gebhart/patrepeval huggingface dataset:
In Silico Design and in Vitro Characterization of Universal Tyrosine Kinase Peptide Substrates (2018)

A majority of the 90 human protein tyrosine kinases (PTKs) are understudied "orphan" enzymes with few or no known substrates. Designing experiments aimed at assaying the catalytic activity of these PTKs has been a long-running problem. In the past, researchers have used polypeptides with a randomized 4:1 molar ratio of glutamic acid to tyrosine as general PTK substrates. However, these substrates are inefficient and perform poorly for many applications. In this work, we apply the KINATEST-ID pipeline for artificial kinase substrate discovery to design a set of candidate "universal" PTK peptide substrate sequences. We identified two unique peptide sequences from this set that had robust activity with a panel of 15 PTKs tested in an initial screen. Kinetic characterization with seven receptor and nonreceptor PTKs confirmed these peptides to be efficient and general PTK substrates. The broad scope of these artificial substrates demonstrates that they should be useful as tools for probing understudied PTK activity.
Identification of translationally controlled tumor protein in promotion of DNA homologous recombination repair in cancer cells by affinity proteomics (2017)

Translationally controlled tumor protein(TCTP) has been implicated in the regulation of apoptosis, DNA repair and drug resistance. However, the underlying molecular mechanisms are poorly defined. To better understand the molecular mechanisms underlying TCTP involved in cellular processes, we performed an affinity purification-based proteomic profiling to identify proteins interacting with TCTP in human cervical cancer HeLa cells. We found that a group of proteins involved in DNA repair are enriched in the potential TCTP interactome. Silencing TCTP by short hairpin RNA in breast carcinoma MCF-7 cells leads to the declined repair efficiency for DNA double-strand breaks on the GFP-Pem1 reporter gene by homologous recombination, the persistent activation and the prolonged retention of γH2AX and Rad51 foci following ionizing radiation. Reciprocal immunoprecipitations indicated that TCTP forms complexes with Rad51 in vivo, and the stability maintenance of Rad51 requires TCTP in MCF-7 cells under normal cell culture conditions. Moreover, inactivation of TCTP by sertraline treatment enhances UVC irradiation-induced apoptosis in MCF-7 cells, and causes sensitization to DNA-damaging drug etoposide and DNA repair inhibitor olaparib. Thus, we have identified an important role of TCTP in promoting DNA double-stand break repair via facilitating DNA homologous recombination processes and highlighted the great potential of TCTP as a drug target to enhance conventional chemotherapy for cancer patients with high levels of TCTP expression.
Synthesis of .ALPHA.-deuterium-labelled clohexylamine and its deamination by rabbit liver microsomes. (1989)

In order to investigate the isotope effect on the microsomal oxidative deamination of cyclohexylamine, alpha-deuterium(D)-labelled cyclohexylamine was synthesized. The deuterium labelling was found exclusively at the alpha-position with a purity of greater than 99 atom percent. Metabolic studies in vitro indicate that a significant deuterium isotope effect operates in the oxidative deamination of alpha-D-labelled cyclohexylamine. On incubation with rabbit liver microsomes in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen, the ratio of apparent deamination rate constants (kH/kD) was 2.0 +/- 0.2 (mean +/- S.D.).
<title>Recombinant modular transporters on the basis of epidermal growth factor for targeted intracellular delivery of photosensitizers</title> (2005)

The search for new pharmaceuticals has raised interest in locally-acting drugs which act over short distances within the cell, and for which different cell compartments have different sensitivities. Thus, photosensitizers used in anti-cancer therapy should be transported to the most sensitive subcellular compartments where their action is most pronounced. Earlier, we described the effects of bacterially expressed modular recombinant transporters for photosensitizers comprising a-melanocyte-stimulating hormone as an internalizable, cell-specific ligand, an optimized nuclear localization sequence, an <i>Escherichia coli</i> hemoglobin-like protein as a carrier, and an endosomolytic amphipathic polypeptide. These transporters delivered photosensitizers into the murine melanoma cells nuclei to result in cytotoxic effects 2 orders of magnitude greater than those of nonmodified photosensitizers. Here we describe new transporters possessing the same modules except for a ligand that is replaced with epidermal growth factor specific for other cancer cell types. The new transporter modules retained their functional activities within the chimera, this transporter delivered photosensitizers into the human carcinoma cells nuclei to result in photocytotoxic effects almost 3 orders of magnitude greater than those of nonmodified photosensitizers. The obtained results show that ligand modules of such transporters are interchangeable, meaning that they can be tailored for particular applications.
Finding the Greatest Common Divisor by Repeated Subtractions (2016)

