gebhart/patrepeval huggingface dataset:
The Preparation of Macrocyclic Calpain Inhibitors by Ring Closing Metathesis and Cross Metathesis* (2014)

Ring closing metathesis and cross metathesis approaches to a new macrocyclic peptidomimetic aldehyde 2 have been developed, with the former route being the most convenient. Aldehyde 2 is a potent inhibitor of calpain II (IC50 of 45 nM) with comparable activity to the benchmark acyclic inhibitor SJA6017 4. Both compounds contain an N-terminal 4-fluorophenylsulfonyl group. The P2 Ile analogue of 2 (16) is significantly less active (IC50 of 2000 nM) which reflects an unusually subtle importance of the P2 residue for active site binding.
Analysis of physical interactions between peptides and HLA molecules and application to the detection of human immunodeficiency virus 1 antigenic peptides. (1990)

The physical association of 40 antigenic peptides and purified HLA class I and class II molecules was monitored using a direct peptide binding assay (PBA) in solid phase and an inhibition peptide binding assay (IPBA) in which the competing peptide was present in a soluble phase. We also examined the ability of different peptides to inhibit the lytic activity of human antiviral cytolytic T cells towards cells incubated with the corresponding target peptide. Our results showed that: (a) Binding of a given human T cell-recognized peptide to several HLA class I and class II molecules occurred frequently. Nevertheless, preferential binding of peptides to their respective restriction molecules was also observed. (b) Binding of HLA molecules to peptides recognized by murine T cells occurred less frequently. (c) 11 of 24 (46%) randomly selected HIV-1 peptides contained agretopic residues allowing their binding to HLA molecules. (d) The kinetics of HLA/peptide association depended on the peptide tested and were faster than or similar to those reported for Ia molecules. Dissociation of these complexes was very low. (e) Peptide/HLA molecule binding was dependent on length, number of positive charges, and presence of hydrophobic residue in the peptide. (f) A correlation was demonstrated between a peptide inhibitory effect in the IPBA and its blocking effect in the cytolytic test. Our data indicated that the restriction phenomenon observed in T cell responses was not strictly related to either an elective HLA/peptide association, or a high binding capacity of a peptide to HLA molecules. These data also showed that the PBA and IPBA are appropriate for the detection of agretopic residues within HIV-1 proteins.
Raman amplification in a single-mode reentrant fiber loop (1985)

Low-loss tunable couplers1 have recently made possible realization of closed optical fiber loops of interest as sensing devices2 as well as signal processors.3,4 Currently, the performance of most of these systems is limited by propagation loss in the fiber. It was, therefore, interesting to attempt implementation of in-line optical amplification in a closed fiber loop to compensate for loss and enhance system performance.
Fast switching electroclinic mixtures based on a series of chloroester homologues (2000)

Abstract Using chloroester homologues, two electroclinic mixtures (M68 and M79) were formed. The mixed systems behaved similarly to the longer chain faster switching compounds. However by adding compounds with shorter alkyl chains attached to the core structure, the rotational viscosity of the system is reduced so that its switching speed is improved when compared with the pure compound. The magnitudes of the electroclinic coefficient for the two mixtures are very similar. However the switching time of M68 is nearly half that of M78. The shortest E-O response time of M68 is 83 ns which was estimated by dielectric measurements. The fastest mixture M68 has been successfully used in a single pixel electro-optic device, which should allow very fast SLMs to be made in the near future.
Dominant Positive and Negative Selection Using a Hygromycin Phosphotransferase–Thymidine Kinase Fusion Gene (1991)

The hygromycin phosphotransferase gene was fused in-frame with the herpes simplex virus type 1 thymidine kinase gene.The resulting fusion gene (termed HyTK) confers hygromycin B resistance for dominant positive selection and ganciclovir sensitivity for negative selection and provides a means by which these selectable phenotypes may be expressed and regulated as a single genetic entity.from tgLS(+)HyTK by inserting the universal translation terminator oligonucleotide (Pharmacia, Uppsala, Sweden), 5'-GCTTAATTAA TTAAGC-3', at the NaeI site located near the junction of the hph and HSV-1 TK sequences of the HyTK selectable fusion gene.A.
True challenges of disposable optical fiber sensors for clinical environment (2007)

