gebhart/patrepeval huggingface dataset:
Structure of (5′S)-8,5′-Cyclo-2′-deoxyguanosine in DNA (2011)

Diastereomeric 8,5'-cyclopurine 2'-deoxynucleosides, containing a covalent bond between the deoxyribose and the purine base, represent an important class of DNA damage induced by ionizing radiation. The 8,5'-cyclo-2'-deoxyguanosine lesion (cdG) has been recently reported to be a strong block of replication and highly mutagenic in Escherichia coli. The 8,5'-cyclopurine-2'-deoxyriboses are suspected to play a role in the etiology of neurodegeneration in xeroderma pigmentosum patients. These lesions cannot be repaired by base excision repair, but they are substrates for nucleotide excision repair. The structure of an oligodeoxynucleotide duplex containing a site-specific S-cdG lesion placed opposite dC in the complementary strand was obtained by molecular dynamics calculations restrained by distance and dihedral angle restraints obtained from NMR spectroscopy. The S-cdG deoxyribose exhibited the O4'-exo (west) pseudorotation. Significant perturbations were observed for the β, γ, and χ torsion angles of the S-cdG nucleoside. Watson-Crick base pairing was conserved at the S-cdG·dC pair. However, the O4'-exo pseudorotation of the S-cdG deoxyribose perturbed the helical twist and base pair stacking at the lesion site and the 5'-neighbor dC·dG base pair. Thermodynamic destabilization of the duplex measured by UV melting experiments correlated with base stacking and structural perturbations involving the modified S-cdG·dC and 3'- neighbor dT·dA base pairs. These perturbations may be responsible for both the genotoxicity of this lesion and its ability to be recognized by nucleotide excision repair.
Replication of Marburg virus in human endothelial cells. A possible mechanism for the development of viral hemorrhagic disease. (1993)

Marburg and Ebola virus, members of the family Filoviridae, cause a severe hemorrhagic disease in humans and primates. The disease is characterized as a pantropic virus infection often resulting in a fulminating shock associated with hemorrhage, and death. All known histological and pathophysiological parameters of the disease are not sufficient to explain the devastating symptoms. Previous studies suggested a nonspecific destruction of the endothelium as a possible mechanism. Concerning the important regulatory functions of the endothelium (blood pressure, anti-thrombogenicity, homeostasis), we examined Marburg virus replication in primary cultures of human endothelial cells and organ cultures of human umbilical cord veins. We show here that Marburg virus replicates in endothelial cells almost as well as in monkey kidney cells commonly used for virus propagation. Our data support the concept that the destruction of endothelial cells resulting from Marburg virus replication is a possible mechanism responsible for the hemorrhagic disease and the shock syndrome typical of this infection.
Selective Toxicity of Persian Gulf Sea Cucumber (Holothuria parva) and Sponge (Haliclona oculata) Methanolic Extracts on Liver Mitochondria Isolated from an Animal Model of Hepatocellular Carcinoma (2015)

Our results suggest that H. parva and H. oculata may be promising therapeutic candidates for the treatment of HCC, following further confirmatory in vivo experiments and clinical trials.
Clinical biochemical aspects of glutaminase toxicity in rabbits and Rhesus monkeys. (1980)

Treatment with a chemically modified glutaminase was lethal to rabbits and Rhesus monkeys at all but the lowest doses. Changes in the serum levels of triglycerides, glucose, creatinine, urea, cholesterol and protein and in the activities of some serum enzymes were the probable result of the development of lesions in liver, kidney and intestine observed at necropsy. Treatment with unmodified glutaminase induced similar changes in rabbits but not in Rhesus monkeys.
Basic Biological Sciences Hydrolysis of Dicalcium Phosphate Dihydrate in the Presence or Absence of Calcium Fluoride (1985)

Effects of temperature (25 and 37 degrees C), pH (4.9-10.5), and CaF2 on CaHPO4.2H2O (DCPD) hydrolysis were studied in a pH-stat. Octa-calcium phosphate (OCP) was the product at pH 6.2-6.8 and 25-37 degrees C; thermodynamically stable apatitic compounds were formed at higher pH and/or higher temperature. In the presence of CaF2, apatite was the product, its crystallinity improved, and the fluoride content increased as pH of the reaction decreased. The results demonstrate the remarkable ability of fluoride to promote the hydrolysis of an acidic calcium phosphate, DCPD, to apatite.
Amino Acid Compositions and Partial Sequences of Two Types of Alkaline Serine Proteases fromNocardiopsis dassonvilleisubsp.prasinaOPC-210 (1990)

