gebhart/patrepeval huggingface dataset:
Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013)

Lymphocytes face major metabolic challenges upon activation. They must meet the bioenergetic and biosynthetic demands of increased cell proliferation and also adapt to changing environmental conditions, in which nutrients and oxygen may be limiting. An emerging theme in immunology is that metabolic reprogramming and lymphocyte activation are intricately linked. However, why T cells adopt specific metabolic programs and the impact that these programs have on T cell function and, ultimately, immunological outcome remain unclear. Research on tumor cell metabolism has provided valuable insight into metabolic pathways important for cell proliferation and the influence of metabolites themselves on signal transduction and epigenetic programming. In this Review, we highlight emerging concepts regarding metabolic reprogramming in proliferating cells and discuss their potential impact on T cell fate and function.
Recent trends in drug delivery systems: intranasal drug delivery. (1999)

Nasal route of drug delivery is commonly known for treatment of local ailments like-cold, cough, rhinitis etc. Recently, efforts have been made to deliver various drugs, specially peptides and proteins, through nasal route for systemic use; utilizing the principles and concepts of rate controlled drug delivery and various polymers and absorption promoters. Considering the large number of problems associated with oral, parenteral, rectal and other routes of drug administration and gradual increase in interest of pharmaceutical scientists towards exploring the possibilities of intranasal delivery of various drugs, this article aims at giving an insight into nasal cavity, consideration of factors affecting and strategies to improve drug absorption through nasal route, pharmaceutical dosage forms and delivery systems with examples of some peptides for intra nasal delivery, its advantages and limitations.
UTOPIA: A consultation system for visit-by-visit diabetes management (1996)

UTOPIA (UTilities for OPtimizing Insulin Adjustment) is a prototype computer system proposed to support home data analysis and therapy recommendations for the individual patient. The paper describes methods of analysis and their incorporation into an overall system design that matches the iterative practices at the physician-patient consultation from visit to visit. Four modules support home data display and comparison with clinical measurements; extraction of blood glucose trends and daily cycles using time series analysis, learning relationships between insulin adjustments and changes in time series patterns via a parametric, linear systems model; and advice generation by solving the linear equation for candidate insulin adjustments. Concepts and methods are placed in context, with a discussion of comparable and related research.
Simplifying and streamlining Escherichia coli‐based cell‐free protein synthesis (2011)

Escherichia coli cell-free protein synthesis (CFPS) uses E. coli extracts to make active proteins in vitro. The basic CFPS reaction mixture is comprised of four main reagent components: (1) energy source and CFPS chemicals, (2) DNA encoding the protein of interest, (3) T7 RNA Polymerase (RNAP) for transcription, and (4) cell extract for translation. In this work, we have simplified and shortened the protocols for preparing the CFPS chemical mixture, cell extract, and T7 RNAP. First, we streamlined the workflow for preparing the CFPS chemical solutions by combining all the chemicals into a single reagent mixture, which we call Premix. We showed that productive cell extracts could be made from cells grown in simple shake flasks, and we also truncated the preparation protocol. Finally, we discovered that T7 RNAP purification was not necessary for CFPS. Crude lysate from cells over-expressing T7 RNAP could be used without deleteriously affecting protein production. Using chloramphenicol acetyltransferase (CAT) as a model protein, we showed that these streamlined protocols still support high-yielding CFPS. These simplified procedures save time and offer greater accessibility to our laboratory's CFPS technology.
Global metabolite analysis of yeast: evaluation of sample preparation methods (2005)

