gebhart/patrepeval huggingface dataset:
The Structure, Function, and Mechanisms of Action of Enterovirus Non-structural Protein 2C (2020)

Enteroviruses are a group of RNA viruses belonging to the family <i>Picornaviridae</i>. They include human enterovirus groups A, B, C, and D as well as non-human enteroviruses. Enterovirus infections can lead to hand, foot, and mouth disease and herpangina, whose clinical manifestations are often mild, although some strains can result in severe neurological complications such as encephalitis, myocarditis, meningitis, and poliomyelitis. To date, research on enterovirus non-structural proteins has mainly focused on the 2A and 3C proteases and 3D polymerase. However, another non-structural protein, 2C, is the most highly conserved protein, and plays a vital role in the enterovirus life cycle. There are relatively few studies on this protein. Previous studies have demonstrated that enterovirus 2C is involved in virus uncoating, host cell membrane rearrangements, RNA replication, encapsidation, morphogenesis, ATPase, helicase, and chaperoning activities. Despite ongoing research, little is known about the pathogenesis of enterovirus 2C proteins in viral replication or in the host innate immune system. In this review, we discuss and summarize the current understanding of the structure, function, and mechanism of the enterovirus 2C proteins, focusing on the key mutations and motifs involved in viral infection, replication, and immune regulation. We also focus on recent progress in research into the role of 2C proteins in regulating the pattern recognition receptors and type I interferon signaling pathway to facilitate viral replication. Given these functions and mechanisms, the potential application of the 2C proteins as a target for anti-viral drug development is also discussed. Future studies will focus on the determination of more crystal structures of enterovirus 2C proteins, which might provide more potential targets for anti-viral drug development against enterovirus infections.
HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120 (2012)

HIV-1 envelope glycoprotein is the primary target for HIV-1-specific antibodies. The native HIV-1 envelope spike on the virion surface is a trimer, but trimeric gp140 and monomeric gp120 currently are believed to induce comparable immune responses. Indeed, most studies on the immunogenicity of HIV-1 envelope oligomers have revealed only marginal improvement over monomers. We report here that suitably prepared envelope trimers have nearly all the antigenic properties expected for native viral spikes. These stable, rigorously homogenous trimers have antigenic properties markedly different from those of monomeric gp120s derived from the same sequences, and they induce potent neutralizing antibody responses for a cross-clade set of tier 1 and tier 2 viruses with titers substantially higher than those elicited by the corresponding gp120 monomers. These results, which demonstrate that there are relevant immunologic differences between monomers and high-quality envelope trimers, have important implications for HIV-1 vaccine development.
The Proximal Promoter Region of the Gene Encoding Human 17β-Hydroxysteroid Dehydrogenase Type 1 Contains GATA, AP-2, and Sp1 Response Elements: Analysis of Promoter Function in Choriocarcinoma Cells* (1997)

The 5'-flanking region from -78 to +9 in the HSD17B1 gene serves as a promoter, and an HSD17B1 silencer element is located in position -113 to -78. In the present studies, we have characterized three regulatory elements in the proximal 5'-flanking regions of the gene, using electrophoretic mobility shift assays and reporter gene analysis. First, nuclear factors recognized by antibodies against Sp1 and Sp3 were found to bind the Sp1 motif in the region from -52 to -43. Mutation of the Sp1-binding site decreased the promoter activity to 30% in JEG-3 cells and to 60% in JAR cells, suggesting that binding to the Sp1 motif has a substantial role in the complete functioning of the HSD17B1 promoter. Second, the binding of AP-2 to its motif in the region from -62 to -53 led to reduced binding of Sp1 and Sp3, and furthermore, mutation of the AP-2 element increased promoter activity to 260% in JEG-3 cells. The data thus implied that AP-2 can repress the function of the HSD17B1 promoter by preventing binding to the Sp1 motif. Finally, GATA factors, GATA-3 in particular, were demonstrated to bind their cognate sequence in the HSD17B1 silencer region, and mutations introduced into the GATA-binding site increased transcriptional activity to the level seen in constructs not containing the silencer element. Thus, GATA-3 seems to prevent transcription in the constructs, and hence, the GATA motif also may operate as a negative control element for HSD17B1 transcription.
Identification of Genes Required for Chronic Persistence ofBrucella abortusin Mice (2000)

