gebhart/patrepeval huggingface dataset:
Dendritic Cell-Mediated, DNA-Based Vaccination against Hepatitis C Induces the Multi-Epitope-Specific Response of Humanized, HLA Transgenic Mice (2014)

Hepatitis C virus (HCV) is the etiologic agent of chronic liver disease, hepatitis C. Spontaneous resolution of viral infection is associated with vigorous HLA class I- and class II-restricted T cell responses to multiple viral epitopes. Unfortunately, only 20% of patients clear infection spontaneously, most develop chronic disease and require therapy. The response to chemotherapy varies, however; therapeutic vaccination offers an additional treatment strategy. To date, therapeutic vaccines have demonstrated only limited success. Vector-mediated vaccination with multi-epitope-expressing DNA constructs alone or in combination with chemotherapy offers an additional treatment approach. Gene sequences encoding validated HLA-A2- and HLA-DRB1-restricted epitopes were synthesized and cloned into an expression vector. Dendritic cells (DCs) derived from humanized, HLA-A2/DRB1 transgenic (donor) mice were transfected with these multi-epitope-expressing DNA constructs. Recipient HLA-A2/DRB1 mice were vaccinated s.c. with transfected DCs; control mice received non-transfected DCs. Peptide-specific IFN-γ production by splenic T cells obtained at 5 weeks post-immunization was quantified by ELISpot assay; additionally, the production of IL-4, IL-10 and TNF-α were quantified by cytokine bead array. Splenocytes derived from vaccinated HLA-A2/DRB1 transgenic mice exhibited peptide-specific cytokine production to the vast majority of the vaccine-encoded HLA class I- and class II-restricted T cell epitopes. A multi-epitope-based HCV vaccine that targets DCs offers an effective approach to inducing a broad immune response and viral clearance in chronic, HCV-infected patients.
cDNA sequence analysis of an antibiotic dodecapeptide from neutrophils (1992)

The full-length cDNA of a neutrophil antibiotic dodecapeptide has been cloned by reverse transcription/PCR from bovine bone marrow RNA. This peptide was originally isolated from bovine neutrophils, and shown to exert a potent antimicrobial activity in vitro on both Escherichia coli and Staphylococcus aureus. The cDNA codes for a polypeptide of 155 amino acid residues with a predicted mass of 17,629 Da and a pI of 8.03. The deduced sequence comprises a putative signal peptide of 29 amino acids, a 114 residue pro-region, and a carboxy-terminal dodecapeptide corresponding to the mature antibiotic. The pro-sequence displays extensive identity to corresponding regions of other structurally unrelated antibiotic peptides of bovine neutrophils recently cloned.
Receptor-associated constitutive protein tyrosine phosphatase activity controls the kinase function of JAK1 (1997)

Exposure of cells to protein tyrosine phosphatase (PTP) inhibitors causes an increase in the phosphotyrosine content of many cellular proteins. However, the level at which the primary signaling event is affected is still unclear. We show that Jaks are activated by tyrosine phosphorylation in cells that are briefly exposed to the PTP inhibitor pervanadate (PV), resulting in tyrosine phosphorylation and functional activation of Stat6 (in addition to other Stats). Mutant cell lines that lack Jak1 activity fail to support PV-mediated [or interleukin 4 (IL-4)-dependent] activation of Stat6 but can be rescued by complementation with functional Jak1. The docking sites for both Jak1 and Stat6 reside in the cytoplasmic domain of the IL-4 receptor alpha-chain (IL-4Ralpha). The glioblastoma-derived cell lines T98G, GRE, and M007, which do not express the IL-4Ralpha chain, fail to support Stat6 activation in response to either IL-4 or PV. Complementation of T98G cells with the IL-4Ralpha restores both PV-mediated and IL-4-dependent Stat6 activation. Murine L929 cells, which do not express the gamma common chain of the IL-4 receptor, support PV-mediated but not IL-4-dependent Stat6 activation. Thus, Stat6 activation by PV is an IL-4Ralpha-mediated, Jak1-dependent event that is independent of receptor dimerization. We propose that receptor-associated constitutive PTP activity functions to down-regulate persistent, receptor-linked kinase activity. Inhibition or deletion of PTP activity results in constitutive activation of cytokine signaling pathways.
SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310 (2010)

