gebhart/patrepeval huggingface dataset:
Helia: Heterogeneous Interconnect for Low Resolution Cache Access in snoop-based chip multiprocessors (2010)

In this work we introduce Heterogeneous Interconnect for Low Resolution Cache Access (Helia). Helia improves energy efficiency in snoop-based chip multiprocessors as it eliminates unnecessary activities in both interconnect and cache. This is achieved by using innovative snoop filtering mechanisms coupled with wire management techniques. Our optimizations rely on the observation that a high percentage of cache mismatches could be detected by utilizing a small subset but highly informative portion of the tag bits. Helia relies on the snoop controller to detect possible remote tag mismatches prior to tag array lookup. Power is reduced as a) our wire management techniques permit slow transmission of a subset of tag bits while tag mismatches are being detected and b) we avoid cache access for mismatches detected at the snoop controller. Our Evaluation shows that Helia reduces power in interconnect (dynamic: 64% to 75%, static: 45% to 50%) and cache tag array (dynamic: 57% to 58%, static: 80%) while improving average performance up to 4.4%.
The Roles of Androgen Receptors and Androgen-Binding Proteins in Nongenomic Androgen Actions (2002)

The biological activity of testosterone and dihydrotestosterone is thought to occur predominantly through binding to the androgen receptor (AR), a member of the nuclear receptor superfamily that functions as a ligand-activated transcription factor. However, androgens have also been reported to induce the rapid activation of kinase-signaling cascades and modulate intracellular calcium levels. These effects are considered to be nongenomic because they occur in cell types that lack a functional AR, in the presence of inhibitors of transcription and translation, or are observed to occur too rapidly to involve changes in gene transcription. Such nongenomic effects of androgens may occur through AR functioning in the cytoplasm to induce the MAPK signal cascade. In addition, androgens may function through the sex hormone binding globulin receptor and possibly a distinct G protein-coupled receptor to activate second messenger signaling mechanisms. The physiological effect of nongenomic androgen action has yet to be determined. However, it may ultimately contribute to regulation of transcription factor activity, including mediation of the transcriptional activity of AR.
Evaluation of Nine Teat Dip Formulation Under Experimental Challenge to Staphylococcus Aureus and Streptococcus Agalactiae (1983)

Nine postmilking teat dips were evaluated by an experimental challenge model against either Staphylococcus aureus, Streptococcus agalactiae, or both. Formulations containing .9 and .6% sodium hypochlorite, 1% sodium dichloro-s-triazene-trione, .55% chlorhexidine gluconate, and .35% povidone iodine reduced incidence of Staphylococcus aureus infections 56.8, 28.3, 75.9, 92.5, and 77.9%. Incidence of infections with Streptococcus agalactiae was reduced 48.1 and 63.2% by 1.7 and 1% sodium dichloro-s-triazene-trione formulations. The 1% chlorhexidine gluconate and .35% povidone iodine products reduced Streptococcus agalactiae infections 71.0 and 67.0%. Three experimental 1% iodophor formulations reduced Streptococcus agalactiae infections 28.9, 44.8, and 50.7%. The experimental challenge model was refined further and provided an efficient method to determine efficacy of postmilking teat dips.
Understanding Disease Susceptibility through Population Genomics (2012)

Genetic epidemiology studies have established that the natural variation of gene expression profiles is heritable and has genetic bases. A number of proximal and remote DNA variations, known as expression quantitative trait loci (eQTLs), that are associated with the expression phenotypes have been identified, first in Epstein-Barr virus-transformed lymphoblastoid cell lines and later expanded to other cell and tissue types. Integration of the eQTL information and the network analysis of transcription modules may lead to a better understanding of gene expression regulation. As these network modules have relevance to biological or disease pathways, these findings may be useful in predicting disease susceptibility.
Ubiquitin Ligases in Cholesterol Metabolism (2014)

