gebhart/patrepeval huggingface dataset:
The Human CD4<sup>+</sup>T Cell Response against Mumps Virus Targets a Broadly Recognized Nucleoprotein Epitope (2019)

Mumps outbreaks among vaccinated young adults stress the need for a better understanding of mumps virus (MuV)-induced immunity. Antibody responses to MuV are well characterized, but studies on T cell responses are limited. We recently isolated a MuV-specific CD4<sup>+</sup> T cell clone by stimulating peripheral blood mononuclear cells (PBMCs) from a mumps case with the viral nucleoprotein (MuV-N). In this study, we further explored the identity and relevance of the epitope recognized by the CD4<sup>+</sup> T cell clone and <i>ex vivo</i> by T cells in a cohort of mumps cases. Using a two-dimensional matrix peptide pool of 15-mer peptides covering the complete MuV-N, we identified the epitope recognized by the T cell clone as MuV-N<sub>110-124</sub> GTYRLIPNARANLTA, present in a well-conserved region of the viral protein. Upon peptide-specific stimulation, the T cell clone expressed the activation marker CD137 and produced gamma interferon, tumor necrosis factor, and interleukin-10 in a HLA-DR4-restricted manner. Moreover, the CD4<sup>+</sup> T cells exerted a cytotoxic phenotype and specifically killed cells presenting MuV-N<sub>110-124</sub> Furthermore, the identified peptide is widely applicable to the general population since it is predicted to bind various common HLA-DR molecules, and epitope-specific CD4<sup>+</sup> T cells displaying cytotoxic/Th1-type properties were found in all tested mumps cases expressing different HLA-DR alleles. This first broadly recognized human MuV-specific CD4<sup>+</sup> T cell epitope could provide a useful tool to detect and evaluate virus-specific T cell responses upon MuV infection or following vaccination.<b>IMPORTANCE</b> Recent outbreaks of mumps among vaccinated young adults have been reported worldwide. Humoral responses against mumps virus (MuV) are well characterized, although no correlate of protection has been elucidated, stressing the need to better understand cellular MuV-specific immunity. In this study, we identified the first MuV T cell epitope, which is derived from the viral nucleoprotein (MuV-N) and was recognized by a cytotoxic/Th1 CD4<sup>+</sup> T cell clone that was isolated from a mumps case. Moreover, the epitope was predicted to bind a broad variety of common HLA-DRB1 alleles, which was confirmed by the epitope-specific cytotoxic/Th1 CD4<sup>+</sup> T cell responses observed in multiple mumps cases with various HLA-DRB1 genotypes. The identified epitope is completely conserved among various mumps strains. These findings qualify this promiscuous MuV T cell epitope as a useful tool for further in-depth exploration of MuV-specific T cell immunity after natural mumps virus infection or induced by vaccination.
Identification of a 1-megabase consensus region of deletion at 1p36.3 in primary neuroblastomas (2000)

We have identified a 1-Mb consensus region of deletion within 1p36.3 defined by primary tumor deletions, constructed a physical map of the region that is being sequenced to completion, and have identified and prioritized candidate genes within this region for further analyses.
Sequence and expression of GLN3, a positive nitrogen regulatory gene of Saccharomyces cerevisiae encoding a protein with a putative zinc finger DNA-binding domain. (1991)

The GLN3 gene of Saccharomyces cerevisiae is required for the activation of transcription of a number of genes in response to the replacement of glutamine by glutamate as source of nitrogen. We cloned the GLN3 gene and constructed null alleles by gene disruption. GLN3 is not essential for growth, but increased copies of GLN3 lead to a drastic decrease in growth rate. The complete nucleotide sequence of the GLN3 gene was determined, revealing one open reading frame encoding a polypeptide of 730 amino acids, with a molecular weight of approximately 80,000. The GLN3 protein contains a single putative Cys2/Cys2 zinc finger which has homology to the Neurospora crassa NIT2 protein, the Aspergillus nidulans AREA protein, and the erythroid-specific transcription factor GATA-1. Immunoprecipitation experiments indicated that the GLN3 protein binds the nitrogen upstream activation sequence of GLN1, the gene encoding glutamine synthetase. Neither control of transcription nor control of initiation of translation of GLN3 is important for regulation in response to glutamine availability.
The Design and Evolution of Disney’s Hyperion Renderer (2018)

