gebhart/patrepeval huggingface dataset:
The effect of enhancing antibodies on TNF interactions with its specific receptor: consequences for in vitro TNF antiviral activity. (1994)

This study examines the interaction of TNF with its receptor(s) in the presence of antibodies which have been previously found to enhance the in vivo antiviral and antitumor activities of this cytokine. The presence of Mab 32 has been previously shown to enhance the binding of 125I-TNF to the surface L929 cells (13), and this property was also found in the present study for HeLa cells. In addition to this, Mab 32 was found to enhance the internalization of the TNF ligand into both L929 and HeLa cells compared to control treated cultures. The consequences of such enhanced TNF-binding on TNF antiviral activity were examined in both L929 cells and HeLa cells. It was discovered that the similarities in antibody-enhanced TNF binding and internalization contrasted dramatically with the sensitivities of these two cell lines to the antiviral actions of TNF, both with and without Mab 32 (viz., L929 cells were sensitive; HeLa cells were resistant). It has been proposed that the modulation of TNF-R expression, particularly by IFNs, is an important factor in TNF's biological effects. It has been shown that the presence of IFN-gamma, with TNF plus specific enhancing antibodies, further augmented antiviral activity in vivo (13). This finding stimulated interest in examining IFN-gamma modulation of TNF-R as a factor in the antiviral activity of TNF. The expression of TNF receptor(s) in TNF- and/or IFN-gamma-exposed cells, both with and without HSV-1 infection, was therefore examined. TNF alone could induce a dose-dependent increase in receptor expression which was not significantly increased by Mab 32. Exposure of L929 cells to IFN-gamma alone also induced TNF receptor expression in mock-infected cells. HSV-1 infection of L929 cells resulted in a significant upregulation of TNF-R expression which was reversed if the cells had been preexposed to IFN-gamma. The inclusion of TNF with IFN-gamma before infection restored TNF-R expression but did not show any further synergistic or additive effects on TNF-R expression. Some minor increases in TNF-R expression were seen if Mab 32 was included with these two cytokines.
Human liver iduronate-2-sulphatase. Purification, characterization and catalytic properties (1990)

Human iduronate-2-sulphatase (EC 3.1.6.13), which is involved in the lysosomal degradation of the glycosaminoglycans heparan sulphate and dermatan sulphate, was purified more than 500,000-fold in 5% yield from liver with a six-step column procedure, which consisted of a concanavalin A-Sepharose-Blue A-agarose coupled step, chromatofocusing, gel filtration on TSK HW 50S-Fractogel, hydrophobic separation on phenyl-Sepharose CL-4B and size separation on TSK G3000SW Ultrapac. Two major forms were identified. Form A and form B, with pI values of 4.5 and less than 4.0 respectively, separated at the chromatofocusing step in approximately equal amounts of recovered enzyme activity. By gel-filtration methods form A had a native molecular mass in the range 42-65 kDa. When analysed by SDS/PAGE, dithioerythritol-reduced and non-reduced form A and form B consistently contained polypeptides of molecular masses 42 kDa and 14 kDa. Iduronate-2-sulphatase was purified from human kidney, placenta and lung, and form A was shown to have similar native molecular mass and subunit components to those observed for liver enzyme. Both forms of liver iduronate-2-sulphatase were active towards a variety of substrates derived from heparin and dermatan sulphate. Kinetic parameters (Km and Kcat) of form A were determined with a variety of substrates matching structural aspects of the physiological substrates in vivo, namely heparan sulphate, heparin and dermatan sulphate. Substrate with 6-sulphate esters on the aglycone residue adjacent to the iduronic acid 2-sulphate residue being attack were hydrolysed with catalytic efficiencies up to 200 times above that observed for the simplest disaccharide substrate without a 6-sulphated aglycone residue. The effect of incubation pH on enzyme activity towards the variety of substrates evaluated was complex and dependent on substrate aglycone structure, substrate concentration, buffer type and the presence of other proteins. Sulphate and phosphate ions and a number of substrate and product analogues were potent inhibitor of form A and form B enzyme activities.
A conserved domain regulates interactions of the v-fps protein-tyrosine kinase with the host cell. (1987)

