gebhart/patrepeval huggingface dataset:
THE T CELL RECEPTOR: Critical Role of the Membrane Environment in Receptor Assembly and Function (2004)

Recent studies have demonstrated that cell membranes provide a unique environment for protein-protein and protein-lipid interactions that are critical for the assembly and function of the T cell receptor (TCR)-CD3 complex. Highly specific polar interactions among transmembrane (TM) domains that are uniquely favorable in the lipid environment organize the association of the three signaling dimers with the TCR. Each of these three assembly steps depends on the formation of a three-helix interface between one basic and two acidic residues in the membrane environment. The same polar TM residues that drive assembly also play a central role in quality control and export by directing the retention and degradation of free subunits and partial complexes, while membrane proximal cytoplasmic signals control recycling and degradation of surface receptors. Recent studies also suggest that interactions between the membrane and the cytoplasmic domains of CD3 proteins may be important for receptor triggering.
SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity (2009)

Chronic inflammation is an important etiology underlying obesity-related disorders such as insulin resistance and type 2 diabetes, and recent findings indicate that the macrophage can be the initiating cell type responsible for this chronic inflammatory state. The mammalian silent information regulator 2 homolog SIRT1 modulates several physiological processes important for life span, and a potential role of SIRT1 in the regulation of insulin sensitivity has been shown. However, with respect to inflammation, the role of SIRT1 in regulating the proinflammatory pathway within macrophages is poorly understood. Here, we show that knockdown of SIRT1 in the mouse macrophage RAW264.7 cell line and in intraperitoneal macrophages broadly activates the JNK and IKK inflammatory pathways and increases LPS-stimulated TNFalpha secretion. Moreover, gene expression profiles reveal that SIRT1 knockdown leads to an increase in inflammatory gene expression. We also demonstrate that SIRT1 activators inhibit LPS-stimulated inflammatory pathways, as well as secretion of TNFalpha, in a SIRT1-dependent manner in RAW264.7 cells and in primary intraperitoneal macrophages. Treatment of Zucker fatty rats with a SIRT1 activator leads to greatly improved glucose tolerance, reduced hyperinsulinemia, and enhanced systemic insulin sensitivity during glucose clamp studies. These in vivo insulin-sensitizing effects were accompanied by a reduction in tissue inflammation markers and a decrease in the adipose tissue macrophage proinflammatory state, fully consistent with the in vitro effects of SIRT1 in macrophages. In conclusion, these results define a novel role for SIRT1 as an important regulator of macrophage inflammatory responses in the context of insulin resistance and raise the possibility that targeting of SIRT1 might be a useful strategy for treating the inflammatory component of metabolic diseases.
Adenovirus–Mediated Expression of Cytokine–Induced Neutrophil Chemoattractant in Rat Liver Induces A Neutrophilic Hepatitis (1997)

C-X-C chemokines are potent chemoattractants that are believed to mediate neutrophilic inflammation in several organs. Recent studies suggest a role for C-X-C chemokines in the pathogenesis of neutrophilic hepatitis but do not prove causation. We investigated the biological consequences of hepatic chemokine production in vivo by transiently overexpressing cytokine-induced neutrophil chemoattractant (CINC), a member of the C-X-C chemokine family, in intact rats. Rats were injected intraportally with a replication-defective recombinant adenovirus containing the CINC complementary DNA (cDNA). Within 4 days, treated animals had high levels of CINC in both liver tissue and plasma Rats overexpressing CINC exhibited an eightfold increase in circulating neutrophils; they also developed severe hepatic injury, characterized by a 6- to 25-fold increase in plasma transaminases and marked hepatic inflammation on biopsy. Liver disease in CINC-producing rats correlated positively with the number of neutrophils sequestered in the hepatic parenchyma. Tissue injury was attributed directly to chemokine overproduction, because control rats infected with adenoviruses lacking the CINC cDNA did not produce CINC and developed only minor hepatic abnormalities. These experiments provide direct evidence that C-X-C chemokines, when expressed in sufficient quantity in the liver in vivo, induce neutrophil recruitment and tissue invasion and provoke severe liver injury. The data suggest that C-X-C chemokines have important pathogenic potential in both clinical and experimental liver disease.
Learning Semantic Feature Map for Visual Content Recognition (2017)

