gebhart/patrepeval huggingface dataset:
Efficacy of Fumaric Acid Esters in the R6/2 and YAC128 Models of Huntington's Disease (2011)

Huntington's disease (HD) is an autosomal dominantly inherited progressive neurodegenerative disease. The exact sequel of events finally resulting in neurodegeneration is only partially understood and there is no established protective treatment so far. Some lines of evidence speak for the contribution of oxidative stress to neuronal tissue damage. The fumaric acid ester dimethylfumarate (DMF) is a new disease modifying therapy currently in phase III studies for relapsing-remitting multiple sclerosis. DMF potentially exerts neuroprotective effects via induction of the transcription factor "nuclear factor E2-related factor 2" (Nrf2) and detoxification pathways. Thus, we investigated here the therapeutic efficacy of DMF in R6/2 and YAC128 HD transgenic mice which mimic many aspects of HD and are characterized by an enhanced generation of free radicals in neurons. Treatment with DMF significantly prevented weight loss in R6/2 mice between postnatal days 80-90. At the same time, DMF treatment led to an attenuated motor impairment as measured by the clasping score. Average survival in the DMF group was 100.5 days vs. 94.0 days in the placebo group. In the histological analysis on day 80, DMF treatment resulted in a significant preservation of morphologically intact neurons in the striatum as well as in the motor cortex. DMF treatment resulted in an increased Nrf2 immunoreactivity in neuronal subpopulations, but not in astrocytes. These beneficial effects were corroborated in YAC128 mice which, after one year of DMF treatment, also displayed reduced dyskinesia as well as a preservation of neurons. In conclusion, DMF may exert beneficial effects in mouse models of HD. Given its excellent side effect profile, further studies with DMF as new therapeutic approach in HD and other neurodegenerative diseases are warranted.
A Simple 3,4‐Ethylenedioxythiophene Based Hole‐Transporting Material for Perovskite Solar Cells (2014)

We report a novel electron-rich molecule based on 3,4-ethylenedioxythiophene (H101). When used as the hole-transporting layer in a perovskite-based solar cell, the power-conversion efficiency reached 13.8 % under AM 1.5G solar simulation. This result is comparable with that obtained using the well-known hole transporting material 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-OMeTAD). This is the first heterocycle-containing material achieving >10 % efficiency in such devices, and has great potential to replace the expensive spiro-OMeTAD given its much simpler and cheaper synthesis.
Dissection of Human Tropoelastin:  Exon-By-Exon Chemical Synthesis and Related Conformational Studies (2003)

Polypeptide sequences encoding the single exons of human tropoelastin were synthesized and their conformations were studied in different solvents and at different temperatures by CD and (1)H NMR. The results demonstrated the presence of labile conformations such as poly-proline II helix (PPII) and beta-turns whose stability is strongly dependent on the microenvironment. Stable, periodic structures, such as alpha-helices, are only present in the poly-alanine cross-linking domains. These findings give a strong experimental basis to the understanding of the molecular mechanism of elasticity of elastin. In particular, they strongly support the description of the native relaxed state of the protein in terms of trans-conformational equilibria between extended and folded structures as previously proposed [Debelle, L., and Tamburro, A. M. (1999) Int. J. Biochem. Cell. Biol. 31, 261-272].
Interleukin-12 Inhibits Antigen-Induced Airway Hyperresponsiveness in Mice (1996)

The airway inflammation observed in allergic asthma is thought to be orchestrated by an antigen-driven T-helper-2 (Th2) lymphocyte response. In vitro data indicate that the presence of interleukin-12 (IL-12) during the primary stimulation of T-lymphocytes with antigen favors the development of Th1 cells. The aim of the present study was to examine the effect of IL-12 in vivo on antigen-induced airway changes in a murine model. C57BL/6 mice were actively sensitized to ovalbumin; 14 d later, they were exposed daily for 7 d to aerosolized ovalbumin. This resulted in airway eosinophilia, production of ovalbumin-specific IgE, and airway hyperresponsiveness to carbachol. Administration of recombinant murine IL-12 (rmIL-12) during the active immunization prevented these antigen-induced changes. In contrast, administration of rmIL-12 to actively immunized mice during the daily aerosol exposure (but not at the time of immunization) abolished airway eosinophilia and hyperresponsiveness without influencing the production of specific IgE. These results suggest that IL-12 can suppress antigen-induced airway changes despite the presence of circulating specific IgE.
Identification, Isolation, and Cloning of a Bacillus thuringiensis CryIAc Toxin-binding Protein from the Midgut of the Lepidopteran Insect Heliothis virescens (1995)

