gebhart/patrepeval huggingface dataset:
Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization in stereocilia (2011)

The mechanotransducer channels of auditory hair cells are gated by tip-links, oblique filaments that interconnect the stereocilia of the hair bundle. Tip-links stretch from the tips of stereocilia in the short and middle rows to the sides of neighboring, taller stereocilia. They are made of cadherin-23 and protocadherin-15, products of the Usher syndrome type 1 genes USH1D and USH1F, respectively. In this study we address the role of sans, a putative scaffold protein and product of the USH1G gene. In Ush1g(-/-) mice, the cohesion of stereocilia is disrupted, and both the amplitude and the sensitivity of the transduction currents are reduced. In Ush1g(fl/fl)Myo15-cre(+/-) mice, the loss of sans occurs postnatally and the stereocilia remain cohesive. In these mice, there is a decrease in the amplitude of the total transducer current with no loss in sensitivity, and the tips of the stereocilia in the short and middle rows lose their prolate shape, features that can be attributed to the loss of tip-links. Furthermore, stereocilia from these rows undergo a dramatic reduction in length, suggesting that the mechanotransduction machinery has a positive effect on F-actin polymerization. Sans interacts with the cytoplasmic domains of cadherin-23 and protocadherin-15 in vitro and is absent from the hair bundle in mice defective for either of the two cadherins. Because sans localizes mainly to the tips of short- and middle-row stereocilia in vivo, we conclude that it belongs to a molecular complex at the lower end of the tip-link and plays a critical role in the maintenance of this link.
Inhibition of UVB‐mediated Oxidative Stress and Markers of Photoaging in Immortalized HaCaT Keratinocytes by Pomegranate Polyphenol Extract POMx (2007)

In recent years there has been an increase in use of botanicals with antioxidant properties as skin photoprotective agents. Pomegranate (Punica granatum L.) fruit possesses strong antioxidant and antiinflammatory properties. Recently, we have shown that pomegranate-derived products rich in anthocyanidins and ellagitannins inhibit UVB-mediated activation of nuclear factor kappa B and modulate UVA-mediated cell proliferation pathways in normal human epidermal keratinocytes. In this study, we evaluated the effect of polyphenol-rich pomegranate fruit extract (POMx) on UVB-induced oxidative stress and photoaging in human immortalized HaCaT keratinocytes. Our data show that pretreatment of HaCaT cells with POMx (10-40 microg mL(-1)) inhibited UVB (15-30 mJ cm(-2))-mediated (1) decrease in cell viability, (2) decrease in intracellular glutathione content and (3) increase in lipid peroxidation. Employing immunoblot analysis we found that pretreatment of HaCaT cells with POMx inhibited UVB-induced (1) upregulation of MMP-1, -2, -7 and -9, (2) decrease in TIMP-1, (3) phosphorylation of MAPKs and (iv) phosphorylation of c-jun, whereas no effect was observed on UVB-induced c-fos protein levels. These results suggest that POMx protects HaCaT cells against UVB-induced oxidative stress and markers of photoaging and could be a useful supplement in skin care products.
Comparison of the Locations of Homologous Fowlpox and Vaccinia Virus Genes Reveals Major Genome Reorganization (1992)

We have derived a restriction enzyme map for the fowlpox virus FP9 strain. Sites for BamHI, PvuII, PstI and NcoI have been mapped mainly by Southern blotting. The size of the genome derived from the restriction maps (254 kb) corresponds to the figure of 260 +/- 8 kb determined from analysis of genomic DNA by pulsed-field electrophoresis. The map can be compared with a previously published map for a different strain of fowlpox virus using the PstI digest which is common to both studies. Some 65 kb of fowlpox virus sequence, in 11 blocks, as well as individual M13 clones have been aligned with the map. Where those blocks correspond with blocks of homologous genes in vaccinia virus, it is possible to compare the genomic locations for those genes in the two viruses. This comparison reveals that, whereas there are blocks of sequence within which genes exist in the same relative position in the two viruses, the genomic location of those sequence blocks differs widely between the two viruses.
Transposons in filamentous fungi-facts and perspectives (1998)

