gebhart/patrepeval huggingface dataset:
Iodophenylarsine oxide and arsenical affinity chromatography: new probes for dithiol proteins. Application to tubulins and to components of the insulin receptor-glucose transporter signal transduction pathway. (1992)

In our studies of the effects of the trivalent arsenical phenylarsine oxide on insulin-dependent hexose uptake in 3T3-L1 adipocytes, we needed direct methods to study arsenical-protein interactions. In this report, we describe two such new tools. The first is the radiolabeled covalent affinity reagent 4-[125I]iodophenylarsine oxide. This compound has effects on 3T3-L1 adipocytes similar to those of phenylarsine oxide both with respect to effects of hexose uptake and the accumulation of pp15, a phosphotyrosine-containing putative mediator of insulin action. Iodophenylarsine oxide labels numerous proteins in intact cells in a concentration-dependent, but apparently insulin-independent fashion. The second tool is trivalent arsenical affinity chromatography, which we use to show novel direct interactions between trivalent arsenicals and several proteins from 3T3-L1 adipocytes including the insulin-responsive glucose transporter GLUT4, the insulin proreceptor, and both the alpha and beta subunits of tubulin. The non-insulin-dependent glucose transporter GLUT1, the mature insulin receptor, and the fatty acid-binding protein 422(aP2) do not show strong interactions with arsenical resin. These results provide a new chemical approach to the study of both insulin-dependent hexose transport and tubulin function.
Synthesis of (S)-N-(2,3-Dihydroxy-3-Methylbutyl)Acetamide (1986)

The absolute configuration of naturally occurring N-(2,3-dihydroxy-3- methylbutyl ) acetamide, from Verbesina enceloiodes, has been established by synthesis of the (S)-enantiomer.
[PMN leukocytes chemotaxis: inhibition by thalidomide (author's transl)]. (1981)

The effects of thalidomide on chemotaxis of normal human peripheral blood PMN leukocytes have been studied in vitro. Chemotaxis factor was generated by interacting normal human serum with zymosan. At concentration of 1, 10 and 100 micrograms/ml, thalidomide failed to inhibit chemotactic factor. Pre-incubation of PMNs with thalidomide caused a marked, dose-independent inhibition of chemotaxis. Random mobility did not appear to be affected. Inhibition of PMN chemotactic ability by thalidomide may account for its ability to improve skin diseases such as aphtosis, discoid lupus erythematosus and other sun-sensitive and/or inflammatory dermatoses.
Superhelically destabilized sites in the E. Coli genome: Implications for promoter prediction in prokaryotes (2004)

Abstract: Stress-induced DNA duplex destabilization (SIDD) analysis exploits the known structural and energetic properties of DNA to predict which sites become susceptible to strand separation under superhelical stress. Experimental results show that this analysis is quantitatively accurate in predicting destabilized sites that occur in transcriptional regulatory regions, matrix/scaffold attachment sites and replication origins. Here we report the results of a SIDD analysis of the complete E. coli genome, performed using a new algorithm specific for long genomic DNA sequences. Our results demonstrate that less than 7 % of the E. coli genome has the propensity to become highly destabilized at physiological superhelical densities. Those SIDD sites with high destabilization potential are statistically significantly associated with divergent and tandem intergenic regions, but not with convergent intergenic or coding regions. More than 80 % of the intergenic regions containing experimentally characterized promoters are found to overlap these SIDD sites. Strong SIDD sites are highly enriched in the 5 ’ upstream regions of genes regulating stress responses in E. coli, suggesting a possible functional role in their regulation. We discuss the possibility of using SIDD properties for promoter prediction, and potential roles of predicted SIDD sites in transcriptional regulation.
The Sequence Glu1811-Lys1818 of Human Blood Coagulation Factor VIII Comprises a Binding Site for Activated Factor IX (1996)

