gebhart/patrepeval huggingface dataset:
Nkx6.1 Controls a Gene Regulatory Network Required for Establishing and Maintaining Pancreatic Beta Cell Identity (2013)

All pancreatic endocrine cell types arise from a common endocrine precursor cell population, yet the molecular mechanisms that establish and maintain the unique gene expression programs of each endocrine cell lineage have remained largely elusive. Such knowledge would improve our ability to correctly program or reprogram cells to adopt specific endocrine fates. Here, we show that the transcription factor Nkx6.1 is both necessary and sufficient to specify insulin-producing beta cells. Heritable expression of Nkx6.1 in endocrine precursors of mice is sufficient to respecify non-beta endocrine precursors towards the beta cell lineage, while endocrine precursor- or beta cell-specific inactivation of Nkx6.1 converts beta cells to alternative endocrine lineages. Remaining insulin(+) cells in conditional Nkx6.1 mutants fail to express the beta cell transcription factors Pdx1 and MafA and ectopically express genes found in non-beta endocrine cells. By showing that Nkx6.1 binds to and represses the alpha cell determinant Arx, we identify Arx as a direct target of Nkx6.1. Moreover, we demonstrate that Nkx6.1 and the Arx activator Isl1 regulate Arx transcription antagonistically, thus establishing competition between Isl1 and Nkx6.1 as a critical mechanism for determining alpha versus beta cell identity. Our findings establish Nkx6.1 as a beta cell programming factor and demonstrate that repression of alternative lineage programs is a fundamental principle by which beta cells are specified and maintained. Given the lack of Nkx6.1 expression and aberrant activation of non-beta endocrine hormones in human embryonic stem cell (hESC)-derived insulin(+) cells, our study has significant implications for developing cell replacement therapies.
Role of Sulfhydryl Groups in Firefly Luciferase* (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRole of Sulfhydryl Groups in Firefly Luciferase*M. DeLuca, G. W. Wirtz, and W. D. McElroyCite this: Biochemistry 1964, 3, 7, 935–939Publication Date (Print):July 1, 1964Publication History Published online1 May 2002Published inissue 1 July 1964https://pubs.acs.org/doi/10.1021/bi00895a015https://doi.org/10.1021/bi00895a015research-articleACS PublicationsRequest reuse permissionsArticle Views112Altmetric-Citations48LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The glucocorticoid receptor type II complex is a target of the HIV-1 vpr gene product. (1995)

The vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a 15-kDa virion-associated protein that functions as a regulator of cellular processes linked to the HIV life cycle. We report the interaction of a 41-kDa cytosolic viral protein R interacting protein 1 (Rip-1) with Vpr in vitro. Rip-1 displays a wide tissue distribution, including relevant targets of HIV infection. Vpr protein induced nuclear translocation of Rip-1, as did glucocorticoid receptor (GR)-II-stimulating steroids. Importantly, Vpr and Rip-1 coimmunoprecipitated with the human GR as part of an activated receptor complex. Vpr complementation of a vpr mutant virus was also mimicked by GR-II-stimulating steroids. Vpr and GR-II actions were inhibited by mifepristone, a GR-II pathway inhibitor. Together these data directly link the activity of the vpr gene product to the glucocorticoid steroid pathway and provide a biochemical mechanism for the cellular and viral activity of Vpr, as well as suggest that a unique class of antivirals, which includes mifepristone (RU486), may influence HIV-1 replication.
Induction of Apoptosis by Human Nbk/Bik, a BH3-Containing Protein That Interacts with E1B 19K (1996)