Journal Article Amino Acid Compositions and Partial Sequences of Two Types of Alkaline Serine Proteases from Nocardiopsis dassonvillei subsp. prasina OPC-210 Get access Hiroshi Tsujibo, Hiroshi Tsujibo Osaka University of Pharmaceutical Sciences, Kawai, Matsubara-shi, Osaka 580, Japan To whom all correspondence should be addressed. Search for other works by this author on: Oxford Academic Google Scholar Katsushiro Miyamoto, Katsushiro Miyamoto Osaka University of Pharmaceutical Sciences, Kawai, Matsubara-shi, Osaka 580, Japan Search for other works by this author on: Oxford Academic Google Scholar Toru Hasegawa, Toru Hasegawa Institute for Fermentation, Osaka, 17-85, Jusohommachi 2-chome, Yodogawa-ku, Osaka 532, Japan Search for other works by this author on: Oxford Academic Google Scholar Yoshihiko Inamori Yoshihiko Inamori Osaka University of Pharmaceutical Sciences, Kawai, Matsubara-shi, Osaka 580, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 54, Issue 8, 1 August 1990, Pages 2177–2179, https://doi.org/10.1080/00021369.1990.10870283 Published: 01 August 1990 Article history Received: 26 March 1990 Published: 01 August 1990
The use of hybrid hybridomas to target human cytotoxic T lymphocytes (1987)

This study describes a general strategy to produce hybrid monoclonal antibodies that are capable of targeting human cytotoxic T lymphocytes (CTL) against any cell carrying the appropriate target antigen. This is done by fusing a HAT-sensitive, G418-resistant anti-T3 hybridoma with immune spleen cells (or with other hybridomas) that produce antibodies against the desired target antigen. In the hybrid hybridomas the reassortment of Ig heavy and light chains results in the production of bifunctional antibody molecules. Because of their double specificity, these antibodies are able to bridge human CTL to target cells and trigger cytotoxic function. We have isolated several stable hybrid hybridomas in which one specificity is against T3 and one either against HLA antigens (class II, DC-1, A3), human Ig (IgM, IgE, kappa), Toxoplasma gondii or an ovary carcinoma-associated antigen. In all of these cases we show that culture supernatants can efficiently and specifically target any CTL clone against any target cell that possesses the relevant surface antigen recognized by the antibody. Furthermore, the killing requires as little as 0.1 ng/ml of antibody, occurs at effector to target ratios comparable to those used in conventional cytotoxic assays and does not affect bystander cells. Nonspecific killing of Fc receptor-positive cells can be avoided using F(ab')2 fragments. As an example, we show that it is possible to change the major histocompatibility complex class and allospecificity of a CTL clone and target CTL against non-major histocompatibility complex antigens such as Ig, parasites and tumor-associated antigens.
Heterogeneity and selectivity of the degeneration of cholinergic neurons in the basal forebrain of patients with Alzheimer's disease (1993)

Cholinergic neurons were studied by immunohistochemistry, with an antiserum against choline acetyltransferase (ChAT), in the basal forebrain (Ch1 to Ch4) of four patients with Alzheimer's disease (AD) and four control subjects. ChAT-positive cell bodies were mapped and counted in Ch1 (medial septal nucleus), Ch2 (vertical nucleus of the diagonal band), Ch3 (horizontal nucleus of the diagonal band) and Ch4 (nucleus basalis of Meynert). Compared to controls, the number of cholinergic neurons in AD patients was reduced by 50% on average. The interindividual variations in cholinergic cell loss were high, neuronal loss ranging from moderate (27%) to severe (63%). Despite the small number of brains studied, a significant correlation was found between the cholinergic cell loss and the degree of intellectual impairment. To determine the selectivity of cholinergic neuronal loss in the basal forebrain of AD patients, NPY-immunoreactive neurons were also investigated. The number of NPY-positive cell bodies was the same in controls and AD patients. The results (1) confirm cholinergic neuron degeneration in the basal forebrain in AD and the relative sparing of these neurons in some patients, (2) indicate that degeneration of cholinergic neurons in the basal forebrain contributes to intellectual decline, and (3) show that, in AD, such cholinergic cell loss is selective, since NPY-positive neurons are preserved in the basal forebrain.
A Joint Speaker-Listener-Reinforcer Model for Referring Expressions (2017)

