gebhart/patrepeval huggingface dataset:
Cytosolic Delivery of Granzyme B by Bacterial Toxins: Evidence that Endosomal Disruption, in Addition to Transmembrane Pore Formation, Is an Important Function of Perforin (1999)

Granule-mediated cell killing by cytotoxic lymphocytes requires the combined actions of a membranolytic protein, perforin, and granule-associated granzymes, but the mechanism by which they jointly kill cells is poorly understood. We have tested a series of membrane-disruptive agents including bacterial pore-forming toxins and hemolytic complement for their ability to replace perforin in facilitating granzyme B-mediated cell death. As with perforin, low concentrations of streptolysin O and pneumolysin (causing <10% (51)Cr release) permitted granzyme B-dependent apoptosis of Jurkat and Yac-1 cells, but staphylococcal alpha-toxin and complement were ineffective, regardless of concentration. The ensuing nuclear apoptotic damage was caspase dependent and included cleavage of poly(ADP-ribose) polymerase, suggesting a mode of action similar to that of perforin. The plasma membrane lesions formed at low dose by perforin, pneumolysin, and streptolysin did not permit diffusion of fluorescein-labeled proteins as small as 8 kDa into the cell, indicating that large membrane defects are not necessary for granzymes (32 to 65 kDa) to enter the cytosol and induce apoptosis. The endosomolytic toxin, listeriolysin O, also effected granzyme B-mediated cell death at concentrations which produced no appreciable cell membrane damage. Cells pretreated with inhibitors of endosomal trafficking such as brefeldin A took up granzyme B normally but demonstrated seriously impaired nuclear targeting of granzyme B when perforin was also added, indicating that an important role of perforin is to disrupt vesicular protein trafficking. Surprisingly, cells exposed to granzyme B with perforin concentrations that produced nearly maximal (51)Cr release (1,600 U/ml) also underwent apoptosis despite excluding a 8-kDa fluorescein-labeled protein marker. Only at concentrations of >4,000 U/ml were perforin pores demonstrably large enough to account for transmembrane diffusion of granzyme B. We conclude that pore formation may allow granzyme B direct cytosolic access only when perforin is delivered at very high concentrations, while perforin's ability to disrupt endosomal trafficking may be crucial when it is present at lower concentrations or in killing cells that efficiently repair perforin pores.
Mechanism of Androgen Receptor Antagonism by Bicalutamide in the Treatment of Prostate Cancer (2011)

The androgen receptor (AR) plays a key role in regulating gene expression in a variety of tissues, including the prostate. In that role, it is one of the primary targets in the development of new chemotherapeutics for treatment of prostate cancer and the target of the most widely prescribed current drug, bicalutamide (Bcu), for this disease. In view of its importance, and the absence of a crystal structure for any antagonist--AR complex, we have conducted a series of molecular dynamics-based simulations of the AR--Bcu complex and quantum mechanical (QM) calculations of Bcu, to elucidate the structural basis for antagonism of this key target. The structures that emerge show that bicalutamide antagonizes AR by accessing an additional binding pocket (B-site) adjacent to the hormone binding site (HBS), induced by displacing helix 12. This distorts the coactivator binding site and results in the inactivation of transcription. An alternative equienergetic conformational state of bicalutamide was found to bind in an expanded hormone pocket without materially perturbing either helix 12 or the coactivator binding site. Thus, both the structural basis of antagonism and the mechanism underlying agonist properties displayed by bicalutamide in different environments may be rationalized in terms of these structures. In addition, the antagonist structure and especially the induced second site (B-site) provide a structural framework for the design of novel antiandrogens.
P3–124: Selenium and cognitive function in rural elderly Chinese (2006)