The E1B 19-kilodalton protein (19K protein) is a potent apoptosis inhibitor and the adenovirus homolog of Bcl-2 (E. White, Genes Dev. 10:1-15, 1996). To obtain a better understanding of the biochemical mechanism by which the E1B 19K protein regulates apoptosis, proteins that interact with 19K have been identified; one of these is Bax (J. Han, P. Sabbatini, D. Perez, L. Rao, D. Mohda, and E. White, Genes Dev. 10:461-477, 1996), and another is Bak (S. N. Farrow, J. H. M. White, I. Martinou, T. Raven, K.-T. Pun, C. J. Grinham, J.-C. Martinou, and R. Brown, Nature (London) 374:731-733, 1995). Bax and Bak are Bcl-2 family members which contain Bcl-2 homology regions 1, 2, and 3 (BH1, BH2, and BH3), which interact with E1B 19K and Bcl-2 and promote apoptosis. Like Bax and Bak, Nbk was cloned from a yeast two-hybrid screen for proteins that interact with E1B 19K. Nbk contained BH3 but not BH1 or BH2. It also interacted with Bcl-2 but not with Bax. Both Bcl-2 and E1B 19K interacted with Nbk in vitro, and this interaction was highly specific. In vivo, the Nbk and E1B 19K proteins may colocalize with cytoplasmic and nuclear membranes. Nbk expression functionally antagonized 19K-mediated inhibition of apoptotic cell death and completely prevented transformation by E1A and E1B 19K. Nbk was sufficient for induction of apoptosis in the presence of mutant p53 and thus low levels of Bax, suggesting that Nbk functions independently of Bax to induce apoptosis. Nbk may therefore represent a novel death regulator which contains only a BH3 that interacts with and antagonizes apoptosis inhibitors such as the E1B 19K protein.
Clenbuterol (‘Spiropent’): a long-acting bronchodilator (1982)

Clenbuterol was compared to an aminophylline preparation in a double-blind crossover trial involving 47 patients with asthma and reversible airways obstruction. Following a 2-week control period, each drug was given for a 4-week period. The patients made daily records of the severity of symptoms and recorded PEFR morning and night. Both drugs produced a highly significant reduction in severity and duration of wheeze by day during the first 4 weeks, but only clenbuterol produced further significant reduction in these symptoms during the second 4 weeks. Only clenbuterol produced a significant reduction in the severity of wheeze at night. When clenbuterol was given first there was a significant increase in the mean PEFR both night and morning but no other significant changes with either drug at other periods. Combining the results from the two treatment groups showed a significant difference between them in favour of clenbuterol in respect of duration of daytime wheeze only (p less than 0.05).
Recognition of Fresh Human Tumor by Human Peripheral Blood Lymphocytes Transduced with a Bicistronic Retroviral Vector Encoding a Murine Anti-p53 TCR (2005)

The p53 protein is markedly up-regulated in a high proportion of human malignancies. Using an HLA-A2 transgenic mouse model, it was possible to isolate high-avidity murine CTLs that recognize class I-restricted human p53 epitopes. We isolated the alpha- and beta-chain of a TCR from a highly avid murine CTL clone that recognized the human p53(264-272) epitope. These genes were cloned into a retroviral vector that mediated high efficiency gene transfer into primary human lymphocytes. Efficiencies of >90% for gene transfer into lymphocytes were obtained without selection for transduced cells. The p53 TCR-transduced lymphocytes were able to specifically recognize with high-avidity, peptide-pulsed APCs as well as HLA-A2.1+ cells transfected with either wild-type or mutant p53 protein. p53 TCR-transduced cells demonstrated recognition and killing of a broad spectrum of human tumor cell lines as well as recognition of fresh human tumor cells. Interestingly, both CD8+ and CD4+ subsets were capable of recognizing and killing target cells, stressing the potential application of such a CD8-independent TCR molecule that can mediate both helper and cytotoxic responses. These results suggest that lymphocytes genetically engineered to express anti-p53 TCR may be of value for the adoptive immunotherapy of patients with a variety of common malignancies.
Continuous model for the shear modulus as a function of pressure and temperature up to the melting point: Analysis and ultrasonic validation (2003)

