gebhart/patrepeval huggingface dataset:
Molecular Cloning of the Type 5, Iron-containing, Tartrate-resistant Acid Phosphatase from Human Placenta (1989)

The type 5, iron-containing, tartrate-resistant acid phosphatase (TR-AP) constitutes a relatively minor intracellular isozyme of acid phosphatase in the human that is immunologically related to uteroferrin, a secreted progesterone-induced protein of the porcine uterus. Here, the purification of small amounts of TR-AP from human placenta is described. When a placental lambda gt11 cDNA library was screened with two short 32P-labeled cDNA clones from within the coding region of uteroferrin, a 1412-base pair cDNA was identified that encodes the entire human TR-AP isozyme. This cDNA contains an open reading frame of 969 base pairs, corresponding to a protein of 323 amino acids. A putative signal sequence of 19 amino acids and two potential glycosylation sites are present. The deduced amino acid sequence of the human TR-AP is 85% identical to that of porcine uteroferrin (whose sequence is also reported here in complete form for the first time) and 82% identical to the corresponding regions of a partial amino acid sequence of a bovine spleen phosphoprotein phosphatase. Northern blotting techniques employing a labeled TR-AP cDNA probe revealed the presence of a 1.5-kilobase transcript in white cells from a patient with hairy cell leukemia, in human K562 erythroleukemic cells, and in Epstein-Barr virus-transformed human B-cells, but not in a human T-cell line. Culture of K562 cells in presence of 10(-8) M phorbol 12-myristate 13-acetate ester for 48-72 h enhanced TR-AP activity per cell about 30-fold and led to a corresponding increase in TR-AP mRNA levels.
Neuromodulation for Brain Disorders: Challenges and Opportunities (2013)

The field of neuromodulation encompasses a wide spectrum of interventional technologies that modify pathological activity within the nervous system to achieve a therapeutic effect. Therapies including deep brain stimulation, intracranial cortical stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation have all shown promising results across a range of neurological and neuropsychiatric disorders. While the mechanisms of therapeutic action are invariably different among these approaches, there are several fundamental neuroengineering challenges that are commonly applicable to improving neuromodulation efficacy. This paper reviews the state-of-the-art of neuromodulation for brain disorders and discusses the challenges and opportunities available for clinicians and researchers interested in advancing neuromodulation therapies.
Radioligand binding methods: practical guide and tips (1993)

Radioligand binding assays are a relatively simple but extremely powerful tool for studying receptors. They allow an analysis of the interactions of hormones, neurotransmitters, growth factors, and related drugs with the receptors, studies of receptor interactions with second messenger systems, and characterization of regulatory changes in receptor number, subcellular distribution, and physiological function. As a result, these assays are widely used (and often misused) by investigators in a variety of disciplines, including pharmacology, physiology, biochemistry, immunology, and cell biology. This article presents a broad overview of the radioligand binding assay technique, primarily for the investigator who has limited experience with this technique. Practical guidelines for setting up a new assay are presented, including the receptor preparation to be used, choice of appropriate radioligand, optimizing assay conditions, and appropriate methods for data analysis. Tips for avoiding some of the common pitfalls in application of these assays are also included. The primary focus is on radioligand binding assays of membrane-bound receptors studied in membrane preparations. However, similar assay techniques can be used to study receptors on intact cells. The unique advantages and disadvantages of these intact cell binding assays are also discussed. In particular, the occurrence of regulatory changes in receptors during the course of intact cell binding assays is considered, with approaches for circumventing these complications and for using intact cell assays to advantage in studying these regulatory changes.
Strategies for treating HIV-related lipodystrophy (2001)