To maintain cholesterol homeostasis, the processes of cholesterol metabolism are regulated at multiple levels including transcription, translation, and enzymatic activity. Recently, the regulation of protein stability of some key players in cholesterol metabolism has been characterized. More and more ubiquitin ligases have been identified including gp78, Hrd1, TRC8, TEB4, Fbw7, and inducible degrader of low density lipoprotein receptor. Their working mechanisms and physiological functions are becoming revealed. Here, we summarize the structure, substrates and function of these ubiquitin ligases. Their potential application in drug discovery is also discussed.
Extracellular Signal-Regulated Protein Kinase Mediates Interleukin 17 (IL-17)-Induced IL-8 Secretion inHelicobacter pylori-Infected Human Gastric Epithelial Cells (2004)

Helicobacter pylori-induced mucosal inflammation results in high production of interleukin 17 (IL-17), a potent inducer of IL-8 in gastric epithelial cells. The aim of this study was to investigate signaling pathways by which IL-17 regulates IL-8 production in human gastric epithelial cells. Activation of mitogen-activated protein (MAP) kinases in both IL-17-stimulated MKN28 cells and epithelial cells isolated from H. pylori-colonized gastric mucosa was assessed by Western blotting. In IL-17-stimulated MKN28 cells the activation of activatior protein 1 (AP-1), nuclear factor (NF)-IL-6, and NF-kappaB was also assessed by electrophoretic mobility shift assay. IL-8 production was evaluated by reverse transcription-PCR and enzyme-linked immunosorbent assay (ELISA) both for IL-17-stimulated MKN28 cells treated with specific MAP kinase inhibitors and gastric biopsy cultures treated with a neutralizing IL-17 antibody. Serum from H. pylori-infected patients was tested for immunoglobulin G response to CagA by ELISA. Treatment of MKN28 cells with IL-17 caused activation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2) but not other MAP kinases and had the downstream effects of AP-1 and NF-kappaB activation and IL-8 synthesis. Blocking ERK 1/2 activity inhibited AP-1-mediated, but not NF-kappaB-mediated, IL-8 induction. Enhanced activation of ERK 1/2 was seen in gastric epithelial cells isolated from H. pylori-infected patients in comparison to uninfected controls, and this was associated with high IL-8. These effects were even more pronounced in patients seropositive for CagA than in seronegative ones. In gastric biopsy cultures, the addition of a neutralizing IL-17 antibody decreased ERK 1/2 activation, thus resulting in a significant inhibition of IL-8. In H. pylori-colonized gastric epithelial cells, IL-17-induced IL-8 synthesis is associated with and depends at least in part on the activation of ERK 1/2 MAP kinase.
Genome-editing Technologies for Gene and Cell Therapy (2016)

Gene therapy has historically been defined as the addition of new genes to human cells. However, the recent advent of genome-editing technologies has enabled a new paradigm in which the sequence of the human genome can be precisely manipulated to achieve a therapeutic effect. This includes the correction of mutations that cause disease, the addition of therapeutic genes to specific sites in the genome, and the removal of deleterious genes or genome sequences. This review presents the mechanisms of different genome-editing strategies and describes each of the common nuclease-based platforms, including zinc finger nucleases, transcription activator-like effector nucleases (TALENs), meganucleases, and the CRISPR/Cas9 system. We then summarize the progress made in applying genome editing to various areas of gene and cell therapy, including antiviral strategies, immunotherapies, and the treatment of monogenic hereditary disorders. The current challenges and future prospects for genome editing as a transformative technology for gene and cell therapy are also discussed.
Heterocycles from Nitrike Oxides. Part V. 4-Amino-D2-1,2,4-oxadiazolines (1989)

Ary1 nltrlle oxldes unaorgo 1.3-dlpoiar cycloaddltlon with alkanone hydrazones r o give 4-am1no-;i-aryi-5.5-d1alkyl~~-1.2.4-oxaalazollnes.Lead tetraacetate oxldatlon or these 4amino-A2-1.2.4-oxadiazol~nes brings about smooth heteror~ng cracking lnto the correapond~ng nltrile.ketone.and nltrosen.Nltrlle oxides are known to undergo 1.3-alpolar c~cloaddltion with Schlff bases.as dipoiaroph~les.leading to ~2 -1 . 2 .4 -o x a d ~a z o l l d -5 .On the other hand, aza-nucieo~hlles, such as amlnes, react readily with nitrlle oxldes to slve the corres-~ondlng nucleophlllc addltlon products6.Dl~olarophlles lncorporatlng a nucleophlllc center.sucn as hydrazones.are antlclpated to react wlth nltrlle a x ~d e s elther by cycloaad~tion lnvolvlng the azomethlne bono or vla nucleophll~c addltlon invalvlng the a n n n o termlnus.It 1s antlclpated that competlrlon berween t n e s e two
CTA1-DD-Immune Stimulating Complexes: a Novel, Rationally Designed Combined Mucosal Vaccine Adjuvant Effective with Nanogram Doses of Antigen (2001)

