gebhart/patrepeval huggingface dataset:
The Pim kinases control rapamycin-resistant T cell survival and activation (2005)

Although Pim-1 or Pim-2 can contribute to lymphoid transformation when overexpressed, the physiologic role of these kinases in the immune response is uncertain. We now report that T cells from Pim-1(-/-)Pim-2(-/-) animals display an unexpected sensitivity to the immunosuppressant rapamycin. Cytokine-induced Pim-1 and Pim-2 promote the rapamycin-resistant survival of lymphocytes. The endogenous function of the Pim kinases was not restricted to the regulation of cell survival. Like the rapamycin target TOR, the Pim kinases also contribute to the regulation of lymphocyte growth and proliferation. Although rapamycin has a minimal effect on wild-type T cell expansion in vitro and in vivo, it completely suppresses the response of Pim-1(-/-)Pim-2(-/-) cells. Thus, endogenous levels of the Pim kinases are required for T cells to mount an immune response in the presence of rapamycin. The existence of a rapamycin-insensitive pathway that regulates T cell growth and survival has important implications for understanding how rapamycin functions as an immunomodulatory drug and for the development of complementary immunotherapeutics.
Analysis of the p16 gene, CDKN2, in 17 Australian melanoma kindreds. (1995)

CDKN2 has been implicated as a melanoma susceptibility gene in some kindreds with a family history of this disease. Mutation analysis of CDKN2 in 17 familial melanoma Australian kindreds revealed a paucity of exon mutations and none of the previously described disease-related mutations. One novel germline mutation was found in exon one, Arg24Pro, which segregates with melanoma in 1/17 kindreds. Two previously described polymorphisms, Ala148Thr and a base change at nucleotide 540 were detected and one novel polymorphism in the untranslated region of exon 3 (nucleotide 580) was also found. Together with other recent reports, these findings provide support for CDKN2 as a susceptibility locus for familial melanoma but suggest that other loci are involved in some hereditary melanoma kindreds.
A hierarchy of signals regulates entry of membrane proteins into the ciliary membrane domain in epithelial cells (2011)

The membrane of the primary cilium is continuous with the plasma membrane but compositionally distinct. Although some membrane proteins concentrate in the cilium, others such as podocalyxin/gp135 are excluded. We found that exclusion reflects a saturable selective retention mechanism. Podocalyxin is immobilized by its PDZ interaction motif binding to NHERF1 and thereby to the apical actin network via ERM family members. The retention signal was dominant, autonomous, and transferable to membrane proteins not normally excluded from the cilium. The NHERF1-binding domains of cystic fibrosis transmembrane conductance regulator and Csk-binding protein were also found to act as transferable retention signals. Addition of a retention signal could inhibit the ciliary localization of proteins (e.g., Smoothened) containing signals that normally facilitate concentration in the ciliary membrane. Proteins without a retention signal (e.g., green fluorescent protein-glycosylphosphatidylinositol) were found in the cilium, suggesting entry was not impeded by a diffusion barrier or lipid microdomain. Thus, a hierarchy of interactions controls the composition of the ciliary membrane, including selective retention, selective inclusion, and passive diffusion.
Sequence differences between glycosylated and non-glycosylated Asn-X-Thr/Ser acceptor sites: implications for protein engineering (1990)

In N-glycosylated glycoproteins, carbohydrate is attached to Asn in the sequence Asn-X-Ser/Thr, where X denotes any amino acid. However, the presence of this consensus peptide does not always lead to glycosylation. We have compiled an extensive collection of glycosylated and non-glycosylated Asn-X-Thr/Ser sites and present a statistical study based on this data set. Our results indicate that non-glycosylated sites tend to be found more frequently towards the C termini of glycoproteins, and that proline residues in positions X and Y in the consensus Asn-X-Thr/Ser-Y strongly reduce the likelihood of N-linked glycosylation. Beyond this, there are no obvious local sequence features that seem to correlate with the absence or presence of N-linked glycosylation. These findings are discussed in terms of the prediction and engineering of glycosylation sites in secretory proteins.
Biomarkers for the Early Detection and Prognosis of Acute Kidney Injury (2016)

