gebhart/patrepeval huggingface dataset:
Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing (2007)

Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8 [HHV8]) and Epstein-Barr virus (EBV/HHV4) are distantly related gammaherpesviruses causing tumors in humans. KSHV latency-associated nuclear antigen 1 (LANA1) is functionally similar to the EBV nuclear antigen-1 (EBNA1) protein expressed during viral latency, although they have no amino acid similarities. EBNA1 escapes cytotoxic lymphocyte (CTL) antigen processing by inhibiting its own proteosomal degradation and retarding its own synthesis to reduce defective ribosomal product processing. We show here that the LANA1 QED-rich central repeat (CR) region, particularly the CR2CR3 subdomain, also retards LANA1 synthesis and markedly enhances LANA1 stability in vitro and in vivo. LANA1 isoforms have half-lives greater than 24 h, and fusion of the LANA1 CR2CR3 domain to a destabilized heterologous protein markedly decreases protein turnover. Unlike EBNA1, the LANA1 CR2CR3 subdomain retards translation regardless of whether it is fused to the 5' or 3' end of a heterologous gene construct. Manipulation of sequence order, orientation, and composition of the CR2 and CR3 subdomains suggests that specific peptide sequences rather than RNA structures are responsible for synthesis retardation. Although mechanistic differences exist between LANA1 and EBNA1, the primary structures of both proteins have evolved to minimize provoking CTL immune responses. Simple strategies to eliminate these viral inhibitory regions may markedly improve vaccine effectiveness by maximizing CTL responses.
Tolerance (2014)

Recently, The Transplantation Society convened a workshop to address the question, "What do we need to have in place to make tolerance induction protocols a 'standard of care' for organ transplant recipients over the next decade?" In a productive 2-day meeting, there was wide-ranging discussion on a broad series of topics, resulting in five consensus recommendations as follows: (1) establish a registry of results for patients enrolled in tolerance trials; (2) establish standardized protocols for sample collection and storage; (3) establish standardized biomarkers and assays; (4) include children 12 years and older in protocols that have been validated in adults; and (5) establish a task force to engage third-party payers in discussions of how to fund tolerance trials. Future planned workshops will focus on progress in implementing these recommendations and identifying other steps that the community needs to take.
Pulmonary Disease Following Respirator Therapy of Hyaline-Membrane Disease (1967)

ALTHOUGH hyaline-membrane disease, the respiratory-distress syndrome of the newborn infant, has been the object of increased clinical and research interest in the past ten years, little attention has been paid to its possible sequelae.1 , 2 It is stated that most of these infants who survive the first three days of life will recover completely, and by seven to ten days of life will have normal lungs radiographically.3 , 4 Recent experience with critically ill infants at the Stanford Premature Infant Research Center demonstrates that intensive therapy may modify the acute syndrome so as to permit the development of a previously unrecorded abnormality of . . .
The apoplastic antioxidant system in Prunus: response to long-term plum pox virus infection (2006)

This work describes, for the first time, the changes taking place in the antioxidative system of the leaf apoplast in response to plum pox virus (PPV) in different Prunus species showing different susceptibilities to PPV. The presence of p-hydroxymercuribenzoic acid (pHMB)-sensitive ascorbate peroxidase (APX) (class I APX) and pHMB-insensitive APX (class III APX), superoxide dismutase (SOD), peroxidase (POX), NADH-POX, and polyphenoloxidase (PPO) was described in the apoplast from both peach and apricot leaves. PPV infection produced different changes in the antioxidant system of the leaf apoplast from the Prunus species, depending on their susceptibility to the virus. In leaves of the very susceptible peach cultivar GF305, PPV brought about an increase in class I APX, POX, NADH-POX, and PPO activities. In the susceptible apricot cultivar Real Fino, PPV infection produced a decrease in apoplastic POX and SOD activities, whereas a strong increase in PPO was observed. However, in the resistant apricot cultivar Stark Early Orange, a rise in class I APX as well as a strong increase in POX and SOD activities was noticed in the apoplastic compartment. Long-term PPV infection produced an oxidative stress in the apoplastic space from apricot and peach plants, as observed by the increase in H2O2 contents in this compartment. However, this increase was much higher in the PPV-susceptible plants than in the resistant apricot cultivar. Only in the PPV-susceptible apricot and peach plants was the increase in apoplastic H2O2 levels accompanied by an increase in electrolyte leakage. No changes in the electrolyte leakage were observed in the PPV-inoculated resistant apricot leaves, although a 42% increase in the apoplastic H2O2 levels was produced. Two-dimensional electrophoresis analyses revealed that the majority of the polypeptides in the apoplastic fluid had isoelectric points in the range of pI 4-6. The identification of proteins using MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) and peptide mass fingerprinting analyses showed the induction of a thaumatin-like protein as well as the decrease of mandelonitrile lyase in peach apoplast due to PPV infection. However, most of the selected polypeptides showed no homology with known proteins. This fact emphasizes that, at least in Prunus, most of the functions of the apoplastic space remain unknown. It is concluded that long-term PPV infection produced an oxidative stress in the leaf apoplast, contributing to the deleterious effects produced by PPV infection in leaves of inoculated, susceptible Prunus plants.
Intracellular trafficking of factor VIII to von Willebrand factor storage granules. (1998)

