gebhart/patrepeval huggingface dataset:
Novel Phage Lysin Capable of Killing the Multidrug-Resistant Gram-Negative Bacterium Acinetobacter baumannii in a Mouse Bacteremia Model (2015)

Acinetobacter baumannii, a Gram-negative multidrug-resistant (MDR) bacterium, is now recognized as one of the more common nosocomial pathogens. Because most clinical isolates are found to be multidrug resistant, alternative therapies need to be developed to control this pathogen. We constructed a bacteriophage genomic library based on prophages induced from 13 A. baumannii strains and screened it for genes encoding bacteriolytic activity. Using this approach, we identified 21 distinct lysins with different activities and sequence diversity that were capable of killing A. baumannii. The lysin (PlyF307) displaying the greatest activity was further characterized and was shown to efficiently kill (>5-log-unit decrease) all tested A. baumannii clinical isolates. Treatment with PlyF307 was able to significantly reduce planktonic and biofilm A. baumannii both in vitro and in vivo. Finally, PlyF307 rescued mice from lethal A. baumannii bacteremia and as such represents the first highly active therapeutic lysin specific for Gram-negative organisms in an array of native lysins found in Acinetobacter phage.
Immunomodulatory and toxic effects of free and liposome-encapsulated tumor necrosis factor alpha in rats. (1990)

Tumor necrosis factor alpha has potent immunomodulatory and antitumor activity, but its therapeutic applications may be limited by its significant host toxicity. We showed that liposome-encapsulated recombinant human tumor necrosis factor alpha (rHuTNF-alpha) retained full anticellular activity in vitro. We then assessed the immunomodulatory and toxic effects of two different doses of i.v. free or liposome-encapsulated rHuTNF-alpha in normal rats. Both free and liposome-encapsulated rHuTNF-alpha significantly enhanced alveolar macrophage- and blood monocyte-mediated interleukin 1 release and tumor cell lysis, as well as natural killer cell cytotoxicity, when compared to buffer-treated controls. However, administration of rHuTNF-alpha in liposomes substantially reduced tumor necrosis factor alpha-mediated toxicity. Animals receiving liposome-encapsulated rHuTNF-alpha showed significantly less tissue injury, gastric retention, and circulating leukocyte shifts than animals receiving free rHuTNF-alpha. In addition, liposome-based delivery significantly increased lung and liver uptake of rHuTNF-alpha. Therefore, liposome-encapsulated rHuTNF-alpha retains immunomodulatory activity, significantly reduces toxic inflammatory effects, and may allow targeting of tumor necrosis factor alpha to selected organs after i.v. administration.
Le début du déclin américain? (2009)

Résumé La crise économique marque un échec du modèle américain mais signifiet- elle pour autant un recul de leur puissance ? Ni l’Europe ni les pays émergents ne sont en position de profiter de leur relatif recul. Du point de vue stratégique, les États-Unis ont beaucoup d’atouts pour tirer parti du monde multipolaire dans lequel nous entrons.
Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor. (1990)

Stimulation of T lymphocytes through their antigen receptor leads to the appearance of several transcription factors, including NF-AT and NF-kappa B, which are involved in regulating genes required for immunologic activation. To investigate the activity of a single transcription factor in individual viable cells, we have applied an assay that uses the fluorescence-activated cell sorter to quantitate beta-galactosidase (beta-gal). We have analyzed the distribution of NF-AT transcriptional activity among T cells undergoing activation by using a construct in which three tandem copies of the NF-AT-binding site directs transcription of the lacZ gene. Unexpectedly, stimulation of cloned stably transfected Jurkat T cells leads to a bimodal pattern of beta-gal expression in which some cells express no beta-gal and others express high levels. This expression pattern cannot be accounted for by cell-cycle position or heritable variation. Further results, in which beta-gal activity is correlated with NF-AT-binding activity, indicate that the concentration of NF-AT must exceed a critical threshold before transcription initiates. This threshold likely reflects the NF-AT concentration-dependent assembly of transcription complexes at the promoter. Similar constructs controlled by NF-kappa B or the entire interleukin-2 enhancer show bimodal expression patterns during induction, suggesting that thresholds set by the concentration of transcription factors may be a common property of inducible genes.
Structural Basis for Potent Cross-Neutralizing Human Monoclonal Antibody Protection against Lethal Human and Zoonotic Severe Acute Respiratory Syndrome Coronavirus Challenge (2008)

Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002, and detailed phylogenetic and epidemiological analyses have suggested that it originated from animals. The spike (S) glycoprotein has been identified as a major component of protective immunity, and 23 different amino acid changes were noted during the expanding epidemic. Using a panel of SARS-CoV recombinants bearing the S glycoproteins from isolates representing the zoonotic and human early, middle, and late phases of the epidemic, we identified 23 monoclonal antibodies (MAbs) with neutralizing activity against one or multiple SARS-CoV spike variants and determined the presence of at least six distinct neutralizing profiles in the SARS-CoV S glycoprotein. Four of these MAbs showed cross-neutralizing activity against all human and zoonotic S variants in vitro, and at least three of these were mapped in distinct epitopes using escape mutants, structure analyses, and competition assays. These three MAbs (S109.8, S227.14, and S230.15) were tested for use in passive vaccination studies using lethal SARS-CoV challenge models for young and senescent mice with four different homologous and heterologous SARS-CoV S variants. Both S227.14 and S230.15 completely protected young and old mice from weight loss and virus replication in the lungs for all viruses tested, while S109.8 completely protected mice from weight loss and clinical signs in the presence of viral titers. We conclude that a single human MAb can confer broad protection against lethal challenge with multiple zoonotic and human SARS-CoV isolates, and we identify a robust cocktail formulation that targets distinct epitopes and minimizes the likely generation of escape mutants.
Rrecursive reduction in finite ring computations (1989)

where the symbol C, implies summation modulo m. This &mg This paper discusses computation over finite rings using recursive reduction networks modelled after the general neural network approach. In this case the neurons are arithmetic elements that have modulo operator characteristics, rather than the usual non-linear, saturating characteristics of learning and associative memory neural network applications. Following an analysis of finite ring arithmetic, a computing model is built based on an iterative, bit-level, modulo reduction scheme, from which is extracted a basic operator. A corresponding sub-net is designed to implement this operator, and its effectiveness is illustrated with an example of a Chinese Remainder Theorem (CRV convener for RNS arithmetic. A structure is developed that is suitable for implementing at the full-custom, or gate array level, and example VLSI layouts illustrate that the technique is efficient Recently, a novel neural-like network computing mechanism for finite ring computational system has been developed, and its effectiveness has been illustrated by simulations[ll. In order to put the technique into practice, an imponant task is to develop an architecture that efficiently maps the basic principles of the FRNN to the VLSI medium. In this paper, we develop such a VLSI architecture,and show that the entire circuitry can be constructed with a sinele cell tvoe.The efficiencv of the
Analysis of the immersed boundary method for Stokes flow (2008)

The immersed boundary method is a numerical scheme for dynamical simulations of solid or elastic bodies immersed in a surrounding fluid. The method was originally introduced by Peskin to model the flow of blood in the human heart. It has since proven to be a general and robust method for diverse flow problems arising in biology and engineering. Recently, the immersed boundary method has been applied to biological problems at the micro-scale or smaller, including swimming microorganisms and biomolecular motors. At these scales, the Stokes equations govern the dynamics of the surrounding fluid, and it is particularly important to represent accurately the hydrodynamic interactions that govern the motion of immersed bodies. In this thesis, we construct a new version of the immersed boundary method for Stokes flow. Our analysis of this new method sheds light on several fundamental questions about the immersed boundary method. In the new method, the structures are immersed in an infinite three-dimensional fluid; no artificial boundaries are necessary. Although we start from a discrete representation of the fluid on an infinite grid, we are able to eliminate the fluid variables and reduce the dynamics to that of a finite collection of Lagrangian points. Asymptotic methods reduce the computational cost and reveal the magnitudes of the numerical errors, as well as the dependence of these errors on the approximate delta function used to regularize singular sources.
Intracellular Signaling Pathways Regulating Pluripotency of Embryonic Stem Cells (2006)

