gebhart/patrepeval huggingface dataset:
A synthetic hexapeptide (Argireline) with antiwrinkle activity (2002)

Botulinum neurotoxins (BoNTs) represent a revolution in cosmetic science because of their remarkable and long-lasting antiwrinkle activity. However, their high neurotoxicity seriously limits their use. Thus, there is a need to design and validate non-toxic molecules that mimic the action of BoNTs. The hexapeptide Ac-EEMQRR-NH(2) (coined Argireline) was identified as a result of a rational design programme. Noteworthy, skin topography analysis of an oil/water (O/W) emulsion containing 10% of the hexapeptide on healthy women volunteers reduced wrinkle depth up to 30% upon 30 days treatment. Analysis of the mechanism of action showed that Argireline significantly inhibited neurotransmitter release with a potency similar to that of BoNT A, although as expected, it displayed much lower efficacy than the neurotoxin. Inhibition of neurotransmitter release was due to the interference of the hexapeptide with the formation and/or stability of the protein complex that is required to drive Ca(2+)-dependent exocytosis, namely the vesicular fusion (known as SNARE) complex. Notably, this peptide did not exhibit in vivo oral toxicity nor primary irritation at high doses. Taken together, these findings demonstrate that Argireline is a non-toxic, antiwrinkle peptide that emulates the action of currently used BoNTs. Therefore, this hexapetide represents a biosafe alternative to BoNTs in cosmetics.
TGN1412 Induces Lymphopenia and Human Cytokine Release in a Humanized Mouse Model (2016)

Therapeutic monoclonal antibodies (mAbs) such as the superagonistic, CD28-specific antibody TGN1412, or OKT3, an anti-CD3 mAb, can cause severe adverse events including cytokine release syndrome. A predictive model for mAb-mediated adverse effects, for which no previous knowledge on severe adverse events to be expected or on molecular mechanisms underlying is prerequisite, is not available yet. We used a humanized mouse model of human peripheral blood mononuclear cell-reconstituted NOD-RAG1-/-Aβ-/-HLADQ(tg+ or tg-)IL-2Rγc-/- mice to evaluate its predictive value for preclinical testing of mAbs. 2-6 hours after TGN1412 treatment, mice showed a loss of human CD45+ cells from the peripheral blood and loss of only human T cells after OKT3 injection, reminiscent of effects observed in mAb-treated humans. Moreover, upon OKT3 injection we detected selective CD3 downmodulation on T cells, a typical effect of OKT3. Importantly, we detected release of human cytokines in humanized mice upon both OKT3 and TGN1412 application. Finally, humanized mice showed severe signs of illness, a rapid drop of body temperature, and succumbed to antibody application 2-6 hours after administration. Hence, the humanized mouse model used here reproduces several effects and adverse events induced in humans upon application of the therapeutic mAbs OKT3 and TGN1412.
Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis (2007)

IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies.
Current Advances and Future Challenges in Adenoviral Vector Biology and Targeting (2007)

Gene delivery vectors based on Adenoviral (Ad) vectors have enormous potential for the treatment of both hereditary and acquired disease. Detailed structural analysis of the Ad virion, combined with functional studies has broadened our knowledge of the structure/function relationships between Ad vectors and host cells/tissues and substantial achievement has been made towards a thorough understanding of the biology of Ad vectors. The widespread use of Ad vectors for clinical gene therapy is compromised by their inherent immunogenicity. The generation of safer and more effective Ad vectors, targeted to the site of disease, has therefore become a great ambition in the field of Ad vector development. This review provides a synopsis of the structure/function relationships between Ad vectors and host systems and summarizes the many innovative approaches towards achieving Ad vector targeting.
Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells. (2003)