Sample preparation is considered one of the limiting steps in microbial metabolome analysis. Eukaryotes and prokaryotes behave very differently during the several steps of classical sample preparation methods for analysis of metabolites. Even within the eukaryote kingdom there is a vast diversity of cell structures that make it imprudent to blindly adopt protocols that were designed for a specific group of microorganisms. We have therefore reviewed and evaluated the whole sample preparation procedures for analysis of yeast metabolites. Our focus has been on the current needs in metabolome analysis, which is the analysis of a large number of metabolites with very diverse chemical and physical properties. This work reports the leakage of intracellular metabolites observed during quenching yeast cells with cold methanol solution, the efficacy of six different methods for the extraction of intracellular metabolites, and the losses noticed during sample concentration by lyophilization and solvent evaporation. A more reliable procedure is suggested for quenching yeast cells with cold methanol solution, followed by extraction of intracellular metabolites by pure methanol. The method can be combined with reduced pressure solvent evaporation and therefore represents an attractive sample preparation procedure for high-throughput metabolome analysis of yeasts.
Haemophilus influenzae Stimulates ICAM-1 Expression on Respiratory Epithelial Cells (2000)

Epithelial cells interact directly with bacteria in the environment and play a critical role in airway defense against microbial pathogens. In this study, we examined the response of respiratory epithelial cells to infection with nontypable Haemophilus influenzae. Using an in vitro cell culture model, we found that epithelial cell monolayers released significant quantities of IL-8 and expressed increased levels of ICAM-1 mRNA and surface protein in response to H. influenzae. In contrast, levels of IL-1beta, TNF-alpha, and MHC class I were not significantly affected, suggesting preferential activation of a specific subset of epithelial genes directed toward defense against bacteria. Induction of ICAM-1 required direct bacterial interaction with the epithelial cell surface and was not reproduced by purified H. influenzae lipooligosaccharide. Consistent with a functional role for this response, induction of ICAM-1 by H. influenzae mediated increased neutrophil adherence to the epithelial cell surface. Furthermore, in an in vivo murine model of airway infection with H. influenzae, increased epithelial cell ICAM-1 expression coincided with increased chemokine levels and neutrophil recruitment in the airway. These results indicate that ICAM-1 expression on human respiratory epithelial cells is induced by epithelial cell interaction with H. influenzae and suggest that an ICAM-1-dependent mechanism can mediate neutrophil adherence to these cells independent of inflammatory mediator release by other cell types. Direct induction of specific epithelial cell genes (such as ICAM-1 and IL-8) by bacterial infection may allow for rapid and efficient innate defense in the airway.
[Vasculitis syndrome]. (2009)

The recent development of biologic therapies capable of selectively targeting components of the immune system has revolutionised the treatment of inflammatory arthritides. The increase in use of biologic agents coupled with the expansion in the knowledge of the pathogenesis of vascular inflammation has led to their application in the treatment of primary systemic vasculitis. Biological therapies appear to have a place in the therapeutic strategy for ANCA-associated systemic vasculitides, at least for patients whose disease is refractory to conventional therapy. The use of biologics as targeted therapies has also, in reverse, improved our understanding of the pathophysiology of vascular inflammation. However, the precise indications for TNFalpha inhibitors or anti-CD20 monoclonal antibodies have not yet been defined. These biologics must be prescribed extremely cautiously and only in trial settings, especially in view of the adverse effects.
Assemblathon 1: A competitive assessment of de novo short read assembly methods (2011)

Low-cost short read sequencing technology has revolutionized genomics, though it is only just becoming practical for the high-quality de novo assembly of a novel large genome. We describe the Assemblathon 1 competition, which aimed to comprehensively assess the state of the art in de novo assembly methods when applied to current sequencing technologies. In a collaborative effort, teams were asked to assemble a simulated Illumina HiSeq data set of an unknown, simulated diploid genome. A total of 41 assemblies from 17 different groups were received. Novel haplotype aware assessments of coverage, contiguity, structure, base calling, and copy number were made. We establish that within this benchmark: (1) It is possible to assemble the genome to a high level of coverage and accuracy, and that (2) large differences exist between the assemblies, suggesting room for further improvements in current methods. The simulated benchmark, including the correct answer, the assemblies, and the code that was used to evaluate the assemblies is now public and freely available from http://www.assemblathon.org/.
Solubility of CO2 in a Choline Chloride + Urea Eutectic Mixture (2008)