The greatest common divisor (GCD) of two or more positive integers is the largest integer that is a common divisor of the given integers - i.e. the largest integer that divides the given integers without leaving a remainder. There are many methods for finding the GCD of two or more integers. Some of the most commonly taught in schools are the methods of factor listing, prime factorisation, and common decomposition using the so-called ladder method. Each of these methods is briefly illustrated below for the pair of integers 18 and 24.
Heterocyclic Vinyl Ethers. XII. The Synthesis of Arylmercaptoacetylenes and a New Cleavage Reaction of Benzo-1,4-dithiadiene1,2 (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHeterocyclic Vinyl Ethers. XII. The Synthesis of Arylmercaptoacetylenes and a New Cleavage Reaction of Benzo-1,4-dithiadiene1,2William E. Parham and Paul L. StrightCite this: J. Am. Chem. Soc. 1956, 78, 18, 4783–4787Publication Date (Print):September 1, 1956Publication History Published online1 May 2002Published inissue 1 September 1956https://pubs.acs.org/doi/10.1021/ja01599a065https://doi.org/10.1021/ja01599a065research-articleACS PublicationsRequest reuse permissionsArticle Views219Altmetric-Citations47LEARN 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
Cobalt Particle Size Effects in the Fischer−Tropsch Reaction Studied with Carbon Nanofiber Supported Catalysts (2006)

The influence of cobalt particle size in the range of 2.6-27 nm on the performance in Fischer-Tropsch synthesis has been investigated for the first time using well-defined catalysts based on an inert carbon nanofibers support material. X-ray absorption spectroscopy revealed that cobalt was metallic, even for small particle sizes, after the in situ reduction treatment, which is a prerequisite for catalytic operation and is difficult to achieve using traditional oxidic supports. The turnover frequency (TOF) for CO hydrogenation was independent of cobalt particle size for catalysts with sizes larger than 6 nm (1 bar) or 8 nm (35 bar), while both the selectivity and the activity changed for catalysts with smaller particles. At 35 bar, the TOF decreased from 23 x 10(-3) to 1.4 x 10(-3) s(-1), while the C5+ selectivity decreased from 85 to 51 wt % when the cobalt particle size was reduced from 16 to 2.6 nm. This demonstrates that the minimal required cobalt particle size for Fischer-Tropsch catalysis is larger (6-8 nm) than can be explained by classical structure sensitivity. Other explanations raised in the literature, such as formation of CoO or Co carbide species on small particles during catalytic testing, were not substantiated by experimental evidence from X-ray absorption spectroscopy. Interestingly, we found with EXAFS a decrease of the cobalt coordination number under reaction conditions, which points to reconstruction of the cobalt particles. It is argued that the cobalt particle size effects can be attributed to nonclassical structure sensitivity in combination with CO-induced surface reconstruction. The profound influences of particle size may be important for the design of new Fischer-Tropsch catalysts.
Synthesis of 6-(2-Amino-2-deoxy-β-d-glucopyranosylamino)- and 6-(β-d-Glucopyranosylamino)purine (1974)

Abstract 6-(β-Glycosylamino)purines have been synthesized in good yields by condensation of 4-amino-5-nitro-6-chloropyrimidine with masked glycosylamines followed by hydrogenation of nitro group, cyclization with triethyl orthoformate and removal of protecting groups.
Influence of the Orinoco River on hydrogen peroxide distribution and production in the eastern Caribbean (1993)

Two cruises were used to investigate the effect of the Orinoco River on the photochemistry of the eastern Caribbean in 1988. Hydrogen peroxide distribution was used as an indicator of the extent of modification and persistence of photochemical activity, with comparisons being made between high (fall) and low (spring) river input. During the spring cruise, H 2 O 2 profiles were typical of oligotrophic waters, with accumulation rates and steady state concentrations similar to those reported for open ocean. Results from the fall cruise were characterized by increased surface concentrations, sharper gradients, and shallower penetration of the photochemically generated H 2 O 2 . The impact of the river water can be traced in the eastern Caribbean by increased dissolved organic matter fluorescence, lower salinity, and faster hydrogen peroxide accumulation rates in surface samples (up to 20 times greater for some stations). It is apparent that peroxide distribution throughout the eastern Caribbean was significantly affected by the Orinoco river input during the fall.
Structural Characterization of the Drug Translocation Path of MRP1/ABCC1 (2014)

Abstract The rapid clearance of drugs from human cells is carried out by MRP1 and other proteins of the ABC transporter superfamily. Selective mutations carried out by DeGorter indicated that replacement of Y324 by phenylalanine (but not by tryptophan or alanine) enhances the capacity of the protein to extrude various drugs. In this study we investigate the effect of mutation on the structure of the isolated transmembrane domain of MRP1 through molecular dynamics simulations of the protein embedded in a POPC membrane. The simulations reveal a persistent tendency of the translocation path to experience a partial constriction, losing ∼50 % of the water inside the conducting path. While the Wt, Y324W and Y324A transporters all experienced the same constriction, the Y324F transporter, the one having a higher clearance rate than the Wt, retains a fully open configuration. The structure of the Y324F mutant reveals an alternate set of stabilizing interactions that force a kink in transmembrane helix 6, which keeps the protein in a fully open outward‐facing configuration thus providing a molecular‐level account for the higher activity of the mutant. The ability of the simulations to corroborate the experimental observations implies that the homology model of MRP1 is a proper representation of the internal interactions between the residues in the protein, and can be used as a reliable model for studying the human multidrug resistance function of the MRP1 protein.
Impact of Chronic Sleep Disturbance for People Living With T1 Diabetes (2015)