Referring expressions are natural language constructions used to identify particular objects within a scene. In this paper, we propose a unified framework for the tasks of referring expression comprehension and generation. Our model is composed of three modules: speaker, listener, and reinforcer. The speaker generates referring expressions, the listener comprehends referring expressions, and the reinforcer introduces a reward function to guide sampling of more discriminative expressions. The listener-speaker modules are trained jointly in an end-to-end learning framework, allowing the modules to be aware of one another during learning while also benefiting from the discriminative reinforcer's feedback. We demonstrate that this unified framework and training achieves state-of-the-art results for both comprehension and generation on three referring expression datasets.
Large Scale Max-Margin Multi-Label Classification with Priors (2010)

We propose a max-margin formulation for the multi-label classification problem where the goal is to tag a data point with a set of pre-specified labels. Given a set of L labels, a data point can be tagged with any of the 2 L possible subsets. The main challenge therefore lies in optimising over this exponentially large label space subject to label correlations. Existing solutions take either of two approaches. The first assumes, a priori, that there are no label correlations and independently trains a classifier for each label (as is done in the 1-vs-All heuristic). This reduces the problem complexity from exponential to linear and such methods can scale to large problems. The second approach explicitly models correlations by pairwise label interactions. However, the complexity remains exponential unless one assumes that label correlations are sparse. Furthermore, the learnt correlations reflect the training set biases. We take a middle approach that assumes labels are correlated but does not incorporate pairwise label terms in the prediction function. We show that the complexity can still be reduced from exponential to linear while modelling dense pairwise label correlations. By incorporating correlation priors we can overcome training set biases and improve prediction accuracy. We provide a principled interpretation of the 1-vs-All method and show
A principled design for scalable internet visual communications with rich media, interactivity, and structured archives (2003)

In contrast to video conferencing, webcasting supports scaleable Internet visual communications, yet it is typically viewed as an ephemeral one-way broadcast medium. We present a principled design for interactive webcasts that are accessible both in real-time and retrospectively. We derive system architecture and functionality from project goals, results from the video communications literature, and observations of prototype implementations in real webcasts. The ePresence system is scalable, interactive, and able to support presenters and engage remote audiences with rich media. It also provides automatically derived, structured, navigable, and searchable archives for the retrospective use of webcasts.
Kollár Ádám Ferenc levelezése (2000)

Abstract In this paper we discuss the basic procedures for the implementation of multivariate statistical process control via control charting. Furthermore, we review multivariate extensions for all kinds of univariate control charts, such as multivariate Shewhart‐type control charts, multivariate CUSUM control charts and multivariate EWMA control charts. In addition, we review unique procedures for the construction of multivariate control charts, based on multivariate statistical techniques such as principal components analysis (PCA) and partial least squares (PLS). Finally, we describe the most significant methods for the interpretation of an out‐of‐control signal. Copyright © 2006 John Wiley &amp; Sons, Ltd.
Measurement of thermal diffusivity for polymer film by flash radiometry (1988)

A new method to determine the thermal diffusivity of polymer film by flash radiometry is presented. The transient infrared radiation from the sample surface was measured after the sample film was heated by a short-duration pulsed light. The thermal diffusivity was determined by fitting the transient infrared signal to the theoretical curve of a one-dimensional heat diffusion model. The transient infrared signal of polymethylmethacrylate (PMMA) film could be well fitted by the theoretical curve using appropriate thermal diffusivity in the wide temperature range between 100 K and near the softening point of PMMA. The temperature dependence of thermal diffusivity of PMMA film showed that the thermal diffusivity sensitively reflects the molecular motion of polymer chain.
Maximizing Diversity from a Kinase Screen: Identification of Novel and Selective pan-Trk Inhibitors for Chronic Pain (2014)