HIV-related lipodystrophy has emerged as one of the most prevalent problems for patients with HIV, since this infection can now be seen as a chronic disease. Despite its growing importance, crucial issues such as aetiopathogenesis, diagnosis, prevention and therapy remain largely unknown and unexplored. Current evidence suggests that aetiology is multifactorial. HIV infection, antiretroviral therapy and patient-related factors probably all contribute to the development of lipodystrophy. The lack of a formal definition and the nature of wasting syndromes that affect HIV-infected patients can hinder the diagnosis and treatment of lipodystrophy. Body fat changes have a major negative impact on the quality of life of patients. Metabolic abnormalities are also well known cardiovascular risk factors that can increase the morbidity and mortality due to cardiovascular disorders in a relatively young population. As yet, we do not know whether lipodystrophy is preventable or reversible. Several therapeutic approaches have been tested with limited success, however potential complications must be considered. These therapeutic approaches include general health measures (diet, exercise and discontinuation of smoking), switching antiretrovirals (from protease inhibitors to non-nucleoside reverse transcriptase inhibitors or abacavir, or from stavudine to other nucleoside reverse transcriptase inhibitors) and use of drugs with metabolic effects (metformin, thiazolidinediones, recombinant growth hormone and anabolic steroids). A judicious use of available data, and opting for an individualised approach seems the best option for management of this problem at present.
Efficient Phantom Source Widening (2013)

Abstract We present a highly efficient filter structure to create power-complementary filter pairs for phantom source widening. It either introduces frequency-dependent phase or amplitude differences in a pair of loudspeaker signals. We evaluate how the perceptual effect is influenced by off-center listening positions in a standard ±30° loudspeaker setup. The evaluation of the phantom source widening effect is based on measurements of the inter-aural cross-correlation coefficient (IACC), which is justified by its pronounced correlation to the perceived phantom source width in prior listening test results.
Costimulation Through CD86 Is Involved in Airway Antigen-Presenting Cell and T Cell Responses to Allergen in Atopic Asthmatics (1998)

Atopic allergic asthma is characterized by activation of Th2-type T cells in the bronchial mucosa. Previous reports have suggested an important role for costimulation through the CD28/CTLA4-CD80/CD86 pathway in allergen activation of T cells in animal models of inhaled allergen challenge. However, human allergen-specific lines and clones were reported to be costimulation independent. We therefore examined CD80 and CD86 dependence of allergen-induced T cell proliferation and cytokine production in peripheral blood and bronchoalveolar lavage from atopic asthmatic subjects and controls. Both allergen-induced proliferation and IL-5 production from PBMC were inhibited by CTLA4-Ig fusion protein and anti-CD86, but not anti-CD80 mAbs. When allergen-specific CD4+ T cell lines from peripheral blood were examined, proliferation and cytokine production were found to be independent of CD80 or CD86 costimulation. However, when cells obtained directly from the airways were examined, allergen-induced proliferation of bronchoalveolar lavage T cells from atopic asthmatic subjects was inhibited by anti-CD86 but not anti-CD80. In addition, bronchoalveolar lavage-adherent cells from asthmatic, but not control subjects showed APC activity to autologous T cells. This was also inhibited by anti-CD86 but not anti-CD80. Thus allergen-induced T cell activation and IL-5 production in the airway in asthmatic subjects is susceptible to blockade by agents interfering with costimulation via CD86, and this may hold therapeutic potential in asthma.
One Permutation Hashing (2012)

Minwise hashing is a standard procedure in the context of search, for efficiently estimating set similarities in massive binary data such as text. Recently, b-bit minwise hashing has been applied to large-scale learning and sublinear time nearneighbor search. The major drawback of minwise hashing is the expensive preprocessing, as the method requires applying (e.g.,) k = 200 to 500 permutations on the data. This paper presents a simple solution called one permutation hashing. Conceptually, given a binary data matrix, we permute the columns once and divide the permuted columns evenly into k bins; and we store, for each data vector, the smallest nonzero location in each bin. The probability analysis illustrates that this one permutation scheme should perform similarly to the original (k-permutation) minwise hashing. Our experiments with training SVM and logistic regression confirm that one permutation hashing can achieve similar (or even better) accuracies compared to the k-permutation scheme. See more details in arXiv:1208.1259. 1
IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells (2007)