Selenium is a trace element associated with the activity of the antioxidant enzyme glutathione peroxidase and is considered to be a protective agent against free radicals through enhanced enzyme activity. Associations between low selenium and increased risk in various disease indices including cancer, cardiovascular disease, reproduction and neonatal health, and asthma have been reported. The limited studies on selenium and cognitive function or Alzheimer's disease, however, have not reached unequivocal conclusions. To examine the association between selenium levels and cognitive function in the elderly. A cross–sectional survey of 2000 rural Chinese age 65 and over from two provinces in China was conducted using the Community Screening Instrument for Dementia, CERAD Word List Learning test, a 14–item story recall, Animal Fluency test, and IU Token Test. Over seventy percent of study participants have lived in the same village since birth. Nail samples were collected and analyzed for selenium contents. Food frequency questionnaires were administrated while local food samples were collected and analyzed for selenium content. APOE genotype was determined using blood samples collected on filter cards. Analysis of covariance models were used to estimate the association between selenium levels measured in nail samples and from food intake and cognitive test scores adjusted for age, gender, education and APOE genotype. Lower selenium levels measured in nail samples and from food intake were significantly associated with poor cognitive function as measured by various cognitive tests. Standardized beta coefficients range from 0.06 to 0.24 on all tests (p<0.01 for all) adjusted for age, gender, education level and APOE genotype. The APO ϵ4 allele was not significantly associated with any cognitive measures and there is no significant interaction between APOE and selenium levels. Our results support the hypothesis that low selenium level is associated with poor cognitive function. Longitudinal follow–up of this cohort will help to establish whether selenium levels affect the rate of cognitive decline associated with aging.
Microsoft Kinect Sensor and Its Effect (2012)

Recent advances in 3D depth cameras such as Microsoft Kinect sensors (www.xbox.com/en-US/kinect) have created many opportunities for multimedia computing. The Kinect sensor lets the computer directly sense the third dimension (depth) of the players and the environment. It also understands when users talk, knows who they are when they walk up to it, and can interpret their movements and translate them into a format that developers can use to build new experiences. While the Kinect sensor incorporates several advanced sensing hardware, this article focuses on the vision aspect of the Kinect sensor and its impact beyond the gaming industry.
Effects of intraperitoneal vitamin E, melatonin and aprotinin on leptin expression in the guinea pig eye during experimental uveitis (2005)

Experimental uveitis causes an increase in leptin expression in the retina, choroid, sclera and episclera of guinea pigs. Vitamin E, melatonin and aprotinin inhibit this increase. Leptin seems to be closely related to ocular inflammation.
Regulation of tissue inhibitor of metalloproteinase‐1 by astrocytes: Links to HIV‐1 dementia (2003)

The neuropathogenesis of HIV-1-associated dementia (HAD) revolves around the secretion of toxic molecules from infected and immune-competent mononuclear phagocytes. Astrocyte activation occurs in parallel but limited insights are available for its role in neurotoxicity and cognitive dysfunction. One means in which astrocytes may affect disease is through their production of tissue inhibitors of metalloproteinases (TIMPs). TIMPs are regulators of matrix metalloproteinases, enzymes that affect blood-brain barrier integrity through altering the extracellular matrix. We hypothesized that in response to injury and inflammation in HAD, astrocytes regulate the production of TIMP-1, the inducible type of TIMP that is important in inflammation. To address astrocyte-mediated TIMP-1 regulation in HAD, we evaluated the responses of primary human to IL-1beta and HIV-1. TIMP-1 levels in plasma, CSF, and brain tissue of control, HIV-1 infected patients without cognitive impairment, and HAD patients were also studied. Our data show that an upregulation of TIMP-1 results from astrocytes acutely activated with IL-1beta. In contrast, CSF and brain tissue samples from HAD patients showed reduced TIMP-1 levels compared to seronegative controls. MMP-2 levels in brains showed the opposite. Consistent with this, prolonged activation of astrocytes led to a reduction in TIMP-1 and MMP-2, but a sustained elevation in MMP-1. Our data suggest that in diseased brain tissue, the ability of astrocytes to counteract the destructive effects of MMP through expression of TIMP-1 is diminished by chronic activation. Our studies reveal new opportunities for repair-based therapeutic strategies in HAD.
Sensitivity Study of the Flow - through Dynamic Flux Chamber Technique for the Soil NO Emissions (2005)

