gebhart/patrepeval huggingface dataset:
Non-Fc Receptor-Binding Humanized Anti-CD3 Antibodies Induce Apoptosis of Activated Human T Cells (2000)

Human trials in organ allografts have demonstrated that murine anti-CD3 mAbs are immunosuppressive. By mimicking Ag, anti-CD3 can produce T cell activation, anergy, or death. Activation of resting T cells in vivo results in dose-limiting cytokine release and is caused by Ab-mediated cross-linking of T cells and Fcgamma receptor (FcR)-bearing cells. With the goal of minimizing cytokine-induced toxicity, anti-CD3 have been engineered to lower Fc binding avidity. Preclinical murine studies have indicated that non-FcR-binding anti-CD3 can induce apoptosis of Ag-activated T cells. Since induction of T cell apoptosis may be an important mechanism of immunosuppression by anti-CD3, we tested whether Fc mutations affect the ability of anti-human CD3 to induce apoptosis of activated T cells. We compared wild-type murine anti-CD3, M291, and OKT3 and their humanized, FcR- and non-FcR-binding structural variants in quantitative assays of T cell apoptosis. Non-FcR-binding variants produced more sustainable phosphorylation of extracellular signal-regulated kinase-2, greater release of IFN-gamma, and more effectively caused activation-dependent T cell apoptosis. Non-FcR-binding variants dissociated more quickly from the T cell surface and caused less internalization of the TCR, which then remained available in greater abundance on the cell surface for signaling. Cross-linking of non-FcR-binding variants by antiglobulin enhanced TCR internalization and minimized induction of T cell apoptosis. We conclude that non-FcR-binding, humanized anti-CD3 have improved ability to induce apoptosis of activated T cells, presumably by allowing durable expression of the TCR and sustained signaling.
A molecular mechanical force field for the conformational analysis of oligosaccharides: comparison of theoretical and crystal structures of Man.alpha.1-3Man.beta.1-4GlcNAc (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA molecular mechanical force field for the conformational analysis of oligosaccharides: comparison of theoretical and crystal structures of Man.alpha.1-3Man.beta.1-4GlcNAcS. W. HomansCite this: Biochemistry 1990, 29, 39, 9110–9118Publication Date (Print):October 2, 1990Publication History Published online1 May 2002Published inissue 2 October 1990https://doi.org/10.1021/bi00491a003Request reuse permissionsArticle Views351Altmetric-Citations333LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1020 KB) Get e-Alertsclose Get e-Alerts
Permanent access to the portal system for cellular transplantation using an implantable port device (2004)

A novel application of the implantable Port-a-Cath (PAC) system is described in the context of cellular transplantation. A silicone catheter was inserted in a collateral branch of the portal vein and connected to a port device positioned subcutaneously on the left thoracic cage. This permanent vascular access allowed iterative intraportal infusions of allogenic hepatocytes without the need of repeated transhepatic catheterization of the portal vein. Using this technique, repeated infusions of cryopreserved and / or fresh hepatocytes were successfully carried out in 3 children with inborn errors of liver metabolism, with the aim of progressively providing a sufficient mass of transplanted liver cells to stabilize the metabolic condition of the patients. We suggest that this technique might also be valuable in pancreatic islet cell transplantation.
Use of Evaporated Acrylate Coatings to Smooth the Surface Of Polyester and Polypropylene Film Substrates (1997)

It is well known that all film substrates have a characteristic surface roughness which depends on the way that it is made and the various chemical additives that it contains. In many cases this roughness is desirable since it provides the sheet material with a low coefficient of friction which prevents blocking during handling. On the other hand these additives may be undesirable since they can lower the water and oxygen barrier properties of a barrier layer applied to this film or reduce the surface reflectivity. This paper attempts to characterize the surface roughness of some common film substrates using scanning electron microscopy and the WYKO RST interferometer surface measurement system. The roughness was visually displayed and quantitative numbers are given for the peak to valley roughness, the number of peaks, and their average height. These substrates were coated by vapor deposition of a radiation curable acrylate monomer in layers of various thicknesses. The effect of these coatings in smoothing out the surface roughness was shown. This paper demonstrates the effectiveness of both evaluation methods in characterizing the roughness of plain and coated film.
HyperText: A Psychological Perspective (1992)

