gebhart/patrepeval huggingface dataset:
Integrin alpha v beta 3 rescues melanoma cells from apoptosis in three-dimensional dermal collagen. (1994)

Human melanoma cells required ligation of the integrin alpha v beta 3 to sustain viability and growth in three-dimensional dermal collagen. Variant melanoma cells, lacking the alpha v subunit, progressed rapidly to apoptosis within this matrix, whereas transfection of these cells with an alpha v cDNA restored alpha v beta 3 expression and prevented apoptosis. Furthermore, inhibition of alpha v beta 3 ligation with a monoclonal antibody promoted cell death. Apoptosis of alpha v(-) cells within this matrix could be overcome by the addition of insulin or serum. However, alpha v(+) melanoma cells had a significant growth advantage in the presence of these growth factors. Initial adhesion of the melanoma cells to type I collagen depended on ligation of alpha 2 beta 1, but these cells can degrade this collagen to expose cryptic alpha v beta 3 binding sites. These findings provide evidence that the survival and growth of transformed cells may be regulated by collagen degradation and integrin-dependent anchorage to this proteolysed matrix.
Large‐scale propagation of four undifferentiated human embryonic stem cell lines in a feeder‐free culture system (2005)

We describe an improved and more robust protocol for transfer and subsequent propagation of human embryonic stem cells under feeder-free conditions. The results show that mechanical dissociation for transfer of the human embryonic stem cells to Matrigel resulted in highest survival rates. For passage of the cultures on the other hand, enzymatic dissociation was found to be most efficient. In addition, this method reduces the time, work, and skills needed for propagation of the human embryonic stem cells. With the present protocol, the human embryonic stem cells have been cultured under feeder-free conditions for up to 35 passages while maintaining a normal karyotype, stable proliferation rate, and high telomerase activity. Furthermore, the feeder-free human embryonic stem cell cultures express the transcription factor Oct-4, alkaline phosphatase, and cell surface markers SSEA-3, SSEA-4, Tra 1-60, Tra 1-81, and formed teratomas in severe combined immunodeficient mice. This method provides distinct advantages compared with previous protocols and make propagation of human embryonic stem cells less laborious and more efficient.
Mechanism of acylphosphatase inactivation by Woodward's reagent K (1997)

The organ common-type (CT) isoenzyme of acylphosphatase is inactivated by Woodward's reagent K (WRK) (N-ethyl-5-phenylisoxazolium-3'-sulphonate) at pH6.0. The inactivation reaction follows apparent pseudo first-order kinetics. The dependence of the reciprocal of the pseudo first-order kinetic constant (kobs) on the reciprocal WRK concentration reveals saturation kinetics, suggesting that the WRK forms a reversible complex with the enzyme before causing inactivation. Competitive inhibitors, such as inorganic phosphate and ATP, protect the enzyme from WRK inactivation, suggesting that this reagent acts at or near to the enzyme active site. The reagent-enzyme adduct, which elicits a strong absorption band with lambdamax at 346 nm, was separated from unreacted enzyme by reverse phase HPLC and the modified protein was cleaved with endoproteinase Glu-C to produce fragments. The HPLC fractionation gave two reagent-labelled peptides (peak 1 and peak 2) that were analysed by ion-spray MS and sequenced. The former is VFFRKHTQAE (residues 20-29 of human CT acylphosphatase) and the latter IFGKVQGVFFRKHTQAE (residues 13-29). MS demonstrated that both peptides are WRK adducts. A fragment ion with m/z of 1171, which is present in the mass spectrum of peak 1, has been identified as a WRK adduct of the peptide fragment 20-26. The lambdamax at 346 nm of WRK adduct suggests that the modified residue is His-25. Five recombinant enzymes mutated in residues included in the 20-29 polypeptide stretch have been produced. Analysis of their reactivities with WRK demonstrates that His-25 is the molecular target of the reagent as its modification causes the inactivation of the enzyme. Since both His-25-->Gln and His-25-->Phe mutants maintain high catalytic activity, we suggest that the observed enzyme inactivation is caused by the reagent (covalently bound to His-25), which shields the active site.
Multiple Cancer/Testis Antigens Are Preferentially Expressed in Hormone-Receptor Negative and High-Grade Breast Cancers (2011)