Transposons are ubiquitous genetic elements discovered so far in all investigated prokaryotes and eukaryotes. In remarkable contrast to all other genes, transposable elements are able to move to new locations within their host genomes. Transposition of transposons into coding sequences and their initiation of chromosome rearrangements have tremendous impact on gene expression and genome evolution. While transposons have long been known in bacteria, plants, and animals, only in recent years has there been a significant increase in the number of transposable elements discovered in filamentous fungi. Like those of other eukaryotes, each fungal transposable element is either of class or of class II. While class I elements transpose by a RNA intermediate and employ reverse transcriptases, class II elements transpose directly at the DNA level. We present structural and functional features for such transposons that have been identified so far in filamentous fungi. Emphasis is given to specific advantages or unique features when fungal systems are used to study transposable elements, e.g., the evolutionary impact of transposons in coenocytic organisms and possible experimental approaches toward horizontal gene transfer. Finally, we focus on the potential of transposons for tagging and identifying fungal genes.
HRG-β1-driven ErbB3 signaling induces epithelial–mesenchymal transition in breast cancer cells (2013)

Our data suggest that HRG-β1 and ErbB3 induce EMT, cancer cell migration and invasion through the PI3k/Akt-phospho-Smad2-Snail signaling pathway in SK-BR-3 and MCF7 breast cancer cells.
Preparation and immunochemical characterization of meningococcal group C polysaccharide-tetanus toxoid conjugates as a new generation of vaccines (1983)

Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugates have been prepared by using high-molecular-weight polysaccharide and purified tetanus toxoid and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide as a coupling reagent. The influence of three conditions of preparation was studied. Biochemical assays, the enzyme-linked immunosorbent assay, and isopycnic CsCl gradient ultracentrifugation have been used to characterize the conjugates. The polysaccharide-to-protein ratios of the various conjugate preparations showed differences. The ability of the group C polysaccharide component to react with specific antibodies was reduced, whereas most of the tetanus toxoid seemed to be hidden by the polysaccharide. The composition of the conjugate was not homogeneous, and at least 10% of free polysaccharide was present. Thermostability in lyophilized condition in the presence of lactose was excellent.
The hydrogen content of plasma-deposited silicon nitride (1978)

The hydrogen content of glow-discharge-deposited silicon nitride (SiN) films made at 330–350 °C has been determined. Preparation conditions were varied to produce a range of compositions of Si/N=0.7–1.4. Quantitative hydrogen profiling of the samples was carried out using the resonant nuclear reaction 15N+H→12C+4He+γ ray. Calibration factors for Si-H (2160 cm−1) and N-H (3350 cm−1) absorption-band areas or absorbances have also been determined, enabling infrared transmission spectra to be used for hydrogen analyses of these films. All samples were homogeneous in hydrogen content and were in the range (1.6–2.1) ×1022 H atoms/cm3, or about 20–25 at.% H. Roughly three-quarters of the H is bonded to Si, the remainder to N. One plasma SiO2 sample made at 300 °C from SiH4 and N2O was measured also, and contained 5.7 at.% H, all as OH. Although there was little variation in the H content of SiN, there is a correlation between the total H concentration and the buffered HF etch rate. Some observations on the effects of the 15N ion beam (6–8 MeV) on the SiN are reported. Many Si-H and N-H bonds are broken, but the liberated H atoms or ions are unable to diffuse out of the film.
Opioids and myocardial reperfusion injury. (2007)

It is well-established that reperfusion is the major method of salvaging ischemic myocardium following prolonged coronary artery occlusion, although the idea of reperfusion injury remains controversial. Moreover, more recent evidence strongly suggests that reperfusion per se is thought to result in further damage to the myocardium and blood vessel endothelium by various biochemical and physical factors including a burst of oxygen-derived free radicals (ROS), cellular or mitochondrial calcium overload and shear stress, to name a few. This has been termed lethal reperfusion injury. It has become increasingly evident that strategies in which interventions are administered during the early stages of reperfusion produce a reduction in reperfusion-mediated damage primarily by reducing massive calcium overload or by altering the intracellular milieu (pH, osmotic stress, etc.) and ROS release upon reperfusion. Furthermore, it is apparent that activation of blood borne elements such as neutrophils and macrophages and factors released by these cells such as cytokines may be responsible for a continuing expansion of infarction in the hours or even days following timely reflow and that inhibiting these factors may attenuate reperfusion injury. The present review will focus on the effect of endogenous and exogenous opioids on ischemic and reperfusion injury since these compounds are routinely used in the surgical arena and may have unappreciated cardioprotective effects in this subset of patients. Particular emphasis will be on the role of opioids in reperfusion injury and their relationship to the newly discovered phenomenon of postconditioning.
Iron‐Catalyzed Enantioselective Hydrosilylation of Ketones (2008)