IL-21, a recently identified member of the common gamma-chain (gammac) receptor cytokine family, has been shown to be an important regulator of both innate and adaptive immune responses. In this study, we investigated whether IL-21 could synergize with another gammac cytokine, IL-7, to induce enhanced proliferation and effector function of tumor antigen-specific CD8(+) T cells. Our results showed that IL-21 could significantly augment the IL-7-induced expansion of cytotoxic T cells, possibly by preventing the cytokine-induced down-regulation of the IL-7Ralpha (CD127) on antigen-stimulated T cells. IL-21 also greatly enhanced the production of T(h)1 and inflammatory cytokines by activated T cells, including IFN-gamma, IL-2, tumor necrosis factor-alpha, granulocyte macrophage colony-stimulating factor, IL-1beta and IL-6. Finally, the addition of IL-21 to IL-7-cultured CTLs resulted in a considerably higher level of cytolytic activity, as measured by specific killing of tumor cells or antigen-pulsed target cells. These results suggest that IL-21 may play a cooperative role with IL-7 in modulating primary CD8(+) T-cell responses and may have important implications for immunotherapy of cancer.
Population density‐dependent regulation of exopolysaccharide formation in the hyperthermophilic bacterium Thermotoga maritima (2004)

Co-cultivation of the hyperthermophiles Thermotoga maritima and Methanococcus jannaschii resulted in fivefold higher T. maritima cell densities when compared with monoculture as well as concomitant formation of exopolysaccharide and flocculation of heterotroph-methanogen cellular aggregates. Transcriptional analysis of T. maritima cells from these aggregates using a whole genome cDNA microarray revealed the induction of a putative exopolysaccharide synthesis pathway, regulated by intracellular levels of cyclic diguanosine 3',5'-(cyclic)phosphate (cyclic di-GMP) and mediated by the action of several GGDEF proteins, including a putative diguanylate cyclase (TM1163) and a putative phosphodiesterase (TM1184). Transcriptional analysis also showed that TM0504, which encodes a polypeptide containing a motif common to known peptide-signalling molecules in mesophilic bacteria, was strongly upregulated in the co-culture. Indeed, when a synthetically produced peptide based on TM0504 was dosed into the culture at ecologically relevant levels, the production of exopolysaccharide was induced at significantly lower cell densities than was observed in cultures lacking added peptide. In addition to identifying a pathway for polysaccharide formation in T. maritima, these results point to the existence of peptide-based quorum sensing in hyperthermophilic bacteria and indicate that cellular communication should be considered as a component of the microbial ecology within hydrothermal habitats.
Introducing Microsoft .Net (2002)

From the Publisher:
Microsoft .NET is an innovative software framework that promises to change software development as we know it. This book answers the question What is Microsoft .NET and how do I profit from it? The author breaks this question down into What problems does Microsoft .NET solve?; What architectural approaches does it take to solve them?; and How do I get started using it? Each chapter is written in a logical, pyramidal format, with simpler, high-level concepts introduced first, followed by a more detailed technical discussion, so readers can easily choose how deep they wish to go into each chapter. As the author progressively adds to the depth of Microsoft .NET information in each chapter, he uses diagrams and a small amount of code in the Microsoft Visual Basic development system to make his points.
Glutathione and thioredoxin systems contribute to recombinant monoclonal antibody interchain disulfide bond reduction during bioprocessing (2017)