NF-κB regulates the expression of a large number of target genes involved in the immune and inflammatory response, apoptosis, cell proliferation, differentiation and survival. In this study, we identified SIRT2 as a deacetylase of the transcription factor p65. SIRT2 is a member of the family of sirtuins, which are NAD(+)-dependent deacetylases involved in several cellular processes. SIRT2 interacts with p65 in the cytoplasm and deacetylates p65 in vitro and in vivo at Lys310. Moreover, p65 is hyperacetylated at Lys310 in Sirt2(-/-) cells after TNFα stimulation, which results in the increase in expression of a subset of p65 acetylation-dependent target genes. Our work provides evidence that p65 is deacetylated by SIRT2 in the cytoplasm to regulate the expression of specific NF-κB-dependent genes.
Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1 (1994)

We have studied the development of the antibody response to the surface glycoprotein gp120 of human immunodeficiency virus type 1 in three individuals who presented with primary human immunodeficiency virus type 1 infection syndrome. Serum anti-gp120 antibodies were first detected 4 to 23 days after presentation, after p24 antigen and infectious-virus titers in the peripheral blood had declined manyfold from their highest values. Whether anti-gp120 antibodies present at undetectable levels are involved in clearance of viremia remains unresolved. Among the earliest detectable anti-gp120 antibodies were those to conformationally sensitive epitopes; these antibodies were able to block the binding of gp120 monomers to soluble CD4 or to a human monoclonal antibody to a discontinuous epitope overlapping the CD4-binding site. Some of these antibodies were type specific to a degree, in that they were more effective at blocking ligand binding to autologous gp120 than to heterologous gp120. However, the appearance of these antibodies did not correlate with that of antibodies able to neutralize the autologous virus in vitro by a peripheral blood mononuclear cell-based assay. Antibodies to the V3 loop were detected at about the same time as, or slightly later than, those to the CD4-binding site. There was a weak correlation between the presence of antibodies to the V3 loop and autologous virus-neutralizing activity in two of three individuals studied. However, serum from the third individual contained V3 antibodies but lacked the ability to neutralize the autologous virus in vitro, even immediately after seroconversion. Thus, no simple, universal correlate of autologous virus-neutralizing activity in a peripheral blood mononuclear cell-based assay is apparent from in vitro assays that rely on detecting antibody interactions with monomeric gp120 or fragments thereof.
Regulating synthetic gene networks in 3D materials (2012)

Combining synthetic biology and materials science will enable more advanced studies of cellular regulatory processes, in addition to facilitating therapeutic applications of engineered gene networks. One approach is to couple genetic inducers into biomaterials, thereby generating 3D microenvironments that are capable of controlling intrinsic and extrinsic cellular events. Here, we have engineered biomaterials to present the genetic inducer, IPTG, with different modes of activating genetic circuits in vitro and in vivo. Gene circuits were activated in materials with IPTG embedded within the scaffold walls or chemically linked to the matrix. In addition, systemic applications of IPTG were used to induce genetic circuits in cells encapsulated into materials and implanted in vivo. The flexibility of modifying biomaterials with genetic inducers allows for patterned placement of these inducers that can be used to generate distinct patterns of gene expression. Together, these genetically interactive materials can be used to characterize genetic circuits in environments that more closely mimic cells' natural 3D settings, to better explore complex cell-matrix and cell-cell interactions, and to facilitate therapeutic applications of synthetic biology.
Urokinase/urokinase receptor system: internalization/degradation of urokinase-serpin complexes: mechanism and regulation. (1995)

The urokinase-type plasminogen activator (uPA) is secreted as a single-chain inactive zymogen (pro-uPA). Upon its secretion, pro-uPA binds to its glycosylphosphatidylinositol-anchored specific cell receptor (uPAR). The activation of pro-uPA to the active two-chain uPA is accelerated with uPAR-bound pro-uPA and is achieved by plasmin and proteases of other classes like cathepsins G and L. uPAR-bound uPA is susceptible to inhibition by its specific inhibitors (PAI-1, PAI-2, and PN-1). uPA-PAI-1 and uPA-PN-1 complexes, but not free uPA, are readily internalized and degraded through a mechanism that involves the multiligand receptors alpha 2-macroglobulin receptor/low density lipoprotein receptor-associated protein (alpha 2-MR) and epithelial glycoprotein 330 (gp330). Upon uPA-inhibitor internalization, uPAR is itself endocytosed and recycled back to the cell surface. PMA-induced differentiation of myeloid cells is accompanied by inhibition of uPA-PAI-1 internalization/degradation and the down-regulation of alpha 2-MR. The regulation of uPAR and alpha 2-MR levels might be part of the differentiation program of myeloid cells.
Virulence Characteristics ofKlebsiellaand Clinical Manifestations ofK. pneumoniaeBloodstream Infections (2007)