The spatial relationship among objects provide rich clues to object contexts for visual recognition. In this paper, we propose to learn Semantic Feature Map (SFM) by deep neural networks to model the spatial object contexts for better understanding of image and video contents. Specifically, we first extract high-level semantic object features on input image with convolutional neural networks for every object proposals, and organize them to the designed SFM so that spatial information among objects are preserved. To fully exploit the spatial relationship among objects, we employ either Fully Convolutional Networks (FCN) or Long-Short Term Memory (LSTM) on top of SFM for final recognition. For better training, we also introduce a multi-task learning framework to train the model in an end-to-end manner. It is composed of an overall image classification loss as well as a grid labeling loss, which predicts the objects label at each SFM grid. Extensive experiments are conducted to verify the effectiveness of the proposed approach. For image classification, very promising results are obtained on Pascal VOC 2007/2012 and MS-COCO benchmarks. We also directly transfer the SFM learned on image domain to the video classification task. The results on CCV benchmark demonstrate the robustness and generalization capability of the proposed approach.
Results and performance of the World Bank Group : IEG annual report 2010 (2010)

This review provides an independent assessment of the World Bank Group's performance in achieving key development objectives, with a special focus on support for environmentally sustainable development consistent with economic growth and poverty reduction.
Two design strategies for enhancement of multilayer–DNA-origami folding: underwinding for specific intercalator rescue and staple-break positioning (2012)

Single-layer DNA origami is an efficient method for programmable self-assembly of nanostructures approximating almost any desired two-dimensional shape from ~5 MDa of DNA building material. In this method, a 7 kilobase single "scaffold" strand is assembled with hundreds of oligodeoxyribonucleotide "staple" strands to form a parallel array of double helices. Multiple layers of such DNA sheets also can be designed to assemble into a stack, enabling construction of solid three-dimensional shapes with considerably greater mechanical rigidity than two-dimensional shapes; however, the folding yield often is much lower and the required folding times are much longer. Here we introduce two strategies for designing multi-layer DNA origami that demonstrate potential for boosting assembly yield: (1) individual base pairs can be inserted between crossovers, allowing for greater bowing of helices at positions away from crossovers and therefore reduced electrostatic repulsion. At the same time, this underwinding of double helices increases a destabilizing torsional strain energy but then also increases affinity for intercalators, and binding of such intercalators can relieve this stress. We also have exploited this enhanced affinity for intercalators to PEGylate the surface of the nanostructures in a noncovalent fashion using PEG-tris-acridine. (2) Positioning of staple-strand breaks in the DNA origami such that each staple strand includes a 14 nucleotide (nt) continuous segment that binds to a complementary 14 nt continuous segment of the scaffold can greatly improve folding yields.
Cloning and sequencing of human intestinal alkaline phosphatase cDNA. (1987)

Partial protein sequence data obtained on intestinal alkaline phosphatase indicated a high degree of homology with the reported sequence of the placental isoenzyme. Accordingly, placental alkaline phosphatase cDNA was cloned and used as a probe to clone intestinal alkaline phosphatase cDNA. The latter is somewhat larger (3.1 kilobases) than the cDNA for the placental isozyme (2.8 kilobases). Although the 3' untranslated regions are quite different, there is almost 90% homology in the translated regions of the two isozymes. There are, however, significant differences at their amino and carboxyl termini and a substitution of an alanine in intestinal alkaline phosphatase for a glycine in the active site of the placental isozyme.
The effect of exercise conditioning, diet, and drug therapy on glycosylated hemoglobin levels in type 2 (NIDDM) diabetics. (1995)

