gebhart/patrepeval huggingface dataset:
Role of ADCC in the in vivo antitumor effects of zalutumumab, a human anti-EGF receptor antibody. (2010)

e13102 Background: Zalutumumab (HuMax-EGFr, clone-2F8), a fully human IgG1 EGFR antibody, currently in phase III clinical trials, was previously demonstrated to have a dual mechanism of action. First, it blocks EGFR signaling by preventing ligand binding and inducing receptor downmodulation. This mechanism was found to be effective in established xenograft tumors at doses giving full receptor occupancy. Second, we observed in vitro induction of antibody-dependent cell-mediated cytotoxicity (ADCC), which was found to be already maximally active at very low, sub-saturating antibody concentrations. Because the contribution of ADCC to the antitumor effects of therapeutic cancer antibodies in solid tumors remains unclear we studied the importance of ADCC induction by zalutumumab in xenograft models. Methods: We prepared human EGFR antibodies with different functionalities for comparison with zalutumumab to: 1) clone 2F8-N297Q a mutant of zalutumumab, which has a nonfunctional Fc part regarding interaction with Fc receptors, 2) clone-018, a non-blocking human EGFR mAb, for which we observed ADCC in vitro as only mechanism of action and 3) clone-018-N297Q which displayed no in vitro activity. Results: Therapeutic treatment of established A431 tumor xenografts with these antibodies showed efficacy for zalutumumab and clone 2F8-N297Q only, indicating that blocking of signaling is crucial in this condition. In contrast, when given on the day of tumor induction, both zalutumumab and clone-018, but not clone-018-N297Q, were effective in preventing A431 tumor xenografts. In an experimental xenograft model, zalutumumab and clone 018 could completely prevent outgrowth of lung metastases, even when given at a low, nonsaturating dosing. Conclusions: Our experiments indicate that blocking of EGFR signaling is required for effectiveness of zalutumumab in established tumors, requiring doses giving full receptor occupancy. We conclude that induction of ADCC represents an additional, independent mechanism, which seems insufficient for reducing primary solid tumors, but is likely to have an important contribution in preventing metastases. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genmab Genmab Genmab
Enhancement of Herbicide Activity with an Isoparaffinic Oil Carrier (1971)

Several herbicides were tested in the greenhouse on ivyleaf morningglory ( Ipomoea hederacea (L.) Jacq.), green foxtail ( Setaria viridis (L.) Beauv.), purple nutsedge ( Cyperus rotundus L.), and quackgrass ( Agropyron repens (L.) Beauv.) to determine the degree of enhancement in activity that could be obtained with an isoparaffinic oil carrier applied at 140 L/ha. The enhancement varied with the herbicide and with the species, ranging from 16-fold enhancement with 2-chloro-4-(ethylamino)-6-(isopropylamino)- s -triazine (atrazine) and 2- sec -butyl-4,6-dinitrophenol (dinoseb) on ivyleaf morningglory to no enhancement of atrazine activity on purple nutsedge and quackgrass or (2,4-dichlorophenoxy)acetic acid (2,4-D) activity on quackgrass and ivyleaf morningglory. An oil adjuvant was less effective in enhancing dinoseb and 3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea (linuron) activity than was the isoparaffinic oil carrier. Also, the isoparaffinic oil carrier emulsified in water was less effective than the undiluted oil in enhancing dinoseb activity on green foxtail, even though equal volumes of the isoparaffinic oil were applied.
Hereditary cancer syndromes: utilizing DNA repair deficiency as therapeutic target (2016)