We studied 455 consecutive episodes of Klebsiella pneumoniae bacteremia occurring in 7 countries. Community-acquired pneumonia and an invasive syndrome of liver abscess, meningitis, or endophthalmitis occurred only in Taiwan and South Africa. Infections by K1 and K2 capsular serotype, the mucoid phenotype, and aerobactin production were important determinants of virulence. The mucoid phenotype was seen in 94% of isolates in patients with community-acquired pneumonia and in 100% of isolates that caused the invasive syndrome in Taiwan and South Africa, compared with only 2% of isolates elsewhere. Mortality of mice injected with mucoid strains (69%) was strikingly higher than that occurring in mice injected with nonmucoid strains (3%, p < 0.001). Differences in clinical features of bacteremic infection with K. pneumoniae are due to the virulence factors expressed by the organism.
ATS-5 and ATS-6 potentials during eclipse (1979)

ATS-5 and ATS-6 data for spacecraft charging during eclipse conditions is analyzed. ATS-5 and ATS-6 charged to voltages greater than 100 volts for about 55% of the eclipse periods examined. The mean spacecraft potential during eclipse was 2 keV for ATS-5, and the highest potential measured was 10 kilovolts. For ATS-6, the mean potential during eclipse was 4 keV, the highest potential measured being 20 keV. The average measured spacecraft potentials for both ATS-5 and 6 depend approximately linearly upon K sub p. This relationship is due mainly to the dependence of electron current density on K sub p near midnight. Spacecraft potentials at geosynchronous orbit may, to a rough approximation, thus be inferred from ground-based measurements of K sub p, the planetary 3-hour index. (Author)
Microwave-Enhanced Aminocarbonylations in Water (2005)

[reaction: see text]. Aryl bromides can be rapidly converted to the corresponding secondary and tertiary benzamides in water. By using Mo(CO)6 as the source of carbon monoxide, aminocarbonylations were conducted under air after only 10 min of high-density microwave heating.
In VivoGene Therapy with a Cationic Polymer Markedly Enhances the Antitumor Activity of Antiangiogenic Genes (1998)

A cationic polymer, Superfect, when complexed to the therapeutic genes, p53 and a TSP fragment, displays a much greater antitumor activity compared to cationic liposomes. At the dosages used, this polymer did not demonstrate any nonspecific antitumor effects in contrast to the liposome carriers. These in vivo findings should further stimulate the development of carrier polymers as well as expedite the evaluation of several antiangiogenic genes.
Overuse Tendinosis, Not Tendinitis (2000)

IN BRIEF: Overuse tendinopathies are common in primary care. Numerous investigators worldwide have shown that the pathology underlying these conditions is tendinosis or collagen degeneration. This applies equally in the Achilles, patellar, medial and lateral elbow, and rotator cuff tendons. If physicians acknowledge that overuse tendinopathies are due to tendinosis, as distinct from tendinitis, they must modify patient management in at least eight areas. These include adaptation of advice given when counseling, interaction with the physical therapist and athletic trainer, interpretation of imaging, choice of conservative management, and consideration of whether surgery is an option.
Cloning and Expression of the Gene for Serine–Glyoxylate Aminotransferase from an Obligate Methylotroph Hyphomicrobium Methylovorum GM2 (1996)

The gene encoding serine-glyoxylate aminotransferase, one of key enzymes for the assimilation of one-carbon compounds in methylotrophs, and its flanking regions were isolated from an obligate methylotrophic bacterium, Hyphomicrobium methylovorum GM2. Nucleotide sequencing of the recombinant plasmids revealed that the serine-glyoxylate aminotransferase gene encodes a 405-amino-acid protein with a calculated molecular mass of 43880 Da. The amino acid sequence of the enzyme showed identity to the sequences of serine-glyoxylate aminotransferase of Methylobacterium extorquens AM1 (57%), aspartate aminotransferase of Methanobacterium thermoformicicum (31%), human peroxisomal alanine-glyoxylate aminotransferase (27%), and serine-pyruvate aminotransferase of rat liver mitochondria (33%). The recombinant plasmid, which was constructed by ligation of the cloned gene and an expression vector pKK223-3, was introduced into Escherichia coli HB101. The recombinant enzyme was purified from transformed E. coli cells and analyzed by immunological and enzymological methods. The overexpressed enzyme was indistinguishable from the wild-type enzyme isolated from H. methylovorum GM2.
Shape-Based Computer-Aided Detection of Lung Nodules in Thoracic CT Images (2009)