The cytokine LIF and its downstream effector STAT3 are essential for maintenance of pluripotency in mouse ES cells. The requirement for the transcription factor Oct3/4 for ES cell pluripotency is also well-documented. However, LIF is not involved in self-renewal of human ES cells, suggesting that other pathways must play an important role in this process. The importance of other signal transduction pathways, including BMP and Wnt signalings, as well as novel transcription factors such as Nanog, is now being recognized. We will review the rapid progress that has been made in identifying and dissecting the intracellular signaling pathways that contribute to self-renewal of pluripotent mouse and human ES cells.
Infective Endocarditis in Adults (2001)

The clinical features of this complex infection have changed in the past several decades. It is now an infection of older people, and mitral-valve prolapse is the most common predisposing cardiovascular problem in developed countries. In contrast, rheumatic heart disease is an important predisposing problem in developing countries. This review article provides a comprehensive assessment of this serious infectious disease, including diagnostic challenges, cardiovascular and neurologic complications, and approaches to therapy.
Effect of sodium butyrate and other differentiation inducers on poorly differentiated human ovarian adenocarcinoma cell lines. (1988)

We have studied the effects of sodium butyrate, retinoic acid, and dimethyl sulfoxide on two human ovarian carcinoma cell lines PE04 and PE01. PE04 cells, after treatment with sodium butyrate at cytostatic doses (2-3 mM for 4 days), exhibited phenotypic changes including induction of alkaline phosphatase and determinants recognized by the monoclonal antibodies 123C3 and 123A8. These effects are not simply the result of cytostasis as they were not produced by dimethyl sulfoxide or retinoic acid. Other markers are also modified by sodium butyrate including lipid, acid mucin, and glycogen. Retinoic acid modulated expression of lipid and CA125, while dimethyl sulfoxide reduced expression of CA125. Other short chain fatty acids such as propionic acid and valeric acid (in addition to butyric acid) also induced alkaline phosphatase and the determinants recognized by 123C3 and 123A8 in PE04 cells. Other differentiation inducers and cytotoxic agents studied did not induce these markers at cytostatic concentrations. The effects of sodium butyrate (and related short chain fatty acids) thus appear to be relatively specific for this cell line.
Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism. (1995)

The transforming growth factor beta s (TGF-beta s) are a group of multifunctional growth factors which inhibit cell cycle progression in many cell types. The TGF-beta-induced cell cycle arrest has been partially attributed to the regulatory effects of TGF-beta on both the levels and the activities of the G1 cyclins and their kinase partners. The activities of these kinases are negatively regulated by a number of small proteins, p21 (WAF1, Cip1), p27Kip1, p16, and p15INK4B, that physically associate with cyclins, cyclin-dependent kinases, or cyclin-Cdk complexes. p21 has been previously shown to be transcriptionally induced by DNA damage through p53 as a mediator. We demonstrate that TGF-beta also causes a rapid transcriptional induction of p21, suggesting that p21 can respond to both intracellular and extracellular signals for cell cycle arrest. In contrast to DNA damage, however, induction of p21 by TGF-beta is not dependent on wild-type p53. The cell line studied in these experiments, HaCaT, contains two mutant alleles of p53, which are unable to activate transcription from the p21 promoter when overexpressed. In addition, TGF-beta and p53 act through distinct elements in the p21 promoter. Taken together, these findings suggest that TGF-beta can induce p21 through a p53-independent pathway. Previous findings have implicated p27Kip1 and p15INK2B as effectors mediating the TGF-beta growth inhibitory effect. These results demonstrate that a single extracellular antiproliferative signal, TGF-beta, can act through multiple signaling pathways to elicit a growth arrest response.
Crosstalk between Chemokine Receptor CXCR4 and Cannabinoid Receptor CB2 in Modulating Breast Cancer Growth and Invasion (2011)

