gebhart/patrepeval huggingface dataset:
Cloning of a Stretch-inhibitable Nonselective Cation Channel (1999)

A homologue of the capsaicin receptor-nonselective cation channel was cloned from the rat kidney to investigate a mechanosensitive channel. We found this channel to be inactivated by membrane stretch and have designated it stretch-inactivated channel (SIC). SIC encodes a 563-amino acid protein with putative six transmembrane segments. The cDNA was expressed in mammalian cells, and electophysiological studies were performed. SIC-induced large cation currents were found to be regulated by cell volume, with currents being stimulated by cell shrinkage and inhibited by cell swelling. Single channel analysis showed a conductance of 250 pS with cation permeability (PCl/PNa < 0.1), and the channel possessed some of the characteristics of a stretch-inactivated channel in that it was permeable to calcium, sensitive to membrane stretch, and blocked by Gd3+. Therefore, we cloned one of the mechanosensitive cation channels of mammals, which is considered to regulate Ca2+ influx in response to mechanical stress on the cell membrane.
Quinazolines as inhibitors of dihydrofolate reductase. 4. Classical analogs of folic and isofolic acids (1977)

Interruptions are a common feature of the modern task environment leading to a loss of accuracy and efficiency. The project examines two facets of interruption ' pre-interruption factors and the character of the interruption ' in order to determine those features that may exacerbate or ameliorate the disruption. We use as a primary task the 5-disc Tower of London (ToL) problem and focus on the execution phase: What factors affect retrieval of the next move in a planned sequence, when execution of this sequence is unexpectedly broken? Theme 1 examines in detail the 'interruption lag', the critical time between warning of an interruption and the onset of the new task (Altmann &Trafton, 2002). We propose that the cost of interruption may be reduced if it is possible to consolidate task goals before they are suspended. Theme 2 investigates factors associated with the character of the interruption, for example whether an interruption more similar to the primary task increases the degree of disruption. In addition to performance data, eye-tracking data will be collected in order to monitor the areas that participants are processing during goal suspension and resumption as this may reveal participant selected strategies under different conditions.
Statins Induce Regulatory T Cell Recruitment via a CCL1 Dependent Pathway (2008)

The statins, a group of inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, are reported to influence a variety of immune system activities through 3-hydroxy-3-methylglutaryl coenzyme A reductase-dependent and -independent mechanisms. How statin treatment regulates immune system function in vivo nonetheless remains to be fully defined. We analyzed the immunomodulatory effects of lovastatin in a Candida albicans-induced delayed-type hypersensitivity reaction in mice. In this model, lovastatin administration reduced the acute inflammatory response elicited by C. albicans challenge. This anti-inflammatory activity of lovastatin was associated with a shift from a Th1 to a Th2 immune response, as well as an increase in the percentage of regulatory T cells at the inflammation site and in the regional draining lymph node. The lovastatin-induced increase in regulatory T cells in the inflamed skin was dependent on expression of CCL1, a chemokine that is locally up-regulated by statin administration. The anti-inflammatory effect of lovastatin was abrogated in CCL1-deficient mice. These results suggest that local regulation of chemokine expression may be an important process in statin-induced modulation of the immune system.
Topographic Aspects of Biosynthesis, Extracellular Secretion, and Intracellular Storage of Proteins in Plant Cells (1985)

Crop loss due to soil salinization is an increasing threat to agriculture worldwide. This review provides an overview of cellular and physiological mechanisms in plant responses to salt. We place cellular responses in a time- and tissue-dependent context ...Read More
Detection of HIV p17 antigen in lymphocytes but not epithelial cells from cervicovaginal secretions of women seropositive for HIV: implications for heterosexual transmission of the virus. (1988)

Human immunodeficiency virus (HIV) has been isolated from cervicovaginal secretions from infected women and is thought to be cell associated. To identify which cells harbour viral antigen, we used monoclonal antibodies to OKT4 and a monoclonal antibody directed against HIV p17 core antigen to perform indirect immunofluorescence assays of genital secretions from 17 HIV seropositive and 17 HIV seronegative women with leucorrhoea. OKT4 positive lymphocytes were detected in all tested samples. HIV p17 antigen was detected in the genital fluid lymphocytes in nine out of 14 seropositive subjects from whom lymphocytes were available. No viral antigen was detected in genital fluid lymphocytes of seronegative subjects, nor in any cervicovaginal epithelial cells. This study shows that lymphocytes are the major source of HIV in cervicovaginal secretions of infected women. Conditions that increase the lymphocyte population in the female genital tract, such as sexually transmitted disease (STD), chronic inflammation of the cervix, and menstruation, may facilitate the transmission of HIV during sexual intercourse.
The variable antigens Vmp7 and Vmp21 of the relapsing fever bacterium Borrelia hermsii are structurally analogous to the VSG proteins of the African trypanosome (1990)