Chronic sleep interruption is highly prevalent in adults with T1D and parents/carers of children with T1D with negative effects on daily functioning and well-being. Appropriate interventions are required to alleviate this burden of T1D, address modifiable risk factors for nocturnal hypoglycemia, and reduce the (perceived) need for nocturnal waking.
Arfgef1 haploinsufficiency in mice alters neuronal endosome composition and decreases membrane surface postsynaptic GABAA receptors (2019)

ARFGEF1 encodes a guanine exchange factor involved in intracellular vesicle trafficking, and is a candidate gene for childhood genetic epilepsies. To model ARFGEF1 haploinsufficiency observed in a recent Lennox Gastaut Syndrome patient, we studied a frameshift mutation (Arfgef1<sup>fs</sup>) in mice. Arfgef1<sup>fs/+</sup> pups exhibit signs of developmental delay, and Arfgef1<sup>fs/+</sup> adults have a significantly decreased threshold to induced seizures but do not experience spontaneous seizures. Histologically, the Arfgef1<sup>fs/+</sup> brain exhibits a disruption in the apical lining of the dentate gyrus and altered spine morphology of deep layer neurons. In primary hippocampal neuron culture, dendritic surface and synaptic but not total GABA<sub>A</sub> receptors (GABA<sub>A</sub>R) are reduced in Arfgef1<sup>fs/+</sup> neurons with an accompanying decrease in the number of GABA<sub>A</sub>R-containing recycling endosomes in cell body. Arfgef1<sup>fs/+</sup> neurons also display differences in the relative ratio of Arf6<sup>+</sup>:Rab11<sup>+</sup>:TrfR<sup>+</sup> recycling endosomes. Although the GABA<sub>A</sub>R-containing early endosomes in Arfgef1<sup>fs/+</sup> neurons are comparable to wildtype, Arfgef1<sup>fs/+</sup> neurons show an increase in the number of GABA<sub>A</sub>R-containing lysosomes in dendrite and cell body. Together, the altered endosome composition and decreased neuronal surface GABA<sub>A</sub>R results suggests a mechanism whereby impaired neuronal inhibition leads to seizure susceptibility.
Light microscopic and heterogeneity analysis of astrocytes in the common marmoset brain (2021)

Astrocytes are abundant cells of the central nervous system (CNS) and are involved in processes including synapse formation/function, ion homeostasis, neurotransmitter uptake, and neurovascular coupling. Recent evidence indicates that astrocytes show diverse molecular, structural, and physiological properties within the CNS. This heterogeneity is reflected in differences in astrocyte structure, gene expression, functional properties, and responsiveness to injury/pathological conditions. Deeper investigation of astrocytic heterogeneity is needed to understand how astrocytes are configured to enable diverse roles in the CNS. While much has been learned about astrocytic heterogeneity in rodents, much less is known about astrocytic heterogeneity in the primate brain where astrocytes have greater size and complexity. The common marmoset (Callithrix jacchus) is a promising non-human primate model because of similarities between marmosets and humans with respect to genetics, brain anatomy, and cognition/behavior. Here, we investigated the molecular and structural heterogeneity of marmoset astrocytes using an array of astrocytic markers, multi-label confocal microscopy, and quantitative analysis. We used male and female marmosets and found that marmoset astrocytes show differences in expression of astrocytic markers in cortex, hippocampus, and cerebellum. These differences were accompanied by intra-regional variation in expression of markers for glutamate/GABA transporters, and potassium and water channels. Differences in astrocyte structure were also found, along with complex interactions with blood vessels, microglia, and neurons. This study contributes to our knowledge of the cellular and molecular features of marmoset astrocytes and is useful for understanding the complex properties of astrocytes in the primate CNS.
Energy Distribution in Impulsively Excited Structures (2012)

This paper presents a novel approach to the study of shock in elastic structures. An energy storage property for linear elastic non-dissipative structures is demonstrated, then extrapolated also to damped systems. This property relates locations of energy accumulation along the structure to the form of its stiffness and mass matrices. This result can be profitable used at a design stage of complex structures undergoing shock excitations. On the theoretical ground, the obtained results disclose indeed general properties of energy distribution in dynamical systems with implications on energy localization as well as on energy equipartitioning Finally, these findings open a new point of view on energy transmission in structures, with potential application in the context of Statistical Energy Analysis.
Use of FT-IR Reflection-Absorbance Spectroscopy to Study Photochemical Degradation of Polymeric Coatings on Mirrors (1982)