Effects of semantically structuring Hypertext knowledge bases on users' knowledge structures teaching with Hypertext - problems and prospects the textbook of the future do readers want Hypertext? an alternative rhetoric for Hypertext - a return to linearity mind tools for learning - Hypertext as a learning adjunct the psychology of learning with Hypertext - past, present and future the psychology of navigation - mental models, superstructures and metaphors.
Regulation of PACE propeptide-processing activity: requirement for a post-endoplasmic reticulum compartment and autoproteolytic activation. (1992)

PACE (paired basic amino acid cleaving enzyme) is a subtilisin-like serine protease involved in processing of propeptides in the constitutive secretory pathway. We here demonstrate that the transmembrane and cytoplasmic domains of PACE are required for retention in the secretory pathway but not for propeptide-cleaving activity. Addition of the endoplasmic reticulum retention signal Lys-Asp-Glu-Leu (KDEL) to the carboxyl terminus of the truncated molecule resulted in intracellular retention of the protein and loss of activity, indicating that the endoplasmic reticulum is an inappropriate environment for propeptide processing. In addition, mutation of a consensus PACE cleavage site within the amino-terminal region prevented processing of PACE to a mature form and destroyed activity. These data indicate that PACE is synthesized as a proprotein which requires autoproteolytic removal of an 81-residue pro sequence for optimal activity. A mutant form of PACE that lacked the pro sequence was nonfunctional, and addition of a pro sequence from a homologous subtilisin-like serine protease, PC2, did not restore activity. By analogy to the bacterial subtilisin family, the propeptide of PACE may guide the folding of PACE into an active enzyme.
Guanosine Triphosphatase Activating Protein (GAP) Interacts with the p21 ras Effector Binding Domain (1988)

A cytoplasmic protein that greatly enhances the guanosine triphosphatase (GTPase) activity of N-ras protein but does not affect the activity of oncogenic ras mutants has been recently described. This protein (GAP) is shown here to be ubiquitous in higher eukaryotes and to interact with H-ras as well as with N-ras proteins. To identify the region of ras p21 with which GAP interacts, 21 H-ras mutant proteins were purified and tested for their ability to undergo stimulation of GTPase activity by GAP. Mutations in nonessential regions of H-ras p21 as well as mutations in its carboxyl-terminal domain (residues 165-185) and purine binding region (residues 117 and 119) did not decrease the ability of the protein to respond to GAP. In addition, an antibody against the carboxyl-terminal domain did not block GAP activity, supporting the conclusion that GAP does not interact with this region. Transforming mutations at positions 12, 59, and 61 (the phosphoryl binding region) abolished GTPase stimulation by GAP. Point mutations in the putative effector region of ras p21 (amino acids 35, 36, and 38) were also insensitive to GAP. However, a point mutation at position 39, shown previously not to impair effector function, did not alter GAP-p21 interaction. These results indicate that GAP interaction may be essential for ras p21 biological activity and that it may be a ras effector protein.
A Prostate-Specific Antigen-Activated Channel-Forming Toxin as Therapy for Prostatic Disease (2007)

Our observations demonstrate the potential safe and effective intraprostatic application of this engineered protoxin.
Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma (2010)

Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic cells more precisely but may be inhibited by concurrent myelosuppressive chemotherapy like temozolomide (TMZ), which produces a survival benefit in GBM. A phase II, multicenter trial was undertaken to assess the immunogenicity of an experimental EGFRvIII-targeted peptide vaccine in patients with GBM undergoing treatment with serial cycles of standard-dose (STD) (200 mg/m2 per 5 days) or dose-intensified (DI) TMZ (100 mg/m2 per 21 days). All patients receiving STD TMZ exhibited at least a transient grade 2 lymphopenia, whereas those receiving DI TMZ exhibited a sustained grade 3 lymphopenia (<500 cells/μL). CD3+ T-cell (P = .005) and B-cell (P = .004) counts were reduced significantly only in the DI cohort. Patients in the DI cohort had an increase in the proportion of immunosuppressive regulatory T cells (TReg; P = .008). EGFRvIII-specific immune responses developed in all patients treated with either regimen, but the DI TMZ regimen produced humoral (P = .037) and delayed-type hypersensitivity responses (P = .036) of greater magnitude. EGFRvIII-expressing tumor cells were also eradicated in nearly all patients (91.6%; CI95: 64.0%–99.8%; P < .0001). The median progression-free survival (15.2 months; CI95: 11.0–18.5 months; hazard ratio [HR] = 0.35; P = .024) and overall survival (23.6 months; CI95: 18.5–33.1 months; HR = 0.23; P = .019) exceeded those of historical controls matched for entry criteria and adjusted for known prognostic factors. EGFRvIII-targeted vaccination induces patient immune responses despite therapeutic TMZ-induced lymphopenia and eliminates EGFRvIII-expressing tumor cells without autoimmunity.
Cancer Pharmacoethnicity: Ethnic Differences in Susceptibility to the Effects of Chemotherapy (2009)

A long-term goal of pharmacogenomics research is the design of individualized therapy based on the genomic sequence of the patient, in order to maximize response and minimize adverse drug reactions. Pharmacoethnicity, or ethnic diversity in drug response or toxicity, is becoming increasingly recognized as an important factor accounting for interindividual variation in anticancer drug responsiveness. Although pharmacoethnicity is determined by genetic and nongenetic factors, there is rapidly accumulating clinical evidence about ethnic differences in the frequencies of polymorphisms within many of the important cancer drug-related genes. This article reviews the current clinical evidence for ethnic differences in anticancer drug disposition and sensitivity while highlighting the challenges, and potential solutions, to acquiring such knowledge. The discovery of "ethnic-specific genetic signatures," representing unique sets of drug susceptibility-governing polymorphisms, may be the outcome of such work. Ultimately, such understanding will further the lofty goal of individualization of chemotherapy based on a person's unique genetic make-up to improve the tolerability and effectiveness of chemotherapy for all patients.
Hybridization patterns of Actinobacillus actinomycetemcomitans serotypes a‐e detected with an rRNA gene probe (1993)

This study reports a genetic characterization of Actinobacillus actinomycetemcomitans strains in relation to serotypes by using rRNA gene restriction patterns. Eighty-eight clinical strains were isolated from 20 unrelated subjects at one or several occasions. The strains were serotyped by using serotype-specific rabbit antisera against serotypes a, b, c, d or e. Three subjects harbored 2 A. actinomycetemcomitans serotypes, 15 subjects 1 serotype and 2 subjects untypable strains. Chromosomal DNA was digested with restriction endonuclease ClaI, BamHI, BglI or HindIII and hybridized to the rrnB ribosomal RNA operon of the Escherichia coli chromosome. Isolates belonging to the same serotype were genetically identical in the same individual but nonidentical if they belonged to different serotypes. Isolates of the same or different serotypes were genetically nonidentical in different individuals. The banding patterns of A. actinomycetemcomitans isolates recovered from the same individuals during several years always remained identical. The hybridization method using pKK3535 as a probe seemed suitable as an epidemiological tool for comparing the clonal identity of A. actinomycetemcomitans strains.
Corticotropin-releasing factor receptor antagonists (2006)

Corticotropin-releasing factor (CRF) coordinates the neural, endocrine and immune responses of the body to stress. Therefore, CRF receptors are important targets for the design of drugs for depression, anxiety and stress-related disorders. Several laboratories have published extensive preclinical and limited clinical research into the role of CRF in human disease. This review covers developments in the patent literature during 2002 - 2006 and outlines the prospects for CRF-based therapy for mental illness.
Peripheral and dual binding site inhibitors of acetylcholinesterase as neurodegenerative disease modifying agents (2003)

