gebhart/patrepeval huggingface dataset:
Oncogene-induced liver neoplasia in transgenic mice. (1989)

Models of hepatocarcinogenesis were generated by directing the expression of SV40 T-antigens, an oncogenic mutant of c-H-ras, or c-myc to the liver of transgenic mice using the albumin enhancer/promoter. The majority of mice carrying the ras transgene (group A) were born with enlarged livers and atypical hepatic architecture, and these all died within several days of birth. The remaining ras transgenic mice (group B) had lower levels of hepatic ras expression, exhibited mild hepatic dysplasia but no liver enlargement, and all ultimately died from development of lung tumors. In contrast, the livers of mice expressing T-antigens were relatively normal at birth, by one month displayed marked dysplasia, and by three to seven months developed multiple nodular adenomas and carcinomas. Myc expression caused mild to severe hepatic dysplasia in young mice, and focal hepatic adenomas in some mice over fifteen months of age. Lines of mice expressing ras (group B), T-antigen, or myc were established and crossed with each other to generate dual transgenic mice expressing oncogene pairs. Each combination resulted in accelerated tumor development, suggesting that these oncoproteins can cooperate with one another during multistep hepatic transformation.
Partial suppression of anchorage-independent growth and tumorigenicity in immunodeficient mice by transfection of the H-2 class I gene H-2Ld into a human colon cancer cell line (HCT). (1988)

Many human tumors, particularly those of epithelial origin, appear to express greatly reduced levels of major histocompatibility complex class I antigens on their surface. It has been previously reported that the class I gene H-2Ld, introduced into adenovirus type 12-transformed mouse cells, induces reversal of oncogenesis in immunocompetent BALB/c mice. We have tested the hypothesis that the H-2Ld gene, when transfected into HCT colon cancer cells, may alter their transformed phenotype. Two H-2Ld transfectants, HCT-Ii and HCT-If, were found to exhibit a markedly reduced-to-virtually suppressed ability to form colonies in soft agar in comparison to a transfectant (HCTh) carrying only the neomycin-resistance gene. We also compared the tumorigenicity of HCTh vs. HCT-If cells in two different strains of immunodeficient mice: nude (T-) and triple-deficient mutants (T-, NK-, B-). At 28 days postinjection of 10(7) and 10(6) cells, the size and growth rate of HCT-If tumors were greatly reduced compared to HCTh cells. Therefore, as assayed in immunodeficient animals, expression of the class I H-2Ld gene in HCT cells appears to correlate with partial suppression of the tumorigenic phenotype, suggesting that the expression of a transfected class I gene may by itself alter the phenotype of the recipient cell and that such phenotypic changes may be independent of the immune system.
Expression of Vascular Endothelial Growt Factor and Its Receptors fit and KDR in Ovarian Carcinoma (1995)

Coexpression of VEGF and KDR by tumor cells in ovarian carcinoma raises the possibility of autocrine stimulation and of therapeutic strategies targeting this receptor-ligand interaction.
Computer-generated watercolor (1997)

This paper describes the various artistic effects of watercolor and shows how they can be simulated automatically. Our watercolor model is based on an ordered set of translucent glazes, which are created independently using a shallow-water fluid simulation. We use a Kubelka-Munk compositing model for simulating the optical effect of the superimposed glazes. We demonstrate how computergenerated watercolor can be used in three different applications: as part of an interactive watercolor paint system, as a method for automatic image "watercolorization," and as a mechanism for nonphotorealistic rendering of three-dimensional scenes.
A Decision Criteria to Select an Associative-Memory Organization That Minimizes the Execution Time of a Mix of Associative-Search Operations (1993)

