gebhart/patrepeval huggingface dataset:
Developing subunit immunogens using B and T cell epitopes and their constructs derived from the F1 antigen ofYersinia pestisusing novel delivery vehicles (2003)

Yersinia pestis is the etiological agent of pneumonic and bubonic plague. As the currently licensed vaccines for plague have their own limitations, there is a need for a rational and more effective form of a subunit vaccine to combat both forms of the disease. Newer methods of antigen delivery coupled with adjuvant offer an alternative approach toward a plague vaccine. In order to develop a new generation vaccine against plague, we chose an immunodominant, outer membrane capsular protein, F1 of Y. pestis. The immunogenicity of the peptide sequences, predicted to possess B (three sequences, B1, B2 and B3) and T (two sequences, T1 and T2) cell determinants, was studied in a murine model with different genetic backgrounds, using alhydrogel and liposomes as delivery vehicles. All the peptide sequences are immunogenic in all mouse strains and showed primary and secondary immune response. B2 peptide was found to be most immunogenic, followed by B1 and B3 peptides. Chimeras made between B and T structures proved highly immunogenic and the antibody levels are comparable with native F1 antigen, thereby proving that T1 and T2 are helper sequences. Interestingly, the liposome mode of immunization was found to be more immunogenic and generated higher affinity antibodies than the alum-based preparation. Immunization using a mixture of all the peptides further proved B2 to be immunodominant. The IgG isotype profile showed predominance of IgG1, IgG2b followed by IgG2a for all the formulations irrespective of mode of antigen delivery. Lymphocyte proliferation of spleen cells primed in vivo with peptides, B-T conjugates and F1 antigen followed by in vitro stimulation with these antigens in soluble (medium) and particulate (liposome) form, showed dose-dependent stimulation of T cells, while B-T constructs showed a higher stimulation index, comparable to F1 antigen. The liposome mode of antigen presentation showed higher lymphoproliferation of spleen cells. Of all the peptides tested, T1 and T2 sequences showed the highest stimulation indices. The pattern of cytokine levels was in the following order: interferon-gamma>interleukin-2>interleukin-4. In vivo protective studies of the B-T conjugates revealed that B1T1 and a mixture of conjugates showed a survival rate of 10 days. Thus, the study highlights the importance of B and T cell epitopes as peptide-based immunogens, being a serious alternative for plague vaccine.
Fine needle cytology of complex thyroid nodules (2007)

Our data show that adopting stylet needles to perform FNAC in CTN may significantly improve the percentage of adequate sampling. On the other hand, preliminary aspiration of CTN with large cystic component does not add any advantage.
Tat as one key to HIV-induced immune pathogenesis and Pat toxoid as an important component of a vaccine (1999)

HIV-induced immune pathogenesis is more complex than simple infection of CD4+ T cells, their subsequent death, replacement by new CD4+ T cells, and eventual immune exhaustion. Even from the earliest period of HIV research, it was clear from in vitro results that the bulk of T cells did not respond properly to antigenic stimuli and even ultimately to mitogenic stimuli, despite the fact that only a small percent of T cells were infected (1, 2). These results, however, were not limited to in vitro experiments. Other studies showed abnormalities of proliferation and sometimes “bystander” apoptosis of uninfected cells in simian immunodeficiency virus-infected macaques (3) and, more recently, regenerative abnormalities that include more generalized effects on hematopoiesis of HIV infected people (4). Consequently, a direct infection and cell killing of CD+ T cells followed by their rapid replacement and ultimate immune exhaustion as suggested in some models does not encompass the overall reality of HIV-induced immune pathogenesis. HIV immune pathogenesis also clearly involves extracellular factors, which have an effect on uninfected cells (Fig. 1). Candidates may include the aberrant production of normal cellular factors, such as the over-production of some cytokines and/or their production at the wrong time and place. In fact, in studies chiefly performed by my collaborator D. Zagury, we have presented evidence that IFN-α may be one such candidate because of its over-production after HIV infection (5), its known anti-proliferative effects (6–8) (Fig. 2), and because we could partially restore T-cell proliferation in vitro to normal when HIV infected peripheral blood mononuclear cell cultures were treated with antibodies to IFN-α (8). Viral proteins, of course, also may be extracellular toxins, and D. Zagury, his collaborators, and I have proposed that Tat is one such toxin and perhaps the most important one (8 …
Recent Decisions of the Court of International Trade Relating to Jurisdiction: A Primer and a Critique (2012)