Medical applications represent a unique chance of expansion for the optical fiber sensors (OFS) market that was confined so far mostly in niche applications where higher technological costs were justified by OFS distinctive advantages. Single use medical devices integrating OFS could however generate a significant growth for this type of technology. Thanks to cost reductions derived from the success of optical fiber used in the telecom industry, it is now possible to produce competitive disposable OFS for clinical environment. Cost reduction is nevertheless not the only challenge for this type of application: materials bio-compatibility and sterilization resistance, packaging issues, design considerations for end-user acceptance and operational simplicity, technology reliability including connectivity and sensor performances, manufacturing process monitoring and outstanding quality control, are among few of the problems that have to be considered to address correctly the complex medical market with successful disposable OFS devices. With a clear understanding of the needs and challenges of clinical applications, it is easier to respond to this reality and to offer commercially suitable solutions.
P‐103: Wide‐Gamut Color Reflective Displays Using iMoD™ Interference Technology (2004)

Abstract The addition of a primary‐color‐specific optical stack to iMoD displays dramatically improves the color gamut of the resulting display. This enables a reflective, bi‐stable display to offer a color gamut representative of transflective TFT LC displays (in transmissive mode) while simultaneously maintaining a reflectance greater than that of reflective TFT LC displays.
Mutation-Selective Tumor Remission with Ras-Targeted, Whole Yeast-Based Immunotherapy (2004)

Activating mutations in Ras oncoproteins represent attractive targets for cancer immunotherapy, but few vectors capable of generating immune responses required for tumor killing without vector neutralization have been described. Whole recombinant yeast heterologously expressing mammalian mutant Ras proteins were used to immunize mice in a carcinogen-induced lung tumor model. Therapeutic immunization with the whole recombinant yeast caused complete regression of established Ras mutation-bearing lung tumors in a dose-dependent, antigen-specific manner. In combination with the genomic sequencing of tumors in patients, the yeast-based immunotherapeutic approach could be applied to treat Ras mutation-bearing human cancers.
15-Deoxy-Δ 12,14 -prostaglandin J 2 : The endogenous electrophile that induces neuronal apoptosis (2002)

Prostaglandin D(2) (PGD(2)), a major cyclooxygenase product in a variety of tissues and cells, readily undergoes dehydration to yield the bioactive cyclopentenone-type PGs of the J(2)-series, such as 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). The observation that the level of 15d-PGJ(2) increased in the tissue cells from patients with sporadic amyotrophic lateral sclerosis suggested that the formation of 15d-PGJ(2) may be closely associated with neuronal cell death during chronic inflammatory processes. In vitro experiments using SH-SY5Y human neuroblastoma cells revealed that 15d-PGJ(2) induced apoptotic cell death. An oligonucleotide microarray analysis demonstrated that, in addition to the heat shock-responsive and redox-responsive genes, the p53-responsive genes, such as gadd45, cyclin G1, and cathepsin D, were significantly up-regulated in the cells treated with 15d-PGJ(2). Indeed, the 15d-PGJ(2) induced accumulation and phosphorylation of p53, which was accompanied by a preferential redistribution of the p53 protein in the nuclei of the cells and by a time-dependent increase in p53 DNA binding activity, suggesting that p53 accumulated in response to the treatment with 15d-PGJ(2) was functional. The 15d-PGJ(2)-induced accumulation of p53 resulted in the activation of a death-inducing caspase cascade mediated by Fas and the Fas ligand.
Gravity and magnetic models of the Midcontinent Rift in eastern Lake Superior (1994)