In previous studies have shown that the interaction between factor IXa and VIII involves the light chain of factor VIII and that this interaction inhibited by the monoclonal antibody CLB-CAg A against the factor VIII region Gln1778-Asp1840 (Lenting, P.J., Donath, M.J.S.H., van Mourik, J.A., and Mertens, K. (1994) J. Biol. Chem. 269, 7150-7155). Employing distinct recombinant factor VIII fragments, we now have localized the epitope of this antibody more precisely between the A3 domain residues Glu1801 and Met1823. Hydropathy analysis indicated that this region is part of a major hydrophilic exosite within the A3 domain. The interaction of factor IXa with this exosite was studied by employing overlapping synthetic peptides encompassing the factor VII region Tyr1786-Ala1834. Factor IXa binding was found to be particularly efficient to peptide corresponding to the factor VIII sequences Lys1804-Lys1818 and Glu1811-Gln1820. The same peptides proved effective in binding antibody CLB-CAg A. Further analysis revealed that peptides Lys1804-Lys1818 and Glu1811-Gln1820 interfere with binding of factor IXa to immobilized factor VIII light chain (Ki approximately 0.2 mM and 0.3 mM, respectively). Moreover, these peptides inhibit factor X activation by factor IXa in the presence of factor VIIIa (Ki approximately 0.2 mM and 0.3 mM, respectively) but not in its absence. Equilibrium binding studies revealed that these two peptides bind to the factor IX zymogen and its activated form, factor IXa, with the same affinity (apparent Kd approximately 0.2 mM), whereas the complete factor VIII light chain displays preferential binding to factor IXa. In conclusion, our results demonstrate that peptides consisting of the factor VIII light chain residues Lys1804-Lys1818 and Glu1811-Gln1820 share a factor IXa binding site that is essential for the assembly of the factor X-activating factor IXa-factor VIIIa complex. We propose that the overlapping sequence Glu1811-Lys1818 comprises the minimal requirements for binding to activated factor IX.
Regulation of Fibroblast Migration on Collagenous Matrix by a Cell Surface Peptidase Complex (2002)

The invasion of migratory cells through connective tissues involves metallo- and serine types of cell surface proteases. We show that formation of a novel protease complex, consisting of the membrane-bound prolyl peptidases seprase and dipeptidyl peptidase IV (DPPIV), at invadopodia of migratory fibroblasts is a prerequisite for cell invasion and migration on a collagenous matrix. Seprase and DPPIV form a complex on the cell surface that elicits both gelatin binding and gelatinase activities localized at invadopodia of cells migrating on collagenous fibers. The protease complex participates in the binding to gelatin and localized gelatin degradation, cellular migration, and monolayer wound closure. Serine protease inhibitors can block the gelatinase activity and the localized gelatin degradation by cells. Antibodies to the gelatin-binding domain of DPPIV reduce the cellular abilities of the proteases to degrade gelatin but do not affect cellular adhesion or spreading on type I collagen. Furthermore, expression of the seprase-DPPIV complex is restricted to migratory cells involved in wound closure in vitro and in connective tissue cells during closure of gingival wounds but not in differentiated tissue cells. Thus, we have identified cell surface proteolytic activities, which are non-metalloproteases, seprase and DPPIV, that are responsible for the tissue-invasive phenotype.
Study of WRKY transcription factor superfamily (2006)

WRKY transcription factors are DNA binding proteins that can specifically bind to W-box, and originally isolated from plants. WRKY proteins contain one or two conserved WRKY domains that is com- posed of about 60 amino acid residues with the WRKYGQK sequence followed by a C2H2 or C2HC zinc finger motif. WRKY is a superfamily of transcription factors in the high plant, and there are many genes in it. A lot of experimental evidence show that WRKY proteins participate in various physiological programs, including disease-resistance, senescence, stress responses of biotic and abiotic, growth and development processes.
Interface synthesis using memory mapping for an FPGA platform (2004)

Several system-on-chip (SoC) platforms have recently emerged that use reconfigurable logic (FPGAs) as a programmable coprocessor to reduce the computational load on the main processor core. We present an interface synthesis approach that forms part of our hardware-software codesign methodology for such an FPGA-based platform. The approach is based on a novel memory mapping algorithm that maps data used by both the hardware and the software to shared memories on the reconfigurable fabric. The memory mapping algorithm couples with a high-level synthesis tool and uses scheduling information to map variables, arrays and complex data structures to the shared memories in a way that minimizes the number of registers and multiplexers used in the hardware interface. We also present three software schemes that enable the application software to communicate with this hardware interface. We demonstrate the utility of our approach and study the trade-offs involved using a case study of the codesign of a computationally expensive portion of the MPEG-1 multimedia application on to the Altera Nios platform.
Anabaena xisF gene encodes a developmentally regulated site-specific recombinase. (1994)