The aim of the present study is to propose a predictive model for the shear modulus versus pressure and temperature G(P,T) to complete the principal known elasto-plastic models implemented in hydrodynamic computer codes. The relevance of the proposed G(P,T) model is discussed in detail. The generic approach is to model G(T) by considering Lindemann theory at the melting point. This article focuses on analysis of the mechanical elastic behavior of a solid to confirm that the melting point and the shear component attenuation are closely connected. The drastic fall of G(T) at the melting point is discussed and compared to experimental data mainly derived from ultrasonics. The original part of this work is the experimental work concentrating on direct measurement of the shear wave velocity. The five materials of interest have melting points ranging from that of tin (505 K) to that of tantalum (3269 K). The corresponding Lindemann constant is determined, leading to an average value of 0.103 for cubic crystalline symmetry (Ta, Cu, Au, and Al) and 0.060 for tetragonal crystalline symmetry (Sn). We propose a relationship between G(P,T) and the melting temperature.
A linear time exact hidden surface algorithm (1980)

This paper presents a new hidden surface algorithm. Its output is the set of the visible pieces of edges and faces, and is as accurate as the arithmetic precision of the computer. Thus calculating the hidden surfaces for a higher resolution device takes no more time. If the faces are independently and identically distributed, then the execution time is linear in the number of faces. In particular, the execution time does not increase with the depth complexity. This algorithm overlays a grid on the screen whose fineness depends on the number and size of the faces. Edges and faces are sorted into grid cells. Only objects in the same cell can intersect or hide each other. Also, if a face completely covers a cell then nothing behind it in the cell is relevant. Three programs have tested this algorithm. The first verified the variable grid concept on 50,000 intersecting edges. The second verified the linear time, fast speed, and irrelevance of depth complexity for hidden lines on 10,000 spheres. This also tested depth complexities up to 30, and showed that perspective scenes with the farther objects smaller are even faster to calculate. The third verified this for hidden surfaces on 3000 squares.
Several Carcinoembryonic Antigens (CD66) Serve as Receptors for Gonococcal Opacity Proteins (1997)

Neisseria gonorrhoeae (GC) is a human pathogen that adheres to and invades genital surfaces. Although pili are required for the initial adherence, the interaction of GC with epithelial cells is also promoted by a family of outer membrane proteins, the opacity (Opa) proteins such as OpaA protein from strain MS11. Studies have demonstrated that the interaction of the OpaA GC with epithelial cells involves binding to heparan sulfate attached to syndecan receptors. However, other Opa proteins interact with CEA gene family member 1 (CGM1) or biliary glycoprotein (BGP), members of the CD66 antigen family. In this study, we demonstrate that, in addition, the 180-kD carcinoembryonic antigen (CEA) is a receptor for Opa proteins. This conclusion was based on the following observations. First, transfected HeLa cells expressing CEA (HeLa-CEA) and the CEA-expressing colon cancer cell line (LS 174T) bound and subsequently engulfed the Opa+ bacteria. These interactions were inhibited by anti-CEA antibody, but could not be inhibited by addition of heparin. Furthermore, OpaI E. coli directly bound purified CEA. We also compared the adherence and invasion by Opa+ bacteria of CD66 transfected HeLa cells: HeLa-BGPa, HeLa-CGM6, HeLa-NCA, HeLa-CGM1a, HeLa-CEA, and HeLa-Neo serving as negative control. Using OpaI as the prototype, the relative ability of the transfected HeLa cell lines to support adherence was (CEA = BGPa >CGM1a >NCA >>CGM6 = Neo). The ability to mediate invasion of the transfectant cells was (CGM1a >CEA >BGPa >NCA >CGM6 = Neo). Among the Opa proteins tested, OpaC proved to be bifunctional, able to mediate adherence to both syndecan receptors and to CD66 antigens.
Ionic liquid‐mediated selective extraction of lignin from wood leading to enhanced enzymatic cellulose hydrolysis (2008)