CT antigens are preferentially expressed in hormone receptor-negative and high-grade breast cancer. Considering the limited treatment options for ER/PR/HER2 triple-negative breast cancer, the potential of CT-based immunotherapy should be explored.
THE PRODUCTION OF HYDROGEN SULFIDE LIMITS MYOCARDIAL ISCHEMIA AND REPERFUSION INJURY AND CONTRIBUTES TO THE CARDIOPROTECTIVE EFFECTS OF PRECONDITIONING WITH ENDOTOXIN, BUT NOT ISCHEMIA IN THE RAT (2006)

We investigated whether (endogenous) hydrogen sulfide (H2S) protects the heart against myocardial ischemia and reperfusion injury. Furthermore, we investigated whether endogenous H2S is involved in the protection afforded by (1) ischemic preconditioning and (2) the second window of protection caused by endotoxin. The involvement of one of the potential (end) effectors of the cardioprotection afforded by H2S was investigated using the mitochondrial KATP channel blocker, 5-hydroxydecanoate (5-HD; 5 mg/kg). Animals were subjected to 25 min regional myocardial ischemia followed by reperfusion (2 h) and were pretreated with the H2S donor, sodium hydrosulfide (3 mg/kg i.v.). Animals were also subjected to shorter periods of myocardial ischemia (15 min) and reperfusion (2 h) and pretreated with an irreversible inhibitor of cystathionine-gamma-lyase, dl-propargylglycine (PAG; 50 mg/kg i.v.). Animals were also pretreated with PAG (50 mg/kg) and subjected to either (1) ischemic preconditioning or (2) endotoxin (1 mg/kg i.p.) 16 h before myocardial ischemia. Myocardial infarct size was determined by p-nitroblue tetrazolium staining. Administration of sodium hydrosulfide significantly reduced myocardial infarct size, and this effect was abolished by 5-HD. Administration of PAG (50 mg/kg) or 5-HD significantly increased infarct size caused by 15 min of myocardial ischemia. The delayed cardioprotection afforded by endotoxin was abolished by 5-HD or PAG. In contrast, PAG (50 mg/kg) did not affect the cardioprotective effects of ischemic preconditioning. These findings suggest that (1) endogenous H2S is produced by myocardial ischemia in sufficient amounts to limit myocardial injury and (2) the synthesis or formation of H2S by cystathionine-gamma-lyase may contribute to the second window of protection caused by endotoxin.
Identification and purification to near homogeneity of the vitamin K-dependent carboxylase. (1991)

Vitamin K-dependent carboxylase catalyzes the modification of specific glutamic acids to gamma-carboxyglutamic acid in several blood-coagulation proteins. This modification is required for the blood-clotting activity of these proteins and has thus been the subject of intense investigation. We have now identified the bovine vitamin K-dependent carboxylase and purified it to near homogeneity by an affinity procedure that uses the 59-amino acid peptide FIXQ/S (residues -18 to 41 of factor IX with mutations Arg----Gln at residue -4 and Arg----Ser at residue -1). The carboxylase as purified has a molecular weight of 94,000. It is also the major protein that can be cross-linked to iodinated FIXQ/S and is the only protein whose cross-linking is prevented by a synthetic factor IX propeptide. The degree of purification is about 7000-fold with reference to ammonium sulfate-fractionated microsomal protein from liver.
Presence of cystine-containing antifreeze proteins in the spruce bud worm, Choristoneura fumiferana (1983)

Using a trichloroacetic acid precipitation procedure and gel permeation high performance liquid chromatography, we have demonstrated the presence of an antifreeze protein in the second instar larvae of the spruce budworm Choristoneura fumiferana. This protein contained a significant amount of half-cystine and only a modest content of alanine. In a radioimmunoassay, it competed with antisera against a cystine-containing antifreeze protein from sea raven, Hemitripterus americanus, thus indicating their immunological cross-reactivity and possibly, some structural homology.
Modulation of Toll‐like Receptor 9 Responses through Synthetic Immunostimulatory Motifs of DNA (2003)