The relapsing fever agent Borrelia hermsii avoids the host's immune response by the strategy of multiphasic antigenic variation. A given Borrelia cell can express one of a number of alleles for polymorphic outer-membrane proteins, known as Vmp proteins. The genes for the variant-specific Vmp proteins of serotypes 7 and 21 of B. hermsii strain HS1 were sequenced. The genes, which were designated vmp7 and vmp21, were obtained from populations of borreliae before and after a switch in serotypes from 7 to 21. The analysis showed that vmp7 and vmp21 are 77% identical in terms of their coding sequence. The deduced translation products of vmp7 and vmp21 are polypeptides of 369 (37.2 kD) and 364 amino acids (37.1 kD), respectively. Vmp7 and Vmp21 have sequence features of prokaryotic lipoproteins and are processed as such during expression in E. coli. The secondary structure predictions of the Vmp proteins reveals analogous structures to the VSG proteins of the African trypanosome.
Transport properties of doped silicon oxycarbide microcrystalline films produced by spatial separation techniques (2002)

Presents results of the role of the oxygen partial pressure (p/sub 02/) used on the properties exhibited by doped /spl mu/c silicon oxycarbide films produced by a two consecutive decomposition and deposition chamber (TCDDC) system, where a spatial separation between the plasma and the growth regions is achieved. The films produced are highly conductive and transparent with suitable properties for optoelectronic applications. The film's structure, composition, morphology and optoelectronic properties were analysed by means of grazing X-ray diffraction, electron secondary chemical analysis (ESCA), secondary ion mass spectroscopy (SIMS) as a function of temperature (T) and optical absorption (ranging from 300 to 80 K) measurements.
Oxygen radical scavengers selectively inhibit interleukin 8 production in human whole blood. (1992)

The hydroxyl radical (OH.) scavenger dimethyl sulfoxide (DMSO) was found to dose-dependently inhibit interleukin 8 (IL-8) production in LPS-stimulated human whole blood. At a concentration of 1% (vol/vol), DMSO blocked IL-8 release by approximately 90% in the presence of 1 microgram/ml LPS at a 24-h time point, but did not affect cell viability or reduce the production of tumor necrosis factor (TNF), interleukin 6, or interleukin-1 beta (IL-1 beta). DMSO was found to directly inhibit IL-8 expression at the level of transcription. Furthermore, this effect was not LPS-specific, in that IL-8 production was reduced by DMSO to a similar extent upon stimulation of blood with phytohemagglutinin, aggregated immune complexes, TNF, or IL-1 beta. Other oxygen radical scavengers that have been shown to inhibit OH.-dependent reactions (dimethyl thiourea, thiourea, mannitol, and ethanol) also inhibited IL-8 production. Conversely, addition of H2O2 caused a dose-dependent stimulation of IL-8 release. These results provide evidence that reactive oxygen metabolites play an important role in the regulation of IL-8 production and suggest that reduction of IL-8 release may contribute to the beneficial effects of antioxidants in experimental models of inflammation and ischemia/reperfusion injury.
PEG–Polypeptide Block Copolymers as pH-Responsive Endosome-Solubilizing Drug Nanocarriers (2014)