We have identified several series of small molecule inhibitors of TrkA with unique binding modes. The starting leads were chosen to maximize the structural and binding mode diversity derived from a high throughput screen of our internal compound collection. These leads were optimized for potency and selectivity employing a structure based drug design approach adhering to the principles of ligand efficiency to maximize binding affinity without overly relying on lipophilic interactions. This endeavor resulted in the identification of several small molecule pan-Trk inhibitor series that exhibit high selectivity for TrkA/B/C versus a diverse panel of kinases. We have also demonstrated efficacy in both inflammatory and neuropathic pain models upon oral dosing. Herein we describe the identification process, hit-to-lead progression, and binding profiles of these selective pan-Trk kinase inhibitors.
Scalable Epidemiological Workflows to Support COVID-19 Planning and Response (2021)

The COVID-19 global outbreak represents the most significant epidemic event since the 1918 influenza pandemic. Simulations have played a crucial role in supporting COVID-19 planning and response efforts. Developing scalable workflows to provide policymakers quick responses to important questions pertaining to logistics, resource allocation, epidemic forecasts and intervention analysis remains a challenging computational problem. In this work, we present scalable high performance computing-enabled workflows for COVID-19 pandemic planning and response. The scalability of our methodology allows us to run fine-grained simulations daily, and to generate county-level forecasts and other counter-factual analysis for each of the 50 states (and DC), 3140 counties across the USA. Our workflows use a hybrid cloud/cluster system utilizing a combination of local and remote cluster computing facilities, and using over 20,000 CPU cores running for 6-9 hours every day to meet this objective. Our state (Virginia), state hospital network, our university, the DOD and the CDC use our models to guide their COVID-19 planning and response efforts. We began executing these pipelines March 25, 2020, and have delivered and briefed weekly updates to these stakeholders for over 30 weeks without interruption.
Construction and Characterization of a 1,3-Propanediol Operon (1998)

The genes for the production of 1,3-propanediol (1,3-PD) in Klebsiella pneumoniae, dhaB, which encodes glycerol dehydratase, and dhaT, which encodes 1,3-PD oxidoreductase, are naturally under the control of two different promoters and are transcribed in different directions. These genes were reconfigured into an operon containing dhaB followed by dhaT under the control of a single promoter. The operon contains unique restriction sites to facilitate replacement of the promoter and other modifications. In a fed-batch cofermentation of glycerol and glucose. Escherichia coli containing the operon consumed 9.3 g of glycerol per liter and produced 6.3 g of 1,3-PD per liter. The fermentation had two distinct phases. In the first phase, significant cell growth occurred and the products were mainly 1,3-PD and acetate. In the second phase, very little growth occurred and the main products were 1,3-PD and pyruvate. The first enzyme in the 1,3-PD pathway, glycerol dehydratase, requires coenzyme B12, which must be provided in E. coli fermentations. However, the amount of coenzyme B12 needed was quite small, with 10 nM sufficient for good 1,3-PD production in batch cofermentations. 1,3-PD is a useful intermediate in the production of polyesters. The 1,3-PD operon was designed so that it can be readily modified for expression in other prokaryotic hosts; therefore, it is useful for metabolic engineering of 1,3-PD pathways from glycerol and other substrates such as glucose.
Calcium Phosphate-Mediated DNA Transfection (1994)

The ability to express foreign genes introduced into cultured cells is a powerful tool for studying gene expression. It permits monitoring not only the transcriptional and translational activities of exogenous DNA but also the regulation of gene expression by other genetic elements. Furthermore, the approach to somatic gene therapy is entirely based on introducing genes either to correct a prior genetic defect or to augment the genetic repertoire of the recipient cell. The technology of gene transfer is truly one of the cornerstones in molecular genetics.
Opportunities for Research and NIH (2009)

The promise of fundamental advances in diagnosis, prevention, and treatment of disease has never been greater.
401. The optical rotatory powers of some 4-substituted benzhydrylamines (1939)

G. R. Clemo, C. Gardner and R. Raper, J. Chem. Soc., 1939, 1958 DOI: 10.1039/JR9390001958
Late Kidney Allograft Loss (2008)