Bortezomib (PS-341), a selective inhibitor of proteasome, induces apoptosis in various tumor cells, but its mechanism of action is unclear. Treatment with PS-341 induces apoptosis in SUDHL6 (DHL6), but not SUDHL4 (DHL4), lymphoma cells. Microarray analysis shows high RNA levels of heat shock protein-27 (Hsp27) in DHL4 versus DHL6 cells, which correlates with Hsp27 protein expression. Blocking Hsp27 using an antisense strategy restores the apoptotic response to PS-341 in DHL4 cells; conversely, ectopic expression of wild-type Hsp27 renders PS-341-sensitive DHL6 cells resistant to PS-341. These findings provide the first evidence that Hsp27 confers PS-341 resistance.
Electron-Transfer Reactions of Ruthenium Trisbipyridyl-Viologen Donor-Acceptor Molecules: Comparison of the Distance Dependence of Electron Transfer-Rates in the Normal and Marcus Inverted Regions (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectron-Transfer Reactions of Ruthenium Trisbipyridyl-Viologen Donor-Acceptor Molecules: Comparison of the Distance Dependence of Electron Transfer-Rates in the Normal and Marcus Inverted RegionsEdward H. Yonemoto, Geoffrey B. Saupe, Russell H. Schmehl, Stefan M. Hubig, Richard L. Riley, Brent L. Iverson, and Thomas E. MalloukCite this: J. Am. Chem. Soc. 1994, 116, 11, 4786–4795Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/ja00090a026https://doi.org/10.1021/ja00090a026research-articleACS PublicationsRequest reuse permissionsArticle Views1747Altmetric-Citations200LEARN 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
Profiling Cellular Protein Complexes by Proximity Ligation with Dual Tag Microarray Readout (2012)

Patterns of protein interactions provide important insights in basic biology, and their analysis plays an increasing role in drug development and diagnostics of disease. We have established a scalable technique to compare two biological samples for the levels of all pairwise interactions among a set of targeted protein molecules. The technique is a combination of the proximity ligation assay with readout via dual tag microarrays. In the proximity ligation assay protein identities are encoded as DNA sequences by attaching DNA oligonucleotides to antibodies directed against the proteins of interest. Upon binding by pairs of antibodies to proteins present in the same molecular complexes, ligation reactions give rise to reporter DNA molecules that contain the combined sequence information from the two DNA strands. The ligation reactions also serve to incorporate a sample barcode in the reporter molecules to allow for direct comparison between pairs of samples. The samples are evaluated using a dual tag microarray where information is decoded, revealing which pairs of tags that have become joined. As a proof-of-concept we demonstrate that this approach can be used to detect a set of five proteins and their pairwise interactions both in cellular lysates and in fixed tissue culture cells. This paper provides a general strategy to analyze the extent of any pairwise interactions in large sets of molecules by decoding reporter DNA strands that identify the interacting molecules.
Modeling X-ray proximity lithography (1993)

Advanced semiconductor circuits, such as DRAMs, are based on very complex fabrication processes. Because of the cost and complexity involved, it is rapidly becoming impossible to adopt a “trial-and-error” approach in the development stage of a new process. Fortunately, the advances in computer power spurred by the new semiconductor devices have made it possible to compute the response of complex systems in a reasonable time on workstations. Thus, the study of a virtual representation of the process (that is, a model) can represent a solution to the high cost of process development—of course, after verification of the model accuracy through controlled experiments. A correct physical interpretation of the process under study is necessary in order to implement a model that is both accurate and extendible. This is particularly true for new approaches, such as those involved in X-ray lithography. We have studied the process of image formation in X-ray lithography and have implemented several models to predict the intensity distribution at the wafer plane. The models can be applied to the definition of an optimal exposure system that will provide the maximum exposure latitude, and to the study of new types of X-ray masks.
Insect baculoviruses: Powerful gene expression vectors (1989)

Abstract Baculovirus vectors have proven useful in producing high levels of biologically active eukaryotic proteins and providing cellular fractions which are enriched in the protein of interest. Expression occurs in infected insect cells which also provide a suitable environment for posttranslational modification and folding of the protein product. Stable baculovirus vectors can be constructed rapidly with a minimum of viral manipulation.
Fixed and Adaptive Sequential Prefetching in Shared Memory Multiprocessors (1993)