Bacillus thuringiensis toxins are insecticidal to a variety of insect species. The selectivity of the toxins produced by these bacteria is dependent on both the toxin structure and the receptor sites that are present in different insect species. One of these toxins, CryIAc, is highly insecticidal to the noctuid pest Heliothis virescens. Using toxin overlay assay, a 120-kDa glycoprotein was identified as a toxin-binding protein. This protein was partially purified, its N-terminal sequence was determined, and the full-length cDNA encoding this protein was isolated from a H. virescens midgut library. The B. thuringiensis toxin-binding protein, BTBP1, has high homology to aminopeptidase N from eukaryotes and prokaryotes.
New Norepinephrine Potentiators: Synthesis and Structure-Activity Relationships of a Series of 4-Phenyl-1,2,3,4-tetrahydroisoquinolin-4-ols. (1994)

A variety of 1,2,3,4-tetrahydroisoquinolin-4-ols (1-6) were prepared as part of our search for new norepinephrine (NE) potentiators and to clarify the structure-activity relationships. These compounds and some previously prepared compounds were compared with 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-4-ol (PI-OH) (1a) for ability to potentiate NE. The potency, for 2-substitution, was found to be in the order: Me > Et > iso-Pr > H. The compounds substituted by a halogen atom at the para position in the 4-phenyl group of PI-OH showed greater activities than did PI-OH, and the observed order of potency for the substitution was Cl > Br > F > H. The compound (4) methylated at the hydroxy group in PI-OH had greatly diminished activity. Although the desoxy compound (6) of PI-OH potentiated the response to NE at low concentrations, the potentiation was progressively masked by an inhibitory activity as the concentration of 6 was increased. In addition, the 4-cyclohexyl analogue (5) failed to potentiate NE. These results show the importance of the beta-phenylethanolamine skeleton of PI-OH for producing NE potentiation without accompanying inhibitory action. The racemic 4-chlorophenyl analogue (2a) was resolved by HPLC to (R)-(+)-2a and (S)-(-)-2a. The NE-potentiating activity was found to reside exclusively in (R)-(+)-2a, which had the highest activity among compounds tested in this study; the activity ratio was 25 at 3 x 10(-6) M. The antidepressant activity of racemic 2a was evaluated by a forced swimming test.(ABSTRACT TRUNCATED AT 250 WORDS)
The Total Synthesis of Tubulysin D (2006)

The first total synthesis of tubulysin D is reported. The development and application of new tert-butanesulfinamide methods allowed for rapid syntheses of the tubuvaline and tubuphenylalanine fragments. Most significantly, a route was devised and implemented to introduce and carry forward the highly labile N,O-acetal functionality. Tubulysin D is the most active member of the tubulysin family, and the efficient synthetic route described herein will allow for the rapid syntheses of analogues to probe the biological activity of this important class of natural products.
Biotransformations in the Synthesis of Enantiopure Bioactive Molecules (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBiotransformations in the Synthesis of Enantiopure Bioactive MoleculesCarl R. JohnsonView Author Information Department of Chemistry, Wayne State University, Detroit, Michigan 48202 Cite this: Acc. Chem. Res. 1998, 31, 6, 333–341Publication Date (Web):May 13, 1998Publication History Received10 September 1997Published online13 May 1998Published inissue 1 June 1998https://pubs.acs.org/doi/10.1021/ar970013qhttps://doi.org/10.1021/ar970013qresearch-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views577Altmetric-Citations56LEARN 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 SUBJECTS:Diols,Hydrocarbons,Molecular structure,Organic compounds,Peptides and proteins Get e-Alerts
Neutrophils in cystic fibrosis (2008)

Lung injury in cystic fibrosis is caused by recurrent airway infection and inflammation. Neutrophils are important in combating these infections but are also the predominate cells involved in the inflammatory process. This review of neutrophils in cystic fibrosis describes the cellular mechanisms involved in their migration into the airways and their role in bacterial phagocytosis. We discuss the inflammatory process and its resolution and ultimately how neutrophil function can be modulated.
High-power superfluorescent source with a side-pumped Yb-doped double-cladding fiber (1998)

A compact superfluorescent source based on an Yb-doped double-cladding fiber amplifier is described. The packaged amplifier is pumped at 975 nm by side-coupling emission from a 2.0-W broad-stripe laser diode through an imbedded V groove. The fiber source generates 485 mW of broadband emission centered at 1055 nm with a 41-nm FWHM flat power spectrum.
Activation of the inflammasome upon Francisella tularensis infection: interplay of innate immune pathways and virulence factors (2007)