In plasma, von Willebrand factor (vWf) associates with Factor VIII (FVIII); however, the site at which these proteins first interact has not been defined. Administration of 1-desamino-8-D-arginine vasopressin (DDAVP) causes a rapid, concomitant elevation in plasma levels of both vWf and FVIII, suggesting the existence of a DDAVP-releasable storage pool for both proteins. To determine whether vWf and FVIII can associate intracellularly and colocalize to storage vesicles, we transfected AtT-20 cells with vWf and FVIII expression plasmids. FVIII alone was not detectable within storage granules; however, transfection of vWf cDNA into the same cell caused FVIII to alter its intracellular trafficking and to undergo granular storage, colocalizing to the vWf-containing granules. In contrast, colocalization of FVIII was not observed when these cells were transfected with plasmids encoding defective FVIII-binding vWf mutants. Transfection of bovine endothelial cells with FVIII further demonstrated vesicular storage of FVIII with vWf in Weibel-Palade bodies. Since gene therapy of hemophilia A may ultimately target endothelium or hematopoietic stem cells, the interaction between vWf and FVIII within a secretory cell is important. Thus, vWf can alter the intracellular trafficking of FVIII from a constitutive to a regulated secretory pathway, thereby producing an intracellular storage pool of both proteins.
Prothrombin is activated on vascular endothelial cells by factor Xa and calcium. (1983)

Vascular endothelial cells derived from adult bovine aorta (ABAE) treated with factor Xa and calcium were found to activate prothrombin. In contrast, nonvascular cells (human foreskin fibroblasts, bovine corneal endothelial cells, or human fetal lung cells) had either no or very little effect on prothrombin activation. In the presence of 6 X 10(5) ABAE cells, 20 ng of factor Xa converted 90 micrograms of prothrombin into 80 units of thrombin after 45 min at 37 degrees C. Exogenous factor V was not required for prothrombin activation, but thrombin generation was enhanced 2- to 4-fold by the addition of factor V (500-2,500 ng/ml). Treatment of ABAE cells with anti-bovine factor V IgG markedly inhibited prothrombin activation by factor Xa and calcium. In cells grown in serum-free medium for 3 months, the amount of factor V activity was equivalent to that found in cells grown with serum, which suggests that these cells probably synthesize factor V. Sparse ABAE cells increased prothrombin activation by factor Xa 6-fold compared to activation in confluent cells. Although previous thrombin treatment of ABAE cells did not enhance prothrombin activation, addition of dansyl arginine-4-ethyl piperidine amide markedly inhibited activation of 125I-labeled prothrombin by factor Xa, indicating that thrombin formation is necessary for optimal prothrombin activation. These data indicate that aortic endothelium may provide a physiologically important surface for activation of prothrombin as well as a mechanism for optimal formation of clots at sites of vascular injury.
Crystal structures of the Klenow fragment of DNA polymerase I complexed with deoxynucleoside triphosphate and pyrophosphate (1993)