To offset the effect of read miss penalties on processor utilization in shared-memory multiprocessors, several software- and hardware-based data prefetching schemes have been proposed. A major advantage of hardware tech niques is that they need no support from the programmer or compiler. Sequential prefetching is a simple hardware-controlled prefetching technique which relies on the automatic prefetch of consecutive blocks following the block that misses in the cache. In its simplest form, the number of prefetched blocks on each miss is fixed throughout the exe cution. However, since the prefetching efficiency varies during the execution of a program, we propose to adapt the number of pref etched blocks according to a dynamic measure of prefetching effectiveness. Simulations of this adaptive scheme show significant reductions of the read penalty and of the overall execution time.
The feasibility of capturing learner interactions based on logs informed by eye-tracking and remote observation studies (2009)

Two small studies, one an eye-tracking study and the other a remote observation study, have been conducted to investigate ways to identify two kinds of online learner interactions: users flicking through the web pages in "browsing" action, and users engaging with the content of a page in "learning" action. The video data from four participants of the two small studies using the OpenLearn open educational resource materials offers some evidence for differentiating between 'browsing' and 'learning'. Further analysis of the data has considered possible ways of identifying similar browsing and learning actions based on automatic user logs. This research provides a specification for researching the pedagogical value of capturing and transforming logs of user interactions into external forms of representations. The paper examines the feasibility and challenge of capturing learner interactions giving examples of external representations such as sequence flow charts, timelines, and table of logs. The objective users information these represent offer potential for understanding user interactions both to aid design and improve feedback means that they should be given greater consideration alongside other more subjective ways to research user experience. <strong>Editors:</strong> Doug Clow and Alexandra Okada (Open University, UK). <strong>Reviewers:</strong> Ann Jones (Open University, UK) and Alexandra Okada (Open University, UK). <strong>Interactive Demonstration:</strong> Readers are encouraged to go through some of the learning units available at OpenLearn. The website may require some computer applications (e.g. pdf viewer, video player, Flash player, etc.) in order to go through some of the materials within OpenLearn such as documents, files, videos, audio, etc.
Characterization of transport-mediated methotrexate resistance in human tumor cells with antibodies to the membrane carrier for methotrexate and tetrahydrofolate cofactors (1992)

An earlier report (Matherly, L. H., Czajkowski, C. A., and Angeles, S. M. (1991) Cancer Res. 51, 3420-3426) described a K562 human erythroleukemia line (K562.4CF), characterized by an elevated uptake capacity for methotrexate (MTX) and 5-formyltetrahydrofolate, and the identification of a highly glycosylated membrane transporter (GP-MTX) by radioaffinity labeling with N-hydroxysuccinimide [3H] methotrexate. In the present study, radioaffinity-labeled GP-MTX from K562.4CF cells was isolated by Ricinus communis agglutinin I-agarose affinity chromatography, coupled with gel filtration and preparative electrophoresis. Antiserum to the purified, radio-labeled protein was raised in a rabbit and screened by immunoblot analysis of K562.4CF plasma membrane proteins or purified GP-MTX. The antiserum detected a broad GP-MTX band centered at 92 kDa on 7.5% gels. On 4-10% gels, the apparent molecular mass for GP-MTX shifted to 99 kDa. Antiserum specificity was established by quantitatively converting the immunoreactive glycoprotein in plasma membrane homogenates to its N- and O-deglycosylated forms with N- and O-glycanases, respectively. Whereas the methotrexate uptake capacity of K562.4CF cells was elevated 6.1-fold over parental cells, the GP-MTX content on immunoblots was increased approximately 3-fold. For two methotrexate-resistant K562 lines (33- and 70-fold), decreased drug uptake (28 and 18% of parental levels) closely correlated with their reduced GP-MTX contents. A GP-MTX isoform was also detected on immunoblots of membrane proteins from CCRF-CEM human lymphoblastic leukemia cells. With a transport-impaired CCRF-CEM line (13% of wild type uptake), an aberrant electrophoretic migration for GP-MTX was observed, establishing the presence of structural modifications in the transport protein. These structural differences were independent of carrier glycosylation since they were detected following the glycosidase treatments. These findings implicate important roles for distinct carrier-specific alterations in the expression of diminished drug transport in methotrexate-resistant human tumor cells.
Peripherally Induced Tregs – Role in Immune Homeostasis and Autoimmunity (2013)