Tularaemia is a zoonotic disease caused by the facultative intracellular bacterium Francisella tularensis. The virulence of this pathogen depends on its ability to escape into the cytosol of host cells. Pathogens are detected by the innate immune system's pattern recognition receptors which are activated in response to conserved microbial molecules (pathogen-associated molecular patterns). Cytosolic bacteria are sensed intracellularly, often leading to activation of the cysteine protease caspase-1 within a multimolecular complex called the inflammasome. Caspase-1 activation leads to both host cell death and release of pro-inflammatory cytokines in a process called pyroptosis. Here we review the pathway leading to, and the consequences of, inflammasome activation upon F. tularensis infection both in vitro and in vivo. Finally, we discuss recent data on how other innate immune pathways and F. tularensis virulence factors control the activation of the inflammasome during infection.
Lymphoproliferative disorders involving Epstein-Barr virus after hemopoietic stem cell transplantation (1999)

Lymphoproliferative disorders involving uncontrolled expansion of donor-derived B cells infected with Epstein-Barr virus (EBV) are a significant problem after hemopoietic stem cell transplantation. Risk factors, which include T cell depletion, major histocompatibility complex mismatch, and intensity of immunosuppression illustrate the importance of T cell immune surveillance. Recent studies have identified viral and host factors that affect the T-cell response to EBV. Monitoring EBV load in the blood by polymerase chain reaction allows early identification of high-risk patients and early institution of therapy. Adoptive immunotherapy approaches using donor T cells have proven effective and EBV-specific cytotoxic T lymphocytes have also been used successfully for prophylaxis. The simplest way of preventing EBV lymphoproliferation, however, may be to deplete B cells from the donor marrow prior to infusion to prevent the transmission of EBV-infected B cells.
RB Protein as a Cellular "Corral" for Growth-promoting Proteins (1991)

The retinoblastoma (RB) susceptibility gene encodes a protein whose function prevents neoplastic transformation in a variety of cell types (for review, see Lee et al. 1988, 1990; Goodrich and Lee 1990). Loss or mutation of the gene elicits tumorigenesis in susceptible cells, and the reintroduction of the wild-type gene effects a reversion to a nontumorigenic state. Because the RB gene is expressed in all mammalian cell types examined so far, and because loss of a functional RB gene is associated with several cancers, the RB protein probably plays a general role in the regulation of cell growth.
Liposomal targeting of leukaemia HL60 cells induced by transferrin‐receptor endocytosis (1996)

A liposomal carrier system able to interact specifically with HL60 leukaemia cells was produced using small unilamellar liposomes made of pure phospholipids chemically cross-linked to human transferrin. The conjugation of transferrin to liposomes was carried out using N-succinimidyl 3-(2-pyridyldithio)-propionate and 2-iminothiolane as activating agents for the liposomes and the protein. The reaction occurred under conditions set to covalently link on the surface of a single vesicle a limited number (one to ten) of transferrin molecules, as verified by means of electron microscopy and immunoenzymic measurements. Before conjugation, the ultrastructure of the liposomes, and the content and distribution of the amino groups within the bilayer, were determined. The reactivity of the liposomes towards amino-derivatizing or thiolating compounds was also measured. Kinetic spectroscopic measurements confirmed that the distribution of the phosphatidylethanolamine in the vesicle bilayer is asymmetrical: 22% of phosphatidylethanolamine was found exposed to the external surface of the liposomes and accessible to the cross-linker. The modified liposomes were able to interact specifically with the cells and to be internalized by active receptor-mediated endocytosis, as demonstrated by the full inhibition of internalization induced by free transferrin.
Isolation of differentiated membrane domains from Escherichia coli and Salmonella typhimurium, including a fraction containing attachment sites between the inner and outer membranes and the murein skeleton of the cell envelope. (1986)

Cell envelopes of Salmonella typhimurium and Escherichia coli were disrupted in a French pressure cell and fractionated by successive cycles of sedimentation and floatation density gradient centrifugation. This permitted the identification and isolation of several membrane fractions in addition to the major inner membrane and murein-outer membrane fractions. One of these fractions (fraction OML) accounted for about 10% of the total cell envelope protein, and is likely to include the murein-membrane adhesion zones that are seen in electron micrographs of plasmolyzed cells. Fraction OML contained inner membrane, murein, and outer membrane in an apparently normal configuration, was capable of synthesizing murein from UDP-[3H]N-acetylglucosamine and UDP-N-acetylmuramylpentapeptide and covalently linking it to the endogenous murein of the preparation, and showed a labeling pattern in [3H]galactose pulse-chase experiments that was consistent with its acting as an intermediate in the movement of newly synthesized lipopolysaccharide from inner membrane to outer membrane. The fractionation procedure also identified two new minor membrane fractions, with characteristic protein patterns, that are usually included in the region of the major inner membrane peak in other fractionation procedures but can be separated from the major inner membrane fraction and from contaminating flagellar fragments by the subsequent floatation centrifugation steps.
Deep networks for saliency detection via local estimation and global search (2015)

