gebhart/patrepeval huggingface dataset:
E-box- and MEF-2-independent muscle-specific expression, positive autoregulation, and cross-activation of the chicken MyoD (CMD1) promoter reveal an indirect regulatory pathway. (1994)

Members of the MyoD family of gene-regulatory proteins (MyoD, myogenin, myf5, and MRF4) have all been shown not only to regulate the transcription of numerous muscle-specific genes but also to positively autoregulate and cross activate each other's transcription. In the case of muscle-specific genes, this transcriptional regulation can often be correlated with the presence of a DNA consensus in the regulatory region CANNTG, known as an E box. Little is known about the regulatory interactions of the myogenic factors themselves; however, these interactions are thought to be important for the activation and maintenance of the muscle phenotype. We have identified the minimal region in the chicken MyoD (CMD1) promoter necessary for muscle-specific transcription in primary cultures of embryonic chicken skeletal muscle. The CMD1 promoter is silent in primary chick fibroblast cultures and in muscle cell cultures treated with the thymidine analog bromodeoxyuridine. However, CMD1 and chicken myogenin, as well as, to a lesser degree, chicken Myf5 and MRF4, expressed in trans can activate transcription from the minimal CMD1 promoter in these primary fibroblast cultures. Here we show that the CMD1 promoter contains numerous E-box binding sites for CMD1 and the other myogenic factors, as well as a MEF-2 binding site. Surprisingly, neither muscle-specific and the other myogenic factors, as well as a MEF-2 binding site. Surprisingly, neither muscle-specific expression, autoregulation, or cross activation depends upon the presence of of these E-box or MEF-2 binding sites in the CMD1 promoter. These results demonstrate that the autoregulation and cross activation of the chicken MyoD promoter through the putative direct binding of the myogenic basic helix-loop-helix regulatory factors is mediated through an indirect pathway that involves unidentified regulatory elements and/or ancillary factors.
Blood treatment of Lyme borreliae demonstrates the mechanism of <scp>CspZ</scp> ‐mediated complement evasion to promote systemic infection in vertebrate hosts (2018)

Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. The spirochetes are transmitted from mammalian and avian reservoir hosts to humans via ticks. Following tick bites, spirochetes colonize the host skin and then disseminate haematogenously to various organs, a process that requires this pathogen to evade host complement, an innate immune defence system. CspZ, a spirochete surface protein, facilitates resistance to complement-mediated killing in vitro by binding to the complement regulator, factor H (FH). Low expression levels of CspZ in spirochetes cultivated in vitro or during initiation of infection in vivo have been a major hurdle in delineating the role of this protein in pathogenesis. Here, we show that treatment of B. burgdorferi with human blood induces CspZ production and enhances resistance to complement. By contrast, a cspZ-deficient mutant and a strain that expressed an FH-nonbinding CspZ variant were impaired in their ability to cause bacteraemia and colonize tissues of mice or quail; virulence of these mutants was however restored in complement C3-deficient mice. These novel findings suggest that FH binding to CspZ facilitates B. burgdorferi complement evasion in vivo and promotes systemic infection in vertebrate hosts.
The Bosch Process - Performance of a Developmental Reactor and Experimental Evaluation of Alternative Catalysts (2010)

Bosch-based reactors have been in development at NASA since the 1960's. Traditional operation involves the reduction of carbon dioxide with hydrogen over a steel wool catalyst to produce water and solid carbon. While the system is capable of completely closing the loop on oxygen and hydrogen for Atmosphere Revitalization, steel wool requires a reaction temperature of 650C or higher for optimum performance. The single pass efficiency of the reaction over steel wool has been shown to be less than 10% resulting in a high recycle stream. Finally, the formation of solid carbon on steel wool ultimately fouls the catalyst necessitating catalyst resupply. These factors result in high mass, volume and power demands for a Bosch system. Interplanetary transportation and surface exploration missions of the moon, Mars, and near-earth objects will require higher levels of loop closure than current technology cannot provide. A Bosch system can provide the level of loop closure necessary for these long-term missions if mass, volume, and power can be kept low. The keys to improving the Bosch system lie in reactor and catalyst development. In 2009, the National Aeronautics and Space Administration refurbished a circa 1980's developmental Bosch reactor and built a sub-scale Bosch Catalyst Test Stand for the purpose of reactor and catalyst development. This paper describes the baseline performance of two commercially available steel wool catalysts as compared to performance reported in the 1960's and 80's. Additionally, the results of sub-scale testing of alternative Bosch catalysts, including nickel- and cobalt-based catalysts, are discussed.
α‐crystallin: a review of its structure and function (2004)