The dissertation develops a decision criteria to select an associative-memory organization that minimizes the execution time of a mix of associative-search operations and a decision criteria to estimate the layout dimensions of each organization for a specified memory size. The dissertation reclassifies Feng's associative-search operations into three hardware-influenced categories: bit-position independent (BPI), record-content independent (RCI); bit-position dependent (BPD), RCI; and BPD, record-content dependent (RCD). It develops a relationship between the categories and three associative-memory organizations: the CAM, the bit-serial word-parallel associative memory (BSWPAM) , and the extreme-search associative memory (ESAM). A version of the CAM, three versions of the BSWPAM, and a version of the ESAM organizations were designed and simulated to show that for most memory sizes, BPI, RCI operations require less time when executed on a CAM, BPD, RCI operations require less time when executed on a BSWPAM organization, and for many memory sizes, BPD, RCD operations require less time when executed on an ESAM. The dissertation calculates the layout dimensions of each memory. The results indicate the CAM is the most area efficient followed by the single, and two BSWPAM, the ESAM, and the four BSWPAM.... Associative memory, Content-addressable memory, Bit-serial word-parallel associative memory.
Tethering human immunodeficiency virus type 1 preintegration complexes to target DNA promotes integration at nearby sites (1997)

Integration of retroviral cDNA in vivo is normally not sequence specific with respect to the integration target DNA. We have been investigating methods for directing the integration of retroviral DNA to predetermined sites, with the dual goal of understanding potential mechanisms governing normal site selection and developing possible methods for gene therapy. To this end, we have fused retroviral integrase enzymes to sequence-specific DNA-binding domains and investigated target site selection by the resulting proteins. In a previous study, we purified and analyzed a fusion protein composed of human immunodeficiency virus integrase linked to the DNA-binding domain of lambda repressor. This fusion could direct selective integration in vitro into target DNA containing lambda repressor binding sites. Here we investigate the properties of a fusion integrase in the context of a human immunodeficiency virus provirus. We used a fusion of integrase to the DNA binding domain of the zinc finger protein zif268 (IN-zif). Initially we found that the fusion was highly detrimental to replication as measured by the multinuclear activation of a galactosidase indicator (MAGI) assay for infected centers. However, we found that viruses containing mixtures of wild-type integrase and IN-zif were infectious. We prepared preintegration complexes from cells infected with these viruses and found that such complexes directed increased integration near zif268 recognition sites.
Destabilization, Oligomerization and Inhibition of the Mitogenic Activity of Acidic Fibroblast‐Growth Factor by Aurintricarboxylic Acid (1997)

The triphenylmethane derivative aurintricarboxylic acid has been used to inhibit angiogenesis, vascular smooth muscle cell proliferation and cell transformation, an effect that has been attributed to its relatively nonspecific inhibitory activity of protein-nucleic acid interactions. Here, we show that this compound binds to acidic fibroblast growth factor, a prototypic member of a family of protein mitogens activated by heparin, altering its physicochemical properties and decreasing its mitogenic activity. Counteraction of the effects of aurintricarboxylic acid by heparin shows that the two compounds have opposite and reversible effects on acidic fibroblast growth factor structure and biological activity. The studies reported here may contribute to a deeper understanding of the inhibition of fibroblast-growth-factor-dependent mitogenesis of relevance to future pharmacologic developments.
Structure and Function of Carnitine Acyltransferases (2004)

Carnitine acyltransferases catalyze the exchange of acyl groups between carnitine and coenzyme A (CoA). These enzymes include carnitine acetyltransferase (CrAT), carnitine octanoyltransferase (CrOT), and carnitine palmitoyltransferases (CPTs). CPT-I and CPT-II are crucial for the beta-oxidation of long-chain fatty acids in the mitochondria by enabling their transport across the mitochondrial membrane. The activity of CPT-I is inhibited by malonyl-CoA, a crucial regulatory mechanism for fatty acid oxidation. Mutation or dysregulation of the CPT enzymes has been linked to many serious, even fatal human diseases, and these enzymes are promising targets for the development of therapeutic agents against type 2 diabetes and obesity. We have determined the crystal structures of murine CrAT, alone and in complex with its substrate carnitine or CoA. The structure contains two domains. Surprisingly, these two domains share the same backbone fold, which is also similar to that of chloramphenicol acetyltransferase and dihydrolipoyl transacetylase. The active site is located at the interface between the two domains, in a tunnel that extends through the center of the enzyme. Carnitine and CoA are bound in this tunnel, on opposite sides of the catalytic His343 residue. The structural information provides a molecular basis for understanding the catalysis by carnitine acyltransferases and for designing their inhibitors. In addition, our structural information suggests that the substrate carnitine may assist the catalysis by stabilizing the oxyanion in the reaction intermediate.
T cell activation results in physical modification of the mouse CD8 beta chain. (1994)