This paper presents a saliency detection algorithm by integrating both local estimation and global search. In the local estimation stage, we detect local saliency by using a deep neural network (DNN-L) which learns local patch features to determine the saliency value of each pixel. The estimated local saliency maps are further refined by exploring the high level object concepts. In the global search stage, the local saliency map together with global contrast and geometric information are used as global features to describe a set of object candidate regions. Another deep neural network (DNN-G) is trained to predict the saliency score of each object region based on the global features. The final saliency map is generated by a weighted sum of salient object regions. Our method presents two interesting insights. First, local features learned by a supervised scheme can effectively capture local contrast, texture and shape information for saliency detection. Second, the complex relationship between different global saliency cues can be captured by deep networks and exploited principally rather than heuristically. Quantitative and qualitative experiments on several benchmark data sets demonstrate that our algorithm performs favorably against the state-of-the-art methods.
SCHEMA-Designed Variants of Human Arginase I and II Reveal Sequence Elements Important to Stability and Catalysis (2012)

Arginases catalyze the divalent cation-dependent hydrolysis of L-arginine to urea and L-ornithine. There is significant interest in using arginase as a therapeutic antineogenic agent against L-arginine auxotrophic tumors and in enzyme replacement therapy for treating hyperargininemia. Both therapeutic applications require enzymes with sufficient stability under physiological conditions. To explore sequence elements that contribute to arginase stability we used SCHEMA-guided recombination to design a library of chimeric enzymes composed of sequence fragments from the two human isozymes Arginase I and II. We then developed a novel active learning algorithm that selects sequences from this library that are both highly informative and functional. Using high-throughput gene synthesis and our two-step active learning algorithm, we were able to rapidly create a small but highly informative set of seven enzymatically active chimeras that had an average variant distance of 40 mutations from the closest parent arginase. Within this set of sequences, linear regression was used to identify the sequence elements that contribute to the long-term stability of human arginase under physiological conditions. This approach revealed a striking correlation between the isoelectric point and the long-term stability of the enzyme to deactivation under physiological conditions.
Alkylation of 2-lithio-N-methylpiperidines and -pyrrolidines: scope, limitations, and stereochemistry (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlkylation of 2-lithio-N-methylpiperidines and -pyrrolidines: scope, limitations, and stereochemistryRobert E. Gawley and Qianhui ZhangCite this: J. Org. Chem. 1995, 60, 18, 5763–5769Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/jo00123a008https://doi.org/10.1021/jo00123a008research-articleACS PublicationsRequest reuse permissionsArticle Views714Altmetric-Citations89LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Pathogenesis of spondylarthropathies (1995)

We have discussed partially mutually exclusive, partially overlapping models for the pathogenesis of the spondylarthropathies. Not all possibilities have been presented here; others are discussed elsewhere (77, 78). Furthermore, we have not addressed the issue of B27-negative spondylarthropathy. However, in our opinion, the key to understanding the pathogenesis of the spondylarthropathies lies in the interaction between the class I MHC molecule HLA-B27 and the T cell response. Although a T cell response driven by persisting bacterial antigen is still an attractive hypothesis, it does not explain all the known aspects of spondylarthropathy pathogenesis. The possibility of autoimmunity triggered by bacterial infection needs also to be considered, especially the new idea of HLA-B27-derived peptides presented by class II MHC molecules. The predominant involvement of joints is not easily explained in the case of autoimmunity. Cross-reactivity to joint-specific structures such as type II collagen (79) and/or bacteria inside the joint at the beginning of the immune response, with induction of local autoimmunity, might be involved. Most of the issues raised here could be tested by experiment, and we can expect to learn soon whether any of these models will explain the pathogenesis, or if we have to look further. The PCR technique will facilitate the search for bacteria not only in peripheral joints, but also now in sacroiliac biopsy samples from patients with AS and other spondylarthropathies. A prospective study on ReA in an endemic area should teach us more about predisposing factors (for example for Shigella-induced enteritis, which occurs in many parts of the world outside Europe and the US) (80).(ABSTRACT TRUNCATED AT 250 WORDS)
Michèle Cohen. Fashioning Masculinity: National Identity and Language in the Eighteenth Century. New York: Routledge. 1997. Pp. xii, 177. $69.95. ISBN 0-415-10736-9. (1998)

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Gene Activity During Pollen Development (1990)

Gene Activity During Pollen Development, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/arplant/41/1/annurev.pp.41.060190.001533-1.gif