Herein we report the potential of click chemistry-modified polypeptide-based block copolymers for the facile fabrication of pH-sensitive nanoscale drug delivery systems. PEG-polypeptide copolymers with pendant amine chains were synthesized by combining N-carboxyanhydride-based ring-opening polymerization with post-functionalization using azide-alkyne cycloaddition. The synthesized block copolymers contain a polypeptide block with amine-functional side groups and were found to self-assemble into stable polymersomes and disassemble in a pH-responsive manner under a range of biologically relevant conditions. The self-assembly of these block copolymers yields nanometer-scale vesicular structures that are able to encapsulate hydrophilic cytotoxic agents like doxorubicin at physiological pH but that fall apart spontaneously at endosomal pH levels after cellular uptake. When drug-encapsulated copolymer assemblies were delivered systemically, significant levels of tumor accumulation were achieved, with efficacy against the triple-negative breast cancer cell line, MDA-MB-468, and suppression of tumor growth in an in vivo mouse model.
Local Protein Dynamics and Catalysis:  Detection of Segmental Motion Associated with Rate-Limiting Product Release by a Glutathione Transferase (2002)

Glutathione transferase rGSTM1-1 catalyzes the addition of glutathione (GSH) to 1-chloro-2,4-dinitrobenzene, a reaction in which the chemical step is 60-fold faster than the physical step of product release. The hydroxyl group of Y115, located in the active site access channel, controls the egress of product from the active site. The Y115F mutant enzyme has a k(cat) (72 s(-)(1)) that is 3.6-fold larger than that of the native enzyme (20 s(-)(1)). Crystallographic observations and evidence from amide proton exchange kinetics are consistent with localized increases in the degree of segmental motion of the Y115F mutant that are coupled to the enhanced rate of product release. The loss of hydrogen bonding interactions involving the hydroxyl group of Y115 is reflected in subtle alterations in the backbone position, an increase in B-factors for structural elements that comprise the channel to the active site, and, most dramatically, a loss of well-defined electron density near the site of mutation. The kinetics of amide proton exchange are also enhanced by a factor between 3 and 12 in these regions, providing direct, quantitative evidence for changes in local protein dynamics affecting product release. The enhanced product release rate is proposed to derive from a small shift in the equilibrium population of protein conformers that permit egress of the product from the active site.
2-Methoxyestradiol-induced Apoptosis in Prostate Cancer Cells Requires Smad7 (2005)

Prostate cancer is the second most common cause of death related to cancer in Western society. 2-Methoxyestradiol (2-ME), an endogenous metabolite of estradiol-17beta, inhibits tumor angiogenesis while also exerting potent cytotoxic effects on various cancer cells. 2-ME has been shown to activate the p38 MAPK and JNK pathways and to induce apoptosis in cells, although the underlying molecular mechanisms for this are unknown. Here we report that the expression of Smad7, an adaptor molecule required to activate p38 MAPK in the transforming growth factor beta signaling pathway, is also required for 2-ME-induced p38 activation and apoptosis in human prostate cancer cells (PC-3U). PC-3U/AS-S7 cells stably transfected with an antisense Smad7 construct, or PC-3U cells transiently transfected with short interfering RNA for Smad7, were protected against 2-ME-induced apoptosis. 2-ME-induced apoptosis was found to involve p38 MAPK and JNK, because simultaneous treatments with 2-ME and a specific p38 inhibitor (SB203580) or an inhibitor of JNK (L-JNK1) prevented 2-ME-induced apoptosis. Most interestingly, Smad7 was shown by both antisense and short interfering RNA techniques to affect levels of beta-catenin, which has been implicated previously in the regulation of apoptosis. Moreover, Smad7 was found to be important for the basal expression of Bim, a pro-apoptotic Bcl-2 family member, and for 2-ME-induced expression of Bim. These results suggest that expression of Smad7 is crucial for 2-ME-induced apoptosis in human prostate cancer cells.
An Overexpressed Gene Transcript in Senescent and Quiescent Human Fibroblasts Encoding a Novel Protein in the Epidermal Growth Factor-Like Repeat Family Stimulates DNA Synthesis (1995)

We carried out subtractive enrichment of a cDNA library derived from mRNA of senescent human diploid fibroblasts (HDF) established from a subject with Werner syndrome of premature aging. By differential screening, we isolated an overexpressed cDNA sequence (S1-5) that codes for a novel protein containing epidermal growth factor (EGF)-like domains which match the EGF-like consensus sequences within several known extracellular proteins that play a role in cell growth, development, and cell signalling. S1-5 mRNA is overexpressed in Werner syndrome and senescent normal HDF, is induced by growth arrest of young normal cells, but is significantly decreased by high serum, conditions which promote cellular proliferation. Paradoxically, microinjection into young HDF of two different lengths of S1-5 mRNA, containing different putative AUG translational start sites, consistently stimulated rather than inhibited DNA synthesis by an apparent autocrine/paracrine mechanism. Thus, the S1-5 gene product may represent a negative and/or positive factor whose ultimate activity is modulated by the cell environment as occurs with other members of EGF-like family.
Recovery of refractive-index profiles of planar graded-index waveguides from measured mode indices: an iteration method (1992)