The solubility of CO2 in choline chloride + urea eutectic mixtures was determined at 313.15 K, 323.15 K, and 333.15 K under pressures up to 13 MPa. The mole ratios of choline chloride to urea selected were 1:1.5, 1:2, and 1:2.5. The Henry’s constants and enthalpy of solution of the gas were calculated from the solubility data. The solubility of CO2 in the mixtures increased with increasing pressure, and the solubility is more sensitive to pressure in the low-pressure range. The solubility of CO2 in the mixtures decreased with increasing temperature at all the pressures. The enthalpy of solution is negative at all conditions.
HER2 status in non-small cell lung cancer: results from patient screening for enrollment to a phase II study of herceptin. (2003)

Gene amplification and HER2 protein overexpression at the 3+ level appear to be uncommon in NSCLC. The concordance between FISH and IHC 3+ disease was good in this study, in addition, ELISA would have detected several patients without IHC/FISH-positive disease.
Commentary on ‘Resveratrol commonly displays hormesis: Occurrence and biomedical significance’ by Calabrese et al (2010)

Resveratrol, a grape skin and red wine-derived polyphenolic phytoalexin, exhibits hormetic action delivering numerous health benefits at lower doses while being detrimental at higher doses. Epidemiologic and clinical trials need to be based on the clear understanding of hormetic health benefits of resveratrol.
Design and Synthesis of Fluorescent Pilicides and Curlicides: Bioactive Tools to Study Bacterial Virulence Mechanisms (2012)

Pilicides and curlicides are compounds that block the formation of the virulence factors pili and curli, respectively. To facilitate studies of the interaction between these compounds and the pili and curli assembly systems, fluorescent pilicides and curlicides have been synthesized. This was achieved by using a strategy based on structure-activity knowledge, in which key pilicide and curlicide substituents on the ring-fused dihydrothiazolo 2-pyridone central fragment were replaced by fluorophores. Several of the resulting fluorescent compounds had improved activities as measured in pili- and curli-dependent biofilm assays. We created fluorescent pilicides and curlicides by introducing coumarin and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores at two positions on the peptidomimetic pilicide and curlicide central fragment. Fluorescence images of the uropathogenic Escherichia coli (UPEC) strain UTI89 grown in the presence of these compounds shows that the compounds are strongly associated with the bacteria with a heterogeneous distribution.
Approaching The Limit: Can One DNA Oligonucleotide Assemble into Large Nanostructures? (2006)

The long and the short of it: A short oligonucleotide is designed to self-assemble into micrometer-long nanotubes, which further serve as templates to fabricate metallic nanowires. This study addresses the question: what is the minimum number of DNA strands that are required for self-assembly of well-defined DNA nanostructures?
Androgens Alter the Cytokine Profile and Reduce Encephalitogenicity of Myelin-Reactive T Cells (1999)

Adoptive transfer of proteolipid protein 139-151-specific T cell lines was used to examine the role of androgens in regulating T cell cytokine secretion and the severity of experimental autoimmune encephalomyelitis (EAE) in the SJL mouse. In this study, we found that T cells from female mice transferred more severe EAE than T cells from male mice and that gender differences in clinical disease were due, at least in part, to differences in donor T cell cytokine secretion. T cell lines were selected from proteolipid protein 139-151-immunized female SJL mice in the presence or absence of exogenous androgens. Androgen-selected T cell lines secreted less IFN-gamma and more IL-10 than untreated cell lines. Clinical disease induced by the adoptive transfer of androgen-selected T cell lines was less severe than disease induced with untreated T cell lines. Furthermore, androgen treatment of naive TCR transgenic T cells, during their first encounter with Ag, resulted in a shift in the balance of Th1/Th2 cytokines. This phenotype was maintained during subsequent stimulations in the absence of androgen. These results suggest that androgen present in the lymphoid microenvironment during the induction of an immune response can alter the development of effector T cells and may play an important role in governing gender differences in the immune response and susceptibility to autoimmune disorders.
Relatedness of an RNA-binding motif in human immunodeficiency virus type 1 TAR RNA-binding protein TRBP to human P1/dsI kinase and Drosophila staufen. (1993)