Crystal structures of the Klenow fragment (KF) of DNA polymerase I from Escherichia coli complexed with deoxynucleoside triphosphate (dNTP) or with pyrophosphate (PPi) determined to 3.9-A resolution by X-ray crystallography show these molecules binding within the cleft of the polymerase domain and surrounded by residues previously implicated in dNTP binding. The dNTP binds adjacent to the O-helix [Ollis, D. L., Brick, P., Hamlin, R., Xuong, N. G., & Steitz, T. A. (1985a) Nature 313, 762-766] with its triphosphate moiety anchored by three positively charged residues, Arg 754, Arg 682, and Lys 758, plus His 734 and Gln 708. The dNTP binding site observed in the crystal is consistent with the results of chemical modification including cross-linking and is also near many of the amino acid residues whose mutation affects catalysis [Polesky, A. H., Steitz, T. A., Grindley, N. D. F., & Joyce, C. M. (1990) J. Biol. Chem. 265, 14579-14591; Polesky, A. H., Dahlberg, M. E., Benkovic, S. J., Grindley, N. D. F., & Joyce, C. M. (1992) J. Biol. Chem. 267, 8417-8428]. However, we conclude that the position of at least the dNMP moiety of dNTP in the binary complex is not likely to be the same as in its catalytically relevant complex with primer-template DNA.
Voice Trigger Detection from Lvcsr Hypothesis Lattices Using Bidirectional Lattice Recurrent Neural Networks (2019)

We propose a method to reduce false voice triggers of a speech-enabled personal assistant by post-processing the hypothesis lattice of a server-side large-vocabulary continuous speech recognizer (LVCSR) via a neural network. We first discuss how an estimate of the posterior probability of the trigger phrase can be obtained from the hypothesis lattice using known techniques to perform detection, then investigate a statistical model that processes the lattice in a more explicitly data-driven, discriminative manner. We propose using a Bidirectional Lattice Recurrent Neural Network (LatticeRNN) for the task, and show that it can significantly improve detection accuracy over using the 1-best result or the posterior.
Is Clostridium difficile a pathogen in the newborn intensive care unit? A prospective evaluation. (1997)

Infants hospitalized in our newborn intensive care unit frequently had stools positive for C. difficile toxin A. When compared with infants with toxin-negative findings, infants with colonization had an increased number of days with gastrointestinal tract symptoms.
Genetic mechanisms of resistance to protease inhibitors and entry inhibitors (2002)

Resistance to protease inhibitors (PIs) often appears as a result of changes at codons within the protease gene, which differ from one drug to another. When PIs are boosted with low doses of ritonavir, multiple mutations at the protease are required to reduce significantly the antiviral activity of these compounds. Moreover, mutations at gag cleavage sites may restore the loss of viral fitness caused by the selection of specific PI resistance mutations. In respect to entry inhibitors, a new class of compounds already in phase II/III clinical trials, resistance may emerge as a result of mutations outside the pol gene. Loss of susceptibility to agents that block virus attachment or the interaction with co-receptors often select HIV strains with mutations in the gp120 envelope-coding region. In contrast, agents that target gp41-dependent fusion select for HIV variants with mutations in the gp41 envelope gene.
Ligand‐Directed Strategy for Zeolite‐Type Metal–Organic Frameworks: Zinc(II) Imidazolates with Unusual Zeolitic Topologies (2006)

Thermally robust porous metal–organic frameworks (MOFs) with zeolitic topologies were constructed by means of a ligand-directed strategy involving molecular tailoring of simple bridging imidazolates with coordinatively unimportant substituents. This led to the isolation of three new MOFs having unusually high symmetries, intriguing topologies such as the supercage shown in the picture, and high thermal stability. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z503778_s.pdf or from the author. 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.
The pituitary gland is required for protection against lethal effects of Salmonella typhimurium. (1991)

One-half of pituitary-intact or sham-operated rats survive infection with 10(9) colony-forming units of Salmonella typhimurium, whereas rats without a pituitary gland all die within a few days. When the dose of S. typhimurium is reduced 600-fold, 15-25% of the hypophysectomized rats survive, and the survival rate is significantly enhanced by administration of tetracycline, recombinant interferon gamma (IFN-gamma), or recombinant growth hormone (GH). The protective effect of GH is abolished by heat inactivation or with an antibody to GH. Spleens from normal and hypophysectomized rats treated with tetracycline, IFN-gamma, or GH have 59-99% fewer bacteria 5 days after infection as compared to control rats. Peritoneal macrophages from hypophysectomized rats that are infected in vitro with S. typhimurium kill half as many extracellular bacteria as compared to pituitary-intact rats, and this bactericidal capacity is significantly augmented 75-95% by either GH or IFN-gamma. These data establish that the pituitary gland is essential for homeostasis during an infectious episode and that GH plays an important role in host resistance by augmenting the ability of macrophages to kill S. typhimurium.
Human X‐Box binding protein‐1 confers both estrogen independence and antiestrogen resistance in breast cancer cell lines (2007)