Human cells have numerous repair mechanisms to counteract various insults incurred on the DNA. Any mutation in these repair mechanisms can lead to accumulation of DNA errors and carcinogenesis. This review aims to discuss the therapeutic options in the two most common DNA repair deficient cancer syndromes, namely Lynch syndrome (hereditary non-polyposis colorectal cancer) and breast cancer susceptibility gene (BRCA) associated ovarian and breast cancer. Deficiency in DNA repair mechanisms renders these tumors with increased sensitivity to platinum agents. There has been increasing amount of information on the utility of the defects in DNA repair as targets for cancer therapy in these syndromes. Novel therapies like poly (ADP-ribose) polymerase (PARP) inhibitors are one of such example where the induction of double stranded breaks in DNA leads to tumoricidal effect in patients with homologous DNA repair deficiency. Interestingly, patients with DNA repair deficiencies tend to have a more favorable prognosis than sporadic malignancies. In microsatellite high colorectal cancer patients, this has been attributed to increased recruitment of CD8+ T lymphocytes in tumor microenvironment. However, these tumors are able to limit the host immune response by activation of immune checkpoints that seem like attractive targets of therapy in the future.
Interconnection system with single phase IGBT PWM CSI between photovoltaic arrays and the utility line (2002)

The single-phase utility interactive photovoltaic (PV) system, including the insulated-gate bipolar-transistor (IGBT) current-source pulse-width modulation (PWM) inverter with two auxilliary IGBTs is described. The system configuration, its operation, and experimental results which include steady-state characteristics with waveforms are presented. It is shown that the system can supply a utility with maximum power corresponding to the insolation with sinusoidal current waveforms at unity power factor. The modulation index and firing angle are fixed, and there is no need for feedback control. In case of emergency, the system can be instantaneously disconnected from the utility line by turning off all the main IGBTs. Simultaneously, the two auxiliary IGBTs are turned on to let the DC current circulate through these IGBTs, the PV array, and the DC reactor.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
La noción de muerte como objeto de investigación de la psicología del desarrollo (2014)

Las ciencias que se ocupan del Hombre han delineado sus objetos de estudio definiendo progresivamente su irreductibilidad a otros campos explicativos. La lingüística, la antropología, la sociología, la psicología, han mostrado que las leyes y procesos que caracterizan los dominios de la lengua, de la cultura, de la sociedad o del psiquismo, no pueden simplificarse y reducirse a los principios postulados a partir de la indagación de objetos naturales.
Prediction of amino acid sequence from structure (2000)

We have developed a method for the prediction of an amino acid sequence that is compatible with a three-dimensional backbone structure. Using only a backbone structure of a protein as input, the algorithm is capable of designing sequences that closely resemble natural members of the protein family to which the template structure belongs. In general, the predicted sequences are shown to have multiple sequence profile scores that are dramatically higher than those of random sequences, and sometimes better than some of the natural sequences that make up the superfamily. As anticipated, highly conserved but poorly predicted residues are often those that contribute to the functional rather than structural properties of the protein. Overall, our analysis suggests that statistical profile scores of designed sequences are a novel and valuable figure of merit for assessing and improving protein design algorithms.
Genomic Diversity of Human T-Lymphotropic Virus Type III (HTLV-III) (1985)

The DNA genomes of human T-lymphotropic virus type III (HTLV-III) isolated from 18 individuals with AIDS or who were at risk for AIDS were evaluated for evidence of variation. Although all of the 18 viral DNA's hybridized throughout their entire genomes to a full-length cloned probe of the original HTLV-III isolate, each of the 18 isolates showed a different restriction enzyme pattern. The number of restriction site differences between isolates ranged from only 1 site in 23 to at least 16 sites in 31. No particular viral genotype was associated with a particular disease state and 2 of the 18 patients had evidence of concurrent infection by more than one viral genotype. Propagation of three different viral isolates in vitro for up to 9 months did not lead to detectable changes in their restriction patterns. These findings indicate that different isolates of HTLV-III comprise a spectrum of highly related but distinguishable viruses and have important implications regarding the pathogenicity of HTLV-III and attempts to develop effective diagnostic, therapeutic, and preventive measures for this virus.
Modeling of competitive phosphono amino acid NMDA receptor antagonists (1992)

A pharmacophore for the phosphono amino acid antagonists of the NMDA receptor has been developed using computer-based molecular modeling techniques. An important feature of this model is that a single binding site is proposed for the phosphonic acid moiety. All competitive antagonists we have examined incorporating amino acid and phosphonate groups in their structure fit the pharmacophore in energetically accessible conformations.
Virus Particle Explorer (VIPER), a Website for Virus Capsid Structures and Their Computational Analyses (2001)