This study provides novel insights into the crosstalk between CB(2) and CXCR4/CXCL12-signaling pathways in the modulation of breast tumor growth and metastasis. Furthermore, these studies indicate that CB(2) receptors could be used for developing innovative therapeutic strategies against breast cancer.
Amplification and sequence analysis of DNA flanking integrated proviruses by a simple two-step polymerase chain reaction method (1993)

We describe a two-step polymerase chain reaction method that can be used for the amplification of cellular DNA sequences adjacent to an integrated retroviral provirus. The technique involves a partly degenerate, arbitrary primer that will hybridize in the provirus-flanking cellular DNA. By using this primer in combination with a biotinylated provirus-specific primer, a provirus-cellular DNA junction fragment can be isolated from the nonspecific amplification products by using streptavidin-coated magnetic beads. A second amplification employing a nested provirus-specific primer and a biotinylated nondegenerate primer derived from the partly degenerate primer followed by purification with streptavidin-coated beads enhances the specificity and the efficiency of recovery of a fragment(s) containing the unknown flanking sequences. In addition to being relevant in studies of viral integration sites, the method should be generally useful to analyze DNA sequences either upstream or downstream from a known sequence.
QSPR Studies on Aqueous Solubilities of Drug-Like Compounds (2009)

A rapidly growing area of modern pharmaceutical research is the prediction of aqueous solubility of drug-sized compounds from their molecular structures. There exist many different reasons for considering this physico-chemical property as a key parameter: the design of novel entities with adequate aqueous solubility brings many advantages to preclinical and clinical research and development, allowing improvement of the Absorption, Distribution, Metabolization, and Elimination/Toxicity profile and "screenability" of drug candidates in High Throughput Screening techniques. This work compiles recent QSPR linear models established by our research group devoted to the quantification of aqueous solubilities and their comparison to previous research on the topic.
Chemical Characterization of Crude Petroleum Using Nanospray Desorption Electrospray Ionization Coupled with High-Resolution Mass Spectrometry (2011)

Nanospray desorption electrospray ionization (nano-DESI) combined with high-resolution mass spectrometry was used for the first time for the analysis of the polar constituents of liquid petroleum crude oil samples. The analysis was performed in both positive and negative ionization modes using three solvents, one of which (acetonitrile/toluene mixture) is commonly used in petroleomics studies while two other polar solvents (acetonitrile/water and methanol/water mixtures) are generally not compatible with petroleum characterization using mass spectrometry. The results demonstrate that nano-DESI analysis efficiently ionizes petroleum constituents soluble in a particular solvent. When acetonitrile/toluene is used as a solvent, nano-DESI generates electrospray-like spectra. In contrast, strikingly different spectra were obtained using acetonitrile/water and methanol/water. Comparison with the literature data indicates that these solvents selectively extract water-soluble constituents of the crude oil. Water-soluble compounds are predominantly observed as sodium adducts in nano-DESI spectra indicating that addition of sodium to the solvent may be a viable approach for efficient ionization of water-soluble crude oil constituents. Nano-DESI enables rapid screening of different classes of compounds in crude oil samples based on their solubility in solvents that are rarely used for petroleum characterization providing better coverage of the crude oil composition as compared to electrospray ionization (ESI). It also enables rapid characterization of water-soluble components of petroleum samples that is difficult to perform using traditional approaches.
DNA microarrays in medical practice (2001)

The completion of the draft sequence of the human genome 1 2 has raised public awareness of "genomics" and of the ways in which the emerging technologies of the genomics "revolution" will have direct applications to patient care. 3DNA microarrays, or biochips, are prominent among these new technologies.The past five years have seen a dramatic rise in the use of DNA microarrays for biomedical research, in some cases with immediate applicability to clinical practice.The uses of microarrays for gene expression profiling, genotyping, mutation detection, and gene discovery are leading to remarkable insights into the function of thousands of genes previously known only by their gene sequence.This review discusses ways in which microarrays have started to affect clinical practice and research and how this role will develop in the next five to 10 years. MethodsThe data for this review reflect my personal views from 10 years of research in molecular medicine and five years on DNA microarrays.My views have developed over this period from discussions with colleagues in my own laboratory and at basic science and biotechnology meetings and from regular reading of Nature Genetics, Nature, Science, and other journals.
The Probabilistic Active Shape Model: From Model Construction to Flexible Medical Image Segmentation (2013)

Automatic processing of three-dimensional image data acquired with computed tomography or magnetic resonance imaging plays an increasingly important role in medicine. For example, the automatic
segmentation of anatomical structures in tomographic images allows to generate three-dimensional visualizations of a patient’s anatomy and thereby supports surgeons during planning of various kinds of
surgeries.