The Court of International Trade (the Court) was created by the Customs Courts Act of 1980.1 One provision of this statute that confers jurisdiction upon the new court, section 1581 of Title 28 of the United States Code (section 1581), essentially reiterates, with some slight modifications, the jurisdiction possessed by the Customs Court. 2 Section 1581, however, also confers on the new court jurisdiction not previously possessed by the Customs Court.These new areas of jurisdiction represent the major concern of this Article.The Customs Courts Act became effective approximately 3 years ago.The Court's first judicial conference seems to be an appropriate time to evaluate the trends that appear to be evolving in the course of the Court's interpretation of section 1581.Accordingly, this Article will examine jurisdictional decisions of the Court and its appellate tribunal s made during the period extending from Director, Commercial Litigation Branch, Civil Division, United States Department of Justice.The views expressed in this Article are solely those of the author and not those of the Department of Justice.
Complete nucleotide sequence of the influenza B/Singapore/222/79 virus hemagglutinin gene and comparison with the B/Lee/40 hemagglutinin (1983)

The complete nucleotide sequence of the hemagglutinin (HA) gene of the human type B influenza virus B/Singapore/222/79 is presented. Comparison with the only other known sequence of a B hemagglutinin (B/Lee/40) shows that antigenic drift in type B HA genes is essentially the same as already observed within the influenza A H3 subtype, i.e., an accumulation of point mutations. The main difference is that the apparent evolution is significantly slower, most likely due to the cumulative effect of a lower occurrence in the population (slower evolution) and/or less immunological pressure. There is a striking cluster of changes at positions 127 until 137 of the HA1 subunit which may represent one of the antigenic sites of the molecule.
Reprogramming human T cell function and specificity with non-viral genome targeting (2017)

Human T cells are central to physiological immune homeostasis, which protects us from pathogens without collateral autoimmune inflammation. They are also the main effectors in most current cancer immunotherapy strategies 1 . Several decades of work have aimed to genetically reprogram T cells for therapeutic purposes 2–5 , but as human T cells are resistant to most standard methods of large DNA insertion these approaches have relied on recombinant viral vectors, which do not target transgenes to specific genomic sites 6, 7 . In addition, the need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells through homology-directed repair (HDR), but to date in human T cells this still requires viral transduction 8, 9 . Here, we developed a non-viral, CRISPR-Cas9 genome targeting system that permits the rapid and efficient insertion of individual or multiplexed large (&gt;1 kilobase) DNA sequences at specific sites in the genomes of primary human T cells while preserving cell viability and function. We successfully tested the potential therapeutic use of this approach in two settings. First, we corrected a pathogenic IL2RA mutation in primary T cells from multiple family members with monogenic autoimmune disease and demonstrated enhanced signalling function. Second, we replaced the endogenous T cell receptor ( TCR ) locus with a new TCR redirecting T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized the tumour antigen, with concomitant cytokine release and tumour cell killing. Taken together, these studies provide preclinical evidence that non-viral genome targeting will enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells.
879. Some preliminary synthetical studies with 5,6,7,8-tetrahydro-8-methylindane-1,5-dione (1960)

C. B. C. Boyce and J. S. Whitehurst, J. Chem. Soc., 1960, 4547 DOI: 10.1039/JR9600004547
Hydrogen blistering of silicon: Progress in fundamental understanding (2007)