Two DNA elements are excised from the chromosome during Anabaena heterocyst differentiation. We have identified the gene xisF which encodes the site-specific recombinase responsible for the excision of a 55-kb element from within the fdxN gene. The cloned xisF gene is sufficient to cause site-specific rearrangement of an artificial substrate in Escherichia coli. Inactivation of xisF in the Anabaena chromosome prevents excision of the fdxN element and growth in nitrogen-deficient medium but does not alter the development of heterocysts. Forced transcription of xisF in vegetative cells did not result in excision of the fdxN element, suggesting that other factors may be involved in cell-type specificity. The predicted XisF protein shows significant similarity to the Bacillus subtilis SpoIVCA recombinase.
Interaction of Neuronal Nitric-oxide Synthase with Caveolin-3 in Skeletal Muscle (1997)

Neuronal nitric-oxide synthase (nNOS) has been shown previously to interact with alpha1-syntrophin in the dystrophin complex of skeletal muscle. In the present study, we have examined whether nNOS also interacts with caveolin-3 in skeletal muscle. nNOS and caveolin-3 are coimmunoprecipitated from rat skeletal muscle homogenates by antibodies directed against either of the two proteins. Synthetic peptides corresponding to the membrane-proximal caveolin-3 residues 65-84 and 109-130 and homologous caveolin-1 residues 82-101 and 135-156 potently inhibit the catalytic activity of purified, recombinant nNOS. Purified nNOS also binds to a glutathione S-transferase-caveolin-1 fusion protein in in vitro binding assays. In vitro binding is completely abolished by preincubation of nNOS with either of the two caveolin-3 inhibitory peptides. Interactions between nNOS and caveolin-3, therefore, appear to be direct and to involve two distinct caveolin scaffolding/inhibitory domains. Other caveolin-interacting enzymes, including endothelial nitric-oxide synthase and the c-Src tyrosine kinase, are also potently inhibited by each of the four caveolin peptides. Inhibitory interactions mediated by two different caveolin domains may thus be a general feature of enzyme docking to caveolin proteins in plasmalemmal caveolae.
Revised estimate of the prevalence of multiple sclerosis in the united states (1992)

Using three adjustments, we have revised a 1976 prevalence count for multiple sclerosis in the United States. The adjustments were made to data from a US national survey; they used 1990 population projections from the US Bureau of the Census, and results of investigations conducted in Weld and Larimer Countries, Colorado, and Olmsted County, Minnesota. It is estimated that approximately 250,000 to 350,000 persons in the United States in 1990 had physician-diagnosed multiple sclerosis.
COMPUTERIZED ASSESSMENT OF DETRUSOR INSTABILITY IN PATIENTS TREATED WITH SACRAL NEUROMODULATION (2001)

Our algorithm accurately diagnoses and grades detrusor instability, and provides parameters with predictive value in regard to the probability that a bladder may or may not become stable with neuromodulation. However, the symptomatic result of this treatment option seems to depend on noncystometric factors.
A Chip-Based Biosensor for the Functional Analysis of Single Ion Channels (2000)

Stable gigaohm seals were obtained between a microstructured silicon chip (1) and an electrophoretically autopositioned giant vesicle (2). The low electrical background noise (<80 fA) of the resulting planar lipid bilayer (3) allows the observation of single ion channel events.
Activation of a fibroblast-specific enhancer of the Pro?2(I) collagen gene in tight-skin mice (2001)

These data suggest that activating signals in Tsk1/+ mice may act via fibroblast-specific regulatory elements within the murine Col1a2 gene. Although TGFbeta has been implicated in the pathogenesis of fibrosis, and reporter genes regulated by the upstream enhancer appear to be TGFbeta responsive in vitro, our results suggest that fibroblast-specific pathways may also be involved.
S/e‐PTFE episcleral buckling implants: An experimental and histopathologic study (2002)