alpha-crystallin, the major protein of the mammalian lens in most species, is an aggregate assembled from two polypeptides, each with a molecular weight around 20,000 Da. It is polydisperse and can be isolated in a variety of forms, including spherical particles with molecular weights ranging upwards from about 200 kDa. Sequence comparisons reveal that it is a member of the small heat shock protein (shsp) family. These proteins are aggregates assembled from polypeptides of 10 to 25 kDa that share a common central domain of about 90 residues (the 'alpha-crystallin domain') with variable N- and C-terminal extensions. alpha-crystallin has been intensively studied for more than 50 years but its three-dimensional structure remains unknown because it has not been possible to obtain crystals for X-ray studies and it is too large for NMR measurements. Structural information has been derived from a variety of solution studies. Because of the protein's polydispersity, interpretation of data has been difficult. This led to different viewpoints and vigorous debate on its structure and properties. Recently, the crystal structures of two closely-related small heat shock proteins have been determined. These have provided some insight into the structure of a-crystallin and explanations of previous observations. Like many other heat shock proteins, alpha-crystallin exhibits chaperone-like properties, including the ability to prevent the precipitation of denatured proteins and to increase cellular tolerance to stress. It has been suggested that these functions are important for the maintenance of lens transparency and the prevention of cataract.
Prohibitin Facilitates Cellular Senescence by Recruiting Specific Corepressors To Inhibit E2F Target Genes (2006)

Prohibitin is a growth regulatory gene that has pleiotropic functions in the nucleus, mitochondria, and cytoplasmic compartments. Earlier studies had proposed a role for prohibitin in modulating cellular senescence, but the underlying mechanisms remain unknown. Here we show that senescence induced by DNA-damaging agents causes the localization of prohibitin to specific heterochromatic foci. Prohibitin could bind to heterochromatin protein 1 (HP1) family proteins and colocalized with HP1gamma in senescence-associated heterochromatic foci. Further, HP1gamma could synergize with prohibitin to repress E2F1-mediated transcriptional activity. The depletion of prohibitin by small interfering RNA or antisense techniques led to a reduction in the senescent phenotype, correlating with a reduced expression of senescence-associated beta-galactosidase and fewer numbers of senescence-associated heterochromatic foci. Chromatin immunoprecipitation assays showed that prohibitin is needed for the recruitment of HP1gamma to E2F1-regulated proliferative promoters, leading to their repression. The ablation of prohibitin prevented the recruitment of HPIgamma, but not Suv39H, to the promoters upon senescence. Prohibitin-mediated recruitment of HP1gamma occurred in only senescent cells, not in quiescent cells; thus, there is a dichotomy in the recruitment of different corepressors by prohibitin, depending on the type of growth arrest. These studies show that prohibitin plays a vital role in inducing cellular senescence.
Elastase Is the Only Human Neutrophil Granule Protein That Alone Is Responsible for In Vitro Killing of <i>Borrelia burgdorferi</i> (1998)

Phagocytosis of Borrelia burgdorferi by human polymorphonuclear leukocytes triggers oxygen-dependent and -independent mechanisms of potentially cidal outcome. Nevertheless, no factor or process has yet been singled out as being borreliacidal. We have studied the B. burgdorferi-killing ability of the myeloperoxidase-H2O2-chloride system and that of primary and secondary granule components in an in vitro assay. We found that neither secondary granule acid extracts nor the chlorinating system could kill these microorganisms, while primary granule extracts were effective. The Borrelia-killing factor was purified to homogeneity and demonstrated to be elastase. Its cidal activity was found to be independent of its proteolytic activity.
Semantics-directed generation of compilers and abstract machines (1996)