Abstract When silicon is implanted with a sufficient concentration of H ions, at low to moderate temperature, and subsequently annealed at high temperature, dome‐shaped gas‐filled blisters and/or craters of exploded blisters appear on the surface. Under particular conditions, blistering can be produced by plasma hydrogenation as well. The phenomenon is another facet of hydrogen behaviour in silicon, a question with both fundamental and applied implications. Blistering is at the origin of the “ion‐cutting” process for the fabrication of silicon‐on‐insulator and other heterostructures; this process is particularly useful whenever atomically sharp interfaces between layers are required. The novelty and vast potential of this process has spurred since the mid‐1990's a burst of experimental activity on blistering. The purposes of those works were either to improve or extend the ion‐cut process, or to clarify its underlying mechanisms. In “mechanisms”, the plural is used to convey the fact that it is a multi‐step phenomenon. Because of this complexity, the theoretical work, in comparison, is far less abundant. Hydrogen blistering of silicon is qualitatively understood in broad terms: H being insoluble in Si, it tends to segregate into cavities which grow and coalesce at high temperature, and the H 2 pressure in the cavities finally deforms the surface. In fact, our understanding of the microscopic mechanisms has progressed much beyond that level thanks to the sophisticated work that has been carried out using techniques such as transmission electron microscopy, Rutherford backscattering in the channelling mode, infrared spectroscopy of local vibrational modes, stress and strain measurements, and others. The effects of n‐ or p‐doping, He ion coimplantation, and isotope substitution have also greatly helped in discriminating between different hypotheses. After a review of the most relevant experimental facts, the blistering mechanisms that have been proposed in the literature will be discussed and their conformity with the data assessed. Finally an attempt will be made to identify the key questions and suggest a few avenues for future work. (© 2007 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Suppressing Posttranslational Gluconoylation of Heterologous Proteins by Metabolic Engineering of Escherichia coli (2007)

Minimization of chemical modifications during the production of proteins for pharmaceutical and medical applications is of fundamental and practical importance. The gluconoylation of heterologously expressed protein which is observed in Escherichia coli BL21(DE3) constitutes one such undesired posttranslational modification. We postulated that formation of gluconoylated/phosphogluconoylated products of heterologous proteins is caused by the accumulation of 6-phosphogluconolactone due to the absence of phosphogluconolactonase (PGL) in the pentose phosphate pathway. The results obtained demonstrate that overexpression of a heterologous PGL in BL21(DE3) suppresses the formation of the gluconoylated adducts in the therapeutic proteins studied. When this E. coli strain was grown in high-cell-density fed-batch cultures with an extra copy of the pgl gene, we found that the biomass yield and specific productivity of a heterologous 18-kDa protein increased simultaneously by 50 and 60%, respectively. The higher level of PGL expression allowed E. coli strain BL21(DE3) to satisfy the extra demand for precursors, as well as the energy requirements, in order to replicate plasmid DNA and express heterologous genes, as metabolic flux analysis showed by the higher precursor and NADPH fluxes through the oxidative branch of the pentose phosphate shunt. This work shows that E. coli strain BL21(DE3) can be used as a host to produce three different proteins, a heterodimer of liver X receptors, elongin C, and an 18-kDa protein. This is the first report describing a novel and general strategy for suppressing this nonenzymatic modification by metabolic pathway engineering.
Multiple tissue-specific elements control the apolipoprotein E/C-I gene locus in transgenic mice (1991)