Walt Disney Animation Studios has transitioned to path-traced global illumination as part of a progression of brute-force physically based rendering in the name of artist efficiency. To achieve this without compromising our geometric or shading complexity, we built our Hyperion renderer based on a novel architecture that extracts traversal and shading coherence from large, sorted ray batches. In this article, we describe our architecture and discuss our design decisions. We also explain how we are able to provide artistic control in a physically based renderer, and we demonstrate through case studies how we have benefited from having a proprietary renderer that can evolve with production needs.
Submillimeter Emission from Optically Pumped <sup>14</sup>NH<sub>3</sub> (1973)

A CO2 TEA laser was used for optical pumping of 14NH3. Thirteen CO2 lines, which deviate by 0.05 cm-1 or less from transitions in 14NH3, were effective in producing submillimeter laser transitions. Most of the 24 emitted lines have wavelengths between 70 and 400 μm and represent rotation-inversion transitions in the ν2 state of NH3. A few short wavelength lines (30-70 μm) are 2ν2 transitions obtained by pumping from the ν2 state.
Expression of three major protein kinase C isozymes in various types of human leukemic cells. (1991)

We examined the levels of protein kinase C (PKC) activity and the expressions of its three major isozymes, designated types I (gamma), II (beta), and III (alpha), in the cytosol and particulate fractions of cells from patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL), in an attempt to elucidate the cell type- or lineage-specific expression of these isozymes. The levels of PKC activities in the cytosol and particulate fractions from AML cells were higher than those from ALL or CLL cells. The average PKC activities of AML cells, ALL cells, and CLL cells were 18.7, 12.2, and 11.3 pmol/min/10(8) cells, respectively, in the cytosol fractions and 4.4, 3.1, and 2.6 pmol/min/10(8) cells, respectively, in their particulate fractions. M1 cells (French-American-British classification) and AML cells with T-lymphocyte-associated surface antigens, such as CD2 and CD7, had significantly lower PKC activities among AML cells. Immunoblot analyses using monoclonal antibodies against each isozyme revealed that all three isozymes were broadly distributed on leukemic cells with considerable variability in the level of expression. All lymphoid leukemic cells expressed PKC-gamma in the cytosol fractions, albeit a minor component; however, this type was observed in cells from only half the number of AML patients. Those AML cells with cytosolic PKC-gamma usually expressed lymphoid surface antigens, such as CD2, CD7, and CD19. On the other hand, cytosolic PKC-beta and PKC-alpha were commonly observed in all types of leukemic cells. AML cells expressed these two types at almost equal levels, but in lymphoid cells, expressions of PKC-beta were usually more abundant than those of PKC-alpha. These data suggest that AML cells with lymphoid antigens might have a lower PKC activity but more predominant expression of cytosolic PKC-gamma than the usual AML cells.
Properties of epitaxial Ba-hexaferrite thin films on A-, R-, and C-plane oriented sapphire substrates (1993)

Thin films of Ba-hexaferrite of the magnetoplumbite structure have been prepared on sapphire substrates of orientation (112̄0), (11̄02), and (0001). Torque magnetometry indicates easy axes parallel, tilted off parallel, and perpendicular to the substrate for the A-, R-, and C-plane substrates. X-ray diffraction shows that this is due to epitaxy between the Ba-ferrite and sapphire. For each substrate orientation, the c axes of the Ba-hexaferrite and sapphire are parallel and the directions of close packing in the close-packed oxygen planes perpendicular to the c axes are parallel. Torque measurements are consistent with the combined effects of crystal and shape anisotropy. These results suggest that Ba-hexaferrite thin films with an easy axis at any angle with respect to the substrate can be prepared by appropriate choice of the sapphire substrate orientation, which may be of interest for microwave and other applications.
The mosquitocidal activity of<i>Bacillus thuringiensis</i>var.<i>israelensis</i>is associated with<i>M</i><sub>r</sub>230 000 and 130 000 crystal proteins (1986)

Crystals from Bacillus thuringiensis var. israelensis appeared to contain three major proteins of Mr 230 000, 130 000 and 28 000. These proteins were solubilized from the crystals by incubation in 10 mM DTT, pH 9.5, and purified by sucrose gradient centrifugation. The Mr 230 000 and 130 000 crystal proteins showed mosquitocidal properties, whereas the Mr 28 000 crystal protein contained haemolytic activity. Immobilization of these proteins on latex beads did not alter these properties. Partial proteolytic degradation showed that the Mr 130 000 and 28 000 proteins are structurally different.
Analysis of virulence and growth of a purine auxotrophic mutant of<i>Xanthomonas oryzae</i>pathovar<i>oryzae</i> (2007)

Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight of rice. A random insertional mutant library of Xoo KACC10331 was constructed using a Tn5-derived transposon, and the virulence of the mutants against the susceptible rice cultivar IR24 was assayed. After the virulence assay, the M793 (purD::Tn5) mutant that had reduced virulence against the rice plants was isolated. Thermal asymmetric interlaced-PCR and sequence analysis revealed that the transposon was inserted into the purD gene (encodes a phosphoribosylamine-glycine ligase) of the M793 mutant. The reverse transcriptase-PCR assay revealed that the mutation of the purD gene did not affect the expression of other purine biosynthesis genes. However, the M793 mutant required exogenous purines and thiamine for growth in minimal media. These results indicate that the purD gene plays a crucial role in the growth and virulence of Xoo.
Enzymic O-glycosylation of synthetic peptides from sequences in basic myelin protein (1979)

Nine synthetic peptides containing sequences in the region of a threonine residue at position 98 of bovine basic myelin protein were prepared by the Merrifield solid-phase method and tested for their ability to be glycosylated with [14C]uridinediphospho-N-acetylgalactosamine and a crude detergent-solubilized preparation of uridinediphospho-N-acetylgalactosamine:mucin polypeptide N-acetylgalactosaminyltransferase obtained from porcine submaxillary glands. The tetrapeptide Thr-Pro-Pro-Pro and all larger peptides containing this sequence were glycosylated. The glycosylation was greater for peptides containing residues N-terminal to the Thr-Pro-Pro-Pro. Under the conditions used, the peptide Val-Thr-Pro-Arg-Thr-Pro-Pro-Pro was glycoslyated twice as much as bovine basic myelin protein. Thr-Pro and Thr-Pro-Pro, as well as 10 other synthetic peptides which did not contain the Thr-Pro-Pro-Pro sequence, were not glycosylated. Treatment of the glycopeptide of Phe-Lys-Asn-Leu-Val-Thr-Pro-Arg-Thr-Pro-Pro-Pro-Ser with an alpha-N-acetylgalactosaminidase released N-acetylgalactosamine from the peptide, indicating that the hexosamine was covalently bonded to the peptide in an alpha linkage.
Correlation of DNA hypomethylation with expression of carcinoembryonic antigen in human colon carcinoma cells. (1988)

Using an assay based on the binding of a carcinoembryonic antigen (CEA)-specific monoclonal antibody, we have examined the expression of carcinoembryonic antigen genes in human colon tumor and normal fibroblast cell lines. CEA expression was not detectable in the normal fibroblast cell lines, whereas varying levels of high CEA expression were found in the colon tumor cell lines LS-174T, GEO, and WIDR. We have used a 550-base pair CEA probe derived from cloned complementary DNA to carry out Southern analysis of the DNA isolated from the normal and colon tumor cell lines. At high stringency, the CEA probe detected seven BamHI fragments in all DNAs analyzed. At low stringency, however, 14 BamHI fragments ranging from 1.5 to 23 kilobases were detected. Results of the Southern analysis demonstrate no amplification or rearrangement of the CEA genes in tumor cells. We used methylation-sensitive restriction endonucleases, HpaII and HhaI, to compare the degree of methylation of CEA family of genes in normal and colon tumor cell lines. Our results demonstrate that the CEA family of genes exists in a state of hypermethylation in the normal cell lines. In contrast, the CEA gene(s) are relatively hypomethylated in the tumor cell lines, suggesting a correlation between the state of methylation and degree of expression of the CEA gene(s). A comparison of the state of methylation of the CEA gene(s) in cells before and after treatment with the gamma-interferon (which up-regulates CEA steady-state mRNA levels) showed no detectable difference in the degree of DNA methylation. The segments of CEA genes that are hypermethylated in normal cells, but are hypomethylated in tumor cells, were also identified. Thus, these studies may help identify the sites of methylation that are crucial for the control of CEA gene regulation.
Evaluation of Hepatoprotective activity of Ethanolic Extract of Nymphaea alba Linn Flower in experimental rats (2013)