A mathematical sensitivity analysis of the flow-through dynamic flux chamber technique, which has been utilized usually for various trace gas flux measurement from soil and water surface, was performed in an effort to provide physical and mathematical understandings of parameters essential for the NO flux calculation. The mass balance equation including chemical reactions was analytically solved for the soil NO flux under the steady state condition. The equilibrium concentration inside the chamber, Ceq, was found to be determined mainly by the balance between the soil flux and dilution of the gas concentration inside the chamber by introducing the ambient air. Surface deposition NO occurs inside the chamber when the Ceq is greater than the ambient NO concentration (C。) introducing to the chamber; NO emission from the soil occurs when the Ceq is less than the ambient NO concentration. A sensitivity analysis of the significance of the chemical reactions of NO with the reactive species (i.e. HO₂, CH₃O₂, O₃) on the NO flux from soils was performed. The result of the analysis suggests that he NO flux calculated in the absence of chemical reactions and wall loss could be in error ranges from 40 to 85% to the total flux.
A Multiphase, Modular, Bidirectional, Triple-Voltage DC–DC Converter for Hybrid and Fuel Cell Vehicle Power Systems (2008)

Electrical power systems in future hybrid and fuel cell vehicles may employ three voltage [14 V, 42 V, and high voltage (HV)] nets. These will be necessary to accommodate existing 14-V loads as well as efficiently handle new heavy loads at the 42-V net and a traction drive on the HV bus. A low-cost DC-DC converter was proposed for connecting the three voltage nets. It minimizes the number of switches and their associated gate driver components by using two half-bridges and a high-frequency transformer. Another salient feature is that the half bridge on the 42-V bus is also utilized to provide the 14-V bus by operating at duty ratios around an atypical value of 1/3. Moreover, it makes use of the parasitic capacitance of the switches and the transformer leakage inductance for soft switching. The use of half bridges makes the topology well suited for interleaved multiphase modular configurations as a means to increase the power level because the capacitor legs can be shared. This paper presents simulation and experimental results on an interleaved two-phase arrangement rated at 4.5 kW. Also discussed are the benefits of operating with an atypical duty ratio on the transformer and a preferred multiphase configuration to minimize capacitor ripple currents.
The fox and the hedgehog in the Ethnic Affairs Commission of New South Wales oral history project (2001)

The Ethnic Affairs Commission of New South Wales developed from the initiatives of the 1970s. Firstly, there was the Ethnic Affairs Section that rose. out of the Department of Youth and Community Services, received a small grant. and was transferred to Premier's Department. It remained there until 1979 when it was fused with other groups to form the NSW Ethnic Affairs Commission. The NSW Ethnic Communities Council, an independent endeavour, was formed in 1975. and has also become an important forum for the many ethnic groups which make up its membership.'
Rebalancing Immune Specificity and Function in Cancer by T-Cell Receptor Gene Therapy (2010)

Adoptive immunotherapy with tumor-specific T lymphocytes has demonstrated clinical benefit in some cancers, particularly melanoma. Yet isolating and expanding tumor-specific cells from patients is challenging and there is limited ability to control T-cell affinity and response characteristics. T-cell receptor (TCR) gene therapy, in which T lymphocytes for immunotherapy are redirected using an introduced rearranged TCR, has emerged as an important alternative. Successful TCR gene therapy requires consideration of a number of issues, including TCR specificity and affinity, optimal gene therapy constructs, types of T cells administered, and the survival and activity of the modified cells. In this review we highlight the rationale for and experience with TCR gene therapy as well as new approaches to enhancing it.
In Vivo Chemistry for Pretargeted Tumor Imaging in Live Mice (2010)

Wie sieht's aus in der Maus? Ein trans-Cycloocten-Antikörper-Konjugat wurde Tumormäusen verabreicht. Die derart chemisch markierten Tumore wurden dann mit einer 111In-markierten Tetrazin-Sonde in einer Diels-Alder-Reaktion mit inversem Elektronenbedarf umgesetzt, die das Addukt in vivo mit einer bemerkenswerten Ausbeute von 52–57 % ergab. Mit diesem nichtinvasiven Verfahren gelang die Abbildung von Tumoren in Mäusen (siehe Bild). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cloning and expression of the human vasoactive intestinal peptide receptor. (1991)

Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator found in the central and peripheral nervous system. Distinct subsets of neural, respiratory, gastrointestinal, and immune cells bear specific high-affinity receptors for VIP, which are associated with a guanine nucleotide-binding (G) protein capable of activating adenylate cyclase. A cDNA clone (GPRN1) encoding the human VIP receptor was identified in libraries prepared from the Nalm 6 line of leukemic pre-B lymphoblasts and the HT-29 line of colon carcinoma cells. The deduced 362-amino acid polypeptide sequence encoded by GPRN1 shares a seven-transmembrane-segment hydropathicity profile with other G protein-coupled receptors. Northern blot analyses identified a 2.7-kilobase transcript of the VIP receptor in Nalm 6 and HT-29 cells as well as in tissues from rat brain, colon, heart, lung, kidney, spleen, and small intestine. COS-6 cells transfected with GPRN1 bound 125I-labeled VIP specifically with a dissociation constant (Kd) of 2.5 nM. VIP--and less effectively secretin, peptide histidine isoleucine (PHI), and glucagon competitively displaced bound 125I-VIP from transfected COS-6 cells, with potencies in the order VIP greater than secretin = PHI much greater than glucagon. VIP stimulated adenylate cyclase activity in stably transfected Chinese hamster ovary K1 cells, inducing a 3-fold increase in the intracellular level of cAMP. When the antisense orientation of the VIP receptor clone was introduced into HT-29 cells, there was a 50% suppression of the specific binding of 125I-VIP and of the VIP-induced increase in cAMP level, relative to untransfected cells. The VIP receptor cloned exhibits less than or equal to 24% homology with other receptors in the same superfamily and thus represents a subset of G protein-coupled receptors for peptide ligands.
Nitrogen profile control by plasma nitridation technique for poly-Si gate HfSiON CMOSFET with excellent interface property and ultra-low leakage current (2004)

A comparative study of plasma and thermal nitridation of HfSiO was performed systematically. We found that over 15 atom% of nitrogen is necessary to obtain sufficient thermal stability and blocking of boron diffusion in a conventional polycrystalline Si gate CMOS process regardless of the nitridation method. However, we demonstrated, for the first time, that plasma nitridation has a great advantage for obtaining thinner equivalent oxide thickness, lower gate leakage current (J/sub g//J/sub g/SiO/sub 2/=1E-4 @ V/sub g/=V/sub fb/-1 V) and higher carrier mobility (/spl mu//sub eff///spl mu//sub eff/SiO/sub 2/=0.85 @ E/sub eff/=0.8 MV/cm for electron, /spl mu//sub eff///spl mu//sub eff/SiO/sub 2/=0.9 @ E/sub eff/=0.5 MV/cm for hole) due to nitridation of HfSiO film without nitridation of Si substrate, compared with thermal nitridation.
Mutational analysis of the ligand binding domain of the low density lipoprotein receptor. (1988)

The ligand binding domain of the low density lipoprotein (LDL) receptor contains seven imperfect repeats of a 40-amino acid cysteine-rich sequence. Each repeat contains clustered negative charges that have been postulated as ligand-binding sites. The adjacent region of the protein, the growth factor homology region, contains three cysteine-rich repeats (A-C) whose sequence differs from those in the ligand binding domain. To dissect the contribution of these different cysteine-rich repeats to ligand binding, we used oligonucleotide-directed mutagenesis to alter expressible cDNAs for the human LDL receptor which were then introduced into monkey COS cells by transfection. We measured the ability of the mutant receptors to bind LDL, which contains a single protein ligand for the receptor (apoB-100), and beta-migrating very low density lipoprotein (beta-VLDL), which contains apoB-100 plus multiple copies of another ligand (apoE). The results show that repeat 1 is not required for binding of either ligand. Repeats 2 plus 3 and repeats 6 plus 7 are required for maximal binding of LDL, but not beta-VLDL. Repeat 5 is required for binding of both ligands. Repeat A in the growth factor homology region is required for binding of LDL, but not beta-VLDL. Repeat B is not required for ligand binding. These results support a model for the LDL receptor in which various repeats play additive roles in ligand binding, each repeat making a separate contribution to the binding event.
Alternative molecular form of human T cell‐specific antigen CD27 expressed upon T cell activation (1989)