The number of icosahedral-capsid structures determined at a near-atomic level of resolution is growing rapidly as advances in synchrotron radiation sources, fast-readout detectors, and computer hardware and software are made. Hence, there is an increasing need to organize these mega-assemblies into a uniform and easy-to-use database. The coordinates of the icosahedral-capsid structures deposited in the Protein Data Bank (PDB) (2) follow a variety of conventions in which the icosahedral symmetry axes are oriented differently in the orthogonal coordinate system. While trying to analyze the various capsid structures en masse, we became aware of the need for a database in which all capsid structures (coordinates) are stored in a standard icosahedral orientation. Such a structural database of viral capsids would indeed facilitate the development of tools for high-throughput analyses of the virus structures. We report here the creation of a web-base (website and database) of virus structures, the Virus Particle Explorer (VIPER), which can be accessed through the World Wide Web (WWW) at the uniform resource locator (URL) http://mmtsb.scripps.edu /viper/. The organization of the VIPER database is shown in Fig. ​Fig.1.1. 



FIG. 1

Flow chart showing the organization of the contents of the VIPER site. The VIPER database contains the structures of viral capsids determined at a nearly atomic-level resolution. Coordinates of the capsid structures are stored in the z(2)-3-5-x(2) convention. ...
Nonepileptic Uses of Gabapentin (1999)

For decades, antiepileptic drugs (AEDs) have been used to treat a variety of nonepileptic conditions such as chronic pain, psychiatric disorders, and movement disorders. As indicated by recent published reports, gabapentin, a relatively new AED, is useful for treating a wide range of neurologic and psychiatric conditions. Although its exact mechanism of action has yet to be determined, gabapentin is likely to have multiple effects. Unlike conventional AEDs used to treat nonepileptic disorders (e.g., carbamazepine, phenytoin, valproate) gabapentin offers the advantages of low toxicity and a favorable side-effect profile. The largest area of nonepileptic use of gabapentin is neuropathic pain, in which it has demonstrated efficacy in treatment of postherpetic neuralgia, diabetic neuropathy, and trigeminal neuralgia. It has also been reported effective as therapy for several psychiatric disorders, most notably bipolar disorder. In addition, review of the published literature reveals the usefulness of gabapentin in movement disorders, migraine prophylaxis, and cocaine dependence. Future clinical studies will provide further insight into the range of conditions for which gabapentin is effective.
Theoretical study on a reaction pathway of Ziegler–Natta-type catalysis (1978)

A b initio SCF–LCAO–MO all-electron calculations have been performed for the catalyzed reaction, related to the Ziegler–Natta polymerization process TiCl4⋅Al(CH3)3+C2H4 →TiCl4⋅Al(CH3)2⋅C3H7. The energy of the Ti–Al–ethylene complex during the reaction pathway is associated to the following processes: First, the ethylene coordinates to the catalyst complex and subsequently it reacts with the methyl moiety producing an activation energy barrier mainly due to the breaking of the ethylene double bond. The computed barrier height (15 kcal/mole) is in reasonable agreement with experimental activation energies. The identification of the energy barrier is based on the analysis of the electron population, bond energies, and molecular orbitals of the system as they evolve during the reaction. A comparison with the qualitative picture resulting from the classical model of Cossee and with semiempirical calculations is presented. From these calculations a model is derived which leads to a tentative suggestion for the enhancement of the catalytic activity. We consider this suggestion (regardless of its practical value), as well as the model, as examples of the type of theoretical results that can be furnished by quantum mechanics.
Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform (2022)

UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.
Endothelial cells derived from human embryonic stem cells (2002)

