gebhart/patrepeval huggingface dataset:
Design and synthesis of small molecule chemical probes for bromodomain-containing proteins. (2014)

Bromodomains (BRDs) are protein modules which bind to acetylated lysines on histones and transcriptional regulating proteins. BRD-containing proteins are involved in a large variety of critical cellular processes and their misregulation, or mutation of the genes encoding for them, has been linked to pathogenesis in humans. The generation of chemical probes (potent, selective and cell permeable small molecules) in cellular experiments to investigate the biological role of the BRDs is thus desirable. A chemical probe for the CREB (cyclic-AMP response element binding protein) binding-protein (CBP) and E1A binding protein (p300) BRDs was developed, starting from a low molecular weight, weak and non-selective dimethylisoxazole benzimidazole compound. Parallel synthesis was used to optimise the initial hit into a weak, but selective CBP inhibitor. Further modification of the two <em>N</em>-1 and <em>C</em>-2 moieties of the benzimidazole scaffold, led to highly potent and selective CBP inhibitors. Structure-guided design was then applied to optimise the selectivity of the series for CBP over the first domain of bromodomain-containing protein 4 BRD4(1). A strategy to reduce the flexibility of the <em>N</em>-1 and <em>C</em>-2 ethylene linker groups through the incorporation of conformational constraints led to inhibitors with increased selectivity. The optimal compound was highly potent for the CBP and p300 BRDs (K<sub>d</sub> 21 nM and 32 nM, respectively) and selective over BRD4(1) (40-fold and 27-fold, respectively). On-target cellular activity was observed in a fluorescence recovery after photobleaching (FRAP) assay (0.1 μM), a p53 reporter gene assay (IC<sub>50</sub> 1.5 μM) and a Förster resonance energy transfer (FRET) assay (5 μM). A weak indolizine bromodomain-containing protein 9 (BRD9) inhibitor was used as the starting point for the development of a BRD9/BRD7 chemical probe. Analogues were synthesised via [3+2] cycloadditions. An optimised compound was found to be highly potent (68 nM) and selective over BRD4(1) (34-fold). On-target cellular activity was observed in a FRAP assay (5 μM). Efforts were made to improve the cellular activity through the introduction of an ionisable centre to aid solubility. A selection of piperazine analogues were shown to be potent and selective, and these compounds warrant further investigation of their selectivity and cellular activity. Overall, the work has led to the first potent and selective inhibitors of the CBP/p300 and BRD9 BRDs. It also highlights the role of structural analysis in the development of inhibitors that modulate protein-protein interactions.
Determination of rubidium isotopes by using saturated absorption spectroscopy and a see-through hollow cathode glow discharge cell (1998)

K. Song, E. Jung, H. Cha, J. Lee, M. Kim and S. Chun Lee, J. Anal. At. Spectrom., 1998, 13, 301 DOI: 10.1039/A707606A
SU-E-I-08: Do CTDI Measurements Approximate Peak Skin Dose for Wide-Beam Volumetric Scans? (2013)

Purpose: To investigate the relationship between peak skin dose and CTDI measurements for wide-beam volumetric (stationary table) CT scanning. Methods: Air-kerma (AK) measurements were performed in head and body CTDI phantoms using conventional CTDI, extended CTDI (CTDIe), and AAPM TG-111 protocols. These measurements were compared to skin dose estimates obtained using a small volume (0.1 ml) ion chamber (IC) mounted on the anterior surface of the phantoms. Measurements were made on a volumetric CT scanner (Toshiba Aquilion ONE) for collimations of 40, 80, 120 and 160 mm and at kVp settings of 80, 100, and 120. Anterior and lateral surface dose measurements were also made on anthropomorphic phantoms at the same fixed techniques. Results: In the CTDI body phantom, peripheral CTDIe nearly equals surface dose while CTDIevol underestimates surface dose by 10–30% over the collimation range. In the CTDI head phantom, either the peripheral or the volume CTDIe values fall within approximately 5% of the surface dose for collimations greater than 80 mm. At smaller collimation, CTDIe values overestimate surface dose in the head phantom. TG-111 f(0) measurements in the anterior peripheral location slightly overestimate anterior surface dose measurement results for both head and body CTDI phantoms. Surface measurements on the anthropomorphic phantoms exhibit variations between anterior and lateral locations, with lateral doses being smaller. Conclusion: Values derived from CTDIe measurements are useful indicators of peak skin dose for cylindrical phantoms at beam widths in excess of 80 mm. In patients, geometrical correction factors similar to the Size Specific Dose Estimate (SSDE) methodology might be used to account for actual body habitus. Toshiba America Medical Systems is supporting an associated research project on the scanner used for this work. Dr Di Zhang is an employee of Toshiba America Medical Systems.
Immobilized <i>Drosophila melanogaster</i> Deoxyribonucleoside Kinase (<i>Dm</i>dNK) as a High Performing Biocatalyst for the Synthesis of Purine Arabinonucleotides (2014)