The CD27 membrane antigen is exclusively present on a large subset of human peripheral blood T lymphocytes and on mature thymocytes. Several observations point towards a specific role of this molecule on activated T cells. Upon T cell activation induced via the T cell receptor complex, CD27 expression greatly increases, while addition of anti-CD27 monoclonal antibodies amplifies the proliferative response. Within the CD4+ subset, only CD27+ T cells provide helper activity for B cell differentiation. Interestingly, CD27 expression differs not only quantitatively, but also qualitatively between resting and activated T cells. On resting cells, CD27 is a disulfide-linked homodimer with subunits of 55 kDa molecular mass. Upon activation, also a 55-kDa monomer seems to occur, while in addition a 32-kDa component is found. The relationship between these two proteins has been investigated. The 55-kDa and 32-kDa molecules do not seem to be physically associated. The two CD27 components are structurally highly homologous as determined by two-dimensional mapping of tryptic peptides. They both express the epitopes recognized by anti-CD27 antibodies, indicating that the 32-kDa molecule is also T cell specific. Both 55-kDa and 32-kDa molecules carry N-linked carbohydrate groups. However, they differ in other, not yet specified, post-translational modifications, and do not arise from a common precursor simply by alternative N-glycosylation. The 32-kDa form may be derived by proteolytic processing from the 55-kDa protein, but most likely not from a larger (common) precursor. Alternatively, both molecules may arise from a common gene by alternative mRNA splicing, or be derived from highly homologous genes. The dramatic change in molecular composition of CD27 suggests a newly acquired function for CD27 on activated T cells.
Communication—Electrochemical Characterization of Commercial Bipolar Membranes under Electrolyte Conditions Relevant to Solar Fuels Technologies (2015)

Water electrolysis using a catholyte and anolyte at different pH values requires a bipolar membrane to sustain the pH difference and 1.23 V to electrolyze water. Bipolar membranes that separated concentrated aqueous acid and base exhibited an open-circuit potential consistent with the Nernst equation and rapid transport of protons and hydroxide ions. When excess supporting electrolyte was added to both solutions the membrane potential was measured to be ~0 V, which suggested that water electrolysis occurred at ≈1.23 V and therefore, protons and hydroxide ions were not the majority ionic charge carriers.
Role of Caco-2 Cell Monolayers in Prediction of Intestinal Drug Absorption (2006)

The usefulness of Caco-2 cell monolayers in determining the intestinal drug absorption of potential drug candidates as such and from delivery systems, elucidating the underlying mechanisms thereof, presystemic metabolism, cellular uptake and cytotoxicological assessment has been exemplified in this review. The role of Caco-2 cell monolayers in studying the effectiveness, involved mechanism and toxicity of various excipients for drug absorption promotion has also been discussed.
Amino acid sequence of the catalytic subunit of bovine type II adenosine cyclic 3',5'-phosphate-dependent protein kinase (1983)

The 350-residue amino acid sequence of the catalytic subunit of bovine cardiac muscle adenosine cyclic 3',5'-phosphate dependent protein kinase is described. The protein has a molecular weight of 40 862, which includes an N-tetradecanoyl (myristyl) group blocking the NH2 terminus and phosphate groups at threonine-197 and serine-338. Seven methionyl bonds in the S-carboxymethylated protein were cleaved with cyanogen bromide to yield eight primary peptides. These fragments, and subpeptides generated by cleavage with trypsin, pepsin, chymotrypsin, thermolysin, and Myxobacter AL-1 protease II, were purified and analyzed to yield the majority of the sequence. The primary peptides were aligned by analyses of overlapping peptides, particularly of methione-containing tryptic peptides generated after in vitro [14C]methyl exchange labeling of methionyl residues in the intact protein.