gebhart/patrepeval huggingface dataset:
Chemoprevention of UV Light-Induced Skin Tumorigenesis by Inhibition of the Epidermal Growth Factor Receptor (2005)

The epidermal growth factor receptor (EGFR) is activated in skin cells following UV irradiation, the primary cause of nonmelanoma skin cancer. The EGFR inhibitor AG1478 prevented the UV-induced activation of EGFR and of downstream signaling pathways through c-Jun NH2-terminal kinases, extracellular signal-regulated kinases, p38 kinase, and phosphatidylinositol 3-kinase in the skin. The extent to which the UV-induced activation of EGFR influences skin tumorigenesis was determined in genetically initiated v-ras(Ha) transgenic Tg.AC mice, which have enhanced susceptibility to skin carcinogenesis. Topical treatment or i.p. injection of AG1478 before UV exposure blocked the UV-induced activation of EGFR in the skin and decreased skin tumorigenesis in Tg.AC mice. AG1478 treatment before each of several UV exposures decreased the number of papillomas arising and the growth of these tumors by approximately 50% and 80%, respectively. Inhibition of EGFR suppressed proliferation, increased apoptotic cell death, and delayed the onset of epidermal hyperplasia following UV irradiation. Genetic ablation of Egfr similarly delayed epidermal hyperplasia in response to UV exposure. Thus, the UV-induced activation of EGFR promotes skin tumorigenesis by suppressing cell death, augmenting cell proliferation, and accelerating epidermal hyperplasia in response to UV. These results suggest that EGFR may be an appropriate target for the chemoprevention of UV-induced skin cancer.
Characterization of the alanine racemases from two Mycobacteria (2001)

D-Alanine is a necessary precursor in the biosynthesis of the bacterial peptidoglycan. The naturally occurring L-alanine isomer is racemized to its D-form through the action of a class of enzymes called alanine racemases. These enzymes are ubiquitous among prokaryotes, and with very few exceptions are absent in eukaryotes, making them a logical target for the development of novel antibiotics. The alanine racemase gene from both Mycobacterium tuberculosis and M. avium was amplified by PCR and cloned in Escherichia coli. Overexpression of the proteins in the E. coli BL21 system, both as native and as His-tagged recombinant products, has been achieved. The proteins have been purified to electrophoretic homogeneity and analyzed biochemically. A D-alanine requiring double knock-out mutant of E. coli (alr, dadX) was constructed and the cloned genes were able to complement its deficiencies.
Insulin Resistance of Glycogen Synthase Mediated byO-Linked N-Acetylglucosamine (2003)

We have investigated the mechanism by which high concentrations of glucose inhibit insulin stimulation of glycogen synthase. In NIH-3T3-L1 adipocytes cultured in low glucose (LG; 2.5 mm), the half-maximal activation concentration (A(0.5)) of glucose 6-phosphate was 162 +/- 15 microm. Exposure to either high glucose (HG; 20 mm) or glucosamine (GlcN; 10 mm) increased the A(0.5) to 558 +/- 61 or 612 +/- 34 microm. Insulin treatment with LG reduced the A(0.5) to 96 +/- 10 microm, but cells cultured with HG or GlcN were insulin-resistant (A(0.5) = 287 +/- 27 or 561 +/- 77 microm). Insulin resistance was not explained by increased phosphorylation of synthase. In fact, culture with GlcN decreased phosphorylation to 61% of the levels seen in cells cultured in LG. Hexosamine flux and subsequent enzymatic protein O-glycosylation have been postulated to mediate nutrient sensing and insulin resistance. Glycogen synthase is modified by O-linked N-acetylglucosamine, and the level of glycosylation increased in cells treated with HG or GlcN. Treatment of synthase in vitro with protein phosphatase 1 increased basal synthase activity from cells cultured in LG to 54% of total activity but was less effective with synthase from cells cultured in HG or GlcN, increasing basal activity to only 13 or 16%. After enzymatic removal of O-GlcNAc, however, subsequent digestion with phosphatase increased basal activity to over 73% for LG, HG, and GlcN. We conclude that O-GlcNAc modification of glycogen synthase results in the retention of the enzyme in a glucose 6-phosphate-dependent state and contributes to the reduced activation of the enzyme in insulin resistance.
Amphiphilic Invertible Polymers (AIPs) (2011)