The T lymphocyte glycoprotein, CD8, is an essential component of the response of class I MHC-restricted T cells to Ag. CD8 is expressed on the surface of class I-restricted T cells as disulfide-bonded heterodimers and higher multimers of two distantly related polypeptides, alpha and beta. The CD8 alpha polypeptide, expressed in transfection studies as homodimers, is able to reproduce both the adhesive and stimulatory properties of CD8, leaving the function of the CD8 beta polypeptide unresolved. Herein we demonstrate that the CD8 beta polypeptide changes physically during T cell maturation and activation by reversibly altering its sialic acid content. These changes occur specifically on CD8 beta not -alpha, indicating that the primary role of the CD8 beta chain may be regulatory, influencing the physical structure of the CD8 complex, and suggesting a novel mechanism of controlling receptor/ligand interactions.
Hydrogen peroxide sensing, signaling and regulation of transcription factors (2014)

The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm-nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M(-1) s(-1) and ≥1.3 × 10(3) M(-1) s(-1) were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.
Inactivation of calpain by peptidyl fluoromethyl ketones (1992)

The syntheses of Z-Leu-Leu-Tyr-CH2F (1) and Z-Tyr-Ala-CH2F (3) are described. The ability of Z-Leu-Leu-Tyr-CH2F (1) and Z-Leu-Tyr-CH2F (2) to inactivate in vitro calcium-activated proteinase from chicken gizzard are compared. Like the analogous diazomethyl ketones 4 and 5, these inhibitors were also found to inactivate cathepsin L in common with other inhibitors under current investigation. However, other specific inactivators for cathepsin L are available, for example, the fluoromethyl ketone 3 and diazomethyl ketone 6 of Z-Tyr-Ala-OH, which have no effect on the calcium-activated proteinase and therefore provide control inhibitors for observations made with Z-Leu-Leu-Tyr-CH2F (1).
Growth of High-Density Titanium Silicide Nanowires in a Single Direction on a Silicon Surface (2007)

Understanding the growth mechanisms of nanowires is essential for their successful implementation in advanced devices applications. In situ ultrahigh-vacuum transmission electron microscopy has been applied to elucidate the interaction mechanisms of titanium disilicide nanowires (TiSi2 NWs) on Si(111) substrate. Two phenomena were observed: merging of the two NWs in the same direction, and collapse of one NW on a competing NW in a different direction when they meet at the ends. On the other hand, as one NW encounters the midsection of the other NW in a different direction, it recedes in favor of bulging of the other NW at the midsection. Since crystallographically the nanowires are favored to grow on Si(110) only in the [1 -1 0] direction, this crucial information has been fruitfully exploited to focus on the growth of a high density of long and high-aspect-ratio Ti silicide NWs parallel to the surface on Si(110) in a single direction. The achievement in growth of high-density NWs in a single direction represents a significant advance in realizing the vast potential for applications of silicide NWs in nanoelectronics devices.
Compositional stability analysis based on dual decomposition (2009)

We propose a compositional stability analysis framework for verifying properties of systems that are interconnections of multiple subsystems. The proposed method assembles stability certificates for the interconnected system based on the certificates for the input-output properties of the subsystems. The decomposition in the analysis is achieved by utilizing dual decomposition ideas from optimization. Decoupled subproblems establish subsystem level input-output properties whereas the ¿master¿ problem imposes and updates the conditions on the subproblems toward ensuring interconnected system level stability properties. Both global stability analysis and region-of-attraction analysis are discussed.
Extra-atrial expression of the gene for atrial natriuretic factor. (1986)