To investigate the mechanisms controlling tissue-specific expression of the human apolipoprotein (apo) E/C-I gene locus, human apoE and apoC-I gene constructs containing various lengths of the 5'-flanking or 3'-flanking region were used to create transgenic mice. Several essential tissue-specific regulatory elements were identified in the region between the apoE and the apoC-I genes, as well as in a distal domain found downstream of the apoC-I gene. Most notably, transcription of both the apoE and apoC-I genes in the liver, their major site of expression, required downstream regulatory elements, possibly located within a common regulatory domain more than 2 kilobases 3' of the apoC-I gene (about 14 kilobases downstream of the apoE gene promoter). In the region between the apoE and apoC-I genes, a single strong positive element directed apoE and apoC-I gene expression in the skin. The intergenic region also contained elements that stimulated apoE gene expression in the brain and silenced apoE gene expression only in the kidney. These results demonstrate that multiple independent regulatory elements control expression of the human apoE/C-I gene locus in various tissues. Transgenic mice expressing human apoC-I in the liver exhibited plasma triglyceride levels that were 2-3-fold higher than those in control mice, an effect not found when transgenic human apoE was produced. This result suggests that apoC-I may modulate the metabolism of triglyceride-rich lipoproteins.
Advances in Tightly Coupled Reservoir/ Wellbore/Surface-Network Simulation (2001)

Summary One of the most perplexing and difficult challenges in the industry is deciding how to develop a new oil or gas field. It is necessary to estimate recoverable reserves, design the most efficient exploitation strategy, decide where and when to drill wells and install surface facilities, and predict the rate of production. This requires a clear understanding of energy distribution and fluid movements throughout the entire system, under any given operational scenario or market-demand situation. Even after a reservoir-development plan is selected, there are many possible facility designs, each with different investment and operating costs. An important, but not always considered, fact is that each facility scheme could result in different future production rates owing to various types, sizes, and configurations of fluid-flow facilities. Selecting the best design for the asset requires the most accurate production forecasts possible over the forecast life cycle. No other single technology has the ability to provide this insight, as well as tightly coupled reservoir and facility simulation, because it combines all pertinent geological and engineering data into a single, comprehensive, dynamic model of the entire oilfield flow system. An integrated oilfield simulation system accounts for all dynamic flow effects and provides a test environment for quickly and accurately comparing alternative designs. This paper provides a brief background of this technology and gives a review of a major development project where it is currently being applied. Finally, we describe some recent significant advances in the technology that make it more stable, accurate, and rigorous.
Music and its effect on the physiological responses and anxiety levels of patients receiving mechanical ventilation: a pilot study (2005)

As indicated by the results of this study, music therapy can act as a simple and safe nursing intervention to allay anxiety and promote patient comfort. Interest and comments on music therapy provided as a relaxation technique should be elicited from both nurses and patients.
Histone Deacetylase Inhibitors Target Diabetes via Chromatin Remodeling or as Chemical Chaperones? (2009)

Globally, obesity and diabetes (particularly type 2 diabetes) represents a major challenge to world health. Despite decades of intense research efforts, the genetic basis involved in diabetes pathogenesis & conditions associated with obesity are still poorly understood. Recent advances have led to exciting new developments implicating epigenetics as an important mechanism underpinning diabetes and obesity related disease. One epigenetic mechanism known as the "histone code" describes the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as lysine acetyltransferases or KATs and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. Some of the known inhibitors of HDACs (HDACi) have also been shown to act as "chemical chaperones" to alleviate diabetic symptoms. In this review, we discuss the available evidence concerning the roles of HDACs in regulating chaperone function and how this may have implications in the management of diabetes.
Non data-aided SNR estimation of OFDM signals (2008)

This letter deals with the problem of non data aided (NDA) signal to noise ratio (SNR) estimation of OFDM signals transmitted through unknown multipath fading channel. Most of existing OFDM SNR estimators are based on the knowledge of pilot sequences which is not applicable in some contexts such as cognitive radio for instance. We show that it is possible to take advantage of the periodic redundancy induced by the cyclic prefix to get an accurate NDA SNR estimator. Numerical simulations highlight the benefit of the proposed method compared with the state of the art.
Selection criteria for probiotic microorganisms. (1996)