The genetic basis for chronic persistence of Brucella abortus in lymphoid organs of mice, cows, and humans is currently unknown. We identified B. abortus genes involved in chronic infection, by assessing the ability of 178 signature-tagged mutants to establish and maintain persistent infection in mice. Each mutant was screened for its ability to colonize the spleens of mice at 2 and 8 weeks after inoculation. Comparison of the results from both time points identified two groups of mutants attenuated for chronic infection in mice. The first group was not recovered at either 2 or 8 weeks postinfection and was therefore defective in establishing infection. Mutants in this group carried transposon insertions in genes involved in lipopolysaccharide biosynthesis (wbkA), in aromatic amino acid biosynthesis, and in type IV secretion (virB1 and virB10). The second group, which was recovered at wild-type levels 2 weeks postinfection but not 8 weeks postinfection was able to establish infection but was unable to maintain chronic infection. One mutant in this group carried a transposon insertion in a gene with homology to gcvB of Mycobacterium tuberculosis, encoding glycine dehydrogenase, an enzyme whose activity is increased during the state of nonreplicating persistence. These results suggest that some mechanisms for long-term persistence may be shared among chronic intracellular pathogens. Furthermore, identification of two groups of genes, those required for initiating infection and those required only for long-term persistence, suggests that B. abortus uses distinct sets of virulence determinants to establish and maintain chronic infection in mice.
Inside Information: The Unique Features of Visceral Sensation (2008)

Most of what is written and believed about pain and nociceptors originates from studies of the "somatic" (non-visceral) sensory system. As a result, the unique features of visceral pain are often overlooked. In the clinic, the management of visceral pain is typically poor, and drugs that are used with some efficacy to treat somatic pain often present unwanted effects on the viscera. For these reasons, a better understanding of visceral sensory neurons-particularly visceral nociceptors-is required. This review provides evidence of functional, morphological, and biochemical differences between visceral and non-visceral afferents, with a focus on potential nociceptive roles, and also considers some of the potential mechanisms of visceral mechanosensation.
Effects of hypoxic and CO hypoxia on isolated hearts (1975)

Isolated perfused dog hearts were made hypoxic by respiring the support dog with low oxygen (hypoxic hypoxia) or with carbon monoxide (CO hypoxia). Each heart was exposed to both types of hypoxia, separately. Effects on coronary flow (Qt), coronary vascular resistance, cardiac oxygen consumption (Vo2), and contractility (%deltadP/dt) were studied. Two series of experiments were done. Series I: At constant perfusion pressure. As oxygen content (Cao2) was lowered from 20 to 5 vol%, Qt doubled with hypoxic hypoxia and almost tripled with CO hypoxia (P less than 0.01). Vo2 and contractility increased with both types of hypoxia. Beta-adrenergic blockade eliminated the increase in VO2 and contractility but not the difference in Qt increase between hypoxic and CO hypoxia. Series II: At constant Qt (with beta-blockade), vascular resistance decreased more with CO than hypoxic hypoxia. Finally, alpha-blockade eliminated the difference in vascular resistance and thus with complete (alpha and beta) blockade, the two types of hypoxia have the same effect and are indistinguishable.
Nucleotides. Part LVII.. Synthesis of phosphoramidite building blocks of 2′‐amino‐2′‐deoxyribonucleosides: New compounds for oligonucleotide synthesis (1998)

Abstract The chemical synthesis of 2′‐amino‐2′‐deoxyribonucleosides of uracil, cytosine, adenine, and guanine, and their conversion into suitably protected 3′‐phosphoramidite building blocks 35 – 40 for oligonucleotide synthesis are described. The aglycone and the 2′‐amino functions were protected using the 2‐(4‐nitrophenyl)ethoxycarbonyl (npeoc) group. The synthesis of the 3′‐ O ‐succinyl (3′‐ O ‐(3‐carboxypropanoyl))‐substituted starting nucleoside 41 is described and its behavior examined in solution and on solid phase with regard to an anticipated migration during 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) deprotection. Oligonucleotides were prepared using the new building blocks, and their hybridization properties were studied by UV‐melting techniques.
Purification and properties of a bacteriophage-induced endo-N-acetylneuraminidase specific for poly-alpha-2,8-sialosyl carbohydrate units. (1987)