Reductions under iron rule: Enantioselective hydrosilylation of prochiral ketones with inexpensive and environmentally benign iron catalysts proceed smoothly in the presence of (S,S)-Me-duphos (see scheme; (S,S)-Me-duphos=1,2-(bis[(2S,5S)]-2,5-dimethylphospholano)benzene). A broad range of aryl ketones is converted into the corresponding secondary alcohols in up to 99 % enantioselectivity and quantitative yields.
Long Distance Control of MHC Class II Expression by Multiple Distal Enhancers Regulated by Regulatory Factor X Complex and CIITA (2004)

MHC class II (MHC-II) genes are regulated by an enhanceosome complex containing two gene-specific transcription factors, regulatory factor X complex (RFX) and CIITA. These factors assemble on a strictly conserved regulatory module (S-X-X2-Y) found immediately upstream of the promoters of all classical and nonclassical MHC-II genes as well as the invariant chain (Ii) gene. To identify new targets of RFX and CIITA, we developed a computational approach based on the unique and highly constrained architecture of the composite S-Y motif. We identified six novel S'-Y' modules situated far away from the promoters of known human RFX- and CIITA-controlled genes. Four are situated at strategic positions within the MHC-II locus, and two are found within the Ii gene. These S'-Y' modules function as transcriptional enhancers, are bona fide targets of RFX and CIITA in B cells and IFN-gamma-induced cells, and induce broad domains of histone hyperacetylation. These results reveal a hitherto unexpected level of complexity involving long distance control of MHC-II expression by multiple distal regulatory elements.
CD4 down-regulation by nef alleles isolated from human immunodeficiency virus type 1-infected individuals. (1993)

PCR was used to clone isolates of the human immunodeficiency virus type 1 (HIV-1) nef gene directly from peripheral blood leukocytes of HIV-1-infected individuals. A transient expression system with human CEM T cells was used to assess the effect of nef on CD4 antigen expression on the cell surface. We show that CD4 down-regulation is a frequent property of primary HIV-1 nef alleles. Mutations in conserved amino acid motifs of Nef disrupted CD4 down-regulation. Our observations strongly suggest that CD4 down-regulation reflects a conserved function of nef, which is selected in vivo in human HIV-1 infection. Methodology described here provides quantitative assays to establish whether alterations in nef correlate with the dynamics of disease progression in human AIDS.
Adverse Nondrug Reactions (1968)

Healthy university students and hospital staff taking no medications were surveyed by questionnaire to obtain data on the occurrence of many symptoms often listed as side effects of drugs. Of 670 people surveyed, 414 indicated that they had had no illnesses and taken no medications during the previous three days and were included in the study. Only 19 per cent of the 414 stated that they had experienced none of 25 symptoms listed in the previous 72 hours. The median number of symptoms experienced per person was two. Thirty people experienced six or more of these symptoms. In the study of adverse drug reactions proper controls are just as important as in any other form of research.
Enhancing the Anticoagulant Potency of Soluble Tissue Factor Mutants by Increasing their Affinity to Factor VIIa (2002)