An iteration method for calculating refractive-index profiles of graded-index waveguides from measured effective indices is presented. The refractive-index profiles recovered from the effective indices for the exponential function indicate that the accuracy of this method is better than ±10−4. We apply this method to Ti in-diffused Fe2O3–LiNbO3 and two-step ion-exchanged glass waveguides and obtain a good agreement between the theoretical and the experimental values.
The role of the combination of IL-2 and TGF-β or IL-10 in the generation and function of CD4+ CD25+ and CD8+regulatory T cell subsets (2003)

Recently, considerable attention has been focused on thymus-derived CD4+ regulatory T cells that constitutively express CD25 and have a contact-dependent, cytokine-independent mechanism in vitro. However, peripheral CD4+ and CD8+ T cells can also be induced to become regulatory T cells. Here we review our studies using the combination of IL-2 and transforming growth factor beta (TGF-beta) to generate regulatory T cell subsets ex vivo, and the work of others using IL-10 to induce suppressive activity. Under certain conditions, the autocrine effects of TGF-beta and IL-10 induce peripheral T cells to produce immunosuppressive levels of each of these cytokines. This effect of TGF-beta is IL-2 dependent. Under other conditions IL-2 and TGF-beta can induce CD4+ cells to develop potent contact-dependent, cytokine-independent regulatory activity. At present, there is considerable confusion concerning the mechanism of action of CD4+ CD25+ cells because cytokine-producing regulatory T cells generated in the periphery can express CD25 and other markers displayed by naturally occurring, thymus-derived regulatory T cells. We, therefore, propose a nomenclature that identifies thymus-derived and peripheral regulatory cells, and that also differentiates T regulatory cells from T helper cells. Because T regulatory cells broadly control T helper cell reactivity, the mechanisms that control regulatory cell function are also reviewed. Finally, the potential use of regulatory T cells generated ex vivo as an adoptive immunotherapy for certain autoimmune diseases, to prevent organ graft rejection, or to prevent pathologic host responses to infectious agents is discussed.
Osteogenic Stem Cells and the Stromal System of Bone and Marrow (1989)

According to current hypothesis, cells of the osteogenic lineage, which includes both osteoblasts and chondroblasts, are derived from a stromal stem cell in the postnatal organism. That there exist osteogenic precursors in association with the soft, fibrous tissue of the marrow stroma is well established. An osteogenic tissue comprised of cartilage and bone is formed when marrow or marrow cell suspensions are cultured in vivo within diffusion chambers. Bone with a functional marrow organ is formed when marrow or marrow cell suspensions are transplanted heterotopically, e.g., under the renal capsule. Cultures of marrow stromal fibroblasts are readily established in vitro from single-cell bone marrow suspensions. Such cultures do not demonstrate overt differentiation in an osteogenic direction in vitro. When transplanted in vivo, however, they differentiate to form cartilage and bone in diffusion chambers and bone with a functional marrow organ when transplanted heterotopically. Single-cell bone marrow suspensions can be cultured in vitro under conditions that facilitate the formation of stromal fibroblast colonies. Circumstantial evidence supports the conclusion that each colony is derived from a single initiating cell termed a colony-forming unit-fibroblastic (CFU-F). A proportion of CFU-F demonstrates extensive proliferative potential both in vitro and in vivo. In vitro the extensive proliferative potential of a subset of CFU-F has been shown to be associated with a capacity for extensive self-renewal. On transplantation in vivo, the progeny of a proportion of CFU-F has been shown to be capable of proliferating and differentiating into all the stromal cell lines necessary for the formation of bone and reconstitution of the hematopoietic inductive microenvironment. These findings provide strong circumstantial evidence to support the hypothesis that there are stem cells present within the marrow stroma that are capable of giving rise to cells of a number of different lineages, including those of the osteogenic lineage (chondroblasts and osteoblasts).
Implicit Detection of Hidden Processes with a Local-Booted Virtual Machine (2008)