Current treatment approaches in Alzheimer’s disease have been dominated by the use of acetylcholinesterase (AChE) inhibitors, which increase the acetylcholine concentration in the brain, thus alleviating the decline in cognitive and mental function associated with this neurodegenerative disorder. However, AChE itself has been implicated in the pathogenesis of Alzheimer’s disease and it appears that AChE may directly interact with β-amyloid, increasing the deposition of this peptide into insoluble plaques. This new role suggests that properly designed or biologically directed screened AChE inhibitors might be able to act as disease-modifying agents rather than as a mere palliative treatment. This review discloses recent discoveries of small molecules targeting the non-cholinergic actions of this well-known cholinergic enzyme.
An output feedback-based start-up technique with automatic disabling for battery-less energy harvesters (2015)

This paper presents a start-up circuit based upon output voltage feedback for thermal energy harvesting. The feedback loop consisting of an output load, a boost converter core, a charge-pump-based doubler and a CMOS inverter switch to track the output voltage and generate a reset signal to kickstart the boost converter. The proposed start-up circuit shows a remarkably improved start-up time of 35μs at the input voltage of 290mV. The start-up circuit is automatically disabled after the boost converter reaches steady-state. Only one off-chip component is required, improving the cost efficiency. The proposed start-up circuit consumes 3.2nW during the steady state, aiding the boost converter to achieve an efficiency of 77% at input voltage of 290mV. It was designed in standard 65-nm CMOS process technology and occupies the area of 0.072mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .
Biogenic Carbon Cycling in the Upper Ocean: Effects of Microbial Respiration (2001)

Food-web processes are important controls of oceanic biogenic carbon flux and ocean-atmosphere carbon dioxide exchange. Two key controlling parameters are the growth efficiencies of the principal trophic components and the rate of carbon remineralization. We report that bacterial growth efficiency is an inverse function of temperature. This relationship permits bacterial respiration in the euphotic zone to be computed from temperature and bacterial production. Using the temperature-growth efficiency relationship, we show that bacterial respiration generally accounts for most community respiration. This implies that a larger fraction of assimilated carbon is respired at low than at high latitudes, so a greater proportion of production can be exported in polar than in tropical regions. Because bacterial production is also a function of temperature, it should be possible to compute euphotic zone heterotrophic respiration at large scales using remotely sensed information.
The Thrombin Mutant W215A/E217A Shows Safe and Potent Anticoagulant and Antithrombotic Effects in Vivo (2002)

Administration of the thrombin mutant W215A/E217A (WE), rationally designed for selective activation of the anticoagulant protein C, elicits safe and potent anticoagulant and antithrombotic effects in a baboon model of platelet-dependent thrombosis. The lowest dose of WE tested (0.011 mg/kg bolus) reduced platelet thrombus accumulation by 80% and was at least as effective as the direct administration of 40-fold more (0.45 mg/kg bolus) activated protein C. WE-treated animals showed no detectable hemorrhage or organ failure. No procoagulant activity could be detected for up to 1 week in baboon plasma obtained following WE administration. These results show that engineered thrombin derivatives that selectively activate protein C may represent useful therapeutic agents for the treatment of thrombotic disorders.
Physical model of a MEMS accelerometer for low-g motion tracking applications (2004)

This paper develops a physical model of a MEMS capacitive accelerometer in order to use the accelerometer effectively in low-g motion tracking applications. The proposed physical model includes common physical parameters used to rate an accelerometer: scale factor, bias, and misalignment. Simple experiments used to reveal the behavior and characteristics of these parameters are described. A phenomenological modeling method is used to establish mathematical representations of these parameters in relation to errors such as nonlinearity, hysteresis, cross-axis effect, and temperature effect, without requiring a complete understanding of the underlying physics. Experimental results are presented, in which the physical model reduces RMSE by 93.1% in comparison with the manufacturer's recommended method.
Natural Gas Processing with Membranes:  An Overview (2008)