TRBP is a human cellular protein that binds the human immunodeficiency virus type 1 TAR RNA. Here, we show that the intact presence of amino acids 247 to 267 in TRBP correlates with its ability to bind RNA. This region contains a lysine- and arginine-rich motif, KKLAKRNAAAKMLLRVHTVPLDAR. A 24-amino-acid synthetic peptide (TR1) of this sequence bound TAR RNA with affinities similar to that of the entire TRBP, thus suggesting that this short motif contains a sufficient RNA-binding activity. Using RNA probe-shift analysis, we determined that TR1 does not bind all double-stranded RNAs but prefers TAR and other double-stranded RNAs with G+C-rich characteristics. Immunoprecipitation of TRBP from human immunodeficiency virus type 1-infected T lymphocytes recovered TAR RNA. This is consistent with a TRBP-TAR ribonucleoprotein during viral infection. Computer alignment revealed that TR1 is highly homologous to the RNA-binding domain of human P1/dsI protein kinase and two regions within Drosophila Staufen. We suggest that these proteins are related by virtue of sharing a common RNA-binding moiety.
Antigen-Presenting Function of the Macrophage (1984)

The functional significance of multiple cells--among lymphoid and nonlymphoid cells--capable of having Ia molecules on their membranes must be critically addressed. Ia is absolutely required before a cell can interact with helper T cells, but it is not clear whether the presence of this protein is all that is needed for antigen presentation. Indeed, at present, except for the macrophage, few cells have been studied for antigen presentation using a wide range of protein antigens, either soluble or particulate. On the basis of the studies discussed in the first section, it appears that the recruitment of most helper-T cell clones takes place by APC that can internalize and process the protein antigens, be they soluble or part of the structure of microorganisms. The fact that helper T cells are programmed to recognize antigen in the context of Ia, and therefore on an APC such as the macrophage, forces recognition of antigens that are altered or processed. Indeed, proteins in their native state may not remain membrane-bound for long periods; the T cells, therefore, have the opportunity to recognize the altered fragments. To this issue is added the requirement for the T-cell receptor to interact with Ia molecules. The available information, therefore, leads one to conclude that APC deficient in their capacity to internalize and process proteins will not be able to present them. The finding that small peptides from a previous catabolism of proteins can be presented without further handling implies that APC with limited processing capacity could be involved in presentation of such small peptides. The different Ia-positive APC of the lymphoid organs may interact to different extents with protein antigens and collaborate with each other to bring about an effective stimulation of the clones of helper T cells. The macrophage, being the most ubiquitous cell and the one capable of interacting with many proteins, is our candidate as the major APC involved in the recruitment and enlargement of clones T cells. The observations that macrophages can release proteins partially altered implies that there may be cooperativity among the various APC. Data for this have been obtained. Most likely B cells will be found to have a limited capacity to present all antigens because of their inherent difficulties in internalizing large particulate materials. In such instances, B cells may interact with the solubilized proteins released by the macrophages. The same may apply to the Langerhans/dendritic cells.(ABSTRACT TRUNCATED AT 400 WORDS)
A high-resolution CMOS time-to-digital converter utilizing a Vernier delay line (2000)

This paper describes a CMOS time-to-digital converter (TDC) integrated circuit utilizing tapped delay lines. A technique that allows the achievement of high resolution with low dead-time is presented, The technique is based on a Vernier delay line (VDL) used in conjunction with an asynchronous read-out circuitry. A delay-locked loop (DLL) is used to stabilize the resolution against process variations and ambient conditions. A test circuit fabricated in a standard 0.7-/spl mu/m digital CMOS process is presented. The TDC contains 128 delay stages and achieves 30-ps resolution, stabilized by the DLL, with the accuracy exceeding /spl plusmn/1 LSB. Test results show that even higher resolutions can be achieved using the VDL method, and resolutions down to 5 ps are demonstrated to be obtainable.
Technical Assessment of the First 20 Years of Research Using Mouse Embryonic Stem Cell Lines (2004)