Complexation of factor VIIa (FVIIa) and tissue factor (TF) initiates the extrinsic pathway of blood coagulation. Inappropriate triggering of this pathway has been linked to thrombotic disorders. We have previously shown that a mutant form ofsoluble tissue factor (sTF, residues 1-219) having Lys165 and Lys166 replaced with alanine residues (hTFAA) gave an antithromboticeffect in a rabbit model of arterial thrombosis. Here we have improved the potency of hTFAA by incorporating amino acid substitutions thatincrease the affinity of sTF for FVIIa. Phage display has been used toselect consensus sequences at two FVIIa-contact regions on sTF, segments 44-50 and 130-140, that individually showed modestly increased (approximately 2-fold) FVIIa-affinity. These consensus sequences have been combined with other previously selected mutations to generate a series of variants (hTFAA-2, hTFAA-3, and hTFAA-4) having 4 to 10-fold increased FVIIa-binding affinity. Surface plasmon resonance measurementsindicate that the increased affinity results mostly from an increase in the association rate constant. All of these variants displayed increased inhibitor potency relative to hTFAA in an assay of Factor X activation catalyzed by the complex of FVIIa with membrane TF. In addition, these affinity improved hTFAA variants are more potent anticoagulants and have increased antithrombotic activity relative to hTFAA in an ex vivo flow chamber model of thrombosis. The potency trend parallels increases in FVIIa-binding affinity; however, the absolute fold increases in potencies are greater than increases in binding affinity, consistent with kinetic studies of the FVIIa-binding event. Through incorporation of 10 amino acid substitutions (hTFAA-3) we have increased the antithrombotic activity of hTFAA by 20-fold.
552. Collateral Circulation under Cerebral Ischemia by Hypoxia Inducible Factor Naked DNA in Rat Indirect-Bypass Model (2006)

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1α, which accumulates under hypoxic conditions, and a constitutively expressed subunit, HIF-1β. In this study, we investigated if HIF-1α naked DNA induced angiogenesis in a cerebral ischemic model in vivo. We utilized a rat encephalo-myo-synangiosis (EMS) model and inoculated naked DNA into the brain surface. We analyzed whether DNA induced angiogenic factors and collateral circulation. We measured and compared infarction volumes to investigate the effect of HIF-1α on cerebral infarction induced by permanent middle cerebral artery (MCA) occlusion in rats. A histological section treated with HIF-1α DNA showed an increased expression of HIF-1α and VEGF with collateral circulation. HIF-1α naked DNA also decreased the infarction volumes, in comparison with control DNA. These results suggest the feasibility of a novel approach for therapeutic collateral circulation of cerebral ischemia in which neovascularization may be achieved indirectly using a transcriptional and cytokine's regulatory strategy.
Okadaic acid induces cellular hypertrophy in AKR-2B fibroblasts: involvement of the p70S6 kinase in the onset of protein and rRNA synthesis. (1996)

At low concentrations (50 nM), okadaic acid (OA), an inhibitor of phosphatases 1 and 2A, inhibits platelet-derived growth factor-induced cell proliferation in late G1 (A. Simm et al., Exp. Cell Res., 210: 160-165, 1994). This inhibition is caused by the interference of OA in the induction and activation of the cell division protein kinases cdk1 and cdk2. OA alone has no effect on cell number, but induces a pronounced increase in cell size. The OA-induced hypertrophy can be divided into two phases. The first phase is characterized by a swelling of the cells. This increase in cellular volume is not accompanied by a change in the level of cellular macromolecules, i.e., protein and RNA. Inhibitor studies indicated a possible role of the Na+/H+ antiporter and Cl- channels in this process. In the second phase, an increase in the cellular protein and RNA content was observed along with a minor change in cell volume. To delineate a possible signaling pathway, the involvement of numerous protein kinases was analyzed. Low concentrations of OA lead to pronounced and sustained activation of the p70S6 kinase. There was little or no effect on various other kinases that can be activated by extracellular signals, e.g., mitogen-activated kinase, ribosomal S6 kinase, or other S6 peptide kinases. Likewise, at these concentrations, OA did not activate the genes for fos, myc, or ornithine decarboxylase. At very low concentrations (ED50, 0.5 nM), rapamycin, a specific inhibitor of the activation of p70S6 kinase, reversed the activation of the p70S6 kinase and the enhancement of RNA synthesis and partially the increase in cell volume and protein synthesis. The OA-induced hypertrophy of AKR-2B fibroblasts may serve as a model system for investigations aimed at the identification of signaling pathways leading to hypertrophy of differentiated nonproliferating cells.
Cloning and functional expression of the first plant fatty acid elongase specific for Δ6-polyunsaturated fatty acids (2000)