Human X-box binding protein-1 (XBP1) is an alternatively spliced transcription factor that participates in the unfolded protein response (UPR), a stress-signaling pathway that allows cells to survive the accumulation of unfolded proteins in the endoplasmic reticulum lumen. We have previously demonstrated that XBP1 expression is increased in antiestrogen-resistant breast cancer cell lines and is coexpressed with estrogen receptor alpha (ER) in breast tumors. The purpose of this study is to investigate the role of XBP1 and the UPR in estrogen and antiestrogen responsiveness in breast cancer. Overexpression of spliced XBP1 [XBP1(S)] in ER-positive breast cancer cells leads to estrogen-independent growth and reduced sensitivity to growth inhibition induced by the antiestrogens Tamoxifen and Faslodex in a manner independent of functional p53. Data from gene expression microarray analyses imply that XBP1(S) acts through regulation of the expression of ER, the antiapoptotic gene BCL2, and several other genes associated with control of the cell cycle and apoptosis. Testing this hypothesis, we show that overexpression of XBP1(S) prevents cell cycle arrest and antiestrogen-induced cell death through the mitochondrial apoptotic pathway. XBP1 and/or the UPR may be a useful molecular target for the development of novel predictive and therapeutic strategies in breast cancer.
High-Resolution Crystal Structure of an Engineered Human β 2 -Adrenergic G Protein–Coupled Receptor (2007)

Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human beta2-adrenergic receptor-T4 lysozyme fusion protein bound to the partial inverse agonist carazolol at 2.4 angstrom resolution. The structure provides a high-resolution view of a human G protein-coupled receptor bound to a diffusible ligand. Ligand-binding site accessibility is enabled by the second extracellular loop, which is held out of the binding cavity by a pair of closely spaced disulfide bridges and a short helical segment within the loop. Cholesterol, a necessary component for crystallization, mediates an intriguing parallel association of receptor molecules in the crystal lattice. Although the location of carazolol in the beta2-adrenergic receptor is very similar to that of retinal in rhodopsin, structural differences in the ligand-binding site and other regions highlight the challenges in using rhodopsin as a template model for this large receptor family.
Interaction of Hsp90 with the Nascent Form of the Mutant Epidermal Growth Factor Receptor EGFRvIII (2003)

EGFRvIII is a mutant epidermal growth factor that promotes aggressive growth of glioblastomas. We made a plasmid that directed the expression of an EGFRvIII with three copies of the Flag epitope at its amino terminus. Flag-tagged EGFRvIII was expressed at the same levels as unmodified EGFRvIII, and showed the same subcellular localization. However, the Flag epitope could only be detected on EGFRvIII present in the endoplasmic reticulum; the epitope was covalently modified during trafficking of the receptor through the Golgi so that it was no longer recognized by anti-Flag antibody. This property was exploited to selectively purify nascent EGFRvIII from glioblastoma cells. Nascent EGFRvIII was found to copurify with a set of other proteins, identified by mass spectrometry as the two endoplasmic reticulum chaperones Grp94 and BiP, and the two cytosolic chaperones Hsc70 and Hsp90. The Hsp90-associated chaperone Cdc37 also co-purified with EGFRvIII, suggesting that Hsp90 binds EGFRvIII as a complex with this protein. Geldanamycin and radicicol, two chemically unrelated inhibitors of Hsp90, decreased the expression of EGFRvIII in glioblastoma cells. These studies show that nascent EGFRvIII in the endoplasmic reticulum associates with Hsp90 and Cdc37, and that the Hsp90 association is necessary to maintain expression of EGFRvIII.
A conserved mechanism of retrovirus restriction in mammals (2000)