The aim of this study was determine the effect of a 15-week individualized exercise conditioning program on glycosylated hemoglobin (HbAlc) levels on Type 2 diabetes. Thirty-nine participants were sedantary, Type 2 diabetics, on an oral hypo-glycemic drug and no specified diet regimen at study onset. Pre and post 15 weeks subjects underwent: maximal incremental exercise tests, blood analysis, body composition analysis. Twenty-one subjects were prescribed an individualized exercise program for 15 weeks. Significant differences were found in the exercise group after 15 weeks in: total body fat, trunk fat, peak oxygen consumption and MET values. Correlations existed in the exercise group between HbAlc, arm muscle area and leg lean mass. Sixty-two percent of this group showed a reduction in HbAlc values. For this group, dietary intakes of riboflavin and potassium maybe associated with HbAlc levels. Exercise in conjunction with oral drug therapy prescribed for the NIDDM individual did not directly modify HbAlc levels, but did result in favorable effects on blood lipid values, fitness levels, and body composition values.
S-Adenosylhomocysteine Metabolism in Various Species (1975)

Eleven microorganisms, four plants, and major organs from the chicken, dog, rat and rabbit were assayed for the presence of S-adenosylhomocysteine hydrolase, S-adenosylhomocysteine nucleosidase, and S-ribosylhomocysteine-cleavage enzyme. All bacteria (procaryotes) were found to possess S-adenosylhomocysteine nucleosidase and S-ribosylhomocysteine-cleavage enzyme but not S-adenosylhomocysteine hydrolase; All eucaryotes tested, including yeasts, plants, birds, and mammals, possessed S-adenosylhomocysteine hydrolase but not S-adenosylhomocysteine nucleosidase or S-ribosylhomocysteine-cleavage enzyme. Of all the organs assayed in the vertebrates, the level of S-adenosylhomocysteine hydrolase was highest in liver, pancreas, and kidney, lower spleen and testis, and very low in brain and heart; In all systems tested, equilibrium of the hydrolase reaction always favored synthesis over hydrolysis. We studied some of the kinetic properties of the hydrolase from rat liver; In the direction of synthesis, the Km value was 1.5 mM for adenosine and 4.5 mM for L-homocysteine, whereas marked substrate inhibition was observed with L-homocysteine. The condensation reaction is subject to product inhibition, and was inhibited by adenine. Results from in-vivo experiments revealed that the cells of the various organs of the dog are impermeable to the exogenously administered S-adenosylhomocysteine.
Transcranial Direct Current Stimulation Modulates Neuronal Activity and Learning in Pilot Training (2016)

Skill acquisition requires distributed learning both within (online) and across (offline) days to consolidate experiences into newly learned abilities. In particular, piloting an aircraft requires skills developed from extensive training and practice. Here, we tested the hypothesis that transcranial direct current stimulation (tDCS) can modulate neuronal function to improve skill learning and performance during flight simulator training of aircraft landing procedures. Thirty-two right-handed participants consented to participate in four consecutive daily sessions of flight simulation training and received sham or anodal high-definition-tDCS to the right dorsolateral prefrontal cortex (DLPFC) or left motor cortex (M1) in a randomized, double-blind experiment. Continuous electroencephalography (EEG) and functional near infrared spectroscopy (fNIRS) were collected during flight simulation, n-back working memory, and resting-state assessments. tDCS of the right DLPFC increased midline-frontal theta-band activity in flight and n-back working memory training, confirming tDCS-related modulation of brain processes involved in executive function. This modulation corresponded to a significantly different online and offline learning rates for working memory accuracy and decreased inter-subject behavioral variability in flight and n-back tasks in the DLPFC stimulation group. Additionally, tDCS of left M1 increased parietal alpha power during flight tasks and tDCS to the right DLPFC increased midline frontal theta-band power during n-back and flight tasks. These results demonstrate a modulation of group variance in skill acquisition through an increasing in learned skill consistency in cognitive and real-world tasks with tDCS. Further, tDCS performance improvements corresponded to changes in electrophysiological and blood-oxygenation activity of the DLPFC and motor cortices, providing a stronger link between modulated neuronal function and behavior.
Botulinum toxin abolishes sweating via impaired sweat gland responsiveness to exogenous acetylcholine (2009)