In this paper, a new computer tomography (CT) lung nodule computer-aided detection (CAD) method is proposed for detecting both solid nodules and ground-glass opacity (GGO) nodules (part solid and nonsolid). This method consists of several steps. First, the lung region is segmented from the CT data using a fuzzy thresholding method. Then, the volumetric shape index map, which is based on local Gaussian and mean curvatures, and the "dot" map, which is based on the eigenvalues of a Hessian matrix, are calculated for each voxel within the lungs to enhance objects of a specific shape with high spherical elements (such as nodule objects). The combination of the shape index (local shape information) and "dot" features (local intensity dispersion information) provides a good structure descriptor for the initial nodule candidates generation. Antigeometric diffusion, which diffuses across the image edges, is used as a preprocessing step. The smoothness of image edges enables the accurate calculation of voxel-based geometric features. Adaptive thresholding and modified expectation-maximization methods are employed to segment potential nodule objects. Rule-based filtering is first used to remove easily dismissible nonnodule objects. This is followed by a weighted support vector machine (SVM) classification to further reduce the number of false positive (FP) objects. The proposed method has been trained and validated on a clinical dataset of 108 thoracic CT scans using a wide range of tube dose levels that contain 220 nodules (185 solid nodules and 35 GGO nodules) determined by a ground truth reading process. The data were randomly split into training and testing datasets. The experimental results using the independent dataset indicate an average detection rate of 90.2%, with approximately 8.2 FP/scan. Some challenging nodules such as nonspherical nodules and low-contrast part-solid and nonsolid nodules were identified, while most tissues such as blood vessels were excluded. The method's high detection rate, fast computation, and applicability to different imaging conditions and nodule types shows much promise for clinical applications.
Successful Therapy of Lethal Murine Visceral Leishmaniasis with Cystatin Involves Up-Regulation of Nitric Oxide and a Favorable T Cell Response (2001)

The virulence of Leishmania donovani in mammals depends at least in part on cysteine proteases because they play a key role in CD4(+) T cell differentiation. A 6-fold increase in NO production was observed with 0.5 microM chicken cystatin, a natural cysteine protease inhibitor, in IFN-gamma-activated macrophages. In a 45-day BALB/c mouse model of visceral leishmaniasis, complete elimination of spleen parasite burden was achieved by cystatin in synergistic activation with a suboptimal dose of IFN-gamma. In contrast to the case with promastigotes, cystatin and IFN-gamma inhibited the growth of amastigotes in macrophages. Although in vitro cystatin treatment of macrophages did not induce any NO generation, significantly enhanced amounts of NO were generated by macrophages of cystatin-treated animals. Their splenocytes secreted soluble factors required for the induction of NO biosynthesis, and the increased NO production was paralleled by a concomitant increase in antileishmanial activity. Moreover, splenocyte supernatants treated with anti-IFN-gamma or anti-TNF-alpha Abs suppressed inducible NO generation, whereas i.v. administration of these anticytokine Abs along with combined therapy reversed protection against infection. mRNA expression and flow cytometric analysis of infected spleen cells suggested that cystatin and IFN-gamma treatment, in addition to greatly reducing parasite numbers, resulted in reduced levels of IL-4 but increased levels of IL-12 and inducible NO synthase. Not only was this treatment curative when administered 15 days postinfection, but it also imparted resistance to reinfection. These studies provide a promising alternative for protection against leishmaniasis with a switch of CD4(+) differentiation from Th2 to Th1, indicative of long-term resistance.
Gene regulation by decoy approach (I): synthesis and properties of photo-crosslinked oligonucleotides. (1997)