In order to elucidate the biosynthesis of longchain polyunsaturated fatty acids (PUFAs) in plants we searched for a cDNA encoding a Δ6-specific PUFA elongase from Physcomitrella patens which is known to contain high proportions of arachidonic acid (20:4 Δ5,8,11,14). An EST clone from P. patens was identified by its low homology to the yeast gene ELO1, which is required for the elongation of medium-chain fatty acids. We functionally characterized this cDNA by heterologous expression in Saccharomyces cerevisiae grown in the presence of several fatty acids. Analysis of the fatty acid profile of the transgenic yeast revealed that the cDNA encodes a protein that leads to the elongation of the C18 Δ6-polyunsaturated fatty acids γ-linolenic acid (18:3 Δ6,9,12) and stearidonic acid (18:4 Δ6,9,12,15), which were recovered to 45–51% as their elongation products. In contrast, linoleic and α-linolenic acids were hardly elongated and we could not measure any elongation of saturated and mono-unsaturated fatty acids (including 18:1 Δ6), indicating that the elongase is highly specific for the polyunsaturated nature of the fatty acid acting as substrate.
Designing activity-aware recommender systems for operating rooms (2011)

This paper presents research in ubiquitous computing focusing on creating context- and activity-aware systems in collaborative environments such as hospitals. These activity-aware systems are able to infer human physical actions and subsequently offer services that support the user's ongoing task. The paper introduces our initial design of an activity-aware recommender system for surgical procedures in operating rooms. Based on sensor input, the system automatically detects and recognizes co-located collaborative and concurrent human actions in the operating room, and uses this to show information and recommend actions to take, which are relevant to the current situation.
Altered wound healing in mice lacking a functional osteopontin gene (spp1). (1998)

Osteopontin (OPN) is an arginine-glycine-aspartate (RGD)- containing glycoprotein encoded by the gene secreted phosphoprotein 1 (spp1). spp1 is expressed during embryogenesis, wound healing, and tumorigenesis; however, its in vivo functions are not well understood. Therefore, OPN null mutant mice were generated by targeted mutagenesis in embryonic stem cells. In OPN mutant mice, embryogenesis occurred normally, and mice were fertile. Since OPN shares receptors with vitronectin (VN), we tested for compensation by creating mice lacking both OPN and VN. The double mutants were also viable, suggesting that other RGD-containing ligands replace the embryonic loss of both proteins. We tested the healing of OPN mutants after skin incisions, where spp1 was upregulated as early as 6 h after wounding. Although the tensile properties of the wounds were unchanged, ultrastructural analysis showed a significantly decreased level of debridement, greater disorganization of matrix, and an alteration of collagen fibrillogenesis leading to small diameter collagen fibrils in the OPN mutant mice. These data indicate a role for OPN in tissue remodeling in vivo, and suggest physiological functions during matrix reorganization after injury.
Designing User Interface Guidelines for Time-Shift Programming on a Video Cassette Recorder (VCR) (1991)

Advances in technology may create additional problems for the user. The average consumer encounters difficulty when programming electronic products which require a series of steps to operate. The user-interfaces of these products vary not only among different types of products, but also within the individual market itself. There are presently no interface guidelines in existence to assist designers in developing easy to use electronic programmable products. This research proposes user interface guidelines to improve the current poor interface designs of the Video Cassette Recorder (VCR). Improving the interfaces of electronic products results in less frustration for users. This study demonstrates the advantages of incorporating human factors design criteria into the interface of electronic programmable devices. Research and testing performed on existing VCRs identified problems and the need to minimize them. The results of the research were used to develop and implement a new interface using HyperPAD TM , a prototyping tool for the IBM/PC. HyperPAD TM was also used to simulate an existing VCR. A data collection program captured the users' keystrokes and errors, and simplified the analysis of the raw data. Test results for the new VCR interface demonstrated a 50% reduction in the number of incorrect recordings and a 50% reduction in the time required to set the clock and program the VCR.
The Angio-Fibrotic Switch of VEGF and CTGF in Proliferative Diabetic Retinopathy (2008)

CTGF is primarily a pro-fibrotic factor in the eye, and a shift in the balance between CTGF and VEGF is associated with the switch from angiogenesis to fibrosis in proliferative retinopathy.