AKI is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. Despite a growing heterogeneity in its causes, providing a timely and certain diagnosis of AKI remains challenging. In this review, we summarize the evolution of AKI biomarker studies over the past few years, focusing on two major areas of investigation: the early detection and prognosis of AKI. We highlight some of the lessons learned in conducting AKI biomarker studies, including ongoing attempts to address the limitations of creatinine as a reference standard and the recent shift toward evaluating the prognostic potential of these markers. Lastly, we suggest current gaps in knowledge and barriers that may be hindering their incorporation into care and a full ascertainment of their value.
The Vitronectin Receptor vfl3 Binds Fibronectin and Acts in Concert with asfll in Promoting Cellular Attachment and Spreading on Fibronectin (1990)

The vitronectin receptor (ot~B3) is a member of the integrin superfamily of adhesive protein recep- tors that mediate a wide spectrum of adhesive cellular interactions, including attachment to vitronectin, yon WiUebrand factor, fibrinogen, and thrombospondin. We have studied the binding of fibronectin to the purified vitronectin receptor, and the role of this receptor in the attachment of cells to fibronectin. A solid-phase microtiter assay was developed to inves- tigate the binding properties of the vitronectin recep- tor. Purified tx433 bound fibronectin with high affinity in a saturable, divalent cation-dependent manner. Binding was inhibited by soluble vitronectin, by RGD-containing peptides, and by LM609, a monoclo- nal antibody against the vitronectin receptor known to inhibit the binding of adhesive proteins to Otvfl3. Im- munoinhibition experiments showed that M21 human melanoma cells, which express the fibronectin recep- tor, aSfll, as well as art3, used both of these integrins to attach and spread on fibronectin. In support of this finding, M21-L cells, a variant cell line that spe- cifically lacks tXvfl3 but expresses otv/31, attached and spread poorly on fibronectin. In addition, otv~ from surface-labeled M21 cells was retained, and selec- tively eluted by RGDS from a fibronectin affinity column. These results indicate that o~B3 acts in con- cert with ot5/3~ in promoting fibronectin recognition by these cells. We conclude that fibronectin binds to the otvfl3 vitronectin receptor specifically and with high affinity, and that this interaction is biologically rele- vant in supporting cell adhesion to matrix proteins.
Ethylene: A Gaseous Signal Molecule in Plants (2000)

Ethylene regulates a multitude of plant processes, ranging from seed germination to organ senescence. Of particular economic importance is the role of ethylene as an inducer of fruit ripening. Ethylene is synthesized from S-adenosyl-L-methionine via 1-aminocyclopropane-1-carboxylic acid (ACC). The enzymes catalyzing the two reactions in this pathway are ACC synthase and ACC oxidase. Environmental and endogenous signals regulate ethylene biosynthesis primarily through differential expression of ACC synthase genes. Components of the ethylene signal transduction pathway have been identified by characterization of ethylene-response mutants in Arabidopsis thaliana. One class of mutations, exemplified by etr1, led to the identification of the ethylene receptors, which turned out to be related to bacterial two-component signaling systems. Mutations that eliminate ethylene binding to the receptor yield a dominant, ethylene-insensitive phenotype. CTR1 encodes a Raf-like Ser/Thr protein kinase that acts downstream from the ethylene receptor and may be part of a MAP kinase cascade. Mutants in CTR1 exhibit a constitutive ethylene-response phenotype. Both the ethylene receptors and CTR1 are negative regulators of ethylene responses. EIN2 and EIN3 are epistatic to CTR1, and mutations in either gene lead to ethylene insensitivity. Whereas the function of EIN2 in ethylene transduction is not known, EIN3 is a putative transcription factor involved in regulating expression of ethylene-responsive genes. Biotechnological modifications of ethylene synthesis and of sensitivity to ethylene are promising methods to prevent spoilage of agricultural products such as fruits, whose ripening is induced by ethylene.
Video Distribution and Streaming (2015)

This chapter evaluates important metrics (e.g., video chunk duration and bit rate) that impact the efficiency of adaptive streaming. An in-depth review on the practical performance of popular adaptive streaming platforms (Apple's Hyper-Text Transfer Protocol Live Streaming (HLS) and Microsoft's smooth streaming (MSS)) over a variety of wireless networks are presented. The video quality of the chunks (i.e., bit rate or resolution) can be switched dynamically and seamlessly to adapt to fluctuating link conditions and end-user device resources. The dynamic adaptive streaming over HTTP (DASH) standard aims to define an interoperable delivery format that provides end users with the best possible media experience by dynamically adapting the media to changing network conditions. The key to the successful adaptive streaming is the ability to switch between different quality levels without a perceptible change in the video quality.
Influence of glucose and other substrates on electric field and polyethylene glycol-mediated transformation of intact yeast cells (1994)