In traditional compiler design the work of a compiler is divided into several phases: lexical, syntactical and semantical analysis, optimizations and code generation. For several of these phases generators exist -- most prominently LEX and YACC for generating lexical and syntactical analyzers. A common feature of all generators is that the phase in the compiler is described using a meta-language (e.g. regular expressions or context-free grammars) and that the generator produces the related compiler module. There exist several good textbooks on compiler design. However, all of these books present ready made mappings from source language constructs to target language constructs, the so called translation schemes, instead of deriving them. Hence, the reader is expected to learn how to design code generators by analysing translation schemes as opposed to from first principles. The same is true for abstract machines. Abstract machines are virtual target architectures which support the concepts of the source language. Typically abstract machines are presented together with translation schemes from the source language to the abstract machine language. There is only little work on how translation schemes and abstract machines are designed. The aim of our work is to detect underlying principles that relate abstract machines to programming language semantics, and to automate part of the design process for abstract machines. Thus, we need to ensure that the behaviour of a source program will be maintained by translating it into the abstract machine language, and then applying the abstract machine. The behaviour of a program will depend on it's semantics. Often this aspect of a programming language is only described in natural language which is both ambiguous and vague. We shall use formal techniques to describe the meaning of programs in a particular language and to prove that our transformations are correct. In this thesis we concentrate on natural semantics, but we also address action semantics.
Parallel Activation of Phosphatidylinositol 4-Kinase and Phospholipase C by the Extracellular Calcium-sensing Receptor (2002)

The calcium-sensing receptor (CaR) is a G protein-coupled receptor that regulates physiological processes including Ca(2+) metabolism, Na(+), Cl(-), K(+), and H(2)0 balance, and the growth of some epithelial cells through diverse signaling pathways. Although many effects of CaR are mediated by the heterotrimeric G proteins Galpha(q) and Galpha(i), not all signaling pathways regulated by CaR have been identified. We used human embryonic kidney (HEK)-293 cells that stably express human CaR to study the regulation of inositol lipid metabolism by CaR. The nonfunctional mutant CaR(R796W) was used as a negative control. We found that CaR regulates phosphatidylinositol (PI) 4-kinase, the first step in inositol lipid biosynthesis. In cells pretreated with to inhibit phospholipase C activation and to block the degradation of PI 4,5-bisphosphate to form [(3)H]inositol trisphosphate (IP(3)), CaR stimulated the accumulation of [(3)H]PI monophosphate (PIP). Additionally, wortmannin, an inhibitor of both PI 3-kinase and type III PI 4-kinase, blocked CaR-stimulated accumulation of [(3)H]PIP and inhibited [(3)H]IP(3) production. CaR-stimulated inositol lipid synthesis was attributable to PI 4-kinase and not PI 3-kinase because CaR did not activate Akt, a downstream target of PI 3-kinase. CaR associates with PI 4-kinase based on the findings that CaR and the 110-kDa PI 4-kinase beta can be co-immunoprecipitated with antibodies against either CaR or PI 4-kinase. The PI-4 kinase in co-immunoprecipitates with anti-CaR antibody was activated in Ca(2+)-stimulated HEK-293 cells, which stably express the wild type CaR. Pertussis toxin did not affect the formation of [(3)H]IP(3) or the rise in intracellular Ca(2+) (Handlogten, M. E., Huang, C. F., Shiraishi, N., Awata, H., and Miller, R. T. (2001) J. Biol. Chem. 276, 13941-13948). RGS4, an accelerator of GTPase activity of members of the Galpha(i) and Galpha(q) families, attenuated the CaR-stimulated PLC activation and IP(3) accumulation, which is mediated by Galpha(q), but did not inhibit CaR-stimulated [(3)H]PIP formation. In HEK-293 cells, which express wild type CaR, Rho was enriched in immune complexes co-immunoprecipitated with the anti-CaR antibody. C(3) toxin, an inhibitor of Rho, also inhibited the CaR-stimulated [(3)H]IP(3) production but did not lead to CaR-stimulated [(3)H]PIP formation, reflecting inhibition of PI 4-kinase. Taken together, our data demonstrate that CaR stimulates PI 4-kinase, the first step in inositol lipid biosynthesis conversion of PI to PI 4-P by Rho-dependent and Galpha(q)- and Galpha(i)-independent pathways.
Silyl Radical Abstraction in the Functionalization of Plasma-Synthesized Silicon Nanocrystals (2015)