Lignocellulose represents a key sustainable source of biomass for transformation into biofuels and bio-based products. Unfortunately, lignocellulosic biomass is highly recalcitrant to biotransformation, both microbial and enzymatic, which limits its use and prevents economically viable conversion into value-added products. As a result, effective pretreatment strategies are necessary, which invariably involves high energy processing or results in the degradation of key components of lignocellulose. In this work, the ionic liquid, 1-ethyl-3-methylimidazolium acetate ([Emim][CH3COO]), was used as a pretreatment solvent to extract lignin from wood flour. The cellulose in the pretreated wood flour becomes far less crystalline without undergoing solubilization. When 40% of the lignin was removed, the cellulose crystallinity index dropped below 45, resulting in > 90% of the cellulose in wood flour to be hydrolyzed by Trichoderma viride cellulase. [Emim] [CH3COO] was easily reused, thereby resulting in a highly concentrated solution of chemically unmodified lignin, which may serve as a valuable source of a polyaromatic material as a value-added product.
Bacterium-host protein-carbohydrate interactions and pathogenicity (1999)

Conference Article| August 01 1999 Bacterium-host protein-carbohydrate interactions and pathogenicity K.-A. Karlsson K.-A. Karlsson 1Institute of Medical Biochemistry, Göteborg University, P.O. Box 440, SE-405 30 Göteborg, Sweden Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1999) 27 (4): 471–474. https://doi.org/10.1042/bst0270471 Article history Received: March 09 1999 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation K.-A. Karlsson; Bacterium-host protein-carbohydrate interactions and pathogenicity. Biochem Soc Trans 1 August 1999; 27 (4): 471–474. doi: https://doi.org/10.1042/bst0270471 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 ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1999 Biochemical Society1999 Article PDF first page preview Close Modal You do not currently have access to this content.
Ultrathin Multilayered Films that Promote the Release of Two DNA Constructs with Separate and Distinct Release Profiles (2008)

‘Charge-shifting’ cationic polymers are used to fabricate ultrathin multilayered films that promote the release of two different DNA constructs with separate and essentially nonoverlapping release profiles. This approach could contribute to the development of thin films and functional coatings capable of regulating the localized release of different DNA constructs (or other agents) to cells or tissues in a broad range of fundamental and applied contexts. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Dealing with Tentative Data Values in Disconnected Work Groups (1994)

This paper describes a problem of weakly-consistent replicated data systems used in support of disconnected groups of people. The problem concerns actions and updates derived from tentative data updates that are ultimately determined to be in conflict. While some such actions and updates can be automatically resolved, many require human intervention. FurthemOre, although some file and database systems support internal conflict detection and resolution. derived actions may be external to those systems, implying that human users must ensure that proper consistency is maintained between independent components of the system. The entire problem becomes exascerbated when disconnected work groups are taken into account, where tentative data values may be seen and acted upon by multiple people.
The neostriatal mosaic. I. compartmental organization of projections from the striatum to the substantia nigra in the rat (1985)