A prepulse incubation with 2% glucose (mannose, fructose) strongly inhibited electrotransformation of intact yeast cells. This inhibitory effect was not due to alterations of cell viability or to cell membrane electropermeabilization, and was not affected by the solution buffer properties of preincubation and pulsing media. The electrotransformation efficiency was not modified by non-metabolized substances, such as sorbitol or alose. The glucose inhibition of electrotransformation was fast, occurring after only a 3-5-min preincubation. The postpulse incubation with substrate also decreased transformation efficiency, but was pH-dependent. We observed a similar, strong inhibitory effect of glucose when cells were transformed chemically. A pH dependence of yeast electrotransformation was established.
A potentially implantable enzyme electrode for amperometric measurement of glucose. (1988)

A membrane limited amperometric enzyme electrode suitable for glucose measurement in biological fluids was developed. The sensor consists of a central platinum wire (0.3 mm) surrounded by a stainless steel tubing (0.8-1.0 mm outer diameter; 2-4 cm length). By successive dipcoating procedures, layers from cellulose acetate, glucose oxidase (crosslinked with glutaraldehyde) and polyurethane are placed on its surface. The platinum is polarized at +700 mV against steel. In vitro results: Electrodes are stable for at least 6 days. They exhibit a linear range extending to 500 mg/dl glucose. Response times are less than 100 sec. The sensors are not dependent on stirring and are relatively insensitive to changes of pH. Dependency of glucose measurement upon dissolved oxygen is negligible at oxygen concentrations above 0.5 mg/l. In vivo results: Preliminary studies in sheep using subcutaneously implanted needles indicate that short term glucose monitoring is feasible.
A structured vector space model for word meaning in context (2008)

We address the task of computing vector space representations for the meaning of word occurrences, which can vary widely according to context. This task is a crucial step towards a robust, vector-based compositional account of sentence meaning. We argue that existing models for this task do not take syntactic structure sufficiently into account.
Redox Characteristics of Nickel and Palladium Complexes of the Open-Chain Tetrapyrrole Octaethylbilindione:  A Biliverdin Model (2000)

Octaethylbiliverdin, C35H46N4O2, is a linear tetrapyrrole that can exist in coordinated form as the fully reduced trianion (OEB)3-, as the two electron oxidized monoanion, (OEBOx)-, or as the one electron oxidized radical, (OEB.)2-. The three-membered electron-transfer series involving [M(OEB)]n with n = +1, 0, and -1, and M = Ni or Pd has been characterized electrochemically. The most highly oxidized members of these series have been isolated in the form of their diamagnetic triiodide salts, [NiII(OEBOx)]I3 and [PdII(OEBOx)]I3, and characterized spectroscopically and by X-ray diffraction. [NiII(OEBOx)]I3 crystallizes in the orthorhombic space group Pbcn with a = 15.121(3) A, b = 16.777(3) A, and c = 14.628(3) A at 130(2) K with Z = 4. Refinement of 3311 reflections with 209 parameters and no restraints yielded wR2 = 0.136 and R = 0.054 for 2643 reflections with I > 2 sigma(I). The structure involves helical coordination of the linear tetrapyrrole ligand about the nickel with all four nitrogen atoms coordinated to the metal and Ni-N distances of 1.867(5) and 1.879(5) A. The triiodide ion is not coordinated to the nickel but sits over one of the meso carbon atoms of the tetrapyrrole. In the solid state, pairs of [NiII(OEBOx)]+ crystallize about a center of symmetry so that two identical tab/slot hydrogen-bonded arrangements involving the lactam oxygen of one complex and methine and two methylene protons of the adjacent cation. Similar hydrogen-bonded motifs are found in other complexes derived from octaethylbilindione. [PdII(OEBOx)]I3 is isomorphic with the nickel analogue and crystallizes in the orthorhombic space group Pbcn with a = 15.2236(6) A, b = 16.7638(7) A, and c = 14.6289(6) A at 90(2) K with Z = 4. Refinement of 6123 reflections with 209 parameters and no restraints yielded wR2 = 0.094 and R = 0.036 for 4042 reflections with I > 2 sigma(I). The odd electron compound PdII(OEB.) has also been isolated and characterized by single-crystal X-ray diffraction. Black PdII(OEB.) crystallizes in the monoclinic space group I2/a with a = 13.274(3) A, b = 18.655(4) A, c = 14.114(3) A, and beta = 116.00(3) degrees at 140(2) K with Z = 4. Refinement of 2030 reflections with 195 parameters and no restraints yielded wR2 = 0.090 and R = 0.042 for 1715 reflections with I > 2 sigma(I). The structure again involves helical coordination of the linear tetrapyrrole to the palladium through the four pyrrole nitrogen atoms. Reduction of the complex causes a slight elongation of the Pd-N bonds from 1.983(2) and 1.986(2) A in [PdII(OEBOx)]I3 to 2.011(4) and 2.012(4) A in PdII(OEB.).
Dendritic cells and macrophages in insulin dependent diabetes mellitus (1995)