Gravity and magnetic models of the Midcontinent Rift (MCR) in eastern Lake Superior supplement recent structural and stratigraphic interpretations based on the seismic reflection method. An algorithm developed to accommodate spatially varying direction and magnitude of magnetization within a magnetic source is used in both forward and inverse modeling procedures. Structural attitudes of rift-filling basalts derived from seismic reflection sections are used to rotate the Keweenawan remanent magnetization vectors in the direction of deformation. An iterative linear inversion routine calculates magnitudes of induced and remanent magnetizations, as well as normal and reversed polarity basalt flow distributions. The results indicate that the Koenigsberger ratios of these basalts generally range from 1 to 3, which is in agreement with values obtained from rock property measurements. The models also suggest that the greater volume of the Keweenawan basalt section in eastern Lake Superior is reversely polarized and that remanent magnetizations persist to depths of up to 20 km. Our results, supplemented by isotopic and paleomagnetic data, suggest that the vast majority of the basalts predate 1097 ± 1 Ma. A prominent positive magnetic anomaly and a corresponding gravity low strike west across the trend of the rift from the vicinity of Michipicoten Island. These anomalies may reflect a relatively strongly magnetized, felsic igneous body of late-middle to upper Keweenawan in age. Forward gravity models suggest clastic sedimentary rocks up to several kilometers thick overlay the volcanic rocks in localized depressions. Deep crustal seismic data used to constrain gravity models provide evidence of anomalously dense lower crust beneath the MCR.
Segmental coronary endothelial dysfunction in patients with minimal atherosclerosis is associated with necrotic core plaques (2009)

This study suggests that local coronary endothelial dysfunction in patients with minimal coronary atherosclerosis is associated with plaque characteristics that are typical of vulnerable plaques.
Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions. (1996)

Polymorphonuclear leukocytes (PMN) infiltration into tissues is frequently accompanied by increase in vascular permeability. This suggests that PMN adhesion and transmigration could trigger modifications in the architecture of endothelial cell-to-cell junctions. In the present paper, using indirect immunofluorescence, we found that PMN adhesion to tumor necrosis factor-activated endothelial cells (EC) induced the disappearance from endothelial cell-to-cell contacts of adherens junction (AJ) components: vascular endothelial (VE)-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Immunoprecipitation and Western blot analysis of the VE-cadherin/catenin complex showed that the amount of beta-catenin and plakoglobin was markedly reduced from the complex and from total cell extracts. In contrast, VE-cadherin and alpha-catenin were only partially affected. Disorganization of endothelial AJ by PMN was not accompanied by EC retraction or injury and was specific for VE-cadherin/catenin complex, since platelet/endothelial cell adhesion molecule 1 (PECAM-1) distribution at cellular contacts was unchanged. PMN adhesion to EC seems to be a prerequisite for VE-cadherin/catenin complex disorganization. This phenomenon could be fully inhibited by blocking PMN adhesion with an anti-integrin beta 2 mAb, while it could be reproduced by any condition that induced increase of PMN adhesion, such as addition of PMA or an anti-beta 2-activating mAb. The effect on endothelial AJ was specific for PMN since adherent activated lymphocytes did not induce similar changes. High concentrations of protease inhibitors and oxygen metabolite scavengers were unable to prevent AJ disorganization mediated by PMN. PMN adhesion to EC was accompanied by increase in EC permeability in vitro. This effect was dependent on PMN adhesion, was not mediated by proteases and oxygen-reactive metabolites, and could be reproduced by EC treatment with EGTA. Finally, immunohistochemical analysis showed that VE-cadherin distribution was affected by PMN adhesion to the vessel wall in vivo too. This work suggests that PMN adhesion could trigger intracellular signals in EC that possibly regulate VE-cadherin /catenin complex disorganization. This effect could increase EC permeability and facilitate PMN transmigration during the acute inflammatory reaction.
Mechanism of synergistic cell killing when methotrexate precedes cytosine arabinoside: study of L1210 and human leukemic cells. (1979)

Synergistic killing of L1210 cells occurs when methotrexate (MTX) is administered just before 1-beta-D-arabinofuranosylcytosine (Ara-C). This pehnomenon is dependent upon both the dose and time of exposure to MTX. Such increased killing of cells can be explained by the enhanced intracellular accumulation of Ara-C in cells exposed to MTX. This enhancement of Ara-C entry into cells was only observed when the dose of MTX was high enough (1, 10, and 100 muM) to result in free intracellular nondihydrofolate reductase-bound MTX. At the highest doses of MTX (10 and 100 muM) Ara-C triphosphate was increased eightfold and deoxycytidine triphosphate was decreased by 50%. Therefore, the maximum synergistic cell kill when MTX precedes Ara-C may be the consequence of greater inhibition of DNA polymerase by th;e increased Ara-C triphosphate in the presence of the decreasing natural substrate of this enzyme, deoxycytidine triphosphate. Enhanced Ara-C accumulation after administration of MTX was also observed in human acute myelogenous leukemia cells.
Weaknesses of Margulis and Ramanujan-Margulis Low-Density Parity-Check Codes (2003)