Combined neuroanatomical techniques were used to examine the organization of the striatal projection to the substantia nigra in the rat. Both double anterograde axonal tracing methods (Phaseolus vulgaris leuco-agglutinin (PHA-L) and 3H-amino acid tract tracing) and double fluorescent retrograde axonal transport tracing methods were used to examine the relationship among striatal neurons projecting to separate areas of the substantia nigra. Additionally, the distributions of retrogradely labeled striatonigral projection neurons were charted relative to the neurochemically distinct striatal "patch" compartment, identified by substance P- or leu-enkephalin-like immunoreactivity, and the complementary "matrix" compartment, identified by somatostatin-like immunoreactive fibers. These studies show two distinct types of organization in the striatonigral projections. One type is topographic in that the mediolateral relationships among these striatal efferent neurons are roughly maintained by their termination patterns in the substantia nigra, while the dorsoventral relationships are inverted. Projections from any part of the striatum, however, are distributed throughout the rostrocaudal axis of the substantia nigra. Despite their general topographic organization, the variable and dispersed nature of such projections from individual striatal loci results in partial overlap of afferent fields from separate striatal areas. The second type of organization is nontopographic and provides a different system for convergence of inputs from separated striatal areas that is superimposed on the rough topographic system. In this other projection system the mediolateral and dorsoventral relationships typical of the topographically ordered system are not maintained and are sometimes reversed. For example, PHA-L injected into the dorsal striatum labels a topographic (inverted relationship) projection to the ventral substantia nigra pars reticulata but also a smaller and separate projection to the dorsal pars reticulata and adjacent pars compacta. Retrograde tracer deposits in the pars compacta label neurons in the ventral striatum (the inverted relationship) but also clusters of neurons in the dorsal striatum. These clusters are in the neurochemically defined patch compartment whereas neurons in the matrix are labeled by injections into the pars reticulata. The dendrites of both retrogradely filled patch and matrix neurons are confined to the compartment containing their cell bodies, suggesting a restriction that would functionally segregate extrinsic striatal afferents shown in other studies to be confined to either patches or matrix.(ABSTRACT TRUNCATED AT 400 WORDS)
Microscale solution IEF combined with 2‐D DIGE substantially enhances analysis depth of complex proteomes such as mammalian cell and tissue extracts (2008)

Current gel-based protein profiling methods such as 2-DE and fluorescent 2-D difference in gel electrophoresis (DIGE) evaluate small portions of complex proteomes. Hence, sample prefractionation is essential for more comprehensive proteome coverage and detection of low-abundant proteins. In this study, we describe the combination of DIGE labeling with microscale solution IEF (MicroSol-IEF) fractionation and subsequent analysis on slightly overlapping narrow pH range 2-D gels. By fluorescently tagging and mixing samples and controls prior to prefractionation, complications resulting from minor run-to-run variations during MicroSol-IEF separations of multiple samples are avoided. This greatly improves the reliability of quantitative comparisons. To illustrate its utility, this 3-D DIGE strategy was applied to analysis of human melanoma cells and mouse lung tissue extracts. Approximately 1000 reproducible spots can be obtained from narrow range 2-D gels of individual MicroSol-IEF fractions, and approximately 6000 spots can be obtained from entire proteomes. Quantitative changes in closely related samples could be more reliably detected and the method has a greatly increased capacity to distinguish between closely related protein isoforms. Thus the 3-D DIGE strategy produces a powerful method for more comprehensive and more reliable quantitative comparisons of protein profiles of very complex proteomes.
Comparison of cooling methods to induce and maintain normo- and hypothermia in intensive care unit patients: a prospective intervention study (2007)

Cooling with water-circulating blankets, gel-pads and intravascular cooling is more efficient compared to conventional cooling and air-circulating blankets. The intravascular cooling system is most reliable to maintain a stable temperature.
Myrcene as a Natural Base Chemical in Sustainable Chemistry: A Critical Review (2009)

Currently, a shift towards chemical products derived from renewable, biological feedstocks is observed more and more. However, substantial differences with traditional feedstocks, such as their "hyperfunctionalization," ethical problems caused by competition with foods, and problems with a constant qualitative/quantitative availability of the natural products, occasionally complicate the large-scale market entry of renewable resources. In this context the vast family of terpenes is often not taken into consideration, although the terpenes have been known for hundreds of years as components of essential oils obtained from leaves, flowers, and fruits of many plants. The simple acyclic monoterpenes, particularly the industrially available myrcene, provide a classical chemistry similar to unsaturated hydrocarbons already known from oil and gas. Hence, this Review is aimed at reviving myrcene as a renewable compound suitable for sustainable chemistry in the area of fine chemicals. The versatility of the unsaturated C(10)-hydrocarbon myrcene, leading to products with several different areas of application, is pointed out.
Anti-transforming growth factor-β therapy in patients with myelofibrosis (2013)

Bone marrow fibrosis (BMF), in the myeloproliferative neoplasm (MPN) myelofibrosis (MF), is the result of a complex and yet not fully understood interaction between megakaryocytes, monocytes, fibro...