Many silicon nanostructures have exhibited favorable optical properties following surface functionalization with molecular groups through a silicon–carbon bond. Here, we show the mechanism of functionalization of silicon nanocrystals synthesized in a nonthermal radiofrequency plasma is fundamentally different than in other silicon systems. In contrast to hydrosilylation, where homolytic cleavage of Si–H surface bonds is typically a prerequisite to functionalization, we demonstrate the dominant initiation step for plasma-synthesized silicon nanocrystals is abstraction of a silyl radical, ·SiH3, and generation of radical at the silicon nanocrystal surface. We experimentally trap the abstracted silyl radical and show this initiation mechanism occurs for both radical- and thermally-initiated reactions of alkenes using complementary FTIR and 1H NMR spectroscopies. These data additionally indicate that silylsilylation, addition of a Si–SiH3 group across an unsaturated hydrocarbon, competes with hydrosilylation. We also present a new empirical sizing curve as a convenient method to determine Si NC size from photoluminescence peak energy.
Books (1996)

Research Article| January 01 1996 Books Randy Moore Randy Moore Search for other works by this author on: This Site PubMed Google Scholar The American Biology Teacher (1996) 58 (1): 6. https://doi.org/10.2307/4450064 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Randy Moore; Books. The American Biology Teacher 1 January 1996; 58 (1): 6. doi: https://doi.org/10.2307/4450064 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentThe American Biology Teacher Search This content is only available via PDF. Copyright 1995 The National Association of Biology Teachers Article PDF first page preview Close Modal You do not currently have access to this content.
Screen for Small Molecules Capable of Expanding Human Hematopoietic Stem Cell Ex Vivo (2011)

Abstract Abstract 1919 Hematopoietic stem cell (HSC) transplantation is a life saving procedure whose applicability is restricted by the lack of suitable donors, by poor responsiveness to mobilization regimens in preparation of autologous transplantations, by insufficient HSC numbers in individual cord blood units, and by the inability to sufficiently amplify HSCs ex vivo. Characterization of Stemregenin (SR1), an aryl hydrocarbon receptor (AHR) antagonist that promotes HSC expansion, provided a proof of principle that low molecular weight (LMW) compounds have the ability to promote HSC expansion. To identify novel putative agonists of HSC self-renewal, we initiated a high throughput screen (HTS) of a library comprising more than 5,000 LMW molecules using the in vitro maintenance of the CD34+CD45RA- phenotype as a model system. Our study was based on the fact that mobilized peripheral blood-derived CD34+CD45RA- cells cultured in media supplemented with: stem cell factor, thrombopoietin, FLT3 ligand and interleukin 6, would promote the expansion of mononuclear cells (MNC) concomitant with a decrease in CD34+CD45RA- population and HSC depletion. LMW compounds preventing this loss could therefore act as agonists of HSC expansion. In a 384-well plate, 2000 CD34+cells were initially cultured/well in 50μl medium comprising 1μM test compounds or 0.1% DMSO (vehicle). The proportions of CD34+CD45RA− cells were determined at the initiation of experiment and after a 7-day incubation. Six of 5,280 LMW compounds (0.11%) promoted CD34+CD45RA− cell expansion, and seventeen (0.32%) enhanced differentiation as determined by the increase in proportions of CD34−CD45RA+ cells compared to control (DMSO). The 6 LMW compounds promoting expansion of the CD34+CD45RA− cell population were re-analyzed in a secondary screen. Four out of these 6 molecules suppressed the transcriptional activity of AHR, suggesting that these compounds share the same molecular pathway as SR1 in stimulating HSC expansion, thus they were not further characterized. The remaining 2 compounds promoted, similar to SR1 or better, a 10-fold and 35-fold expansion of MNC during 7 and 12-day incubations, respectively. The expanded cell populations comprised 65–75% of CD34+ cells compared to 12–30% determined for DMSO controls. During 12-day incubation with these compounds, the numbers of CD34+ cells increased ∼25-fold over their input values, or ∼ 6-fold above the values determined for controls. This expansion of CD34+ cells was associated with a ∼5-fold increase in the numbers of multilineage CFC (granulocyte, erythroid, monocyte, and megakaryocyte, or CFU-GEMM) compared to that found in DMSO control cultures. The ability of the 2 newly identified compounds to expand functional HSCs is currently being evaluated in vivo usingimmunocompromised mice. In conclusion, results of our initial screen suggest that other mechanism, besides inhibition of AhR, are at play for expansion of human HSC. Disclosures: No relevant conflicts of interest to declare.
Advice on personal safety for women with learning disabilities (2015)