A technique is presented for in situ study of degradative changes in polymeric coatings on metallic substrates. The technique uses a controlled environment chamber in conjunction with a Fourier-transform infrared (FT-IR) spectrophotometer. The chamber design permits collection of IR reflection-absorbance spectra from a sample undergoing exposure to controlled ultraviolet (uv) radiation, gas mixtures, and temperatures. Initial data presented confirm the ability of the technique to provide information regarding the bulk photochemistry of bisphenol-A polycarbonate coatings on gold and aluminum substrates. Refinements of this technique should allow a detailed kinetic study of degradative reactions at the polymer/metal interface.
The Information Furnace: User-friendly Home Control † (2002)

The Information Furnace is a basement-installed PC-type device that integrates existing consumer home-control, infotainment, security, and communication technologies to transparently provide user-friendly access and value-added services.
Dragon Gene Start Finder identifies approximate locations of the 5' ends of genes (2003)

Recognition of gene starts is a difficult and yet unsolved problem. We present a program, Dragon Gene Start Finder (DGSF), which assesses the gene start in mammalian genomes and predicts a region which should overlap with the first exon of the gene or be in its proximity. The program has been rigorously tested on human chromosomes 4, 21 and 22, and in a strand specific search achieves an overall sensitivity of approximately 65% and a positive predictive value of approximately 78%. The sensitivity for the CpG-island related promoters is >88%. DGSF is free for academic and non-profit users at http://sdmc.lit.org.sg/promoter/dragonGSF1_0/genestart.htm; the download version of the program integrated within the TRANSPLORER package can be obtained from Biobase GmbH, at http://www.biobase.de/.
Featured Cover (2021)

The cover image is based on the Short Report Novel pathogenic variants in NLRP7, NLRP5, and PADI6 in patients with recurrent hydatidiform moles and reproductive failure by Maryam Rezaei et al., https://doi.org/10.1111/cge.13941 . image
Carbon-skeleton rearrangement of an amino acid derivative as mediated by hydrophobic vitamin B12 covalently bound to a lipid species in a bilayer membrane (1995)

Diethyl 2-acetylamino-2-methylpropanedioate co-ordinated to a hydrophobic vitamin B12 Covalently bound to a peptide lipid underwent a carbon-skeleton rearrangement to afford diethyl 2-acetylaminobutanedioate in the single-walled vesicle of N,N-bis(hexadecyl)-Nα-(6-sulfohexanoyl)-L-alaninamide under photolysis conditions.
Dynamic software updates for parallel high‐performance applications (2010)

Abstract Despite using multiple concurrent processors, a typical high‐performance parallel application is long‐running, taking hours, even days to arrive at a solution. To modify a running high‐performance parallel application, the programmer has to stop the computation, change the code, redeploy, and enqueue the updated version to be scheduled to run, thus wasting not only the programmer's time, but also expensive computing resources. To address these inefficiencies, this article describes how dynamic software updates (DSU) can be used to modify a parallel application on the fly, thus saving the programmer's time and using expensive computing resources more productively. The net effect of updating parallel applications dynamically can reduce the total time that elapses between posing a problem and arriving at a solution, otherwise known as time‐to‐discovery . To explore the benefits of dynamic updates for high performance applications, this article takes a two‐pronged approach. First, we describe our experiences of building and evaluating a system for dynamically updating applications running on a parallel cluster. We then review a large body of literature describing the existing state of the art in DSU and point out how this research can be applied to high‐performance applications. Our experimental results indicate that DSU have the potential to become a powerful tool in reducing time‐to‐discovery for high‐performance parallel applications. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Bleach boosting and direct brightening by multiple xylanase treatments during peroxide bleaching of kraft pulps (1997)

The effects of multiple xylanase treatments were assessed during the peroxide bleaching of three pulps: Douglas-fir (kraft); Western hemlock (oxygen delignified kraft); and trembling Aspen (kraft). The addition of a xylanase treatment stage, either before or after the peroxide bleaching stage(s), resulted in the enhanced brightening of all pulps. A higher brightness was achieved using two enzyme treatments, one before and one after the peroxide stage(s). Both bleach boosting and direct brightening seemed to contribute to the enhancement of the peroxide bleaching. Compared to xylanase prebleaching, xylanase posttreatment of peroxide bleached pulps solubilized less lignin and chromophores and made smaller amounts of these materials alkaline soluble. Nevertheless, the final brightness achieved by xylanase posttreatment was similar or superior to that achieved with xylanase prebleaching of the corresponding unbleached pulps. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 312–318, 1997.