Amphiphilic invertible polymers (AIPs) are composed of the hydrophilic, poly(ethylene glycol), and hydrophobic, aliphatic dicarboxylic acid moieties, alternately distributed along the main backbone. They build micelles, self-assemble by increasing concentration and are capable of accommodating otherwise insoluble substances in aqueous medium. The resulting complex nanostructures can undergo inverse conformational changes and are functional in both polar and non-polar environments, giving potentially broad use in many applications, especially in the pharmaceutical industry, agriculture, and cosmetics.
Adenoviral Gene Transfer of Activated Phosphatidylinositol 3′-Kinase and Akt Inhibits Apoptosis of Hypoxic Cardiomyocytes In Vitro (1999)

IGF-1 activates PI 3-kinase and Akt in cardiomyocytes. Activated PI 3-kinase and Akt are each sufficient to protect hypoxic cardiomyocytes against apoptosis in vitro. Adenoviral gene transfer provides a useful tool for investigating the role of these signaling pathways in cardiomyocyte apoptosis.
Live dense reconstruction with a single moving camera (2010)

We present a method which enables rapid and dense reconstruction of scenes browsed by a single live camera. We take point-based real-time structure from motion (SFM) as our starting point, generating accurate 3D camera pose estimates and a sparse point cloud. Our main novel contribution is to use an approximate but smooth base mesh generated from the SFM to predict the view at a bundle of poses around automatically selected reference frames spanning the scene, and then warp the base mesh into highly accurate depth maps based on view-predictive optical flow and a constrained scene flow update. The quality of the resulting depth maps means that a convincing global scene model can be obtained simply by placing them side by side and removing overlapping regions. We show that a cluttered indoor environment can be reconstructed from a live hand-held camera in a few seconds, with all processing performed by current desktop hardware. Real-time monocular dense reconstruction opens up many application areas, and we demonstrate both real-time novel view synthesis and advanced augmented reality where augmentations interact physically with the 3D scene and are correctly clipped by occlusions.
Oligo Safety Working Group Exaggerated Pharmacology Subcommittee Consensus Document (2013)

This document summarizes the current consensus opinion of the Exaggerated Pharmacology (EP) Subcommittee of the Oligonucleotide Safety Working Group on the appropriate strategies to assess potential adverse effects caused by an "exaggerated" degree of the intended pharmacologic activity of an oligonucleotide (ON). The Subcommittee focused its discussions primarily on the ON subclasses that impact expression of "host" (i.e., human gene products--antisense, small interfering RNAs, and related ONs that target messenger RNA), with later and more limited discussions on aptamer, immunostimulatory, and microRNA subclasses. It is expected that many of these principles will be relevant to other subclasses but will need to be carefully considered as those development programs advance towards clinical trials. The recommendations may also serve as a frame of reference when designing Good Laboratory Practice safety studies with ONs, with regard to the study design elements that address assessment of EP. It is also hoped that these recommendations will establish a foundation for discussion with regulatory agencies on this subject.
Modulation of Platelet Activation In Vitro by Thrombopoietin (1995)

Effect of human recombinant thrombopoietin (TPO) on platelet activation in vitro was studied. Although TPO itself did not cause platelet aggregation, it upregulated ADP-induced aggregation, especially the second wave of aggregation. This effect was dose-dependent for up to 5 ng/ml of TPO. When platelets were activated by epinephrine, collagen, or alpha-thrombin, similar effect was observed. However, TPO did not affect A23187- or PMA-induced aggregation, suggesting that TPO may have modulated the signal transduction pathway upstream of inositol 1,4,5-trisphosphate and diacylglycerol production. TPO also upregulated thrombin-induced alpha-granule secretion. To clarify the involvement of protein tyrosine phosphorylation, platelets were activated by TPO and/or suboptimal concentration of ADP, then tyrosine phosphorylation was detected by immunoblot analysis, using anti-phosphotyrosine monoclonal antibody. TPO by itself caused significant tyrosine phosphorylation of 146, 130, 122, 108, 97, 94, and 88 kDa proteins. Further, by using antibodies against signal transduction molecules for immunoprecipitation, we observed the significant tyrosine phosphorylation in Jak2 and Tyk2 molecules after TPO-stimulation. The results of the present experiment clearly indicate that TPO directly activated platelets and modulated intracellular signal transduction pathway.
Lymphoid Neoplasia Associated with the Acquired Immunodeficiency Syndrome (AIDS) (1988)