Objective: In the present study Hepatoprotective activity of Ethanolic Extract of flower of Nymphaea alba Linn were investigated. Material and Method: The hepatoprotective activity of Ethanolic Extract of flower of Nymphaea alba were evaluated by Carbon Tetra Chloride and Paracetamol induced hepatotoxicity in experimental rats. The Etnanolic Extract of Nymphaea alba (200 and 400 mg/kg) treat the hepatotoxicity and produced significant inhibition in the wet liver weight and wet liver volumes and the serum enzymes (SGOT, SGPT and ALP), bilirubin and cholesterol levels. Result: Preliminary phytochemical analysis of Ethanolic Extract of Nymphaea alba revealed that the presence of various phytoconstituents Alkaloids, Carbohydrates (Polysaccharides), Glycosides, Steroids, Flavonoids and Tannin and Phenolic compound. The ethanolic extract (200 and 400 mg/kg) showed significant reduction in SGOT, SGPT, ALP, Bilirubin and cholesterol level as compared to control group. Maximum inhibition was obtained at dose 400 mg/kg of Ethanolic Extract of Nymphaea alba in both model. Conclusion: The present study suggests that Ethanolic Extract of flower of Nymphaea alba Linn possess strong and potential Hepatoprotective activity in both model. So it has immense scope as an effective source to develop drug for the treatment of liver related diseases. These results may further suggest that ethanolic extract was found to possess hepatoprotective activity.
Understanding the mechanism of copurification of “difficult to remove” host cell proteins in rituximab biosimilar products (2019)

Host cell proteins (HCPs) are considered a critical quality attribute and are linked to safety and efficacy of biotherapeutic products. Researchers have identified 10 HCPs in Chinese hamster ovary (CHO) that exhibit common characteristics of product association, coelution, and age-dependent expression and therefore are "difficult to remove" during downstream purification. These include cathepsin D, clusterin, galectin-3-binding protein, G-protein coupled receptor 56, lipoprotein lipase, metalloproteinase inhibitor, nidogen-1 secreted protein acidic and rich in cysteine (SPARC), sulfated glycoprotein, and insulin-like growth factor-2 RNA-binding protein. While the levels of HCPs in the investigated biosimilars were within the acceptable range of <100 ppm, certain "difficult to remove" HCPs were found in the biosimilar samples. This article aims to elucidate the underlying interactions between these "difficult to remove" HCPs and the mAb product. Surface study of rituximab exhibited unstable discontinuous patches of residues on the protein surface that have high propensity to get buried and lower the solvent exposed area. The higher order structure and the receptor binding were not affected, except for one of the biosimilars, owing to extremely low-HCP levels in its final drug product. Finally, based on the combined experimental and computational data from this study, a probable mechanism of retention for the 10 HCPs is proposed. The results presented here can guide downstream process design or avenues for protein engineering during product discovery to achieve more effective removal of the impurities.
Single cell multiple biomarker analysis in archival breast fine-needle aspiration specimens: quantitative fluorescence image analysis of DNA content, p53, and G-actin as breast cancer biomarkers. (1998)

Fine-needle aspiration (FNA) is a sensitive and cost-effective method for evaluating breast lesions. However, the diagnosis of early premalignant lesions is less reliable by FNA because of a lack of distinctive cytological features. Accurately defining the risk of such lesions at the individual level may have significant impact in breast cancer prevention and management. The main objective of this preliminary study was to develop a method to study multiple biomarkers on archival FNA slides using quantitative fluorescence image analysis (QFIA). Biomarkers p53, G-actin, and DNA content were labeled with an immunofluorescence technique and measured by QFIA simultaneously on a single cell basis. QFIA allows the labeling and measurement procedures to be carried out in situ, without the need to remove cells from the slide while preserving the morphology of the cells. FNA slides from 72 incident patients were obtained for this study. Fifty-six cases had an adequate number of cells for the actual analysis (25 benign breast lesions, 14 proliferative breast diseases with nuclear atypia, and 17 malignant lesions). The DNA content (> or = 5c) and G-actin (average gray mean, > 90) were positive in 81% and 88% of malignant lesions, respectively. These were significantly higher than the corresponding positive rates in benign lesions (7% and 15%, respectively; P <0.01 for both). None of the benign cases were positive for G-actin and DNA simultaneously, and none of the malignant cases were negative for G-actin and DNA together. p53 was positive in 33% of malignant lesions and 8% of benign lesions (P >0.05). Our study demonstrates the feasibility of evaluating multiple biomarkers by QFIA on archival FNA-fixed specimens. The G-actin and DNA content assayed by QFIA may be potential intermediate end point markers for breast cancer individual risk assessment.
Pharmacokinetics of a New Benzimidazole Sulfoxide Derivative, E3810. (2): Absorption, Distribution, Metabolism and Excretion in Rats. (1994)