Bacterial, plasmid, and synthetic DNA containing unmethylated CpG dinucleotides in specific sequence contexts activate the vertebrate innate immune system. A pattern recognition receptor (PRR), toll-like receptor 9 (TLR9), recognizes CpG DNA and activates signaling cascade leading to the secretion of a number of cytokines and chemokines. Our extensive structure-immunostimulatory activity relationship studies showed that a number of synthetic pyrimidine (Y) and purine (R) nucleotides are accepted by the receptor as substitutes for natural deoxycytidine and deoxyguanosine in a CpG dinucleotide. These studies permitted development of synthetic immunostimulatory motifs YpG, CpR, and YpR and established the nucleotide motif recognition pattern of the receptor. A number of site-specific chemical modifications in the flanking sequences to the CpG dinucleotide permitted modulation of immunostimulatory affects in a predictable manner. Our studies also showed that TLR9 recognizes and reads the CpG DNA sequence from the 5'-end. Design of oligonucleotides with two 5'-ends, immunomers, resulted in potent immunomodulatory agents with distinct cytokine profiles. Immunomers containing synthetic immunostimulatory motifs produced different cytokine induction profiles compared with natural CpG motifs. Importantly, some of these synthetic motifs showed optimal activity in both mouse and human systems without requiring to change sequences, suggesting overriding the species-dependent specificity of the receptor by the use of synthetic motifs. In this article, we review current understanding of structural recognition and functional modulation of TLR9 receptor by second-generation immunomodulatory oligonucleotides and their potential application as wide spectrum therapeutic agents.
A robust stabilization problem of fuzzy control systems and its application to backing up control of a truck-trailer (1994)

A robust stabilization problem for fuzzy systems is discussed in accordance with the definition of stability in the sense of Lyapunov. We consider two design problems: nonrobust controller design and robust controller design. The former is a design problem for fuzzy systems with no premise parameter uncertainty. The latter is a design problem for fuzzy systems with premise parameter uncertainty. To realize two design problems, we derive four stability conditions from a basic stability condition proposed by Tanaka and Sugeno: nonrobust condition, weak nonrobust condition, robust condition, and weak robust condition. We introduce concept of robust stability for fuzzy control systems with premise parameter uncertainty from the weak robust condition. To introduce robust stability, admissible region and variation region, which correspond to stability margin in the ordinary control theory, are defined. Furthermore, we develop a control system for backing up a computer simulated truck-trailer which is nonlinear and unstable. By approximating the truck-trailer by a fuzzy system with premise parameter uncertainty and by using concept of robust stability, we design a fuzzy controller which guarantees stability of the control system under a condition. The simulation results show that the designed fuzzy controller smoothly achieves backing up control of the truck-trailer from all initial positions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Influence of a Perfusing Bath on the Foot of the Cardiac Action Potential (2000)

Recently, Spach et al (Circ Res. 1998;83:1144-1164) measured the transmembrane action potential 150 to 200 microm below the tissue surface during longitudinal and transverse propagation. They found that "during longitudinal propagation there was initial slowing of V(m) [action potential] foot that resulted in deviations from a simple exponential. " (p 1144). They attributed this behavior to the effects of capillaries on propagation. The purpose of this commentary is to show that the perfusing bath plays an important role in determining the time course of the action potential foot, even when the transmembrane potential is measured 150 microm below the tissue surface. Using numerical simulations based on the bidomain model, we find that the action potential foot for transverse propagation is nearly exponential (tau(foot)=314 micros). For longitudinal propagation, the action potential foot is not exponential because of an initial slowing (best-fit tau(foot)=483 micros). We conclude that the perfusing bath must be taken into account when interpreting data showing differences in the shape of the action potential foot with propagation direction, even if the transmembrane potential is measured 150 microm below the tissue surface.
Role of Caveolae and Caveolins in Health and Disease (2004)