Thymically derived Foxp3(+) regulatory T cells (tTregs) constitute a unique T cell lineage that is essential for maintaining immune tolerance to self and immune homeostasis. However, Foxp3 can also be turned on in conventional T cells as a consequence of antigen exposure in the periphery, under both non-inflammatory and inflammatory conditions. These so-called peripheral Tregs (pTregs) participate in the control of immunity at sites of inflammation, especially at the mucosal surfaces. Although numerous studies have assessed in vitro generated Tregs (termed induced or iTregs), these cells most often do not recapitulate the functional or phenotypic characteristics of in vivo generated pTregs. Thus, there are still many unanswered questions regarding the T cell receptor (TCR) repertoire and function of pTregs as well as conditions under which they are generated in vivo, and the degree to which these characteristics identify specialized features of pTregs versus features that are shared with tTregs. In this review, we summarize the current state of our understanding of pTregs and their relationship to the tTreg subset. We describe the recent discovery of unique cell surface markers and transcription factors (including Neuropilin-1 and Helios) that can be used to distinguish tTreg and pTreg subsets in vivo. Additionally, we discuss how the improved ability to distinguish these subsets provided new insights into the biology of tTregs versus pTregs and suggested differences in their function and TCR repertoire, consistent with a unique role of pTregs in certain inflammatory settings. Finally, these recent advances will be used to speculate on the role of individual Treg subsets in both tolerance and autoimmunity.
Strain-balanced silicon-germanium materials for near-IR photodetection in silicon-based optical interconnects (1998)

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1998.
Microfluidic switch for embryo and cell sorting (2004)

We present measurements and simulation of fluid flow and sphere motion in a pressure-driven microfluidic sorter designed for Drosophila embryos. We simulated the flow fields for different channel layouts and flow parameters to find geometries and conditions for optimised embryo movement. The microfluidic switch has a designed switching time of 360 /spl mu/s. We validated the sorter design with fluid experiments in devices fabricated from silicon and Pyrex wafers. The experimental and simulated results are compared both qualitatively and quantitatively by examining the concentration distribution of fluids. This type of microfluidic sorter is promising for micromanipulation of a variety of biological cells, and provides automated operations for higher throughput and accuracy.
Distinct Subdomains of the EphA3 Receptor Mediate Ligand Binding and Receptor Dimerization (1998)

Eph receptor tyrosine kinases and their ligands (ephrins) are highly conserved protein families implicated in patterning events during development, particularly in the nervous system. In a number of functional studies, strict conservation of structure and function across distantly related vertebrate species has been confirmed. In this study we make use of the observation that soluble human EphA3 (HEK) exerts a dominant negative effect on somite formation and axial organization during zebrafish embryogenesis to probe receptor function. Based on exon structure we have dissected the extracellular region of EphA3 receptor into evolutionarily conserved subdomains and used kinetic BIAcore analysis, mRNA injection into zebrafish embryos, and receptor transphosphorylation analysis to study their function. We show that ligand binding is restricted to the N-terminal region encoded by exon III, and we identify an independent, C-terminal receptor-dimerization domain. Recombinant proteins encoding either region in isolation can function as receptor antagonists in zebrafish. We propose a two-step mechanism of Eph receptor activation with distinct ligand binding and ligand-independent receptor-receptor oligomerization events.
Comprehensive handbook on hydrosilylation (1992)