Probiotics are preparations of live microorganisms which beneficially affect the host by improving the properties of the indigenous microbes. Since the human intestinal flora plays an important role in health and disease of man, probiotics are used to improve intestinal health and to stimulate the immune system. The microbes commonly used as probiotics for humans are the lactic acid bacteria (LAB). In early studies the strains used for fermenting milk products for human consumption were frequently used as probiotics. Subsequently, it was realised that it would be more appropriate if the strains originated from the human intestinal tract and that in addition to LABs, other microorganisms could be used either singly or in combination. Today, strict selection criteria are employed to obtain functional probiotic strains. It is generally agreed that the strain should be of host origin, well characterised, able to survive the rigours of the digestive tract and possibly colonise, biologically active against the target as well as to be stable and amenable to commercial production and distribution. In addition, information on dosages and evidence of efficacy needs to be obtained. In vitro and in vivo studies are frequently combined to allow investigation of the various parameters, and ultimately clinical trials are required. Although lactic acid bacteria have been generally recognised as safe, the question of safety is discussed for LAB and non-LAB probiotic strains in terms of potential pathogenicity of the strains and risk to the individual and the community. Finally, even though the techniques for genetic manipulation of many probiotic strains are available, it is not envisaged that this issue will be addressed in the near future because of regulatory implications. It is proposed that when this type of selection criteria is employed, probiotics strains with demonstrable efficacy can be obtained.
Phosphodiesterase I, A Novel Adhesion Molecule and/or Cytokine Involved in Oligodendrocyte Function (1997)

One of the more complex developmental processes occurring postnatally in the CNS is the formation of the myelin sheath by oligodendrocytes. To examine the molecular events that take place during myelination, we isolated oligodendrocyte-derived cDNA clones, one of which (p421.HB) represents a putative alternatively spliced isoform of rat brain-specific phosphodiesterase I (PD-Ialpha) and a species homolog of the human cytokine autotaxin. Analysis of the structural composition of the p421.HB/PD-Ialpha protein suggests a transmembrane-bound ectoenzyme, which, in addition to the phosphodiesterase-active site contains presumed cell recognition and Ca2+-binding domains. Consequently, it may be involved in extracellular signaling events. Expression of p421.HB/PD-Ialpha is enriched in brain and spinal cord, where its mRNA can be detected in oligodendrocytes and in cells of the choroid plexus. Expression in the brain increases during development with an intermediate peak of expression around the time of active myelination and maximal expression in the adult. We have identified four presumably alternatively spliced isoforms, two of which appear to be CNS-specific. Decreased levels of p421.HB/PD-Ialpha mRNA in the dysmyelinating mouse mutant jimpy, but not shiverer, suggest a role for p421.HB/PD-Ialpha during active myelination and/or late stages of oligodendrocyte differentiation. Furthermore, p421.HB/PD-Ialpha mRNA levels were reduced in the CNS at onset of clinical symptoms in experimental autoimmune encephalomyelitis. These data together implicate the importance of p421.HB/PD-Ialpha in oligodendrocyte function, possibly through cell-cell and/or cell-extracellular matrix recognition.
Cancer et fatigue (2003)

La fatigue liee au cancer affecte souvent plus la vie quotidienne du patient que la douleur. Elle est trop souvent negligee, contrairement a la douleur. Son evaluation devrait etre faite systematiquement atitre preventif. Son etiologie est multi-factorielle et, sauf quelques cas particuliers, encore mal elucidee. Le traitement, lorsqu'il est possible, est a entreprendre le plus tot possible.
On Fréchet differentiability of convex functions on Banach spaces (1995)

summary:Equivalent conditions for the separability of the range of the subdifferential of a given convex Lipschitz function $f$ defined on a separable Banach space are studied. The conditions are in terms of a majorization of $f$ by a $C^1$-smooth function, separability of the boundary for $f$ or an approximation of $f$ by Fréchet smooth convex functions.