The onset of diabetes mellitus is characterized by various symptoms, all the result of a\\ndisturbed glucose metabolism. The main symptoms are thirst and polydypsia, polyuria,\\nglucosuria, and weight loss. The faster the onset of diabetes, the more prominent these\\nsymptoms will be.\\nThe disturbed glucose metabolism underlying these symptoms, is due to an absolute\\ndeficiency of insulin secretion, a reduction in its biologic effectiveness or both.\\nDiabetes mellitus is nowadays classified in two major types:\\nType 1, or insulin-dependent diabetes mellitus (100M), occurs most commonly in\\njuveniles. It is a catabolic disorder in which circulating insulin is virtually absent, since\\nthe pancreatic p-cells, due to their absence, cannot respond to any insulinogenic\\nstimulus. Administration of exogenous insulin is therefore required to reverse the\\ncatabolic state, to prevent ketosis and to bring the elevated blood glucose level down.\\nType 2, or non-insulin\\xc2\\xb7dependent diabetes mellitus (NIDDM). represents a group of\\nmilder forms of diabetes that occur predominantly in adults. Circulating endogenous\\ninsulin is almost always sufficient to prevent ketoacidosis, but is often either subnormal\\nor relatively inadequate in the face of the increased needs owing to tissue insensitivity.\\nThe longer diabetes mellitus exists, the greater the chance of developing the\\ncharacteristic complications: micro- and macroangiopathy, and neuropathy.\\nMicroangiopathy may cause retinopathy and nephropathy, while macroangiopathy gives\\nrise to an elevated incidence of coronary heart disease, cerebro-vascular accidents, and\\nischemic complications in the legs. The quality of life of diabetic patients can be\\nprofoundly reduced by these complications, while also the life-expectancy is\\nconsiderably shorter for diabetic patients.\\nTherefore, prevention of late complications, and prevention of the disease itself, are\\nmajor goals in diabetes research. Prevention of the disease can only be expected if the\\nmechanisms leading to the disease will be better understood. Though some studies have\\nindicated that some type 2 patients show characteristics of type 1 disease, and\\nthat the boundaries between type 1 and type 2 diabetes might be not as absolute, it\\nis nevertheless generally assumed that the mechanisms leading to either type 1 or type\\n2 diabetes are different.\\nThis thesis considers aspects of the mechanism leading to IDDM or type 1 diabetes\\nmellitus.
RIGorous Detection: Exposing Virus Through RNA Sensing (2010)

Virus infection in mammals elicits a variety of defense responses that are initiated by signals from virus-sensing receptors expressed by the host. These receptors include the ubiquitously expressed RIG-I-like receptor (RLR) family of RNA helicases. RLRs are cytoplasmic proteins that act in cell-intrinsic antiviral defense by recognizing RNAs indicative of virus presence. Here, we highlight recent progress in understanding how RLRs discriminate between the RNA content of healthy versus virus-infected cells, functioning as accurate sensors of virus invasion.
Periplasmic Superoxide Dismutase in Meningococcal Pathogenicity (1998)