Atrial natriuretic factor (ANF) is a group of peptides, originally isolated from the cardiac atria, that have a number of important effects on blood pressure, renal function, and salt balance. In the current study, expression of the ANF gene in certain extra-atrial tissues of the rat has been examined by radioimmunoassay of extracted ANF protein and by blot-hybridization, nuclease S1 analysis, and primer-extension analysis of the ANF mRNA. ANF peptides and mRNA were detected in cardiac ventricles, lung, and pituitary gland at levels generally less than or equal to 1% those of cardiac atria. The ANF transcripts in extra-atrial tissue appear to be very similar to those synthesized in the atria. They are polyadenylylated, are equivalent in overall length (950-1050 nucleotides), and have identical 5' termini. A secondary transcription start site mapping approximately 80 base pairs upstream from the primary start site is employed in atria and to a lesser extent in other tissues. The ANF transcript is present throughout the cardiac ventricles from apex to base and in the septum as well as the ventricular free walls. The transcript is more prevalent in the left ventricle and interventricular septum than in the right ventricle. Immunocytochemistry using various anti-rat ANF antibodies localized ANF immunoreactivity to the atrial myocytes; the ventricular myocytes, particularly along the endothelial surface of the ventricular chamber; perialveolar cells in the lung; and the gonadotropin-producing cells of the pituitary. The data indicate that the capacity for ANF gene expression extends beyond atrial tissue, albeit at much reduced levels, and may suggest alternative, perhaps paraendocrine, functions for the peptide in these tissues.
Cell surface heparan sulfate proteoglycans from human vascular endothelial cells. Core protein characterization and antithrombin III binding properties. (1992)

Human aortic endothelial cells (HAEC) and human umbilical vein endothelial cells (HUVEC) were labeled with 35SO(4)2- for 48 h. The membrane-associated proteoglycans were solubilized from these monolayers with detergent and purified by ion-exchange chromatography on Mono Q, incorporation in liposomes, and gel filtration. The liposome-intercalated proteoglycans were 125I-iodinated and treated with heparitinase before SDS-polyacrylamide gel electrophoresis. Radio-labeled proteins with apparent molecular masses of 130, 60, 46, 35, and 30 kDa (HAEC) and 180, 130, 62, 43, and 35 kDa (HUVEC) were detected by autoradiography. Further characterization by affinity chromatography on immobilized monoclonal antibodies and by Northern blot analysis provided evidence for the expression of syndecan, glypican, and fibroglycan in human endothelial cells. Most of the heparan sulfate which accumulated in the subendothelial matrix was implanted on a 400-kDa core protein. This protein was immunologically related to perlecan and bound to fibronectin. Binding studies on immobilized antithrombin III suggested that all membrane-associated heparan sulfate proteoglycan forms had the capacity to bind to antithrombin III but that high affinity binding was more typical for glypican. Most of the proteoglycans isolated from the extracellular matrix also bound only with low affinity to antithrombin III. These results imply that glypican may specifically contribute to the antithrombotic properties of the vascular wall.
Characterization of Clinical Mastitis in Primiparous Heifers (1995)

Using data from health records for cows in Finland from between 1983 and 1991, we investigated the general trend for frequency of mastitis in heifers, seasonal variation, breed differences, and etiology of the disease. The performance of the heifers was monitored during first lactation. Treatment of heifer mastitis, defined as mastitis treatment 1 wk before and 1 wk after calving, increased from 1.8 to 4.4% between 1983 and 1991. The increase can be partly attributed to increased milk production, subsequent reduced resistance to mastitis, and the general trend toward more efficient treatment of mastitis. Heifer mastitis was a characteristic disease of well-managed, productive herds with low SCC and a high frequency of mastitis treatments administered by a veterinarian. Of the feeding factors studied, only use of homemade concentrates was associated with higher mastitis frequency. Mastitic heifers had higher genetic potential for milk production than control heifers, but actual milk production was 70 to 80 kg lower than expected. Most mastitic heifers recovered well and were not more susceptible than control heifers to further incidence of mastitis or other diseases. However, heifer mastitis caused more heifers than usual to be culled.
Cloning and characterization of a phospholipase gene from Erwinia chrysanthemi EC16. (1992)