All cytoplasmic protein-tyrosine kinases (PTKs) share a noncatalytic domain, termed SH2, which comprises approximately 100 residues located immediately N-terminal to the kinase domain. A linker in the AX9m mutant of Fujinami avian sarcoma virus (FSV) introduces a dipeptide insertion into the SH2 domain of the P130gag-fps PTK, which abolishes its ability to transform Rat-2 cells. However, at 36 degrees C AX9m FSV elicits focus formation and agar colony formation in infected chicken embryo fibroblasts (CEF) with single hit kinetics. At 41.5 degrees C AX9m FSV is nontransforming for CEF, and the mutant is therefore both host and temperature dependent for transforming activity. Both in vitro and in vivo, the specific kinase activity of AX9m FSV P130gag-fps, measured by autophosphorylation and phosphorylation of exogenous substrates, correlated with transforming activity. The consequences of the AX9m mutation for enzymatic function and transforming activity therefore depend on the cellular environment in which the altered v-fps protein is expressed. We conclude that the SH2 domain directs the interaction of the P130gag-fps catalytic domain with cellular proteins such as substrates for phosphorylation or regulators of kinase activity important for its transforming ability.
The chemoreceptor superfamily in the honey bee, Apis mellifera : Expansion of the odorant, but not gustatory, receptor family (2006)

The honey bee genome sequence reveals a remarkable expansion of the insect odorant receptor (Or) family relative to the repertoires of the flies Drosophila melanogaster and Anopheles gambiae, which have 62 and 79 Ors respectively. A total of 170 Or genes were annotated in the bee, of which seven are pseudogenes. These constitute five bee-specific subfamilies in an insect Or family tree, one of which has expanded to a total of 157 genes encoding proteins with 15%-99% amino acid identity. Most of the Or genes are in tandem arrays, including one with 60 genes. This bee-specific expansion of the Or repertoire presumably underlies their remarkable olfactory abilities, including perception of several pheromone blends, kin recognition signals, and diverse floral odors. The number of Apis mellifera Ors is approximately equal to the number of glomeruli in the bee antennal lobe (160-170), consistent with a general one-receptor/one-neuron/one-glomerulus relationship. The bee genome encodes just 10 gustatory receptors (Grs) compared with the D. melanogaster and A. gambiae repertoires of 68 and 76 Grs, respectively. A lack of Gr gene family expansion primarily accounts for this difference. A nurturing hive environment and a mutualistic relationship with plants may explain the lack of Gr family expansion. The Or family is the most dramatic example of gene family expansion in the bee genome, and characterizing their caste- and sex-specific gene expression may provide clues to their specific roles in detection of pheromone, kin, and floral odors.
TOP2A and HER2 gene amplification as predictors of response to anthracycline treatment in breast cancer (2006)

The purpose of this study was to evaluate amplification of topoisomerase IIalpha (TOP2A) and HER2 genes as predictors of response to chemotherapy in advanced breast cancer. Gene copy number of TOP2A and HER2 were analysed with chromogenic in situ hybridization (CISH) on paraffin-embedded tissue sections from the primary tumour of 85 patients treated with anthracycline containing chemotherapy. TOP2A gene amplification was present in 14 (16%) and HER2 gene amplification in 38 (45%) of the primary tumours. Two of the 14 cases with TOP2A amplification were amplified without concurrent HER2 amplification. Neither TOP2A nor HER2 gene amplification were significantly associated with response to chemotherapy (p = 0.35 and p = 0.49, respectively).
Construction of multilocus genetic linkage maps in humans. (1987)

Human genetic linkage maps are most accurately constructed by using information from many loci simultaneously. Traditional methods for such multilocus linkage analysis are computationally prohibitive in general, even with supercomputers. The problem has acquired practical importance because of the current international collaboration aimed at constructing a complete human linkage map of DNA markers through the study of three-generation pedigrees. We describe here several alternative algorithms for constructing human linkage maps given a specified gene order. One method allows maximum-likelihood multilocus linkage maps for dozens of DNA markers in such three-generation pedigrees to be constructed in minutes.
Targeting Heat Shock Protein 90 Overrides the Resistance of Lung Cancer Cells by Blocking Radiation-Induced Stabilization of Hypoxia-Inducible Factor-1α (2009)