These results demonstrate that BTX is capable of inhibiting sweat secretion by reducing the responsiveness of the sweat gland to acetylcholine, while not altering acetylcholine-mediated cutaneous vasodilatation.
Recombinant antibodies: alternative strategies for developing and manipulating murine-derived monoclonal antibodies. (1996)

Since the introduction of hybridoma technology 20 years ago, numerous monoclonal antibodies with specificity to cellular, bacterial, and viral proteins have been developed. Application of monoclonal antibodies in biomedical research has substantially contributed to our understanding of the structural and physiologic components of intra- and extracellular protein interactions. Monoclonal antibodies that target antigens specific to infective agents or tumor cells may also be used as therapeutic agents. Despite the versatility of these molecules, monoclonal antibody/hybridoma production is labor-intensive and requires the use of live animals. The fact that monoclonal antibodies are derived from animals limits their use as systemic therapeutic agents in humans. This can be attributed to the human anti-mouse antibody response that is mounted against these therapeutically administered foreign proteins. Recent advances in our understanding of immunoglobulin structure through three-dimensional studies--using nuclear magnetic resonance and X-ray crystallography and increased computer-assisted molecular modeling capabilities, combined with the application of recombinant approaches--has led to the evolution of a new class of antibody-like molecules or man-made antibodies. The potential of recombinant antibodies has been realized globally by academic and industrial institutions; the efficacy, toxicity, and pharmacokinetics of these antibody-derived compounds are being tested in a variety of animal models. This review summarizes various approaches for producing recombinant antibodies and discusses their potential as anti-cancer compounds so that those who are involved in relevant experimental animal protocols may gain a better understanding of this rapidly growing area. Additionally, by mimicking the affinity maturation of antibodies in vitro, phage display strategies have the potential to reduce or eliminate the use of animals in antibody production protocols.
The mutations of hepatitis B virus core promoter gene isolated from both HBeAg and HBeAb positive patients (2002)

Objective To investigate the mutations of hepatitis B virus (HBV) core promoter gene isolated from both HBeAg and HBeAb positive patients.Methods HBV markers were detected by dissociation enhanced lanthanide fluoroimmunoassay (DELFIA),HBV core promoter gene was amplified by polymerase chain reaction and sequenced directly in ABI 310 machine.The core promoter gene sequences were compared with the representative sequences in Genbank,then the mutations were found.Results 13 of 17 patients were positive for HBV DNA;the sequence analysis showed that all sequences had mutations.T1762 and A1764 mutations were found in all patients.Conclusion T1762 and A1764 can be detected in all patients who had HBe seroconversion
Characterization of allergens from deer: cross‐reactivity with allergens from cow dander (1997)

Deer allergy is a rare sensitization mainly affecting persons exposed to deer, who displayed an atopic disposition. From our results it can be assumed that this hypersensitivity is partly associated with allergy to cow dander.
Recombinant Human Erythropoietin for Patients with AIDS Treated with Zidovudine (1990)

Bone marrow suppression and anemia are frequent side effects of treatment of the acquired immunodeficiency syndrome (AIDS) with zidovudine (formerly azidothymidine [AZT]). We conducted a randomized, double-blind, placebo-controlled clinical trial of recombinant human erythropoietin (100 U per kilogram of body weight thrice weekly by intravenous bolus) in 63 patients with AIDS treated with zidovudine (29 in the erythropoietin group and 34 in the placebo group). Reductions in the number of units of red cells transfused and the number of patients given transfusions per month became apparent in the second and third months of the trial. The reductions were observed in patients with endogenous erythropoietin levels less than or equal to 500 IU per liter at base line, but not in patients whose levels were greater than 500 IU per liter at the beginning of the study. Although the hematocrit and hemoglobin level were not used as the primary criteria of efficacy because the patients received transfusions when their physicians decided that they needed them, a significantly higher rate of increase in the hematocrit was observed in the patients treated with recombinant human erythropoietin whose levels of endogenous erythropoietin were less than or equal to 500 IU per liter (0.00353 points per week) than in the patients given placebo (0.00116 points per week). This effect was not seen in patients with higher levels of endogenous erythropoietin. Serious side effects did not occur more often in the group treated with erythropoietin than in the placebo group. We conclude that recombinant human erythropoietin may be useful in patients with AIDS treated with zidovudine, although the indicators for its use remain to be clarified.
Glucokinase Gene Locus Transgenic Mice Are Resistant to the Development of Obesity-Induced Type 2 Diabetes (2001)