Antibody interchain disulfide bond reduction during biopharmaceutical manufacturing has received increased attention since it was first reported in 2010. Antibody reduction leads to loss of product and reduced product stability. It is therefore critical to understand the underlying mechanisms of reduction. To date, the thioredoxin system has been reported as the sole contributor to antibody reduction during bioprocessing. In this work, we show that the glutathione system, in addition to the thioredoxin system, is involved in reducing antibody molecules and the contributions of the two systems can vary depending upon the cell culture process. The roles of the glutathione and thioredoxin systems were evaluated for three molecules with different IgG subclass where reduction was observed during manufacturing: mAb A, mAb B, and mAb C representing an IgG<sub>1</sub> , IgG<sub>2</sub> , and IgG<sub>4,</sub> respectively. The expression of enzymes for both the thioredoxin and glutathione systems were confirmed in all three cell lines. Inhibitors were evaluated using purified mammalian reductases to evaluate their specificity. The optimized experimental conditions enabled both the determination of reductase activity contributed from as well as the amount of antibody reduced by each enzymatic system. Our results demonstrate that the underlying enzymatic mechanisms are different depending upon the cell culture process; one of the two systems may be the dominant mechanism, or both enzymatic systems may be involved. Specifically, the glutathione system was found to be the major contributor to mAb A reduction while the thioredoxin system was the major contributor to mAb C reduction. Intriguingly, mAb B experienced significant reduction from both enzymatic systems. In summary, we have demonstrated that in addition to the thioredoxin pathway, the glutathione system is a second major pathway contributing to antibody reduction and this knowledge can be leveraged to develop more specific antibody reduction mitigation strategies targeted at the dominant reduction mechanism. Biotechnol. Bioeng. 2017;114: 1469-1477. © 2017 Wiley Periodicals, Inc.
Macromolecular Modeling with Rosetta (2008)

Advances over the past few years have begun to enable prediction and design of macromolecular structures at near-atomic accuracy. Progress has stemmed from the development of reasonably accurate and efficiently computed all-atom potential functions as well as effective conformational sampling strategies appropriate for searching a highly rugged energy landscape, both driven by feedback from structure prediction and design tests. A unified energetic and kinematic framework in the Rosetta program allows a wide range of molecular modeling problems, from fibril structure prediction to RNA folding to the design of new protein interfaces, to be readily investigated and highlights areas for improvement. The methodology enables the creation of novel molecules with useful functions and holds promise for accelerating experimental structural inference. Emerging connections to crystallographic phasing, NMR modeling, and lower-resolution approaches are described and critically assessed.
Rationally Designed TLR4 Ligands for Vaccine Adjuvant Discovery (2017)

Adjuvant properties of bacterial cell wall components like MPLA (monophosphoryl lipid A) are well described and have gained FDA approval for use in vaccines such as Cervarix. MPLA is the product of chemically modified lipooligosaccharide (LOS), altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are few. We have developed bacterial enzymatic combinatorial chemistry (BECC) as a method to generate rationally designed, functionally diverse lipid A. BECC removes endogenous or introduces exogenous lipid A-modifying enzymes to bacteria, effectively reprogramming the lipid A biosynthetic pathway. In this study, BECC is applied within an avirulent strain of <i>Yersinia pestis</i> to develop structurally distinct LOS molecules that elicit differential Toll-like receptor 4 (TLR4) activation. Using reporter cell lines that measure NF-κB activation, BECC-derived molecules were screened for the ability to induce a lower proinflammatory response than <i>Escherichia coli</i> LOS. Their structures exhibit varied, dose-dependent, TLR4-driven NF-κB activation with both human and mouse TLR4 complexes. Additional cytokine secretion screening identified molecules that induce levels of tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) comparable to the levels induced by phosphorylated hexa-acyl disaccharide (PHAD). The lead candidates demonstrated potent immunostimulation in mouse splenocytes, human primary blood mononuclear cells (PBMCs), and human monocyte-derived dendritic cells (DCs). This newly described system allows directed programming of lipid A synthesis and has the potential to generate a diverse array of TLR4 agonist candidates.<b>IMPORTANCE</b> There is an urgent need to develop effective vaccines against infectious diseases that continue to be major causes of morbidity and mortality worldwide. Making effective vaccines requires selecting an adjuvant to strengthen an appropriate and protective immune response. This work describes a practical method, bacterial enzymatic combinatorial chemistry (BECC), for generating functionally diverse molecules for adjuvant use. These molecules were analyzed in cell culture for their ability to initiate immune stimulatory activity. Several of the assays described herein show promising <i>in vitro</i> cytokine production and costimulatory molecule expression results, suggesting that the BECC molecules may be useful in future vaccine preparations.
Noise reduction for magnetic resonance images via adaptive multiscale products thresholding (2003)