Hypoxia-inducible factor-1 (HIF-1) has been suggested to play a major role in tumor radioresistance. However, the mechanisms through which irradiation regulates HIF-1alpha expression remain unclear. The purpose of this study was to investigate the mechanisms that mediate HIF-1 activation and thus radioresistance. Here, we show that irradiation induces survival and angiogenic activity in a subset of radioresistant lung cancer cell lines by elevating HIF-1alpha protein expression. Radiation induced HIF-1alpha protein expression mainly through two distinct pathways, including an increase in de novo protein synthesis via activation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and stabilization of HIF-1alpha protein via augmenting the interaction between heat shock protein 90 (Hsp90) and HIF-1alpha protein. Whereas the PI3K/Akt/mTOR pathway was activated by irradiation in all the lung cancer cells examined, the Hsp90-HIF-1alpha interaction was enhanced in the resistant cells only. Inhibition of Hsp90 function by 17-allylamino-17-demethoxygeldanamycin or deguelin, a novel natural inhibitor of Hsp90, suppressed increases in HIF-1alpha/Hsp90 interaction and HIF-1alpha expression in radioresistant cells. Furthermore, combined treatment of radiation with deguelin significantly decreased the survival and angiogenic potential of radioresistant lung cancer cells in vitro. We finally determined in vivo that systemic administration of deguelin resulted in profound inhibition of tumor growth and angiogenesis when combined with radiation. These results provide a strong rationale to target Hsp90 as a means to block radiation-induced HIF-1alpha and thus to circumvent radioresistance in lung cancer cells.
Trunk Muscle Balance and Muscular Force (1987)

An investigation of the absolute strength of the human muscle was carried out on the in vivo erector spinae muscle using magnetic resonance tomography coupled with dynamic muscular testing. The absolute strength of the erector spinae was calculated to be 48 N/cm2. The area of the rectus abdominis was 15.1 cm2, and the area of the erector spinae was 54.5 cm2. The internal moment arm for the rectus abdominis and erector spinae muscles was 7.04 and 5.64 cm, respectively. The static force measures showed the trunk extensor moment to be only 30% greater than the flexor moment. The difference is discussed in terms of the absolute strength of muscle, and other anatomic factors.
Viral and Host Factors in Human Respiratory Syncytial Virus Pathogenesis (2007)

Human respiratory syncytial virus (RSV) was first isolated in 1956 from a laboratory chimpanzee with upper respiratory tract disease (for general reviews, see references 21, 57, 102, and 145).RSV was quickly determined to be of human origin and was shown to be the leading worldwide viral agent of serious pediatric respiratory tract disease.In a 13-year prospective study of infants and children in the United States, RSV was detected in 43%, 25%, 11%, and 10% of pediatric hospitalizations for bronchiolitis, pneumonia, bronchitis, and croup, respectively (110).Approximately two-thirds of infants are infected with RSV during the first year of life, and 90% have been infected one or more times by 2 years of age.The rate of hospitalization for primary infection is approximately 0.5% but can vary by situation and ethnic group and can be as high as 25% (77).RSV also is a significant cause of morbidity and mortality in the elderly, with an impact approaching that of nonpandemic influenza virus (39).RSV readily infects severely immunocompromised individuals, most notably allogeneic bone marrow transplant recipients, causing high mortality.RSV also makes a substantial contribution to upper respiratory tract disease in individuals of all ages (59, 65).Globally, the World Health Organization estimates that RSV causes 64 million infections and 160,000 deaths annually (Initiative for Vaccine Research: respiratory syncytial virus, World Health Organization [http: //www.who.int/vaccine_research/diseases/ari/en/index3.html,accessed 5 December 2005]).Although RSV has a single serotype, reinfection can occur throughout life.RSV in yearly winter/early spring epidemics in temperate regions; elsewhere, the timing of RSV activity can vary widely with the locale.The RSV reservoir in the offseason is unknown.Strains circulate quickly around the earth (150).Neither a vaccine nor an effective antiviral therapy is available, although there is active research in both areas (23,78, 138).However, infants at high risk for serious disease can receive passive immunoprophylaxis during the epidemic season by a monthly injection of a commercial RSV-neutralizing monoclonal antibody, palivizumab (Synagis), which provides a 55% reduction in RSV-associated hospitalization (17).
Expression of retinoic acid receptor-alpha mRNA in human leukemia cells with variable responsiveness to retinoic acid. (1989)

