vectors for dendritic cell‐based cancer immunotherapy (2013)

Dendritic cell (DC)-based immunotherapy has recently demonstrated a great potential for clinical applications; however, additional progress in the methods of tumor-specific antigen delivery to DCs is necessary for the further development of anti-tumor vaccines. To this end, a capsid-optimized adeno-associated virus serotype 6 (AAV6-T492V+S663V) vector was developed by site-directed mutagenesis of surface-exposed serine (S) and threonine (T) residues, which have a critical role in intracellular trafficking of AAV vectors. This double-mutant AAV6 vector had ∼ 5-fold greater transduction efficiency in monocyte-derived DCs (moDCs) compared with wild-type (WT)-AAV6 vectors. The increase in the transduction efficiency correlated with the improved nuclear translocation of AAV6-T492V+S663V over that of the WT-AAV6 vector. Additional studies of the CD11c promoter identified critical regulatory elements that fit into the AAV expression cassette and drive EGFP expression in moDCs. Development of a chimeric promoter (chmCD11c) that contains functional modules of CD11c and a Simian virus (SV40) enhancer element dramatically increased the EGFP expression in moDCs. MoDCs transduced by the capsid-optimized AAV6 vector carrying human prostate-specific antigen (hPSA) driven by CBA (AAV6-T492V+S663V-CBA-hPSA) or chmCd11c (AAV6-T492V+S663V-chmCD11c-hPSA) generated specific T-cell clone proliferation and superior cytotoxic T lymphocytes (CTLs) with higher killing capability against human prostate adenocarcinoma cells, LNCaP, compared with WT-AAV6 induced CTLs. Taken together, these studies suggest that optimization of capsid and promoter components of AAV vectors can be a useful approach for efficient targeting of moDCs and may prove to be a promising tool for cancer immunotherapy.
Multiplicity of positive solutions for a nonlinear differential equation with nonlinear boundary conditions (1998)

We study the existence and multiplicity of positive solutions of the nonlinear equation u''(x) + λh(x)f(u(x)) = 0 subject to nonlinear boundary conditions. The method of upper and lower solutions and degree theory arguments are used.
Antidiabetic effects of interleukin 1. (1989)

Interleukin 1 (IL-1), a cytokine released mainly by activated macrophages-monocytes, affects glucose homeostasis and may mediate some of the metabolic derangements observed during certain inflammatory and infectious processes. In this report, it is shown that IL-1 acts as a hypoglycemic agent not only in normal animals but also in mice at early stages of alloxan-induced diabetes and in genetically diabetic, insulin-resistant C57BL/Ks db/db mice and C57BL/6J ob/ob mice. In these animal models, a single injection of a low dose of human recombinant IL-1 normalized glucose blood levels for several hours. This effect was not mediated by possible insulin secretagogue actions of the cytokine. Furthermore, IL-1 markedly reduced the levels of triglycerides in blood of streptozotocin-induced diabetic mice at later stages of the disease. Although the final mechanism of action is at present unknown, the results showed that IL-1 is a hormone with powerful antidiabetic properties. Defective production of this cytokine associated with diabetes could contribute to aggravate the course of the disease during infectious and inflammatory processes.
High-temperature performance of AlGaN/GaN HFETs on SiC substrates (1997)

The performance results AlGaN-GaN Heterostructure Field Effect Transistors (HFETs) grown on SiC substrates are reported. The maximum transconductance of these devices was 142 mS/mm and the source-drain current was as high as 0.95 A/mm. The maximum dissipated DC power at room temperature was 0.6 MW/cm/sup 2/, which is more than three times higher than that in similar devices grown on sapphire. This high thermal breakdown threshold was achieved primarily due to the effective heat sink through the SiC substrate. These devices demonstrated stable performance at elevated temperatures up to 250/spl deg/C. The source-drain current saturation was observed up to 300/spl deg/C. The leakage current in the below threshold regime was temperature-activated with an activation energy of 0.38 eV.