To investigate tissue changes induced by the implantation of a silicone band coated with expanded polytetrafluoroethylene (S/e-PTFE) used as scleral buckling, an experimental and histopathological study was performed in rabbits. The right eyes of eight rabbits were implanted for 28-85 days with S/e-PTFE. No complications were encountered in any of the eyes, so histopathological examinations could be performed. Encapsulations combined with numerous giant cells were found to be surrounding the implants in seven eyes, and deposits from the mineral salts of calcium were found in three eyes, forming granulomas possibly caused by irregularities of the implant surface. The porous structure allowed a peripheral colonization by fibrovascular tissue. Taking into account the histological results, the use of this material does not appear suitable. However, this inflammation was limited and did not merge on surrounding tissues.
The B7 Family of Ligands and Its Receptors: New Pathways for Costimulation and Inhibition of Immune Responses (2002)

T cell activation is dependent upon signals delivered through the antigen-specific T cell receptor and accessory receptors on the T cell. A primary costimulatory signal is delivered through the CD28 receptor after engagement of its ligands, B7-1 (CD80) or B7-2 (CD86). Engagement of CTLA-4 (CD152) by the same B7-1 or B7-2 ligands results in attenuation of T cells responses. Recently, molecular homologs of CD28 and CTLA-4 receptors and their B7-like ligands have been identified. ICOS is a CD28-like costimulatory receptor with a unique B7-like ligand. PD-1 is an inhibitory receptor, with two B7-like ligands. Additional members of B7 and CD28 gene families have been proposed. Integration of signals through this family of costimulatory and inhibitory receptors and their ligands is critical for activation of immune responses and tolerance. Understanding these pathways will allow development of new strategies for therapeutic intervention in immune-mediated diseases.
Targeting siRNA Missiles to HER2+ Breast Cancer (2007)

Abstract : The most significant findings here are that HerPBK10-siRNA complexes retain stability in whole serum and evade serum nuclease mediated degradation of the siRNA, thus providing an encouraging prediction that the complex will be stable in vivo. We also show that HerPBK10- siRNA complexes induce targeted cell death to HER2+ but not HER2- cells in culture, suggesting that in vivo tumor targeting and cell death, as anticipated in the third year of this project, will be feasible. We show that the complex induces IFN-alpha secretion from HER2+ but not HER2- cells, which likely contributes to the mechanism of targeted cell death by these complexes. Interestingly, we also found that the HerPBK10 protein alone also induced a similar pattern of IFN-alpha secretion, and will be examining the contribution of the carrier protein and siRNA toward the targeted cell death observed here. Finally, we show that the siRNA carrier, HerPBK10, undergoes tumor-preferential accumulation in tumor-bearing mice, and preferentially avoids of normal tissues and organs.
Delayed hippocampal damage in humans following cardiorespiratory arrest (1987)

Transient ischemia in animals produces delayed cell death in vulnerable hippocampal neurons. To see if this occurs in humans, we reexamined brain slides from all patients with anoxic-ischemic encephalopathy and a well-documented cardiorespiratory arrest. Eight patients dying 18 hours or less after cardiac arrest had minimal damage in hippocampus and moderate damage in cerebral cortex and putamen. Six patients living 24 hours or more had severe damage in all four regions. The increase in damage with time postarrest was significant only in the hippocampus. Delayed hippocampal injury now documented in humans provides a target for possible therapy that can be initiated after cardiopulmonary resuscitation.
Neuronal Death Resulting from Targeted Disruption of the Snf2 Protein ATRX Is Mediated by p53 (2008)

ATRX, a chromatin remodeling protein of the Snf2 family, participates in diverse cellular functions including regulation of gene expression and chromosome alignment during mitosis and meiosis. Mutations in the human gene cause alpha thalassemia mental retardation, X-linked (ATR-X) syndrome, a rare disorder characterized by severe cognitive deficits, microcephaly and epileptic seizures. Conditional inactivation of the Atrx gene in the mouse forebrain leads to neonatal lethality and defective neurogenesis manifested by increased cell death and reduced cellularity in the developing neocortex and hippocampus. Here, we show that Atrx-null forebrains do not generate dentate granule cells due to a reduction in precursor cell number and abnormal migration of differentiating granule cells. In addition, fewer GABA-producing interneurons are generated that migrate from the ventral telencephalon to the cortex and hippocampus. Staining for cleaved caspase 3 demonstrated increased apoptosis in both the hippocampal hem and basal telencephalon concurrent with p53 pathway activation. Elimination of the tumor suppressor protein p53 in double knock-out mice rescued cell death in the embryonic telencephalon but only partially ameliorated the Atrx-null phenotypes at birth. Together, these findings show that ATRX deficiency leads to p53-dependent neuronal apoptosis which is responsible for some but not all of the phenotypic consequences of ATRX deficiency in the forebrain.
Neutral sphingomyelinase. (1993)