Mucosally active vaccine adjuvants that will prime a full range of local and systemic immune responses against defined antigenic epitopes are much needed. Cholera toxin and lipophilic immune stimulating complexes (ISCOMS) containing Quil A can both act as adjuvants for orally administered Ags, possibly by targeting different APCs. Recently, we have been successful in separating the adjuvant and toxic effects of cholera toxin by constructing a gene fusion protein, CTA1-DD, that combines the enzymatically active CTA1-subunit with a B cell-targeting moiety, D, derived from Staphylococcus aureus protein A. Here we have extended this work by combining CTA1-DD with ISCOMS, which normally target dendritic cells and/or macrophages. ISCOMS containing a fusion protein comprising the OVA(323-339) peptide epitope linked to CTA1-DD were highly immunogenic when given in nanogram doses by the s.c., oral, or nasal routes, inducing a wide range of T cell-dependent immune responses. In contrast, ISCOMS containing the enzymatically inactive CTA1-R7K-DD mutant protein were much less effective, indicating that at least part of the activity of the combined vector requires the ADP-ribosylating property of CTA1. No toxicity was observed by any route. To our knowledge, this is the first report on the successful combination of two mechanistically different principles of adjuvant action. We conclude that rationally designed vectors consisting of CTA1-DD and ISCOMS may provide a novel strategy for the generation of potent and safe mucosal vaccines.
Control of the wavelength dependent thermo-optic coefficients in structured fibres (2006)

By controlling the fibre geometry, the fraction of optical field within the holes and the inserted material of a photonic crystal fibre, we demonstrate that it is possible to engineer any arbitrary wavelength-dependent thermo-optic coefficient. The possibility of making a fibre with a zero temperature dependent thermo-optic coefficient, ideal for packaging of structured fibre gratings, is proposed and explored.
Generation of Antitumor Responses by Genetic Modification of Primary Human T Cells with a Chimeric NKG2D Receptor (2006)

To create more effective T cells against human tumors, we have designed a strategy to allow T cells to recognize tumor cells using natural killer (NK) cell receptors but retain the effector responses of T lymphocytes. NKG2D is an activating cell surface receptor expressed on NK cells and on some T-cell subsets. Its ligands are primarily expressed on tumor cells. We have shown that by linking mouse NKG2D to the CD3zeta chain, it was possible to generate a chimeric NKG2D (chNKG2D) receptor that allowed activation of murine T cells on engagement with NKG2D ligand-positive tumor cells leading to antitumor responses in mice. In this study, a human version of the chNKG2D receptor was expressed on primary human T cells, and antitumor responses were determined. Human peripheral blood mononuclear cell-derived T cells were retrovirally transduced with a human chNKG2D receptor gene. These chNKG2D-bearing human T cells responded to NKG2D ligand-positive tumor cells by producing T-helper 1 cytokines, proinflammatory chemokines, and significant cellular cytotoxicity. This response could be blocked by anti-NKG2D antibodies, and it was dependent on NKG2D ligand expression on the target cells but not on expression of MHC molecules. In addition, the activity of chNKG2D-bearing T cells remained unimpaired after exposure to a soluble NKG2D ligand, soluble MICA, at concentrations as high as 1.5 mug/mL. These data indicate the feasibility of using chNKG2D receptors in primary human T cells and suggest that this approach may be a promising means for cancer immunotherapy.
Activation of humoral immunity and eosinophils in neuromyelitis optica (2004)