Despite dramatic improvements in immunosuppression, late graft loss after kidney transplantation remains a common and difficult problem. Histologic evaluation may reveal changes related to BK polyomavirus infection, hypertension, or calcineurin inhibitor toxicity, which can help to guide therapy. The designation chronic allograft nephropathy should thus be reserved for biopsies with tubular atrophy and interstitial fibrosis without an apparent cause. Although the cause clearly includes both antigen-dependent and antigen-independent events, the approach remains largely to exclude immune mechanisms. Although this review discusses the potential contribution of antibody to chronic injury, it focuses on the basic elements of kidney injury, the role of parenchymal cells in promoting injury, and the proliferative and inflammatory responses that accompanying injury. Strategies to manage these recipients include close attention to accompanying hypertension, diabetes, and hyperlipidemia, as well as consideration for altering immunosuppression; however, therapies that limit epithelial-to-mesenchymal transition or directly block fibrosis pathways may reduce chronic allograft fibrosis and may prove to be useful. Understanding the basic pathogenesis sufficiently to allow early intervention may finally benefit patients who are at high risk for tubular atrophy and interstitial fibrosis and promote their long-term graft function.
Advanced Fault Analysis Software System (or AFAS) for Distribution Power Systems (2007)

An Advanced Fault Analysis Software System (or AFAS) is currently being developed at Concurrent Technologies Corporation (CTC) to automatically detect and locate low and high impedance, momentary and permanent faults in distribution power systems. Microsoft Visual Studio is used to integrate advanced software packages and analysis tools (including DEW, AEMPFAST, PSCAD, and CTC's DSFL) under the AFAS platform. AFAS is an intelligent, operational, decision-support fault analysis tool that utilizes PSCAD to simulate fault transients of distribution systems to improve fault location accuracy of DSFL tool and to enhance DSFL capabilities for predicting low and high impedance, momentary and permanent faults. The implementation and evaluation results of this software tool have been presented.
Targeting and killing glioblastoma with monoclonal antibody to O-acetyl GD2 ganglioside (2016)

There are still unmet medical needs in the treatment of glioblastoma, the most common and the most aggressive glioma of all brain tumors. Here, we found that O-acetyl GD2 is expressed in surgically resected human glioblastoma tissue. In addition, we demonstrated that 8B6 monoclonal antibody specific for O-acetylat GD2 could effectively inhibit glioblastoma cell proliferation in vitro and in vivo. Taken together, these results indicate that O-acetylated GD2 represents a novel antigen for immunotherapeutic-based treatment of high-grade gliomas.
The role of material structure and mechanical properties in cell–matrix interactions (2014)

Cellular interactions with the extracellular matrix (ECM) are of fundamental importance in many normal and pathological biological processes, including development, cancer, and tissue homeostasis, healing and regeneration. Over the past few years, the mechanisms by which cells respond to the mechanical characteristics of the ECM have come under increased scrutiny from many research groups. Such research often involves placing cells on materials with tuneable stiffnesses, including synthetic polymers and natural proteins, or culturing cells on bendable micropost arrays. These techniques are often aimed at defining empirically the stiffnesses that cells experience in their interactions with the ECM, and measuring phenotypically how cells and tissues respond. In this review, we will summarise the evolution of materials for investigating cell and tissue mechanobiology. We then will discuss how material properties such as elastic modulus may be interpreted, particularly with regard to analytic measurements as an approximation of how cells themselves sense elastic modulus. Finally we will discuss how factors such as interfacial chemistry, ligand spacing, substrate thickness, elasticity and viscoelasticity affect mechanosensing in cells.
Category Translation: Learning to Understand Information on the Internet. (1995)

This paper investigates the problem of automatically learning declarative models of information sources available on the Internet. We report on ILA, a domain-independent program that learns the meaning of external information by explaining it in terms of internal categories. In our experiments, ILA starts with knowledge of local faculty members, and is able to learn models of the Internet service whois and of the personnel directories available at Berkeley, Brown, Caltech, Cornell, Rice, Rutgers, and UCI, averaging fewer than 40 queries per information source. ILA&amp;apos;s hypothesis language is first-order conjunctions, and its bias is compactly encoded as a determination. We analyze ILA&amp;apos;s sample complexity within the Valiant model, and using a probabilistic model specifically tailored to ILA. Keywords: machine learning, empirical This paper has not already been accepted by and is not currently under review for a journal or another conference. Nor will it be submitted for such during IJCAI...