We report weaknesses in two algebraic constructions of low-density parity-check codes based on expander graphs. The Margulis construction gives a code with near-codewords, which cause problems for the sum-product decoder; The Ramanujan-Margulis construction gives a code with low-weight codewords, which produce an error-floor.
Akt Protein Kinase Enhances Human Telomerase Activity through Phosphorylation of Telomerase Reverse Transcriptase Subunit (1999)

With the amino acid sequences of all reported Akt kinase physiological substrates, the possible Akt kinase substrate specificity has been suggested. The serine/threonine residue to be phosphorylated in these proteins is placed within stretches of amino acids with homology, and the arginine residues on the -5 and -3 positions and a hydrophobic amino acid on the +2 position are conserved relative to those of serine/threonine residues (XXRXRXXS/TXX). We noticed two putative Akt kinase phosphorylation sites (220GARRRGGSAS229) and (817AVRIRGKSYV826) in human telomerase reverse transcriptase (hTERT) subunit. To demonstrate that hTERT is an Akt kinase substrate protein, we performed the nonradioactive protein kinase assay with the fluorescein hTERT peptide (817AVRIRGKSYV826). We observed the phosphorylation of hTERT peptide by the human melanoma cell lysate or the activated recombinant Akt kinase proteins in vitro. With the treatment of the growth factor deprivation or okadaic acid, we also observed the up-regulation of both hTERT peptide phosphorylation and the telomerase activity. We noticed that Wortmannin down-regulates hTERT peptide phosphorylation and telomerase activity together. In addition, we observed the enhancement of telomerase activity with the pretreatment of Akt kinase in vitro. Thus, these observations suggest that Akt kinase enhances human telomerase activity through phosphorylation of hTERT subunit as one of its substrate proteins.
Polymeric micelles: a star model (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolymeric micelles: a star modelA. HalperinCite this: Macromolecules 1987, 20, 11, 2943–2946Publication Date (Print):November 1, 1987Publication History Published online1 May 2002Published inissue 1 November 1987https://pubs.acs.org/doi/10.1021/ma00177a051https://doi.org/10.1021/ma00177a051research-articleACS PublicationsRequest reuse permissionsArticle Views1806Altmetric-Citations363LEARN 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
Synthesis, Characterization, and High Temperature Stability of Si(B)CN ‐Coated Carbon Nanotubes Using a Boron‐Modified Poly(ureamethylvinyl)Silazane Chemistry (2012)

Carbon nanotubes ( CNT ) and polymer‐derived ceramics ( PDC s) are of interest due to their unique multifunctional properties. CNT s, however, tend to lose their well‐defined structure and geometry at about 400°C in air. PDC s on the other hand are structureless in X‐ray diffraction but show high chemical and thermal stability in air (up to ~1400°C). Herein, we demonstrate synthesis of a composite nanowire structure consisting of polymer‐derived silicon boron‐carbonitride ( Si–B–C–N ) shell with a multiwalled carbon nanotube core. This was achieved through a novel process involving preparation of a boron‐modified liquid polymeric precursor through a reaction of trimethyl borate and poly (ureamethylvinyl) silazane under normal conditions; followed by conversion of polymer to ceramic on carbon nanotube surfaces through controlled heating. Chemical structure of the polymer was studied by liquid‐Nuclear Magnetic Resonance ( NMR ) while evolution of various ceramic phases was studied by solid‐ NMR , Fourier transform infrared and X‐ray photoelectron spectroscopy. Electron microscopy and X‐ray diffraction confirm presence of amorphous Si(B)CN coating on individual nanotubes for all specimens processed below 1400°C. Thermogravimetric analysis, followed by R aman spectroscopy and transmission electron microscopy revealed high temperature stability of the carbon nanotube core in flowing air up to 1000°C.
Enantioselective modulation of GABAergic synaptic transmission by steroids and benz[e]indenes in hippocampal microcultures (1998)