Every year, the world uses close to 100 trillion scf (standard cubic feet) of natural gas. All of this gas requires treatment before it enters the pipeline, making natural gas processing by far the largest market for industrial gas separation processes and equipment. Of this huge market, membranes have less than a 5% share, but this is changing; membrane-based removal of natural gas contaminants is growing faster than any other segment of the membrane gas separation business. This paper gives an overview of the membrane technology in current use for natural gas treatment and outlines the future prospects.
Soluble Epoxide Hydrolase Gene Deletion Is Protective Against Experimental Cerebral Ischemia (2008)

sEH gene deletion is protective against ischemic stroke by a vascular mechanism linked to reduced hydration of circulating EETs.
Tumour cell killing by tumour necrosis factor: inhibition by anaerobic conditions, free-radical scavengers and inhibitors of arachidonate metabolism. (1987)

Previous work on the mechanism of tumour-cell killing by the macrophage product tumour necrosis factor (TNF) is consistent with a free radical-induced process. In this study, free-radical involvement was sought by (i) investigating the effects on TNF cytolysis of anaerobic conditions, free-radical scavengers and inhibitors of two potential pathways of free-radical generation (oxidative phosphorylation and arachidonate metabolism) and (ii) looking for increased malonyldialdehyde (MDA) production in TNF-treated cells (MDA is a free radical-induced lipid peroxidation product). Although TNF cytolysis of L929 cells was inhibited by anaerobic conditions, only limited effects were seen with free-radical scavengers. Suppression of arachidonate metabolism by steroids effectively inhibited TNF cytolysis but the mitochondrial poison rotenone did not. There was a marked, but late, increase in MDA production in TNF-treated cells. Overall, these results indicate that if free radicals are involved it is at a late stage in the cytolytic process. However the most striking observation in this study is that arachidonate metabolism is an essential link in the cytolytic process.
Mechanism of action of the antiherpesvirus biflavone ginkgetin (1992)

Screening of plant extracts found that a biflavone from Cephalotaxus drupacea, which was found to be ginkgetin, is active against herpes simplex virus type 1 (HSV-1). This compound caused dose-dependent inhibition of virus replication with a 50% cytotoxic activity at 12.8 micrograms/ml and 50% anti-HSV-1 activity at 0.91 micrograms/ml, the therapeutic index being 14.1. Ginkgetin also showed inhibitory effects against HSV type 2 and human cytomegalovirus with therapeutic indices of 13.8 and 11.6, respectively. Ginkgetin had a weak virucidal activity against HSV-1 at more than 5 micrograms/ml. Both adsorption of HSV-1 to host cells and virus penetration into cells were unaffected by this agent. Ginkgetin suppressed viral protein synthesis when added at various steps of HSV-1 replication and exerted strong inhibition of transcription of the immediate-early genes.
Deep Neural Network Approximation for Custom Hardware: Where We've Been, Where We're Going (2019)

Deep neural networks have proven to be particularly effective in visual and audio recognition tasks. Existing models tend to be computationally expensive and memory intensive, however, and so methods for hardware-oriented approximation have become a hot topic. Research has shown that custom hardware-based neural network accelerators can surpass their general-purpose processor equivalents in terms of both throughput and energy efficiency. Application-tailored accelerators, when co-designed with approximation-based network training methods, transform large, dense and computationally expensive networks into small, sparse and hardware-efficient alternatives, increasing the feasibility of network deployment. In this article, we provide a comprehensive evaluation of approximation methods for high-performance network inference along with in-depth discussion of their effectiveness for custom hardware implementation. We also include proposals for future research based on a thorough analysis of current trends. This article represents the first survey providing detailed comparisons of custom hardware accelerators featuring approximation for both convolutional and recurrent neural networks, through which we hope to inspire exciting new developments in the field.