Transgenic mice that overexpress the entire glucokinase (GK) gene locus have been previously shown to be mildly hypoglycemic and to have improved tolerance to glucose. To determine whether increased GK might also prevent or diminish diabetes in diet-induced obese animals, we examined the effect of feeding these mice a high-fat high-simple carbohydrate low-fiber diet (HF diet) for 30 weeks. In response to this diet, both normal and transgenic mice became obese and had similar BMIs (5.3 +/- 0.1 and 5.0 +/- 0.1 kg/m2 in transgenic and non-transgenic mice, respectively). The blood glucose concentration of the control mice increased linearly with time and reached 17.0 +/- 1.3 mmol/l at the 30th week. In contrast, the blood glucose of GK transgenic mice rose to only 9.7 +/- 1.2 mmol/l at the 15th week, after which it returned to 7.6 +/- 1.0 mmol/l by the 30th week. The plasma insulin concentration was also lower in the GK transgenic animals (232 +/- 79 pmol/l) than in the controls (595 +/- 77 pmol/l), but there was no difference in plasma glucagon concentrations. Together, these data indicate that increased GK levels dramatically lessen the development of both hyperglycemia and hyperinsulinemia associated with the feeding of an HF diet.
Processor autonomy on SIMD architectures (1993)

Flynn classified high speed (parallel) computers into four categories. Of these, the single instruction stream, multiple data stream (SIMD) processor array machines have become very popular in practical parallel processing. The commercially available processor array machines display important architectural variety, while belonging to SIMD category of machines. In this paper, we further categorize the SIMD class of machines on the basis of processor autonomy of the machines, which is the capability of the individual processing elements (PEs) to act autonomously in some significant way. For each autonomy class, we provide examples and illustrate some of its important algorithmic features. We also discuss how each type of autonomy can be simulated on machines without it. We study the addressing autonomous class of machines in greater detail by discussing three algorithms on machines with and without that type of autonomy. A discussion on how processor autonomy appears in algorithms in the literature and what impact they can have in the future machines also is provided.
IL‐12‐Engineered Dendritic Cells Serve as Effective Tumor Vaccine Adjuvants in Vivoa (1996)

The recent identification of tumor-associated antigens (TAA) and TAA-derived peptides presented by MHC molecules to T cells has provided the tools to design and test clinical vaccines for treating human malignancies, such as melanoma. While the most effective adjuvant for use in vaccine formulation remains unclear, autologous dendritic cells (DC) appear to be good candidate adjuvants. We have previously shown that syngeneic bone marrow-derived DC when pulsed ex vivo with relevant TAA-derived peptides can effectively vaccinate mice against a subsequent challenge with tumor or can effectively treat animals bearing established tumors. In this report, we have engineered murine interleukin-12 (mIL-12), a potent stimulator of cell-mediated immunity, into murine DC using retroviral-mediated or plasmid-based transfection procedures. Transfectants produced up to 25 ng rIL-12/10(6) cells/48 hours. These engineered cells are capable of promoting enhanced anti-tumor, antigen-specific CTL responses compared to nontransduced DC.
Oxidative stress and aging: beyond correlation (2002)

The oxidative stress theory of aging has become increasingly accepted as playing a role in the aging process, based primarily on a substantial accumulation of circumstantial evidence. In recent years, the hypothesis that mitochondrially generated reactive oxygen species play a role in organismal aging has been directly tested in both invertebrate and mammalian model systems. Initial results imply that oxidative damage, specifically the level of superoxide, does play a role in limiting the lifespans of invertebrates such as Drosophila melanogaster and Caenorhabditis elegans. In mammalian model systems, the effect of oxidative stress on lifespan is less clear, but there is evidence that antioxidant treatment protects against age-related dysfunction, including cognitive decline.