We identified 105 patients with lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS) at the New York University Medical Center from 1981 through 1986: 89 had non-Hodgkin lymphoma; 13, Hodgkin disease; and 3, chronic lymphocytic leukemia. Immunophenotypic and antigen receptor gene rearrangement analysis showed the B-cell origin of all non-Hodgkin lymphomas studied and the clonal suppressor-cytotoxic T-cell subset origin of the chronic lymphocytic leukemias. We classified 69% of the non-Hodgkin lymphomas as high grade (small, noncleaved and large cell, immunoblastic-plasmacytoid) and 31% as intermediate grade (diffuse large cell). Each histopathologic category was correlated with distinct clinical features, including a statistically significant difference in median survival. Patients with Hodgkin disease had an atypical, aggressive clinical course, whereas patients with T-cell chronic lymphocytic leukemia had an indolent clinical course. These studies show the clinical, morphologic, and immunophenotypic spectrum of AIDS-associated lymphoid neoplasia, that the natural history of Hodgkin disease is altered in patients with AIDS, and support the Centers For Disease Control's recent revision in diagnostic criteria for AIDS to include intermediate-grade diffuse, aggressive non-Hodgkin lymphomas occurring in patients seropositive for human immunodeficiency virus.
Cap-independent enhancement of translation by a plant potyvirus 5' nontranslated region (1990)

The RNA genome of tobacco etch virus (TEV), a plant potyvirus, functions as an mRNA for synthesis of a 346-kilodalton polyprotein that undergoes extensive proteolytic processing. The RNA lacks a normal 5' cap structure at its terminus, which suggests that the mechanism of translational initiation differs from that of a normal cellular mRNA. We have identified a translation-enhancing activity associated with the 144-nucleotide, 5' nontranslated region (NTR) of the TEV genome. When fused to a reporter gene encoding beta-glucuronidase (GUS), the 5' NTR results in an 8- to 21-fold enhancement over a synthetic 5' NTR in a transient-expression assay in protoplasts. A similar effect was observed when the 5' NTR-GUS fusions were expressed in transgenic plants. By using a cell-free translation system, the translation enhancement activity of the TEV 5' NTR was shown to be cap independent, whereas translation of GUS mRNA containing an artificial 5' NTR required the presence of a cap structure. Translation of GUS transcripts containing the TEV 5' NTR was relatively insensitive to the cap analog m7GTP, whereas translation of transcripts containing the artificial 5' NTR was highly sensitive. The 144-nucleotide TEV 5' NTR synthesized in vitro was shown to compete for factors that are required for protein synthesis in the cell-free translation reaction mix. Competition was not observed when a transcript representing the initial 81 nucleotides of the TEV 5' NTR was tested. These results support the hypothesis that the TEV 5' NTR promotes translation in a cap-independent manner that may involve the binding of proteins and/or ribosomes to internal sites within the NTR.
Newcastle Disease Virus (NDV) Marker Vaccine: an Immunodominant Epitope on the Nucleoprotein Gene of NDV Can Be Deleted or Replaced by a Foreign Epitope (2002)