The effects of enantiomers of the neurosteroid analogues, 3alpha-hydroxy-5alpha-pregnan-20-one (DHP) and 3alpha-hydroxy-5alpha-androstane-17beta-carbonitrile (ACN), and the benz[e]indene, BI-1, on synaptic currents were examined in microcultures of rat hippocampal neurons. Over the range of 0.1-10 microM, the (+)-enantiomers were more potent and effective than their (-)-enantiomeric counterparts in enhancing gamma-aminobutyric acid (GABA)A receptor-mediated evoked synaptic currents. The (+)-enantiomers had small effects on peak currents, but slowed the decay of inhibitory synaptic currents, resulting in 2-3-fold increases in charge transfer during inhibitory synaptic events at 10 microM. Similar prolongations of spontaneous miniature inhibitory postsynaptic currents (IPSCs) and responses to brief GABA pulses to outside-out patches suggest that the prolongations of evoked synaptic currents result primarily from postsynaptic effects. In contrast, the (-)-enantiomers had little effect on evoked IPSCs at concentrations < or = 1 microM, but enhanced inhibitory transmission at 10 microM. At concentrations < or = 1 microM, neither the (+)- nor (-)-enantiomers altered glutamate-mediated excitatory synaptic currents. At 10 microM, (+)-DHP and (+)-ACN depressed excitatory responses in a bicuculline-sensitive fashion, suggesting that direct chloride channel gating by the steroids contributed to the depression. These data indicate that certain steroids and benz[e]indenes augment inhibitory synaptic transmission enantioselectively and provide strong support for the hypothesis that steroids act at specific sites on synaptic GABA(A) receptors rather than via alteration of membrane lipids.
Ligand Binding Alters the Backbone Mobility of Intestinal Fatty Acid-Binding Protein as Monitored by 15N NMR Relaxation and 1H Exchange (1997)

The backbone dynamics of the liganded (holo) and unliganded (apo) forms of Escherichia coli-derived rat intestinal fatty acid-binding protein (I-FABP) have been characterized and compared using amide 15N relaxation and 1H exchange NMR measurements. The amide 1H/15N resonances for apo and holo I-FABP were assigned at 25 degrees C, and gradient- and sensitivity-enhanced 2D experiments were employed to measure l5N T1, T2, and [1H]15N NOE values and relative 1H saturation transfer rates. The 15N relaxation parameters were analyzed using five different representations of the spectral density function based on the Lipari and Szabo formalism. A majority of the residues in both apo and holo I-FABP were characterized by relatively slow hydrogen exchange rates, high generalized order parameters, and no conformational exchange terms. However, residues V26-N35, S53-R56, and A73-T76 of apo I-FABP were characterized by rapid hydrogen exchange, low order parameters, and significant conformational exchange. These residues are clustered in a single region of the protein where variability and apparent disorder were previously observed in the chemical shift analyses and in the NOE-derived NMR structures of apo I-FABP. The increased mobility and discrete disorder in the backbone of the apo protein may permit the entry of ligand into the binding cavity. We postulate that the bound fatty acid participates in a series of long-range cooperative interactions that cap and stabilize the C-terminal half of helix II and lead to an ordering of the portal region. This ligand-modulated order-disorder transition has implications for the role of I-FABP in cellular fatty acid transport and targeting.
New Helical Foldamers:  Heterogeneous Backbones with 1:2 and 2:1 α:β-Amino Acid Residue Patterns (2006)

Foldamers, oligomers with strong folding propensities, are subjects of growing interest because such compounds offer unique scaffolds for the development of molecular function. We report two new foldamer classes, oligopeptides with regular 1:2 or 2:1 patterns of alpha- and beta-amino acid residues. Two distinct helical conformations are detected via 2D NMR in methanol for each backbone. One of the helices for each backbone is characterized via X-ray crystallography.