Although they were discovered more than 50 years ago, caveolae have remained enigmatic plasmalemmal organelles. With their characteristic "flasklike" shape and virtually ubiquitous tissue distribution, these interesting structures have been implicated in a wide range of cellular functions. Similar to clathrin-coated pits, caveolae function as macromolecular vesicular transporters, while their unique lipid composition classifies them as plasma membrane lipid rafts, structures enriched in a variety of signaling molecules. The caveolin proteins (caveolin-1, -2, and -3) serve as the structural components of caveolae, while also functioning as scaffolding proteins, capable of recruiting numerous signaling molecules to caveolae, as well as regulating their activity. That so many signaling molecules and signaling cascades are regulated by an interaction with the caveolins provides a paradigm by which numerous disease processes may be affected by ablation or mutation of these proteins. Indeed, studies in caveolin-deficient mice have implicated these structures in a host of human diseases, including diabetes, cancer, cardiovascular disease, atherosclerosis, pulmonary fibrosis, and a variety of degenerative muscular dystrophies. In this review, we provide an in depth summary regarding the mechanisms by which caveolae and caveolins participate in human disease processes.
Specificity of OKT4+ cytotoxic T lymphocyte clones. (1982)

OKT4+, HLA-DR-specific CTL were cloned by limiting dilution, and two clones were evaluated. One clone, B8, specifically recognized DR6 antigens, whereas another cloned, C6, recognized an Ia-like determinant on some DR 3, 5, and 6 target cells. Both clones were OKT3+, OKT4+, and OKT8-, and their cytolysis could be blocked by OKT3 and OKT4, but not OKT8, antibodies. A panel of monoclonal antibodies that recognize DR molecules blocked target cell recognition by these OKT+ CTL. Although cloned B8 recognized a DR6-specific determinant, clone C6 appeared to recognize a supratypic determinant that may be common to some DR molecules (e.g., MT2) or possibly another human Ia-like antigen (e.g., SB). The availability of OKT+ CTL clones should help to dissect the Ia-like antigens recognized by human T cells.
Mental disorders detected in an Irish prison sample (1996)

Abstract In the Republic of Ireland, as elsewhere, there have been changes in patterns of health service for people with a mental disorder. Fears are often expressed that these changes have had an impact on the prison population. A total of 109 pre‐trial and 126 sentenced prisoners were randomly selected from a 1992–93 12‐month resident population of male prisoners in the Republic of Ireland's largest prison – Mountjoy. Experienced psychiatrists conducted unstructured and semi‐structured clinical interviews with them and diagnoses were made according to criteria in the American Diagnostic and Statistical Manual (DSM‐III‐R). Rates of major mental illness, mainly functional psychosis, were higher than would be expected for the general population, but it was the prevalence of alcohol and also substance misuse that gave rise for greatest concern about unmet need. In the absence of longitudinal data further comment cannot be made on impressions of increase in psychiatric disorder in Irish prisons in the 1980s and 1990s, but there is certainly a major problem with levels of disorder in the study population, for which health service provision does not appear to be meeting need. Innovations in mental health legislation and practical approaches to such people are urgently required. Copyright © 1996 Whurr Publishers Ltd.
Conserved mechanism of negative gene regulation by extracellular calcium. Parathyroid hormone gene versus atrial natriuretic polypeptide gene. (1992)

We found that a negative calcium-responsive element (nCaRE) originally reported in the human parathyroid hormone gene is conserved among several genes. The results of the present study show that expression of one of the genes, the rat atrial natriuretic polypeptide gene, was negatively regulated in the heart by extracellular calcium by using an in vivo infusion system. Moreover, transfection of the cultured cells revealed that this DNA element conferred negative regulation by extracellular calcium on the reporter gene. It is suggested that there is a gene family whose expression is negatively regulated by extracellular calcium through this conserved DNA motif, nCaRE.
Yeast Physiology and Biotechnology (1998)

Introduction to Yeasts. Yeast Cytology. Yeast Nutrition. Yeast Growth. Yeast Metabolism. Yeast Technology. Index.
Exploring Helical Folding of Oligoureas During Chain Elongation by High‐Resolution Magic‐Angle‐Spinning (HRMAS) NMR Spectroscopy (2008)