The soluble form of a bacteriophage-induced endo-N-acetylneuraminidase (Endo-N) specific for hydrolyzing oligo- or poly-alpha-2,8-linked sialosyl units in sources as disparate as bacterial and neural membrane glycoconjugates was purified approximately 10,000-fold and characterized. The enzyme appears homogenous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and has a subunit Mr 105,000. This corresponds to one of the higher Mr phage proteins which comprises 7.5% (by weight) of the total phage protein. The holoenzyme is active at neutral pH and has a Mr by gel filtration of 328,000, suggesting that the active enzyme is a trimer. Endo-N requires a minimum of 5 sialyl residues (DP5, where DP represents degree of polymerization) for activity. The limit digest products from the alpha-2,8-linked polysialic acid capsule of Escherichia coli K1 are DP4 with some DP3 and DP1,2. DP2-4 do not appear to inhibit depolymerization of polysialic acid. Endo-N digestion of the polysialosyl moiety on neural cell adhesion molecules yields sialyl oligomers with DP3 and DP4. The presence of a terminal sialitol changes both the distribution of limit digestion products and the apparent minimum substrate size. Higher Mr alpha-2,8-linked sialyl polymers (approximately DP200) are better substrates (Km 50-70 microM) than sialyl oligomers of approximately DP10-20 (Km 1.2 mM). Endo-N activity is inhibited by DNA and several other poly-anions tested. An examination of the distribution of intermediate products shows that Endo-N binds and cleaves at random sites on the polysialosyl chains, in contrast to initiating cleavage at one end and depolymerizing processively. Endo-N can serve as a specific molecular probe to detect and selectively modify poly-alpha-2,8-sialosyl carbohydrate units which have been implicated in bacterial meningitis and neural cell adhesion.
The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells (1985)

Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease-derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio-immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large-cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell-related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an "activation state." In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.
Review B cells in rheumatoid arthritis (2000)

Normally the immune response is restricted to the peripheral secondary lymphoid organs. However, additional ectopic lymphoid tissue may develop at chronic sites of inflammation. In the synovium of rheumatoid arthritis patients the local production of proinflammatory cytokines seems to support the formation of a precisely structured microenvironment, which allows an antigen dependent immune response to take place. The analysis of the V-gene repertoire expressed in synovial B cells demonstrated that in the inflamed synovium a germinal centre reaction takes place. Antigen presented by a network of follicular dendritic cells may activate synovial B cells and support their differentiation into plasma cells secreting high affinity antibodies. The specificity of these antibodies remains to be determined.
Polymerase chain reaction products analyzed by charge detection mass spectrometry (1999)

Charge detection mass spectrometry (CDMS) has been used to rapidly analyze polymerase chain reaction (PCR) products with a minimum of sample cleanup after the PCR reaction.PCR products of 1525 base pairs (bp ), 1982 bp and 2677 bp were detected by CDMS, where simultaneous measurement of the charge and velocity of an electrostatically accelerated ion allows a mass determination of the ion.We extended the investigation to a longer doublestranded, linear DNA sample by also analyzing linearized pBR322 (4361 bp).Positive ion mass spectra and ion charge-state distributions were obtained for these electrosprayed DNA samples.Instrumental conditions were studied using a commercially available, linearized pUC18 sample (2682 bp).
Prosody Generation for Speech-to-Speech Translation (2006)

This paper deals with speech synthesis in the framework of speech-to-speech translation. Our current focus is to translate speeches or conversations between humans so that a third person can listen to them in its own language. In this framework the style is not written but spoken and the original speech includes a lot of non-linguistic information (as speaker emotion). In this work we propose the use of prosodic features in the original speech to produce prosody in the target language. Relevant features are found using an unsupervised clustering algorithm that finds, in a bilingual speech corpus, intonation clusters in the source speech which are relevant in the target speech. Preliminary results already show a significant improvement in the synthetic quality (from MOS=3.40 to MOS=3.65)
Effects of oral supplementation with stable strontium. (1981)

The biologic effects of stable strontium, a naturally occurring trace element in the diet and the body, have been little investigated. This paper discusses the effects of oral supplementation with stable strontium in laboratory studies and clinical investigations. The extent of intestinal absorption of various doses of orally administered strontium was estimated by determining serum and tissue levels with atomic absorption spectrophotometry. The central observation is that increased oral intake produces a direct increase in serum levels and intracellular uptake of strontium. The results of these studies, as well as those of other investigators, demonstrate that a moderate dosage of stable strontium does not adversely affect the level of calcium either in the serum or in soft tissues. In studies of patients receiving 1 to 1.5 g/d of strontium gluconate, a sustained increase in the serum level of strontium produced a 100-fold increase in the strontium:calcium ratio. In rats, studies indicate that an increase in intracellular strontium content following supplementation may exert a protective effect on mitochondrial structure, probably by means of a stabilizing effect of strontium on membranes. The strontium:calcium ratio in animals receiving a standard diet is higher in the cell than in the extracellular fluid; this may be of physiologic significance. An increase in density that corresponded to the deposition of stable strontium was observed in areas of bone lesions due to metastatic cancer in patients receiving stable strontium supplementation. This suggests the possibility of using strontium to mineralize osteophenic areas and to relieve bone pain. Also, because of reports of an inverse relation between the incidence of dental caries and a high strontium content in drinking water, the use of natural water containing relatively high levels of stable strontium should be considered. In each of these instances it is important to maintain a normal dietary intake of calcium.
5-Fluoro- and 5-chlorocyclophosphamide: synthesis, metabolism, and antitumor activity of the cis and trans isomers (1981)