Human embryonic stem cells have the potential to differentiate into various cell types and, thus, may be useful as a source of cells for transplantation or tissue engineering. We describe here the differentiation steps of human embryonic stem cells into endothelial cells forming vascular-like structures. The human embryonic-derived endothelial cells were isolated by using platelet endothelial cell-adhesion molecule-1 (PECAM1) antibodies, their behavior was characterized in vitro and in vivo, and their potential in tissue engineering was examined. We show that the isolated embryonic PECAM1+ cells, grown in culture, display characteristics similar to vessel endothelium. The cells express endothelial cell markers in a pattern similar to human umbilical vein endothelial cells, their junctions are correctly organized, and they have high metabolism of acetylated low-density lipoprotein. In addition, the cells are able to differentiate and form tube-like structures when cultured on matrigel. In vivo, when transplanted into SCID mice, the cells appeared to form microvessels containing mouse blood cells. With further studies, these cells could provide a source of human endothelial cells that could be beneficial for potential applications such as engineering new blood vessels, endothelial cell transplantation into the heart for myocardial regeneration, and induction of angiogenesis for treatment of regional ischemia.
Sequence relationships among the hemagglutinin genes of 12 subtypes of influenza A virus. (1981)

Nucleotide sequences of the 3' 20% of the hemagglutinin gene of 32 influenza A virus strains from the 12 known hemagglutinin subtypes have been determined. Although the sequences of hemagglutinin genes and proteins of different subtypes differ greatly, cysteine and some other amino acid residues are totally conserved, presumably reflecting evolution of the 12 different hemagglutinins from a single gene. When viruses of one subtype, isolated over a period of time, are compared, the hemagglutinin gene and protein sequences show a slow accumulation of nucleotide changes and some amino acid changes. Since sequence data from the genes coding for the matrix and nonstructural proteins also show an accumulation of changes with time, it seems that antigenic selection (of the surface antigens) does not contribute significantly to the rate of change on influenza gene sequences. Although the rate of nucleotide change during drift is more than sufficient to account for the amino acid sequence differences observed in the 12 subtypes, there is a clear distinction, by antigenic as well as sequence analyses, between viruses of one subtype (0-9% amino acid variation) and viruses of other subtypes (20-74% amino acid variation). No virus has yet been found that is intermediate between subtypes.
Neural Attention Models for Sequence Classification: Analysis and Application to Key Term Extraction and Dialogue Act Detection (2016)

Recurrent neural network architectures combining with attention mechanism, or neural attention model, have shown promising performance recently for the tasks including speech recognition, image caption generation, visual question answering and machine translation. In this paper, neural attention model is applied on two sequence classification tasks, dialogue act detection and key term extraction. In the sequence labeling tasks, the model input is a sequence, and the output is the label of the input sequence. The major difficulty of sequence labeling is that when the input sequence is long, it can include many noisy or irrelevant part. If the information in the whole sequence is treated equally, the noisy or irrelevant part may degrade the classification performance. The attention mechanism is helpful for sequence classification task because it is capable of highlighting important part among the entire sequence for the classification task. The experimental results show that with the attention mechanism, discernible improvements were achieved in the sequence labeling task considered here. The roles of the attention mechanism in the tasks are further analyzed and visualized in this paper.
Mice lacking dipeptidyl peptidase IV are protected against obesity and insulin resistance (2003)

Dipeptidyl peptidase IV (DP-IV), a member of the prolyl oligopeptidase family of peptidases, is involved in the metabolic inactivation of a glucose-dependent insulinotropic hormone, glucagon-like peptide 1 (GLP-1), and other incretin hormones. Here, we investigated the impact of DP-IV deficiency on body weight control and insulin sensitivity in mice. Whereas WT mice displayed accelerated weight gain and hyperinsulinemia when fed a high-fat diet (HFD), mice lacking the gene encoding DP-IV (DP-IV-/-) are refractory to the development of obesity and hyperinsulinemia. Pair-feeding and indirect calorimetry studies indicate that reduced food intake and increased energy expenditure accounted for the resistance to HFD-induced obesity in the DP-IV-/- mice. Ablation of DP-IV also is associated with elevated GLP-1 levels and improved metabolic control in these animals, resulting in improved insulin sensitivity, reduced pancreatic islet hypertrophy, and protection against streptozotocin-induced loss of beta cell mass and hyperglycemia. Together, these observations suggest that chronic deletion of DP-IV gene has significant impact on body weight control and energy homeostasis, providing validation of DP-IV inhibition as a viable therapeutic option for the treatment of metabolic disorders related to diabetes and obesity.
Expression of E-selectin mRNA during ischemia/reperfusion injury. (1995)