ラットに14C-E3810あるいは[alpha methylene-14C]E3810を投与したときの吸収，分布，代謝，排泄について検討した．1．ラットに14C-E3810(20mg/kg)を十二指腸内投与したとき，14C-E3810は速やかに吸収され，投与後15分で血液中放射能濃度は最高値(3.86μg eq./ml)に達し，それ以降，血液中放射能の消失は緩徐であった．しかしながら，血漿中からの放射能の消失は極めて速やかであった．[alpha methylene-14C]E3810を投与したときの血液中放射能の消失は，14C-E3810の投与の場合より速やかであった．2．ラットに14C-E3810(20mg/kg)を十二指腸内投与したときの放射能は，甲状腺を除く臓器，組織に速やかに分布した．脳への移行は低かった．組織からの放射能の消失は，血球および甲状腺を除き速やかであった．[alpha methylene-14C]E3810を投与したときの血球および甲状腺中の放射能の消失は14C-E3810を用いた場合より速やかであった．このことから，血球および甲状腺への残留は，E3810分子構造中のベンズイミダゾール環部分が関与しているものと考えられた．また，14C-E3810をin vitroで新鮮な血液に添加したときの血球への放射能の移行性は，ラットがヒト，イヌに比べ高いことが認められた．3．ラットに14C-E3810を静脈内投与したときの，全身オートラジオグラフィーによる体内分布および計測分布の検討から，標的組織である胃粘膜に放射能が局在することが認められた．4，ラットに14C-E3810(20mg/kg)を十二指腸内投与したときの血漿中未変化体の存在比は投与後15分で12.1%，2時間で1.9%であり，血漿中主代謝物は，UM-1，UM-2であり，その他M-1，M-2が認められた．門脈血液においては大半が未変化体であることから，肝臓における代謝が大きいものと推察された．5．ラットに14C-E3810(20mg/kg)を十二指腸内投与したときの尿，糞中排泄率は，投与後8日までにそれぞれ39.75%，56.32%であった．また，[alphamethylene-14C]E3810を投与したときの尿，糞中排泄率は，投与後7日までにそれそれ53.0%，47.20%であった．ラットに14C-E3810(20mg/kg)を十二指腸内投与したときの胆汁中排泄率は，投与後24時間で60.86%であった．
The structure and function of surfactant protein A. Hydroxyproline- and carbohydrate-deficient mutant proteins. (1994)

Pulmonary surfactant protein A (SP-A) regulates the uptake and secretion of phospholipid by alveolar type II cells and is an important component of surfactant lipid aggregates. In an attempt to understand how specific structural domains of SP-A relate to the function of the protein, we used site-directed mutagenesis of the cDNA for SP-A and heterologous expression with baculovirus vectors. Synthesis of the wild type SP-A in insect cells resulted in a form of the protein in which proline residues were not hydroxylated and that is denoted SP-Ahyp. Three mutant SP-As with substitutions in the consensus sequences for glycosylation (SP-Ahyp,glc) to prevent N-linked oligosaccharide attachment at Asn1 and Asn187 were produced, individually and in tandem. The SP-Ahyp was glycosylated at both the Asn1 and Asn187 positions, demonstrated partial sulfhydryl-dependent oligomerization, and formed incomplete oligomers in solution. The SP-Ahyp and SP-Ahyp,glc bound to immobilized carbohydrate and to phospholipid liposomes and partially competed for occupancy of a plasma-membrane receptor for SP-A. The SP-Ahyp and the SP-Ahyp,glc were equally effective inhibitors of the secretion of surfactant lipids from isolated type II cells (IC50 = 0.5 microgram/ml) and aggregated phospholipid liposomes at 20 degrees C. All of the recombinant SP-As demonstrated markedly reduced aggregation of lipid at 37 degrees C. We conclude that the hydroxylation of proline residues is required for perfect oligomerization of SP-A and for thermal stability in the interaction with lipid. Furthermore, recombinant SP-A is able to inhibit the secretion of phospholipid from isolated type II cells and to aggregate lipid vesicles independent of the presence of N-linked carbohydrate or the site of glycosylation.
A novel method to stop neural network training (2000)

A novel approach of stopping neural network training has been evaluated. The approach improves data utilization, provides a statistical rationale to stop training, and seems to present a robust method for automating the stopping of neural network training.
Detection of Severe Acute Respiratory Syndrome Coronavirus in the Brain: Potential Role of the Chemokine Mig in Pathogenesis (2005)

This study provides direct evidence that SARS human coronavirus is capable of infecting the central nervous system, and that Mig might be involved in the brain immunopathology of SARS.
Adherence to Treatment and Health Outcomes (1993)

Adherence (or compliance) is the extent to which a person's behavior coincides with medical or health advice. Recent evidence indicates that patients who adhere to treatment, even when that treatment is a placebo, have better health outcomes than poorly adherent patients. Based on this evidence, we now believe that the outcomes of treatment are not solely attributable to the specific action of a drug, but may also depend on other nonspecific therapeutic effects. We consider the implications of these findings for the design and interpretation of clinical research as well as for the care of patients.