To explore gene regulation by double stranded oligonucleotides as decoy molecules for transcriptional factors, oligodeoxyribonucleotides (ODN) and the complementary oligo(deoxyribonucleoside phosphorothioate)s (OPT) were photo-crosslinked by use of psoralen. UV melting curves showed that the thermal stability of crosslinked duplexes increased compared with that of non-crosslinked ones. CD spectra showed that the photo-crosslinked duplexes formed B-DNA structure. In addition, cross-linked duplexes were resistant against digestion by snake venom phosphodiesterase. These results suggest that the photo-crosslinked duplexes have desirable characteristics as decoy molecules.
A blinded, randomized, placebo‐controlled, dose determination trial of lokivetmab (ZTS‐00103289), a caninized, anti‐canine IL‐31 monoclonal antibody in client owned dogs with atopic dermatitis (2016)

Lokivetmab (0.5, 2.0 mg/kg) reduced pruritus compared to placebo for at least 1 month. Level and duration of response increased with increasing dose. Further studies are needed to better understand variability in individual responses across a broader population of dogs with AD.
Differential expression of a basic helix-loop-helix phosphoprotein gene, G0S8, in acute leukemia and localization to human chromosome 1q31. (1995)

A basic helix-loop-helix phosphoprotein gene, G0S8, was recently isolated by differential screening of cDNA from human blood mononuclear cells stimulated with a T cell mitogen and cycloheximide. In this study, G0S8 expression was examined in normal and malignant hematopoietic cells by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). G0S8 expression was observed in most fresh samples of acute myelogenous leukemia (AML) (28/30) and most cases of adult acute lymphoblastic leukemia (ALL) (9/11) regardless of clinical classification. G0S8 mRNA was also detected in all cases tested of chronic myelogenous leukemia (CML) in blast crisis. However, G0S8 expression was not detected in CML patients in chronic phase, nor in normal bone marrow or other hematopoietic cells. G0S8 has been mapped using fluorescence in situ hybridization (FISH) to human chromosome 1q31, the same site reported for the B cell homolog BL34/1R20 and within a region implicated in the development of hematological malignancies. The consistent observation of G0S8 mRNA in patient samples of acute leukemia suggests that G0S8 expression may either play a role in leukemogenesis or represent a common consequence of dysregulated growth.
Polymer field-effect transistor gated via a poly(styrenesulfonic acid) thin film (2006)

A polyanionic proton conductor, named poly(styrenesulfonic acid) (PSSH), is used to gate an organic field-effect transistor (OFET) based on poly(3-hexylthiophene) (P3HT). Upon applying a gate bias, large electric double layer capacitors (EDLCs) are formed quickly at the gate-PSSH and P3HT-PSSH interfaces due to proton migration in the polyelectrolyte. This type of robust transistor, called an EDLC-OFET, displays fast response (&amp;lt;1ms) and operates at low voltages (&amp;lt;1V). The results presented are relevant for low-cost printed polymer electronics.
A novel electromagnetically coupled microstrip antenna with a rotatable patch for personal handy-phone system units (1998)

In this paper, we propose a novel electromagnetically coupled microstrip antenna with a rotatable patch to overcome the problems associated with the conventional whip antenna for the personal handy-phone system (PHS). The structure of the newly developed antenna installed in actual PHS units is described. Its fundamental characteristics such as radiation pattern, bandwidth, and gain are shown. The performance of the antenna in actual propagation environments is also clarified. It is shown that this novel antenna is superior to the conventional whip antenna and achieves efficient performance in commercial PHS service.
Concurrent DNA hypermethylation of multiple genes in acute myeloid leukemia. (1999)

Hypermethylation in cancer often occurs in CpG islands that span the promoter regions of tumor suppressor genes. However, it is not clear if hypermethylation is limited to single target genes or if multiple genes are simultaneously methylated. To understand the extent of aberrant de novo methylation, we have analyzed the methylation pattern of a number of tumor-related genes in leukemia from the same cohort of patients. We used bisulfite genomic sequencing to characterize the methylation pattern of the CpG islands associated with the calcitonin, estrogen receptor, E-cadherin, p15, p16, Rb, GST-Pi, and HIC1 genes in the bone marrow from 9 normal and 20 patients with acute myeloid leukaemia (AML). All of the normal control samples were essentially unmethylated for each of the eight tumor-related genes studied. In contrast, 19 of 20 (95%) of the AML patients had an abnormal methylation pattern in at least one gene, and 15 of 20 (75%) had abnormal methylation patterns in two or more of the target genes. We conclude that there is a general deregulation of CpG island methylation in leukemia and that hypermethylation is not limited to single genes, but a number of genes are methylated concurrently. Moreover, the subset of genes that are commonly methylated in leukemia appear to be cancer type specific.