To better understand molecular and cellular processes involved in tissue inflammation, we have examined expression of endothelial leukocyte adhesion molecule 1 (E-selectin) mRNA in adult male rats after ischemia/reperfusion (I/R) injury and after intravenous injection of lipopolysaccharide (LPS). The polymerase chain reaction was used to generate a rat E-selectin cDNA fragment by using heart total RNA from rats exposed to LPS. This partial cDNA fragment spanned sequences from complement repeat region-5 to the second cytoplasmic tail domain. Comparison of the predicted amino acid sequence from the rat cDNA fragment to mouse and human E-selectin protein sequences showed significant conservation. The rat E-selectin cDNA fragment was used as a probe to examine the regulation of E-selectin mRNA expression by Northern blot analysis. As previously described in other animal species, E-selectin mRNA expression was induced after intravenous injection of LPS. In contrast, ischemia did not induce E-selectin mRNA expression, except in the setting of I/R injury. I/R injury triggered expression of E-selectin mRNA in the kidney. These experiments represent a first in vivo examination of E-selectin mRNA expression after I/R injury and constitute an initial step in characterizing a model system for investigating inflammation in the setting of acute ischemic injury.
A physiological effect of an alternating magnetic field (1910)

Abstract Down to the present time it has been held by all physicists and by all physiologists that magnetism produces no physiological effect either on the human subject or on any living organism. Many persons have looked for such effects. Lord Lindsay (now the Earl of Crawford), assisted by Mr. Cromwell F. Varley, constructed many years ago an enormous electromagnet, now in the Observatory at Edinburgh, so large that it would admit between its poles the head of any person who wished to test whether was perceived as the result. I have, however, recently succeeded in domonstrating a real physiological effect due to magnetism. Some six years ago, when experimenting with an alternating electro-magnet which had been constructed for showing Prof. Elihu Thomson’s well-known experiments on the repulsion of copper rings, I observed a faint visual effect when my forehead was placed close to the magnet.
Purification and catalytic properties of a CO‐oxidizing:H2‐evolving enzyme complex from Carboxydothermus hydrogenoformans (2002)

From the membrane fraction of the Gram‐positive bacterium Carboxydothermus hydrogenoformans , an enzyme complex catalyzing the conversion of CO to CO 2 and H 2 was purified. The enzyme complex showed maximal CO‐oxidizing:H 2 ‐evolving enzyme activity with 5% CO in the headspace (450 U per mg protein). Higher CO concentrations inhibited the hydrogenase present in the enzyme complex. For maximal activity, the enzyme complex had to be activated by either CO or strong reductants. The enzyme complex also catalyzed the CO‐ or H 2 ‐dependent reduction of methylviologen at 5900 and 180 U per mg protein, respectively. The complex was found to be composed of six hydrophilic and two hydrophobic polypeptides. The amino‐terminal sequences of the six hydrophilic subunits were determined allowing the identification of the encoding genes in the preliminary genome sequence of C. hydrogenoformans . From the sequence analysis it was deduced that the enzyme complex is formed by a Ni‐containing carbon monoxide dehydrogenase (CooS), an electron transfer protein containing four [4Fe−4S] clusters (CooF) and a membrane bound [NiFe] hydrogenase composed of four hydrophilic subunits and two membrane integral subunits. The hydrogenase part of the complex shows high sequence similarity to members of a small group of [NiFe] hydrogenases with sequence similarity to energy conserving NADH:quinone oxidoreductases. The data support a model in which the enzyme complex is composed of two catalytic sites, a CO‐oxidizing site and a H 2 ‐forming site, which are connected via a different iron–sulfur cluster containing electron transfer subunits. The exergonic redox reaction catalyzed by the enzyme complex in vivo has to be coupled to energy conservation, most likely via the generation of a proton motive force.
Carbon Dioxide Laser-Treatment of Resistant Verrucae Vulgaris: Retrospective Analysis (1998)

The carbon dioxide laser is an effective treatment of resistant verrucae vulgaris.