This review assesses the effect that mouse embryonic stem (ES) cells have had on biomedical research during the 20 years that followed their isolation in 1981. Notable scientific discoveries enabled by these cell lines--including insights into cell cycle regulation, spatial and temporal relationships during development, and the roles of transcription factors and homeobox genes in developmental pathways--are discussed. The acceleration of basic discovery of gene function and the genetic basis of disease using a breakthrough technology (homologous recombination between modified gene constructs and the ES cell genome) became the principal enabling method to establish transgenic laboratory animals with single targeted genetic change. This review also examines the widespread influence of mouse ES cells as an enabling technology by highlighting their effect on drug development paradigms, directed differentiation to treat specific diseases, nuclear transfer protocols used in cloning, and establishment of methodologies for isolating non-rodent ES cells. This review concludes with a brief analysis of the most influential mouse ES cell lines of the first 20 years as viewed within the twin contexts of human disease application and contributions to the primary literature.
New Insights into the Structure and Properties of Electroactive Polymer Films Derived from [Ni(salen)] (1997)

Oxidative electrochemical polymerization of (N,N ‘-ethylenebis(salicylideneaminato)) nickel(II), [Ni(salen)], in acetonitrile/TEAP was reinvestigated. The polymers were characterized by in situ FTIR and UV−visible spectroscopies in order to explore film structure and to clarify the electronic states as a function of the electrochemically controlled applied redox potential; oxidized species involved in polymerization and oxidative switching of the polymer were also assessed by ex situ EPR experiments. Integration of data from all techniques revealed that (a) electropolymerization of [Ni(salen)] is ultimately a ligand-based-process that takes place through a mixture of o- and p-linking of the phenyl rings and (b) poly[Ni(salen)] exhibits physical/chemical properties that cannot be attributed to an aggregation of individual complexes, behaving rather like a polyphenylene compound, with the metal ion acting as a bridge between biphenylene moieties.
MuonTrap: Preventing Cross-Domain Spectre-Like Attacks by Capturing Speculative State (2020)

The disclosure of the Spectre speculative-execution attacks in January 2018 has left a severe vulnerability that systems are still struggling with how to patch. The solutions that currently exist tend to have incomplete coverage, perform badly, or have highly undesirable performance edge cases. MuonTrap allows processors to continue to speculate, avoiding significant reductions in performance, without impacting security. We instead prevent the propagation of any state based on speculative execution, by placing the results of speculative cache accesses into a small, fast L0 filter cache, that is non-inclusive, non-exclusive with the rest of the cache hierarchy. This isolates all parts of the system that can’t be quickly cleared on any change in threat domain. MuonTrap uses these speculative filter caches, which are cleared on context and protection-domain switches, along with a series of extensions to the cache coherence protocol and prefetcher. This renders systems immune to cross-domain information leakage via Spectre and a host of similar attacks based on speculative execution, with low performance impact and few changes to the CPU design.
Metabotropic glutamate receptors are involved in amygdaloid plasticity (2002)

The amygdala plays an important role in emotional learning. Synaptic plasticity underlying the acquisition of conditioned fear occurs in the lateral nucleus of the amygdala: long-term potentiation (LTP) of synapses in the pathway of the conditioned stimulus (CS) has shown to be a neural correlate of this kind of emotional learning. The present study is based on previous results of our laboratory showing an important role of the metabotropic glutamate receptor subtype 5 (mGluR5) in fear conditioning. Here, we explored whether mGlu5 receptors within the lateral nucleus of the amygdala are involved in the plasticity underlying fear conditioning. We used an in vivo approach investigating the acquisition, consolidation and expression of conditioned fear by the fear-potentiated startle paradigm and by the inhibition of motor activity during CS presentation. Additionally, we used an in vitro approach inducing LTP in the lateral amygdala by patch-clamp recordings in rat brain slices. Acquisition of conditioned fear, but not consolidation and expression, was blocked by intra-amygdaloid injections of the specific mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) in vivo. Furthermore, induction of amygdaloid LTP but not synaptic transmission was disrupted by MPEP application in vitro. These experiments show for the first time in vivo and in vitro that mGluR5 receptors are necessary for plasticity in the amygdala.