A single gene (plcA) was cloned from a cosmid library of Erwinia chrysanthemi EC16 DNA that encoded an extracellular phospholipase. The gene was subcloned and DNA sequence data showed the presence of a single open reading frame encoding a protein with a predicted size of 39 kDa. The coding region was G+C-rich and the protein had a predicted basic isoelectric point. The protein showed no significant homology with others in the PIR library, including other phospholipases. When overexpressed in Escherichia coli cells, the plcA gene directed production of a c. 39 kDa protein that was largely localized in the periplasm, but its N-terminal amino acid sequence was that of the native protein predicted from DNA sequence data. Unlike the wild-type bacterium, an E. chrysanthemi EC16 marker exchange mutant of the plcA gene did not secrete extracellular phospholipase activity in the medium. However, no detectable change was observed in terms of the virulence of the mutant strain on potato tubers or chrysanthemum stems.
Mechanisms of action of a second generation growth hormone-releasing peptide (Ala-His-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2) in rat anterior pituitary cells. (1993)

The mechanism by which GH-releasing peptides elicit GH secretion has remained largely unknown. In this study, the effects of a second generation GH-releasing peptide, Ala-His-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2(GHRP-1), on cAMP, intracellular Ca2+ ([Ca2+]i), and GH release were examined using rat pituitary gland static monolayer cell cultures. It was found that GHRP-1 increased GH release in a dose-dependent manner up to 3-fold, while having no effect on cAMP levels. In contrast, simultaneous elevations of cAMP and GH were observed after treatment with GHRH. To further define the underlying mechanism of GHRP-1-mediated GH release, its effect on [Ca2+]i was determined using a fluorescent Ca2+ indicator, fura-2. GHRP-1 dose dependently increased [Ca2+]i up to 45.5 nM +/- 5.6 nM. A similar elevation of [Ca2+]i was observed after GHRH treatment. Similar to GHRH, GHRP-1-induced increases in [Ca2+]i and GH release were inhibited by somatostatin. Furthermore, the GHRP-1-induced increases in [Ca2+]i and GH were also suppressed by nifedipine. The interaction between the voltage-dependent Ca2+ channels and GHRP-1 was investigated in cells maximally stimulated by KCl. The addition of GHRP-1 had no effect on the KCl-stimulated GH release. To investigate the possible interaction between the adenylyl cyclase pathway and GHRP-1, cells were maximally stimulated with forskolin or (Bu)2cAMP. Addition of GHRP-1 stimulated GH release beyond that observed using cAMP elevating agents. Similar results were obtained in the presence of a protein kinase C, 4 beta-phorbol 12-myristate 13-acetate (PMA). The GHRP-1-stimulated GH release was additive to that observed with PMA stimulation. Based on these findings, it was concluded that 1) GHRP-1 treatment leads to an increase in [Ca2+]i; 2) unlike GHRH, GHRP-1 releases GH via a Ca(2+)-dependent, cAMP-independent mechanism; 3) GHRP-1-induced increases in [Ca2+]i and GH release are sensitive to somatostatin inhibition; and 4) cAMP-elevating agents and PMA have an additive effect on the GHRP-1-stimulated GH release, indicating these agents stimulate GH release via a mechanism separate from that of GHRP-1.
Multiorgan dysfunction syndrome in sickle cell disease. (2005)

Acute multiorgan failure is a life threatening complication of SCD, which can exhibit without any evidence of chronic organ damage and is easily reversed by prompt and aggressive transfusion therapy.