Retinoic acid receptor (RAR)-alpha mRNA expression was studied in a variety of myeloid leukemia cells with variable responsiveness to the induction of terminal differentiation by retinoic acid (RA). Cells from both the wild-type (wt), RA-responsive HL-60 promyelocytic leukemia cell line and a selected greater than or equal to 300-fold RA-resistant subline expressed approximately equal amounts of two RAR-alpha transcripts, 4.0 and 3.1 kb in size. In wt cells, the RAR-alpha did not change during induction of granulocyte differentiation by RA or macrophagic differentiation by 12-0-tetradecanoylphorbol-13-acetate (TPA). Relative to HL-60 cells, other cultured and fresh myeloid leukemia cells expressed 2.5-fold less to equal amounts of the RAR-alpha transcripts. The relative expression in six cases of acute promyelocytic leukemia (APL; two RA-responsive; one, previously treated with 13-cis-RA in vivo, equivocally RA-responsive) and one case of acute myelogenous leukemia (AML) with promyelocytosis (RA unresponsive) was 0.91 +/- 0.14 versus 0.53 +/- 0.14 for eight cases of nonpromyelocytic AML (p congruent to 0.001). Lymphoid leukemia cells expressed 2- to 5-fold less RAR-alpha mRNA. No qualitative variations in the mRNA transcripts were observed, although the 3.1 kb transcript was relatively decreased in three cases. The RAR-alpha gene was not amplified or detectably rearranged in any DNA source, although an apparent EcoRI restriction fragment length polymorphism was observed. It is concluded (a) that the steady-state level of RAR-alpha mRNA is not tightly correlated with natural responsiveness/unresponsiveness or, in some instances, acquired resistance to RA-induced differentiation and (b) that further studies are needed to determine if the mean 1.7-fold higher RAR-alpha mRNA level in APL cells could be an essential factor in the RA-responsiveness of APL cells, as primarily regulated at a different molecular level.
Enantioselective Organocatalytic Michael Addition Reactions between N-Heterocycles and Nitroolefins (2006)

[reaction: see text] A method for Michael addition of N-heterocycles to nitroolefins has been developed. The process is promoted by a cinchona alkaloid derivative to give Michael adducts in moderate to high enantioselectivities.
Water‐Soluble Fluorescent Silver Nanoclusters (2010)

Ag nanoclusters consist of several to roughly a hundred atoms and possess sizes comparable to the Fermi wavelength of electrons; they exhibit molecule-like properties, including discrete electronic transitions and strong fluorescence. These nanoclusters are of significant interest because they provide the bridge between atomic and nanoparticle behavior in noble metals. Since the first observations of photoluminescence from Ag nanoclusters, substantial effort has been made to prepare Ag nanoclusters and explore their potential applications. The synthesis of well-defined Ag nanoclusters, however, is difficult due to aggregation of nanoclusters, especially in aqueous solutions. In this Research News article, we highlight some recent progress on solution-based synthesis of water-soluble Ag nanoclusters using radiolytic, chemical reduction and photochemical approaches to prepare fluorescent Ag nanoclusters.
Synchronization of Meiosis in Porcine Oocytes by Exposure to Dibutyryl Cyclic Adenosine Monophosphate Improves Developmental Competence Following in Vitro Fertilization1 (1997)

The effect of stage of maturation of the germinal vesicle of porcine oocytes at the time of in vitro maturation on subsequent developmental competence was examined. A large variation exists in the germinal vesicle morphology of oocytes at the time of collection of cumulus-oocyte complexes (COCs) and after culture in the absence of dibutyryl cAMP (dbcAMP) for 20 h. However, the morphology of the germinal vesicle was synchronized to a specific stage after culture in the presence of 1 mM dbcAMP for 20 h. There was no difference in germinal vesicle breakdown rate (total mean, 75.0 +/- 5.4%) or in maturation rate (total mean, 82.1 +/- 2.1 %) at 28 and 44 h of culture, respectively. However, differences in meiotic progress of oocytes were observed (p < 0.05) at 36 h of culture when COCs were exposed to dbcAMP for the first 20 h of maturation, as compared to controls. The incidence of embryos that developed to the blastocyst stage after in vitro fertilization was higher (p < 0.05) when COCs were exposed to dbcAMP (21.5 +/- 2.5%) as compared to controls (9.2 +/- 1.6%). After transfer of experimental embryos to four recipient gilts, the three pregnant recipients delivered 19 live piglets. These results indicate that exposure of COCs to dbcAMP for the first 20 h of culture for maturation increases the homogeneity of oocyte nuclear maturation and improves the efficiency of in vitro production of swine embryos.
Polysaccharide Biosynthesis Locus Required for Virulence ofBacteroides fragilis (2001)