Anita Murphy and colleagues discuss how a series of group sessions were arranged to give women with learning disabilities a safe space to talk about sexual health and relationships
Registration Extensions (REGEXT) for Signalling User Adaptation Layers Status of this Memo (2006)

This memo describes Registration Extensions (REGEXT) that provides the ability for an Application Server Process (ASP) to modify existing Routing (Link) Keys with a Signalling Gatewa y( SG). Current procedures in the SS7 Signalling User Adaptation Layers (UAs) [M2UA], [M3UA], [ISUA], [SUA], [TUA] do not provide for the modification of Routing (Link) Keys without deactivation of the Application Server (AS). This causes problems in making changes to live systems. The extensions described in this memo permit modification of Signalling Link membership in Application Servers for SS7 MTP2-User Adaptation Layer [M2UA], modification of Circuit Identification Code (CIC) ranges for the SS7 MTP3-User Adaptation Layer [M3UA], modification of Circuit Identification Code (CIC) ranges for the SS7 ISUP-User Adaptation Layer [ISUA], modificiation of Destination Local Reference (DLR) ranges for SS7 SCCP-User Adaptation Layer [SUA], and modification of T ransaction Identifier (TID) ranges for SS7 TCAP-User Adaptation Layer [TUA].
Mathematical Model for Design of Battery Electrodes: I . Potential Distribution (1982)

The potential distribution in thin electrodes of the automotive battery type was determined experimentally and predicted from a model. Potentials at various locations on the plates were measured in cells at various discharge rates and for different plate widths. A model, based on the application of Kirchoff's law to each intersection of grid members, was solved numerically to predict potential distribution. The measured and calculated potential distributions were in excellent agreement. The implications of the model are discussed with emphasis on the interaction between grid design, grid weight, and plate performance. Performance is measured in terms of the maximum (i.e., the tab‐to‐corner) ohmic potential loss.
Anti-ganglioside antibody-induced tumor cell death by loss of membrane integrity (2008)

Gangliosides have been involved in multiple cellular processes such as growth, differentiation and adhesion, and more recently as regulators of cell death signaling pathways. Some of these molecules can be considered as tumor-associated antigens, in particular, N-glycolyl sialic acid-containing gangliosides, which are promising candidates for cancer-targeted therapy because of their low expression in normal human tissues. In this study, we provided the molecular and cellular characterization of a novel cell death mechanism induced by the anti-NGcGM3 14F7 monoclonal antibody (mAb) in L1210 murine tumor cell line but not in mouse normal cells (B and CD4(+) T lymphocytes) that expressed the antigen. Impairment of ganglioside synthesis in tumor cells abrogated the 14F7 mAb cytotoxic effect; however, exogenous reincorporation of the ganglioside did not restore tumor cell sensitivity to 14F7 mAb-induced cytotoxicity. 14F7 F(ab')(2) but not Fab fragments retained the cytotoxic capacity of the whole mAb. By contrary, other mAb, which recognizes N-glycolylated gangliosides, did not show any cytotoxic effect. These mAbs showed quite different capacities to bind NGcGM3-positive cell lines measured by binding inhibition experiments. Interestingly, this complement-independent cell death mechanism did not resemble apoptosis, because no DNA fragmentation, caspase activation, or Fas mediation were observed. However, NGcGM3 ganglioside-mediated 14F7 mAb-induced cell death was accompanied by cellular swelling, membrane lesion formation, and cytoskeleton activation, suggesting an oncosis-like phenomenon. This novel mechanism of cell death lets us to support further therapeutic approaches using NGcGM3 as a molecular target for antibody-based cancer immunotherapy.