The nucleoprotein (NP) of Newcastle disease virus (NDV) functions primarily to encapsidate the virus genome for the purpose of RNA transcription, replication, and packaging. This conserved multifunctional protein is also efficient in inducing NDV-specific antibody in chickens. Here, we localized a conserved B-cell immunodominant epitope (IDE) spanning residues 447 to 455 and successfully generated a recombinant NDV lacking the IDE by reverse genetics. Despite deletion of NP residues 443 to 460 encompassing the NP-IDE, the mutant NDV propagated in embryonated specific-pathogen-free chicken eggs to a level comparable to that of the parent virus. In addition, a B-cell epitope of the S2 glycoprotein of murine hepatitis virus (MHV) was inserted in-frame to replace the NP-IDE. Recombinant viruses properly expressing the introduced MHV epitope were successfully generated, demonstrating that the NP-IDE not only is dispensable for virus replication but also can be replaced by foreign sequences. Chickens immunized with the hybrid recombinants produced specific antibodies against the S2 glycoprotein of MHV and completely lacked antibodies directed against the NP-IDE. These marked-NDV recombinants, in conjunction with a diagnostic test, enable serological differentiation of vaccinated animals from infected animals and may be useful tools in ND eradication programs. The identification of a mutation-permissive region on the NP gene allows a rational approach to the insertion of protective epitopes and may be relevant for the design of NDV-based cross-protective marker vaccines.
Abstract 2392: Hyaluronan-dependent growth of human triple negative breast cancer MDA-MB-468 in mouse xenograft models (2015)

Abstract Hyaluronan (also known as hyaluronic acid or HA) is a nonsulfated glycosaminoglycan in the extracellular matrix. Elevated levels of HA in the tumor microenvironment have been associated with poor prognosis of several human cancers, including pancreatic, breast, colon and prostate. In many cases of breast cancer, HA is found to be associated with the stromal compartment. To understand the interaction between tumor cells and HA containing stromal compartment, we engineered a HA-high stromal cell line by overexpressing the human HAS3 gene in Balb/c 3T3 fibroblast cells. In vitro, the 3T3/HAS3 cells produced and secreted HA, which was shown to bind to the HA-low/CD44-high breast cancer cell line MDA-MB-468 at the cell surface. When co-grafted with MDA-MB-468 cells in mice, 3T3/HAS3 cells promoted the in vivo growth of MDA-MB-468 cells. Furthermore, depletion of HA with PEGPH20 (a pegylated form of the recombinant human PH20 protein) significantly inhibited the growth of MDA-MB-468 cells co-grafted with 3T3/HAS3 cells, suggesting that the HA provided by 3T3/HAS3 cells is critical for the growth of MDA-MB-468 cells in vivo. Immunohistochemical analysis of tumor xenograft samples showed that HA-low MDA-MB-468 cells were surrounded by HA-high stromal cells, resembling the tumor morphology observed in certain breast cancer patients. To model for breast cancers with tumor cell-associated HA, we overexpressed the human HAS3 gene directly in MDA-MB-468 cells. The in vivo growth of MDA-MB-468 was significantly enhanced by HAS3 overexpression. Depletion of HA by PEGPH20 synergized with Abraxane and improved its anti-cancer efficacy in the MDA-MB-468/HAS3 xenograft model compared to PEGPH20 and Abraxane alone. Taken together, we have developed tumor xenograft models that mimic HA-high breast cancers and can be used to test the pharmacological activity of anticancer agents. Further characterization of these models will provide insights into the understanding of the mechanisms by which increased levels of HA and the associated changes in the tumor microenvironment promote the disease progression in breast cancer and how depletion of HA can interfere with this process and synergize with chemotherapies to inhibit tumor progression. Citation Format: Chunmei Zhao, Mathieu Marella, Susan Zimmerman, Lei Huang, H. Michael Shepard, Zhongdong Huang. Hyaluronan-dependent growth of human triple negative breast cancer MDA-MB-468 in mouse xenograft models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2392. doi:10.1158/1538-7445.AM2015-2392
Nicotinic Acetylcholine Receptor Polymorphism, Smoking Behavior, and Tobacco-Related Cancer and Lung and Cardiovascular Diseases: A Cohort Study (2011)

Although smoking is associated with major tobacco-related diseases in the general population, the nicotinic acetylcholine receptor polymorphism is associated with additional increased risk of lung cancer, bladder cancer, and chronic obstructive pulmonary disease after adjustment for smoking.
Logic Design Principles: With Emphasis on Testable Semicustom Circuits (1986)

Logic design principles: with emphasis on testable semicustom circuits , Logic design principles: with emphasis on testable semicustom circuits , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Engineering platelets for tumour targeting (2016)