Bacteroides fragilis, though only a minor component of the human intestinal commensal flora, is the anaerobe most frequently isolated from intra-abdominal abscesses. B. fragilis 9343 expresses at least three capsular polysaccharides-polysaccharide A (PS A), PS B, and PS C. Purified PS A and PS B have been tested in animal models and are both able to induce the formation of intra-abdominal abscesses. Mutants unable to synthesize PS B or PS C still facilitate abscess formation at levels comparable to those of wild-type 9343. To determine the contribution of PS A to abscess formation in the context of the intact organism, the PS A biosynthesis region was cloned, sequenced, and deleted from 9343 to produce a PS A-negative mutant. Animal experiments demonstrate that the abscess-inducing capability of 9343 is severely attenuated when the organism cannot synthesize PS A, despite continued synthesis of the other capsular polysaccharides. The PS A of 9343 contains an unusual free amino sugar that is essential for abscess formation by this polymer. PCR analysis of the PS A biosynthesis loci of 50 B. fragilis isolates indicates that regions flanking each side of this locus are conserved in all strains. The downstream conserved region includes two terminal PS A biosynthesis genes that homology-based analyses predict are involved in the synthesis and transfer of the free amino sugar of PS A. Conservation of these genes suggests that this sugar is present in the PS A of all serotypes and may explain the abscessogenic nature of B. fragilis.
Microstructure and mechanical properties of poly(L‐lactide) scaffolds fabricated by gelatin particle leaching method (2005)

Abstract Biodegradable poly( L ‐lactide) (PLLA) scaffolds with well‐controlled interconnected irregular pores were fabricated by a porogen leaching technique using gelatin particles as the porogen. The gelatin particles (280–450 μm) were bonded together through a treatment in a saturated water vapor condition at 70°C to form a 3‐dimensional assembly in a mold. PLLA was dissolved in dioxane and was cast onto the gelatin assembly. The mixtures were then freeze‐dried or dried at room temperature, followed by removal of the gelatin particles to yield the porous scaffolds. The microstructure of the scaffolds was characterized by scanning electron microscopy with respect to the pore shape, interpore connectivity, and pore wall morphology. Compression measurements revealed that scaffolds fabricated by freeze‐drying exhibited better mechanical performance than those by room temperature dying. Along with the increase of the polymer concentration, the porosity of the scaffolds decreased whereas the compressive modulus increased. When the scaffolds were in a hydrated state, the compressive modulus decreased dramatically. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1373–1379, 2005
Massively Parallel Single-Cell RNA-Seq for Marker-Free Decomposition of Tissues into Cell Types (2014)

In multicellular organisms, biological function emerges when heterogeneous cell types form complex organs. Nevertheless, dissection of tissues into mixtures of cellular subpopulations is currently challenging. We introduce an automated massively parallel single-cell RNA sequencing (RNA-seq) approach for analyzing in vivo transcriptional states in thousands of single cells. Combined with unsupervised classification algorithms, this facilitates ab initio cell-type characterization of splenic tissues. Modeling single-cell transcriptional states in dendritic cells and additional hematopoietic cell types uncovers rich cell-type heterogeneity and gene-modules activity in steady state and after pathogen activation. Cellular diversity is thereby approached through inference of variable and dynamic pathway activity rather than a fixed preprogrammed cell-type hierarchy. These data demonstrate single-cell RNA-seq as an effective tool for comprehensive cellular decomposition of complex tissues.
Composition of the Vitreous Humor in Relation to That of Plasma and Aqueous Humors (1960)

The present investigation was undertaken to provide information concerning the comparative composition of those substances present in highest concentrations in the vitreous humor, the aqueous humors, particularly that from the posterior chamber, and the plasma. Such information is needed to interpret and quantitate the results of dynamic studies on the intraocular fluids because loss or gain of a substance to or from the vitreous humor is one of the factors determining the steady state between blood and aqueous humor of the posterior chamber. The composition of the vitreous humor in relation to that of plasma and anterior aqueous humor has been studied by a number of investigators, 1-15 but none has reported analytical data on the composition of aqueous taken from the posterior chamber, and it is this information which is needed most for studies of intraocular fluid dynamics. From the point of view of most accurately establishing concentration gradients