Chapter headings and selected sections. Introduction. Catalytic Aspects of Hydrosilylation. Free-radical addition. Methods of silyl radical generation. Hydrosilylation of the C=C bond: mechanism, stereochemistry and examples. Addition of silicon hydrides to other multiple bonds. Nucleophilic-electrophilic catalysis. Homogeneous catalysis by transition metal complexes. Catalysis by supported transition metal complexes. The Reactivity in Hydrosilylation of Particular Types of Organic Compounds With Multiple Bonds. Hydrocarbons with an isolated C=C bond. Dienes with isolated double bonds. Alkene and cycloalkene derivatives with functional groups. Alkyne derivatives with functional groups. Saturated carbonyl compounds. Unsaturated carbonyl compounds. The Effect of Substituents at Silicon on the Reactivity of the Si-H Bond in Hydrosilylation. Effect of the structure of silicon hydrides on the rate and yield in hydrosilylation processes. Influence of the structure of the silicon hydride on regio- and stereoselectivity in hydrosilylation. Practical choice of silicon hydride in the hydrosilylation reaction. The Hydrosilylation of Unsaturated Organosilicon Compounds. Addition of substituted hydrosilanes to carbon-carbon double bonds in unsaturated silanes. Curing organosilicon polymers by hydrosilylation. Intra- and intermolecular hydrosilylation. The Application of Hydrosilylation Processes. Silanes as coupling agents. Reduction of organic compounds by hydrosilylation. Modification of polymers via hydrosilylation. A Compilation of Information on Hydrosilylation Studies Over the Period from 1965 to 1990. List of tables. Abbreviations. Tables/Figures.Bibliography. Reviews. Papers. Patents. Index.
Development of a Peptide Inhibitor of Hyaluronan-Mediated Leukocyte Trafficking (2000)

Hyaluronan (HA), a high molecular weight glycosaminoglycan, is expressed abundantly in the extracellular matrix and on cell surfaces. Although HA is known to bind many adhesion molecules, little information has been available with respect to its direct physiological role. In this study, we developed a novel 12-mer (GAHWQFNALTVR) peptide inhibitor of HA, termed "Pep-1," by using phage display technology. Pep-1 showed specific binding to soluble, immobilized, and cell-associated forms of HA, and it inhibited leukocyte adhesion to HA substrates almost completely. Systemic, local, or topical administration of Pep-1 inhibited the expression of contact hypersensitivity responses in mice by blocking skin-directed homing of inflammatory leukocytes. Pep-1 also inhibited the sensitization phase by blocking hapten-triggered migration of Langerhans cells from the epidermis. These observations document that HA plays an essential role in "two-way" trafficking of leukocytes to and from an inflamed tissue, and thus provide technical and conceptual bases for testing the potential efficacy of HA inhibitors (e.g., Pep-1) for inflammatory disorders.
Enterococcus faecalis pheromone binding protein, PrgZ, recruits a chromosomal oligopeptide permease system to import sex pheromone cCF10 for induction of conjugation. (1996)

Conjugative transfer of the plasmid pCF10 by Enterococcus faecalis donor cells occurs in response to a peptide sex pheromone, cCF10, secreted by recipients. The plasmid-encoded cCF10 binding protein, PrgZ, is similar in sequence to binding proteins (OppAs) encoded by oligopeptide permease (opp) operons. Mutation of prgZ decreased the sensitivity of donor cells to pheromone, whereas inactivation of the chromosomal E. faecalis opp operon abolished response at physiological concentrations of pheromone. Affinity chromatography experiments demonstrated the interaction of the pheromone with several putative intracellular regulatory molecules, including an RNA molecule required for positive regulation of conjugation functions. These data suggest that processing of the pheromone signal involves recruitment of a chromosomal Opp system by PrgZ and that signaling occurs by direct interaction of internalized pheromone with intracellular effectors.