The development of novel folding oligomers (foldamers) for biological and biomedical applications requires both precise structural information and appropriate methods to detect folding propensity. However, the synthesis and the systematic conformational investigation of large arrays of oligomers to determine the influence of factors, such as chain length, side chains, and surrounding environment, on secondary structure can be quite tedious. Herein, we show for 2.5-helical N,N'-linked oligoureas (gamma-peptide lineage) that the whole process of foldamer characterization can be accelerated by using high-resolution magic-angle-spinning (HRMAS) NMR spectroscopy. This was achieved by monitoring a simple descriptor of conformational homogeneity (e.g., chemical shift difference between diastereotopic main chain CH2 protons) at different stages of oligourea chain growth on a solid support. HRMAS NMR experiments were conducted on two sets of oligoureas, ranging from dimer to hexamer, immobilized on DEUSS, a perdeuterated poly(oxyethylene)-based solid support swollen in solvents of low to high polarity. One evident advantage of the method is that only minute amount of material is required. In addition, the resonance of the deuterated resin is almost negligeable. On-bead NOESY spectra of high quality and with resolution comparable to that of liquid samples were obtained for longer oligomers, thus allowing detailed structural characterization.
Numerical Simulations of Subsurface Probing in Diffusely Scattering Media Using Spatially Offset Raman Spectroscopy (2005)

We present the first elementary model predicting how Raman intensities vary for a range of experimental variables for spatially offset Raman spectroscopy (SORS), a recently proposed technique for the effective retrieval of Raman spectra of subsurface layers in diffusely scattering media. The model was able to reproduce the key observations made from the first SORS experiments, namely the dependence of Raman signal intensities on the spatial offset between the illumination and collection points and the relative contributions to the overall spectrum from the top layer and sub-layer. The application of the SORS concept to a three-layer system is also discussed. The model also clearly indicates that an annular geometry, rather than a point-collection geometry, which was used in the earlier experiments, would yield much improved data.
Distributed Differential Privacy and Applications (2015)

Recent growth in the size and scope of databases has resulted in more research into making productive use of this data. Unfortunately, a significant stumbling block which remains is protecting the privacy of the individuals that populate these datasets. As people spend more time connected to the Internet, and conduct more of their daily lives online, privacy becomes a more important consideration, just as the data becomes more useful for researchers, companies, and individuals. As a result, plenty of important information remains locked down and unavailable to honest researchers today, due to fears that data leakages will harm individuals. Recent research in differential privacy opens a promising pathway to guarantee individual privacy while simultaneously making use of the data to answer useful queries. Differential privacy is a theory that provides provable information theoretic guarantees on what any answer may reveal about any single individual in the database. This approach has resulted in a flurry of recent research, presenting novel algorithms that can compute a rich class of computations in this setting. In this dissertation, we focus on some real world challenges that arise when trying to provide differential privacy guarantees in the real world. We design and build runtimes that achieve the mathematical differential privacy guarantee in the face of three real world challenges: securing the runtimes against adversaries, enabling readers to verify that the answers are accurate, and dealing with data distributed across multiple domains.
Introduction to Scanning Tunneling Microscopy (2007)

Abstract The scanning tunneling microscope (STM) and the atomic force microscope (AFM), both capable of visualizing and manipulating individual atoms, are the cornerstones of nanoscience and nanotechnology today. The inventors of STM, Gerd Binnig and Heinrich Rohrer, were awarded with the Nobel Prize of physics in 1986. Both microscopes are based on mechanically scanning an atomically sharp tip over a sample surface, with quantum-mechanical tunneling or atomic forces between the tip and the atoms on the sample as the measurable quantities. This book presents the principles of STM and AFM, and the experimental details. Part I presents the principles from a unified point of view: the Bardeen theory of tunneling phenomenon, and the Herring-Landau theory of covalent-bond force. The similarity between those two theories, both rooted from the Heisenberg-Pauling concept of quantum-mechanical resonance, points to the equivalence of tunneling and covalent-bond force. The Tersoff-Hamann model of STM is presented, including the original derivation. The mechanisms of atomic-scale imaging of both STM and AFM are discussed. Part II presents the instrumentation and experimental techniques of STM and AFM, including piezoelectric scanners, vibration isolation, electronics and control, mechanical design, tip treatment and characterization, scanning tunneling spectroscopy, and atomic force detection techniques. Part II ends with illustrative applications of STM and AFM in various fields of research and technology.