Because organs in medical images often exhibit a low contrast to adjacent structures, and because the image quality may be hampered by noise or other image acquisition artifacts, the development of segmentation algorithms that are both robust and accurate is very challenging. In order to increase the robustness, the use of model-based algorithms is mandatory, as for example algorithms that incorporate prior knowledge about an organ’s shape into the segmentation process. Recent research has proven that Statistical Shape Models are especially appropriate for robust medical image segmentation. In these models, the typical shape of an organ is learned from a set of training examples. However, Statistical Shape Models have two major disadvantages: The construction of the models is relatively difficult, and the models are often used too restrictively, such that the resulting segmentation does not delineate the organ exactly.

This thesis addresses both problems: The first part of the thesis introduces new methods for establishing correspondence between training shapes, which is a necessary prerequisite for shape model learning. The developed methods include consistent parameterization algorithms for organs with spherical and genus 1 topology, as well as a nonrigid mesh registration algorithm for shapes with arbitrary topology. The second part of the thesis presents a new shape model-based segmentation algorithm that allows for an accurate delineation of organs. In contrast to existing approaches, it is possible to integrate not only linear shape models into the algorithm, but also nonlinear shape models, which allow for a more specific description of an organ’s shape variation.

The proposed segmentation algorithm is evaluated in three applications to medical image data: Liver and vertebra segmentation in contrast-enhanced computed tomography scans, and prostate segmentation in magnetic resonance images.
Relationship between beta-globin gene carrier state and insulin resistance (2012)

The risk of developing diabetes and insulin resistance in patients with thalassemia minor is two times greater than the general population. Considering the high serum levels of CRP in these cases, the inflammation noted in liver cells could be considered as the underlying cause of insulin resistance, impaired glucose tolerance and diabetes in these patients.
The Product of the Human c- erb B-2 Gene: a 185-Kilodalton Glycoprotein with Tyrosine Kinase Activity (1986)

Antibodies were raised against a synthetic peptide corresponding to 14 amino acid residues at the COOH-terminus of a protein deduced from the human c-erbB-2 nucleotide sequence. These antibodies immunoprecipitated a 185-kilodalton glycoprotein from MKN-7 adenocarcinoma cells. Incubation of the immunoprecipitates with (gamma-32P)ATP resulted in the phosphorylation of this protein on tyrosine residues. These results indicate that the human c-erbB-2 gene product is the 185-kilodalton glycoprotein that is associated with tyrosine kinase activity. Although the c-erbB-2 protein was predicted to encode a protein very similar to epidermal growth factor (EGF) receptor, EGF did not stimulate this kinase activity either in vivo or in vitro.
Differential Effects of Retinoic Acid and N‐(4‐hydroxyphenyl)retinamide on Head and Neck Squamous Cell Carcinoma Cells (1996)

Both retinoic acid (RA) and the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) have shown efficacy in head and neck cancer chemoprevention trials. To compare their activity and mechanism of action, the 1483 oral head and neck squamous cell carcinoma (HNSCC) cell line was grown in organotypic culture, an in vitro system that allows cellular stratification and simulates carcinoma in situ, and was exposed to 10 micromol/L of either RA or 4HPR. Extensive apoptosis, as evidenced by in situ deoxyribonucleic acid end-labeling, occurred in 4HPR-treated cultures after 9 days, with >80% cell loss (P< .001). In contrast, the growth of cultures treated with RA was inhibited by only 32%, with no evidence of apoptosis. Because 4HPR has low systemic toxicity and is a potent inducer of apoptosis in HNSCC cells, its role in chemoprevention of head and neck cancers, including cancers that are resistant to RA-induction therapy, warrants further investigation.