In seeking analogues of cyclophosphamide (1) having improved antitumor activity by virtue of accelerated formation of the cytotoxic metabolite phosphoramide mustard, cis and trans isomers of 5-fluoro- and 5-chlorocyclophosphamide (9, 10, 11 and 12, respectively) were synthesized by condensation of the appropriate 3-amino-2-halopropan-1-ol (13 or 26) with N,N-bis(2-chloroethyl)phosphoramidic dichloride (14). The metabolism of the halocyclophosphamides by rat liver microsomes was stereoselective; the cis isomers (9 and 11) were poorly metabolized, whereas the trans isomers (10 and 12) were metabolized with efficiency comparable to that of cyclophosphamide. However, there was no evidence that the yield of phosphoramide mustard produced by the trans analogues were significantly greater than that from cyclophosphamide following microsomal 4-hydroxylation. Hence, the halogen substituents did not accelerate beta-elimination of acrolein from the acyclic aldehydo tautomers. As expected, the poorly metabolized cis-5-fluoride (9) had little activity against the ADJ/PC6 tumor in mice. However, the cis-5-chloride (11) was as active as the trans isomer (12) and each had approximately half the therapeutic index of 1. The trans-5-fluoride (10) was much less active, having an ED90 value some 16-fold that of 1.
Active immunotherapy of cancer with a nonreplicating recombinant fowlpox virus encoding a model tumor-associated antigen. (1995)

Some tumor cells express Ags that are potentially recognizable by T lymphocytes and yet do not elicit significant immune responses. To explore new immunotherapeutic strategies aimed at enhancing the recognition of these tumor-associated Ags (TAA), we developed an experimental mouse model consisting of a lethal clone of the BALB/c tumor line CT26 designated CT26.WT, which was transduced with the lacZ gene encoding beta-galactosidase, to create CT26.CL25. The growth rate and lethality of CT26.CL25 and CT26.WT were virtually identical despite the expression by CT26.CL25 of the model tumor Ag in vivo. A recombinant fowlpox virus (rFPV), which is replication incompetent in mammalian cells, was constructed that expressed the model TAA, beta-galactosidase, under the influence of the 40-kDa vaccinia virus early/late promoter. This recombinant, FPV.bg40k, functioned effectively in vivo as an immunogen, eliciting CD8+ T cells that could effectively lyse CT26.CL25 in vitro. FPV.bg40k protected mice from both subcutaneous and intravenous tumor challenge by CT26.CL25, and most surprisingly, mice bearing established 3-day pulmonary metastasis were found to have significant, Ag-specific decreases in tumor burden and prolonged survival after treatment with the rFPV. These observations constitute the first reported use of rFPV in the prevention and treatment of an experimental cancer and suggest that changing the context in which the immune system encounters a TAA can significantly and therapeutically alter the host immune response against cancer.
Cerebral Magnetic Resonance Image Segmentation Using Data Fusion (1996)

This simple, reliable, and valid method can be employed in clinical research for quantification of gray and white matter and CSF volumes in MR head scans. Increase in white matter volume may reflect ongoing axonal growth and myelination, and gray matter reductions may reflect synaptic pruning or cell death in the age span of 4-18 years.
Using the matrix pencil method to estimate the parameters of a sum of complex exponentials (1995)

The approximation of a function by a sum of complex exponentials is a problem that is at least two centuries old. Fundamentally, all techniques discussed in this article proceed from using the same sequence of data samples and vary only, but importantly, in how those samples are used in achieving the parameter estimation. All of these techniques, in other words, seek the same quantitative parameters to represent the sampled data, but use different routes to get there. The techniques for estimating the parameters are either linear or nonlinear. The linear techniques are emphasized in this presentation. In particular, the matrix pencil method is described, which is more robust to noise in the sampled data. The matrix pencil approach has a lower variance of the estimates of the parameters of interest than a polynomial-type method (Prony's method belongs to this category), and is also computationally more efficient. A bandpass version of the matrix pencil can be implemented in hardware, utilizing an AT&T DSP32C chip operating in real time. A copy of the computer program implementing the matrix pencil technique is given in the appendix.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>