Edge-preserving denoising is of great interest in medical image processing. This paper presents a wavelet-based multiscale products thresholding scheme for noise suppression of magnetic resonance images. A Canny edge detector-like dyadic wavelet transform is employed. This results in the significant features in images evolving with high magnitude across wavelet scales, while noise decays rapidly. To exploit the wavelet interscale dependencies we multiply the adjacent wavelet subbands to enhance edge structures while weakening noise. In the multiscale products, edges can be effectively distinguished from noise. Thereafter, an adaptive threshold is calculated and imposed on the products, instead of on the wavelet coefficients, to identify important features. Experiments show that the proposed scheme better suppresses noise and preserves edges than other wavelet-thresholding denoising methods.
An HLA-A2-restricted tyrosinase antigen on melanoma cells results from posttranslational modification and suggests a novel pathway for processing of membrane proteins. (1996)

T lymphocytes recognize antigens consisting of peptides presented by class I and II major histocompatibility complex (MHC) molecules. The peptides identified so far have been predictable from the amino acid sequences of proteins. We have identified the natural peptide target of a CTL clone that recognizes the tyrosinase gene product on melanoma cells. The peptide results from posttranslational conversion of asparagine to aspartic acid. This change is of central importance for peptide recognition by melanoma-specific T cells, but has no impact on peptide binding to the MHC molecule. This posttranslational modification has not been previously described for any MHC-associated peptide and represents the first demonstration of posttranslational modification of a naturally processed class I-associated peptide. This observation is relevant to the identification and prediction of potential peptide antigens. The most likely mechanism for production of this peptide leads to the suggestion that antigenic peptides can be derived from proteins that are translated into the endoplasmic reticulum.
Extraordinarily slow nuclear spin relaxation in frozen laser-polarizedXe129 (1993)

We studied the very slow nuclear spin-lattice relaxation of solid $^{129}\mathrm{Xe}$ as a function of temperature and magnetic field using laser-polarized nuclei. Relaxation times in excess of 500 h were measured. We present evidence for a new relaxation mechanism which results from a Raman spin-phonon scattering process involving the spin-rotation interaction. We also establish the existence of cross relaxation between $^{129}\mathrm{Xe}$ and the other magnetic isotope $^{131}\mathrm{Xe}$ and demonstrate that laser-polarized $^{129}\mathrm{Xe}$ can be used to cross polarize other nuclei that are present in the lattice.
Conditional human VEGF-mediated vascularization in chicken embryos using a novel temperature-inducible gene regulation (TIGR) system (2003)

Advanced heterologous transcription control systems for adjusting desired transgene expression are essential for gene function assignments, drug discovery, manufacturing of difficult to produce protein pharmaceuticals and precise dosing of gene-based therapeutic interventions. Conversion of the Streptomyces albus heat shock response regulator (RheA) into an artificial eukaryotic transcription factor resulted in a vertebrate thermosensor (CTA; cold-inducible transactivator), which is able to adjust transcription initiation from chimeric target promoters (P(CTA)) in a low-temperature- inducible manner. Evaluation of the temperature-dependent CTA-P(CTA) interaction using a tailored ELISA-like cell-free assay correlated increased affinity of CTA for P(CTA) with temperature downshift. The temperature-inducible gene regulation (TIGR) system enabled tight repression in the chicken bursal B-cell line DT40 at 41 degrees C as well as precise titration of model product proteins up to maximum expression at or below 37 degrees C. Implantation of microencapsulated DT40 cells engineered for TIGR-controlled expression of the human vascular endothelial growth factor A (hVEGF121) provided low-temperature-induced VEGF-mediated vascularization in chicken embryos.