These observations suggest that neuromyelitis optica is associated with a major humoral immune response (particularly anti-MOG IgM production) and eosinophil activation present exclusively in CSF.
Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c (2004)

We explored the effects of bile acids on triglyceride (TG) homeostasis using a combination of molecular, cellular, and animal models. Cholic acid (CA) prevents hepatic TG accumulation, VLDL secretion, and elevated serum TG in mouse models of hypertriglyceridemia. At the molecular level, CA decreases hepatic expression of SREBP-1c and its lipogenic target genes. Through the use of mouse mutants for the short heterodimer partner (SHP) and liver X receptor (LXR) alpha and beta, we demonstrate the critical dependence of the reduction of SREBP-1c expression by either natural or synthetic farnesoid X receptor (FXR) agonists on both SHP and LXR alpha and LXR beta. These results suggest that strategies aimed at increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia.
Interactively shaping agents via human reinforcement (2009)

As computational learning agents move into domains that incur real costs (e.g., autonomous driving or financial investment), it will be necessary to learn good policies without numerous high-cost learning trials. One promising approach to reducing sample complexity of learning a task is knowledge transfer from humans to agents. Ideally, methods of transfer should be accessible to anyone with task knowledge, regardless of that person's expertise in programming and AI. This paper focuses on allowing a human trainer to interactively shape an agent's policy via reinforcement signals. Specifically, the paper introduces "Training an Agent Manually via Evaluative Reinforcement," or TAMER, a framework that enables such shaping. Differing from previous approaches to interactive shaping, a TAMER agent models the human's reinforcement and exploits its model by choosing actions expected to be most highly reinforced. Results from two domains demonstrate that lay users can train TAMER agents without defining an environmental reward function (as in an MDP) and indicate that human training within the TAMER framework can reduce sample complexity over autonomous learning algorithms.
Actor-Action Semantic Segmentation with Grouping Process Models (2016)

Actor-action semantic segmentation made an important step toward advanced video understanding: what action is happening, who is performing the action, and where is the action happening in space-time. Current methods based on layered CRFs for this problem are local and unable to capture the long-ranging interactions of video parts. We propose a new model that combines the labeling CRF with a supervoxel hierarchy, where supervoxels at various scales provide cues for possible groupings of nodes in the CRF to encourage adaptive and long-ranging interactions. The new model defines a dynamic and continuous process of information exchange: the CRF influences what supervoxels in the hierarchy are active, and these active supervoxels, in turn, affect the connectivities in the CRF, we hence call it a grouping process model. By further incorporating the video-level recognition, the proposed method achieves a large margin of 60% relative improvement over the state of the art on the recent A2D large-scale video labeling dataset, which demonstrates the effectiveness of our modeling.
The Structure and Airway Biology of Mast Cell Proteinases (1991)

Abstract Recent studies have led to a rapid expansion of knowledge concerning the structure and biology of the two major mast cell proteinases, tryptase and chymase. Tryptase is an abundant, trypsin-like enzyme found in the secretory granules of all human lung mast cells. The subunits of the heparin-associated tryptase tetramer appear to be the products of a multigene family whose intron-exon organization is unique and is not closely related to that of other mast cell or leukocyte serine proteinases. In vitro studies suggest that tryptases may participate in lung and airway responses by regulating airway neuropeptide activity, bronchomotor tone, and fibroblast mitogenesis. Mast cell chymases are chymotrypsin-like proteinases related closely to neutrophil cathepsin G and lymphocyte granzymes. The cDNA-derived structures of tryptase and chymase suggest that the two enzymes may differ in modes of activation from proenzyme forms, although the mature enzymes are packaged and released together. Chymase expression appears to be limited to a subset of human lung mast cells most prevalent in the airway submucosa. Possible roles for chymase include inactivation of sensory neuropeptides, regulation of submucosal gland secretion, and potentiation of histamine-induced vascular permeability.
Human umbilical cord blood: A clinically useful source of transplantable hematopoietic stem/progenitor cells (1990)