Human platelets are small (2μm), anucleate, discoid-shaped living cells that play essential roles in vascular haemostasis, thrombosis and inflammation [1]. While platelets are primarily confined to blood vessels, they may also accumulate in tumour microenvironments where they modulate functions of both tumour and immune cells [1]. It is known that platelets gain access to tumour microenvironments by passive diffusion across leaky capillaries, and through associations with activated immune cells [1]. Given this privileged access, one could, by imparting human platelets with new molecular functions, repurpose them as vehicles for tumour cell-targeting, in vivo imaging and delivery of therapeutic agents. This idea however, is undermined by the fact that human platelets aggregate easily in response to the types of chemical and physical manipulations envisaged for their repurposing. We have found a simple solution to address this issue that involves incubating freshly acquired human platelets with a membrane-permeable natural product drug that inhibits actin polymerization or blocks platelet activation [2]. Moreover, we have developed robust protocols to introduce aggregation incompetent human platelets with surface-coupled antibodies against tumor biomarkers, and with cytosol-trapped small molecule probes for magnetic resonance- or near infra-red fluorescence (NIRF) imaging, and also with cytotoxins for tumour therapy. The reactions used to repurpose the platelets as vehicles for in vivo imaging and therapy are typically complete within 60-minutes, and may be conducted within a custom-built automated device. Significantly, we have shown that the repurposed platelets engage in specific interactions with tumour cells in xenotransplants where they can generate an intense Cy7-fluorescence signal, allowing for high-contrast NIRF imaging of early stage tumours [2].
Regulation of Arterial Thrombolysis by Plasminogen Activator Inhibitor-1 in Mice (1998)

PAI-1 is an important determinant of thrombolysis at sites of arterial injury. Application of this model to other genetically altered mice should prove useful for studying the molecular determinants of arterial thrombosis and thrombolysis.
Complete cDNA sequence of human complement C1s and close physical linkage of the homologous genes C1s and C1r (1987)

Overlapping molecular clones encoding the complement subcomponent Cls were isolated from a human liver cDNA library. The nucleotide sequence reconstructed from these clones spans about 85% of the length of the liver Cls messenger RNAs, which occur in three distinct size classes around 3 kilobases in length. Comparisons with the sequence of Clr, the other enzymatic subcomponent of Cl, reveal 40% amino acid identity and conservation of all the cysteine residues. Beside the serine protease domain, the following sequence motifs, previously described in Clr, were also found in Cls: (a) two repeats of the type found in the Ba fragment of complement factor B and in several other complement but also noncomplement proteins, (b) a cysteine-rich segment homologous to the repeats of epidermal growth factor precursor, and (c) a duplicated segment found only in Clr and Cls. Differences in each of these structural motifs provide significant clues for the interpretation of the functional divergence of these interacting serine protease zymogens. Hybridizations of Clr and Cls probes to restriction endonuclease fragments of genomic DNA demonstrate close physical linkage of the corresponding genes. The implications of this finding are discussed with respect to the evolution of Clr and Cls after their origin by tandem gene duplication and to the previously observed combined hereditary deficiencies of Clr and Cls.
Contribution of the repeating domains of membrane cofactor protein (CD46) of the complement system to ligand binding and cofactor activity (1991)

Membrane cofactor protein (MCP) (CD46) of the C system binds to C3b and C4b, functions as a cofactor for their cleavage, and protects autologous cells from C-mediated injury. The predominant structural motif of MCP is the short consensus repeat (SCR), a repeating domain involved in ligand binding of other related C regulatory proteins. SCR deletion mutants were constructed to determine which of the four SCR of MCP contribute to ligand binding and cofactor activity. ELISA were developed to evaluate binding efficiency of mutants to ligand. Analysis of the deletion mutants indicated that the third and fourth SCR were important for both ligand binding and cofactor activity of C3b (iC3) and C4b. In addition, the same SCR were required for efficient binding of an mAb known to inhibit MCP function. The mutant deleted of SCR-2 bound but lacked cofactor activity for iC3. It did not bind or possess cofactor activity for C4b. Deletion of the first (amino-terminal) SCR had a minimal effect on iC3 binding and cofactor activity but reduced the efficiency of C4b binding. The results identify the SCR of MCP that contribute to ligand binding and cofactor activity. The data also suggest the presence of distinguishable iC3 and C4b binding sites and provide evidence that iC3 binding is not always sufficient for cofactor activity.