The murine Fv1 gene restricts infection by N- or B-tropic murine leukemia viruses at a postentry, preintegration stage. The Fv1-sensitive viruses previously used for the study of Fv1 encode an ecotropic envelope gene and thus only infect rodent cells. Consequently, the study of Fv1 restriction has been carried out solely in mice and murine cell lines. By infection with retroviral vectors containing N- or B-tropic core and pantropic vesicular stomatitis virus-G envelope protein, we now demonstrate that cell lines derived from various mammalian species, including humans, have an Fv1-like retrovirus restriction function, preventing N-tropic vector infection. Like Fv1, restriction is directed at amino acid 110 of the viral capsid protein. In contrast to Fv1, the novel restriction is characterized by the absence of reverse-transcribed viral DNA. We speculate that these activities have been selected for by retroviral epidemics in the distant past.
The Valosin-containing Protein (VCP) Is a Target of Akt Signaling Required for Cell Survival (2006)

The serine/threonine kinase Akt is a key mediator of cell survival and growth, but its precise mechanism of action, and more specifically, the nature of its signaling partners largely remain to be elucidated. We show, using a proteomics-based approach, that the valosin-containing protein (VCP), a member of the AAA (ATPases associated with a variety of cellular activities) family, is a target of Akt signaling. SDS-PAGE of Akt co-immunoprecipitated proteins obtained from MCF-7 breast cancer cells revealed the increase of a 97-kDa band under Akt activation. Mass spectrometry analysis allowed the identification of VCP, and we have shown a serine/threonine phosphorylation on an Akt consensus site upon activation by growth factors. Site-directed mutagenesis identified Ser-351, Ser-745, and Ser-747 as Akt phosphorylation sites on VCP. Confocal microscopy indicated a co-localization between Akt and VCP upon Akt stimulation. Interestingly, small interfering RNA against VCP induced an inhibition of the growth factor-induced activation of NF-kappaB and a potent pro-apoptotic effect. Together, these data identify VCP as an essential target of Akt signaling.
Establishment of a human hepatocellular carcinoma cell line highly expressing sodium iodide symporter for radionuclide gene therapy. (2004)

NIS-based gene therapy using beta-emitting radionuclides has the potential to be used in hepatocellular carcinoma management.
The Multi-Agent Reinforcement Learning in MalmÖ (MARLÖ) Competition (2019)

Learning in multi-agent scenarios is a fruitful research direction, but current approaches still show scalability problems in multiple games with general reward settings and different opponent types. The Multi-Agent Reinforcement Learning in MalmÖ (MARLÖ) competition is a new challenge that proposes research in this domain using multiple 3D games. The goal of this contest is to foster research in general agents that can learn across different games and opponent types, proposing a challenge as a milestone in the direction of Artificial General Intelligence.
Point Mutational Inactivation of the Retinoblastoma Antioncogene (1989)

The retinoblastoma (Rb) antioncogene encodes a nuclear phosphoprotein, p105-Rb, that forms protein complexes with the adenovirus E1A and SV40 large T oncoproteins. A novel, aberrant Rb protein detected in J82 bladder carcinoma cells was not able to form a complex with E1A and was less stable than p105-Rb. By means of a rapid method for the detection of mutations in Rb mRNA, this defective Rb protein was observed to result from a single point mutation within a splice acceptor sequence in J82 genomic DNA. This mutation eliminates a single exon and 35 amino acids from its encoded protein product.
Soluble tumour necrosis factor receptors p55 and p75 in the urine monitor disease activity and the efficacy of treatment of inflammatory bowel disease. (1995)

The aim of the study was to discover if soluble tumour necrosis factor receptors (sTNF-R p55 and p75) in the urine of patients with inflammatory bowel disease (IBD) could be used to monitor the different stages of the activity of the diseases. Twenty five patients with either Crohn's disease or ulcerative colitis were followed up during a longterm study. The 16 patients who become acutely ill with either Crohn's disease or ulcerative colitis had significantly higher concentrations of sTNF-R p55 and p75 in their urine compared with those who were in remission, or those who were normal controls. There was a significant correlation between increased concentrations (> 20 ng/ml) of both sTNF-R p55 and p75 in the urine and a high Crohn's disease activity index (CDAI) and colitis activity index (CAI). Therefore, determination of sTNF-R is a good non-invasive parameter that can be used to assess the activity of disease and the efficacy of treatment.