This is a review and discussion of studies leading to the first use of human umbilical cord blood, material usually discarded, for the provision of stem/progenitor cells for clinical hematopoietic reconstitution. This prospect arose as a result of extensive studies of the harvesting and cryopreservation of cord blood and of its numerical content of progenitor cells demonstrable in vitro. A male patient with Fanconi anemia (FA) was conditioned with a modified regimen of cyclophosphamide and irradiation that accommodates the abnormally high sensitivity to these agents that is characteristic of FA. Cryopreserved cord blood had been retrieved at birth from a female sibling known from prenatal testing to be unaffected by FA and to be human leukocyte antigen (HLA)-compatible with the prospective sibling recipient. After conditioning and therapeutic infusion of thawed cord blood, successful hematopoietic reconstitution was indicated by the general health of the patient, who had previously required supportive transfusions, by satisfactory hematological criteria and by counts of hematopoietic progenitor cells of various types in the bone marrow. Complete engraftment of the myeloid system with donor cells was evident from cytogenetics, ABO typing, study of DNA polymorphisms, and normal cellular resistance to cytotoxic agents that reveal the fragility of FA cells; the blood contained a residuum of host lymphocytes exhibiting chromosomal damage, but the trend has been towards eliminating these damaged cells. This implies that cord blood from a single individual should provide sufficient reconstituting cells for effective hematopoietic repopulation of an autologous or an HLA-compatible allogeneic recipient.
Therapeutic Potential of Inhibiting Brutons Tyrosine Kinase, (BTK) (2004)

BTK (Bruton's tyrosine kinase) is a member of the TEC family of tyrosine kinases that plays a central but diverse modulatory role in various cellular processes. The unique role of BTK in a multitude of signaling pathways, its function as a dual regulator of apoptosis and its involvement in a number of developmental processes makes BTK a desirable target for potential anti-cancer, anti-inflammatory and anti-viral agents as well as other treatments. The biochemistry and signaling networks of BTK were well described in numerous detailed reviews written by members of our team and others before us. Therefore in this particular review we are going to concentrate on the possible practical application of previously obtained knowledge to specific diseases and disorders.
The N-myristoylated Rab-GTPase m-Rabmc is involved in post-Golgi trafficking events to the lytic vacuole in plant cells (2004)

We report on the sub-cellular localisation and function of m-Rab(mc), a N-myristoylated plant-specific Rab-GTPase previously characterised at the molecular level and also by structural analysis in Mesembryanthemum crystallinum. By confocal laser scanning microscopy, we identified m-Rab(mc) predominantly on the prevacuolar compartment of the lytic vacuole but also on the Golgi apparatus in various plant cell types. Two complementary approaches were used immunocytochemistry and cyan fluorescent protein (CFP)/yellow fluorescent protein (YFP)-fusion proteins. Co-localisation studies of m-Rab(mc) with a salinity stress modulated integral calcium-ATPase suggest involvement of m-Rab(mc) in a plant-specific transport pathway to the prevacuolar compartment of the lytic vacuole. This hypothesis was strengthened by the inhibition of the transport of aleurain fused to green fluorescent protein (GFP), a marker of the lytic vacuole, in the presence of the dominant negative mutant m-Rab(mc)(N147I) in Arabidopsis thaliana protoplasts. The inhibitory effect of m-Rab(mc)(N147I) was specific for the transport pathway to the lytic vacuole, since the transport of chitinase-YFP, a marker for the neutral vacuole, was not hindered by the mutant.
Posterior Capsular Opacification (2009)

Posterior capsular opacification (PCO) is the most frequent complication of cataract surgery. Advances in surgical techniques, intraocular lens materials, and designs have reduced the PCO rate, but it is still a significant problem. The only effective treatment for PCO, Nd:YAG laser capsulotomy carries vision-related complications and risks and puts a significant financial burden on the health care system. This review contains current knowledge about the mechanisms of PCO development. Posterior capsular opacification is caused mainly by remnant lens epithelial cell proliferation and migration, epithelial-mesenchymal transition, collagen deposition, and lens fiber generation. All of these processes are influenced by cytokines, growth factors, and extracellular matrix proteins. We also describe advances and improvements in surgical techniques, intraocular lens materials, and the designs and use of therapeutic agents leading to safe, effective, and less expensive strategies to eradicate PCO.