Currently stealth malware is becoming a major threat to the PC computers. Process hiding is the technique commonly used by stealth malware to evade detection by anti-malware scanners. On the defensive side, previous host-based approaches will be defeated once the privileged stealth malware controls a lower reach of the system. The virtual machine (VM) based solutions gain tamper resistance at the cost of losing the OS-level process view. Moreover, existing VM-based approaches cannot introspect the preinstalled OS which is just the protecting concern for PC users. In this paper, we present a new VM-based approach called Libra which accurately reproduces the software environment of the underlying preinstalled OS within the Libra VM and provides an OS-level semantic view of the processes. With our new local-booting technology, Libra VM just boots from the underlying host OS but not a newly installed OS image. Thus, Libra provides a way to detect the existing process-hiding stealth malware in the host OS. In addition, instead of depending on the guest information which is subvertable to the privileged guest malware, Libra adopts a unique technique to implicitly construct the trusted view of process list (TVPL) from within the virtualized hardware layer. Our evaluation results with real-world hiding-process rootkits, which are widely used by stealth malware, demonstrate its practicality and effectiveness.
Biomarkers for Psychiatry: The Journey from Fantasy to Fact, a Report of the 2013 CINP Think Tank: Figure 1. (2015)

Since a single measure is unlikely to suffice, multi-modal strategies look more promising, although they bring greater technical and implementation complexities. Identifying reproducible, robust biomarkers will probably require pre-competitive consortia to provide the resources needed to identify, validate, and develop the relevant clinical tests.
Control of MHC Restriction by TCR V α CDR1 and CDR2 (1996)

Individual T cell receptor (TCR) Valpha elements are expressed preferentially in CD4 or CD8 peripheral T cell subsets. The closely related Valpha3.1 and Valpha3.2 elements show reciprocal selection into CD4 and CD8 subsets, respectively. Transgenic mice expressing site-directed mutants of a Valpha3.1 gene were used to show that individual residues in either the complementarity-determining region 1 (CDR1) or CDR2 were sufficient to change selection from the CD4 subset to the CD8 subset. Thus, the germline-encoded Valpha elements are a major influence on major histocompatibility class complex (MHC) restriction, most likely by a preferential interaction with one or the other class of MHC molecule.
Epidermal Growth Factor-mediated Activation of the ETS Domain Transcription Factor Elk-1 Requires Nuclear Calcium (2002)

Cytosolic and nuclear Ca(2+) have been shown to differentially regulate transcription. However, the impact of spatially distinct Ca(2+) signals on mitogen-activated protein kinase-mediated gene expression remains unknown. Here we investigated the role of nuclear and cytosolic Ca(2+) signals in epidermal growth factor (EGF)-induced transactivation of the ternary complex factor Elk-1 using a GAL4-Elk-1 construct. EGF increased Ca(2+) in both the nucleus and cytosol of HepG2 or 293 cells. Pretreatment with the intracellular Ca(2+) chelator bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid significantly reduced EGF-induced transactivation of Elk-1, indicating that EGF-stimulated Elk-1 transcriptional activity is dependent on intracellular Ca(2+). To determine the relative contribution of nuclear and cytosolic Ca(2+) signals during EGF-mediated Elk-1 transactivation, Ca(2+) signals in either compartment were selectively impaired by targeted expression of the Ca(2+)-binding protein parvalbumin to either the nucleus or cytosol. Suppression of nuclear but not cytosolic Ca(2+) signals inhibited EGF-induced transactivation of Elk-1. However, suppression of nuclear Ca(2+) signals did not affect the ability of ERK either to become phosphorylated or to undergo translocation to the nucleus in response to EGF. Elk-1 phosphorylation and nuclear localization following EGF stimulation were also unaffected by suppressing nuclear Ca(2+) signals. These results suggest that nuclear Ca(2+) is required for EGF-mediated transcriptional activation of Elk-1 and that phosphorylation of Elk-1 alone is not sufficient to induce its transcriptional activation in response to EGF. Thus, subcellular targeting of parvalbumin reveals a distinct role for nuclear Ca(2+) signals in mitogen-activated protein kinase-mediated gene transcription.
Getting sepsis therapy right (2015)

Is decreasing inflammation or increasing the host immune response the better approach? [Also see Report by Weber et al. ]