Meningococcal sodC encodes periplasmic copper- and zinc-cofactored superoxide dismutase (Cu,Zn SOD) which catalyzes the conversion of the superoxide radical anion to hydrogen peroxide, preventing a sequence of reactions leading to production of toxic hydroxyl free radicals. From its periplasmic location, Cu,Zn SOD was inferred to acquire its substrate from outside the bacterial cell and was speculated to play a role in preserving meningococci from the action of microbicidal oxygen free radicals produced in the context of host defense. A sodC mutant was constructed by allelic exchange and was used to investigate the role of Cu,Zn SOD in pathogenicity. Wild-type and mutant meningococci grew at comparable rates and survived equally long in aerobic liquid culture. The mutant showed no increased sensitivity to paraquat, which generates superoxide within the cytosol, but was approximately 1,000-fold more sensitive to the toxicity of superoxide generated in solution by the xanthine/xanthine oxidase system. These data support a role for meningococcal Cu,Zn SOD in protection against exogenous superoxide. In experiments to translate this into a role in pathogenicity, wild-type and mutant organisms were used in an intraperitoneal mouse infection model. The sodC mutant was significantly less virulent. We conclude that periplasmic Cu,Zn SOD contributes to the virulence of Neisseria meningitidis, most likely by reducing the effectiveness of toxic oxygen host defenses.
Using avidin‐mediated binding to enhance initial endothelial cell attachment and spreading (1998)

Binding between the protein avidin and the vitamin biotin was used as an extrinsic, high affinity receptor–ligand system to augment the intrinsic integrin-dependent cellular adhesion mechanism. Glass substrates were coupled with avidin receptors through an adsorbed film of biotinylated bovine serum albumin (b-BSA). The avidin-treated slides then were seeded with biotinylated bovine aortic endothelial cells (BAEC). A 3:1 ratio of BSA:b-BSA provided the best results in terms of specific cellular attachment, growth, and spreading. Control surfaces consisted of bare glass or glass with adsorbed BSA. Attachment of unmodified BAEC to glass decreased in the presence of anti-β1 integrin antibody. Adhesion of biotinylated BAEC to avidin-treated slides was not affected by anti-β1 integrin antibody, consistent with integrin-independent avidin-mediated adhesion. The initial rate of cell spreading was greatest for avidin–biotin-mediated adhesion (80.0 ± 25.6 μm2/h), followed by integrin-dependent cellular adhesion on plain glass (35.7 ± 7.7 μm2/h) and, finally, by adhesion on BSA-coated protein surfaces (10.2 ± 0.3 μm2/;h). Biotinylated and unmodified BAEC, cultured for 1 h in serum-containing media, were subjected to laminar flow in a variable-height flow chamber that provided a range of shear stresses from 0.2 to 75 dynes/cm2. The critical shear stress required to detach 50% of the cells in serum-containing media increased from 4.6 ± 0.8 dynes/cm2 for integrin-dependent adhesion to 12.6 ± 1.2 dynes/cm2 for avidin–biotin-mediated adhesion. Avidin-mediated attachment for biotinylated BAEC increased initial cellular spreading rates and strength of attachment (i.e., at 1 h) by a factor of two and three, respectively. These results support the hypothesis that integrin-mediated cell attachment and spreading can be enhanced using high affinity integrin-independent binding. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 40, 57–65, 1998.
Prominin: A Story of Cholesterol, Plasma Membrane Protrusions and Human Pathology (2001)

Prominin is the first identified member of a novel family of polytopic membrane proteins conserved throughout the animal kingdom. It has an unusual membrane topology, containing five transmembrane domains and two large glycosylated extracellular loops. In mammals, prominin is expressed in various embryonic and adult epithelial cells, as well as in nonepithelial cells, such as hematopoietic stem cells. At the subcellular level, prominin is selectively localized in microvilli and other plasma membrane protrusions, irrespective of cell type. At the molecular level, prominin specifically interacts with membrane cholesterol and is a marker of a novel type of cholesterol-based lipid 'raft'. A frameshift mutation in the human prominin gene, which results in a truncated protein that is no longer transported to the cell surface, is associated with retinal degeneration. Given that prominin is concentrated in the plasma membrane evaginations at the base of the outer segment of rod photoreceptor cells, which are essential precursor structures in the biogenesis of photoreceptive disks, it is proposed that prominin has a role in the generation of plasma membrane protrusions, their lipid composition and organization and their membrane-to-membrane interactions.