Although we have accumulated few data that would definitely designate the role of N-SMase in modern cell biology, current evidence indicates that N-SMase may play a central role in signal transduction (Fig. 7). Biomodulators such as hormones, antibiotics, drugs, growth factors, and lipoproteins may interact with N-SMase either directly or in combination with other components (receptors) on the cell surface. The cell surface topology would provide easy access for such interactions. According to our hypothetical model shown in Fig. 7, activation of N-SMase via biomodulators, e.g., TNF-alpha, leads to the mobilization of cell surface cholesterol to the interior of the cell. We speculate that this process may be facilitated by sterol carrier proteins. This phenomenon may alter the lipid bilayer and make N-SMase accessible to its substrate, sphingomyelin. Ceramide released as a consequence of N-SMase reaction would then carry out various biological phenomena, such as cell proliferation and differentiation. Cholesterol on the other hand, may undergo oxidation and inhibit HMG-CoA reductase activity; it may also be utilized by ACAT to form cholesteryl esters. A decrease in cell membrane cholesterol levels may stimulate LDL receptor activity and LDL receptor recycling and/or synthesis. In contrast, inactivation or decreased activity of N-SMase, as in the case of gentamicin-treated cells, may have the opposite effect, i.e., decreased LDL receptor activity and decreased cholesteryl ester synthesis. Thus, N-SMase may indirectly modulate cholesterol metabolism in cells independent of LDL. It can also modify LDL, allowing its rapid uptake and foam cell formation in macrophages. We can safely conclude that N-SMase action may be required to carry out a myriad of important cellular functions either directly or by cholesterol mobilization, or generation of ceramide, ceramide-1-phosphate, and sphingoid bases. The present data support the view that N-SMase action may initiate signal transduction for such biomodulators as growth factors, lipoprotein, and hormones.
A RELIABILITY‐BASED MODEL TO PREDICT SCATTER IN FATIGUE CRACK NUCLEATION LIFE (1998)

This paper investigates the scatter inherent in the early stages of fatigue life. A probabilistic fatigue model is proposed which relates the microstructural heterogeneity to the scatter in crack nucleation life. The crack nucleation life is defined as the number of cycles necessary to develop a crack with a length equal to the grain size. The model assumes homogeneity at the level of the grain size. A fracture mechanics‐based microstructural model is used to describe the response of the grains. The primitive random variables which drive crack nucleation are identified and recent developments recorded in the literature are used to describe their statistical characteristics. First order reliability methods are used to predict the statistical distribution of fatigue crack nucleation life. Comparisons are made with trends in experimental observations.
Site-directed mutagenesis of recombinant rat DNA polymerase .beta.: involvement of arginine-183 in primer recognition (1990)

By site-directed mutagenesis using synthetic oligonucleotides, amino acid residues 181Phe-Arg-Arg183 of recombinant rat DNA polymerase beta were replaced by other amino acids to clarify the roles of these residues in the DNA synthesizing reaction. Replacement of Phe-181 by alanine reduced the enzyme activity only 30%. Replacement of Arg-182 by alanine and glutamine resulted in reduction of the activity by about 67% and 95%, respectively. The Arg-182----Gln replacement increased the binding strength to single-stranded DNA but did not significantly change the Km's for the primer and dTTP, suggesting that Arg-182 is involved in modulation of binding to the template rather than to the primer or deoxyribonucleoside triphosphate. Replacement of Arg-183 by Gln resulted in reduction of the activity by about 95%, and this change, although causing little change in binding strength to single-stranded DNA, resulted in a 3-4-fold increase in the Km's for the primer and deoxyribonucleoside triphosphate. A more dramatic change was observed when Arg-183 was replaced by Ala, which resulted in a 99.98% reduction of enzyme activity. Although the Km for deoxyribonucleoside triphosphate of this mutant enzyme was hardly changed, that for the primer increased 159-fold. Therefore, it is concluded that Arg-183 occupies an important part of the primer recognition site of DNA polymerase beta.