Abstract Fruit fly ( Drosophila melanogaster ) deoxyribonucleoside kinase ( Dm dNK; EC: 2.7.1.145) was characterized for its substrate specificity towards natural and non‐natural nucleosides, confirming its potential in the enzymatic synthesis of modified nucleotides. Dm dNK was adsorbed on a solid ion exchange support (bearing primary amino groups) achieving an expressed activity >98%. Upon cross‐linking with aldehyde dextran, expressed activity was 30‐40%. Both biocatalysts (adsorbed or cross‐linked) were stable at pH 10 and room temperature for 24 h (about 70% of retained activity). The cross‐linked Dm dNK preparation was used for the preparative synthesis of arabinosyladenine monophosphate (araA‐MP) and fludarabine monophosphate (FaraA‐MP). Upon optimization of the reaction conditions (50 mM ammonium acetate, substrate/ATP ratio=1:1.25, 2 mM MgCl 2 , 37 °C, pH 8) immobilized Dm dNK afforded the title nucleotides with high conversion (>90%), whereas with the soluble enzyme lower conversions were achieved (78–87%). Arabinosyladenine monophosphate was isolated in 95% yield and high purity (96.5%). magnified image
ANALYSIS OF HIGH-PRESSURE DIESEL SPRAY FORMATION IN THE EARLY STAGE OF INJECTION (1997)

The characteristics of a high-pressure diesel spray in the early stage of injection are examined by use of enlarged shadowgraphy, under both atmospheric and pressurized conditions. To clarify the mechanisms of the initial stage development, two kinds of injection pressure history and a wide range of valve opening pressures are covered. Until 0.3 ms after the start of injection, there is a region at which the tip penetration is insensitive to the ambient pressure, which becomes shorter with an increase in the valve opening pressure. This characteristic feature of the spray formation process is related to the eddy motion generated in the spray.
Thwart the insider threat: a proactive approach to personnel security (2006)

The Coca-Cola espionage case that the US Department of Justice is investigating shows the high level at which espionage occurs. The rotten core of espionage is often at the heart of an organisation – with its employees. But fraudster insiders can be blocked from getting into your organisation in the first place with the right personnel background checks. And employees who leave must be stripped of all intellectual property. Employees who are dismissed deserve extra caution and must be escorted from the building for fear of revenge. Potential employees must be checked comprehensively to make sure the employer knows exactly what it is hiring. All to often, skeletons can be unearthed without too much difficulty with a few routine checks. As we all move deeper and deeper into the global economy of the 21st Century, the spectre of economic espionage grows larger and larger. Consider some recent news stories from around the world:
Validation of the Postimplantation Rat Whole-embryo Culture Test in the International ECVAM Validation Study on Three <i>In Vitro</i> Embryotoxicity Tests (2004)

A detailed report is presented on the performance of the postimplantation rat whole-embryo culture (WEC) test in a European Centre for the Validation of Alternative Methods (ECVAM)-sponsored formal validation study on three in vitro tests for embryotoxicity. Twenty coded test chemicals, classified as non-embryotoxic, weakly embryotoxic or strongly embryotoxic on the basis of their in vivo effects in animals and/or humans, were tested in four laboratories. The outcome showed that the WEC test can be considered to be a scientifically validated test, which is ready for consideration for use in assessing the embryotoxic potentials of chemicals for regulatory purposes.
Aquantum-chemicalstudyofhydridetransferin catalytictransformationsofparaffinsonzeolites. Pathwaysthroughadsorbednonclassicalcarboniumions (1997)

A quantum-chemical investigation of the hydride transfer reaction in catalytic transformations of hydrocarbons on zeolites has been performed. Ab initio calculations at the MP2/6-31aaG//HF/6-31G level demonstrated that the activated complexes of hydride transfer reaction in catalytic transformations of paraffins on zeolites very much resemble adsorbed nonclassical carbonium ions. However, these transient species are strongly held at the surface active sites by the Coulomb interaction. The calculated activationenergiesforreactionsinvolvingpropaneandisobutaneareinareasonableagreementwiththeexperimentaldata.
Free fat, surface fat and dairy powders: interactions between process and product. A review (2007)

Nowadays, fat-filled spray-dried dairy powders have acquired an economic importance. Increasing the fat content leads to further quality implications such as off-flavors, and poor rehydration and flowing properties. However, the control of the drying operation and of the powder properties is still rather empirical in this case and few studies have focused on the whole issue up to now. This review aims at giving an overview of research work on fat-filled powders. The so-called “free fat” is often related to fat-filled powders, but the review also highlights the relevance of “surface fat” to powder physical properties. Quantitative and qualitative analytical techniques, mainly referring to free fat, are described here. This review focuses on the specific and combined influence of composition constituents (fat, protein, lactose and mineral elements) and process steps (such as heat treatments, homogenization, drying and storage) on physical properties of fat-filled powders (oxidation, wettability, dispersibility, solubility and flowing properties).
Applying RFID Techniques for the Next-Generation Automotive Services (2017)

This chapter presents innovative ideas for the new applications, with more emphasis on automotive applications. It briefly reviews several radio frequency identification device (RFID) services and the existing automotive services. The chapter introduces innovative ideas for the next-generation RFID automotive services, and discusses architecture for the new services. The automotive industry is one of the best development targets for an RFID application. There have been huge developments in automotive electronics toward user-oriented services. RFID technology could generate many new user-oriented automotive applications. RFID can provide a better solution to implement the road information system. In order to implement RFID systems with the existing automotive systems, the knowledge about the current car networking and telematics systems is needed. The TalusRFID reader can be seen as a prototype for the RFID reader that will be used for the next generation automotive RFID system.
Rapid Genotyping of Mouse Tissue Using Sigma's Extract-N-Amp Tissue PCR Kit (2008)

Genomic detection of DNA via PCR amplification and detection on an electrophoretic gel is a standard way that the genotype of a tissue sample is determined. Conventional preparation of tissues for PCR-ready DNA often take several hours to days, depending on the tissue sample. The genotype of the sample may thus be delayed for several days, which is not an option for many different types of experiments. Here we demonstrate the complete genotyping of a mouse tail sample, including tissue digestion and PCR readout, in one and a half hours using Sigma's SYBR Green Extract-N-Amp Tissue PCR Kit. First, we demonstrate the fifteen-minute extraction of DNA from the tissue sample. Then, we demonstrate the real time read-out of the PCR amplification of the sample, which allows for the identification of a positive sample as it is being amplified. Together, the rapid extraction and real-time readout allow for a prompt identification of genotype of a variety different types of tissues through the reliable method of PCR.
A numerical optimization method using the simplex algorithm for control of modular multilevel converters (2017)

International audience
Mapping genes for fatness and growth on pig chromosome 13: a search in the region close to the pig <i>PIT1</i> gene (1999)

Previous research has shown that PIT1 polymorphisms in several resource populations and the chromosomal region near PIT1 in some populations have been significantly associated with fatness and growth QTLs on pig chromosome 13. To confirm these previous results and to clarify the role of the PIT1 gene in the putative QTL region, this research project was enlarged to include two microsatellite markers flanking each side of the PIT1 gene ( Swr1008 , S0068 , Sw398 and Sw1056 ). The ISU Chinese × US resource families were used and the traits analysed were birth weight, 21 day weight, 42 day weight, longissimus muscle area, back‐fat thickness at several locations, meat colour, marbling and firmness on the carcass, and growth rate for selected time periods. The total number of F 2 pigs used ranged from 241 to 330. The data were analysed using interval mapping for each breed‐cross separately as well as with the pooled data, and single marker least squares analyses for the pooled data. Significant evidence of a QTL for first rib back‐fat thickness was detected approximately 20 cM from the PIT1 gene by using both single marker (p < 0.01) and interval mapping analyses in the pooled data (p < 0.0001) as well as in one family (p < 0.01). Evidence of a QTL for birth weight was detected at the estimated PIT1 position in the interval mapping analysis by using the pooled data (p < 0.014) and verified by the single marker analyses. These results confirmed the previously published QTL work on pig chromosome 13 for the birth weight QTL but suggest that other genes in the region may be partly responsible for the earlier results on the back‐fat thickness QTL in our resource families.
The Stereochemistry and Reactivity of the cis-5-Hydrindanyl Derivatives<sup>1</sup> (1954)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Stereochemistry and Reactivity of the cis-5-Hydrindanyl Derivatives1William G. Dauben and James JiuCite this: J. Am. Chem. Soc. 1954, 76, 17, 4426–4429Publication Date (Print):September 1, 1954Publication History Published online1 May 2002Published inissue 1 September 1954https://doi.org/10.1021/ja01646a044Request reuse permissionsArticle Views67Altmetric-Citations10LEARN 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 InReddit PDF (512 KB) Get e-Alertsclose Get e-Alerts
Hepatitis B virus and hepatitis C virus infections and risk of pancreatic ductal adenocarcinoma (2015)

Pancreatic ductal adenocarcinoma (PADC) represents a highly lethal cancer with a very dismal prognosis. Absence of early symptoms, advanced stage at diagnosis, aggressive biological behaviour and lack of effective systemic treatment are the most important factors, explaining its elevated mortality rate and its low overall five-year survival (< 5%). Until now, the causes of this malignancy remain still largely unknown and further efforts are underway to reach a better knowledge of PADC aetiology and to improve our understanding of mechanisms involved in carcinogenesis of this organ. In the last years it has progressively emerged that viruses play a key role in human carcinogenesis. Unfortunately, some host and viral factors have contributed to make the study of the pancreas extremely difficult and to hamper the identification of pathogenetic processes involved in cancer development, including its retroperitoneal localization as well as the small size of precursor cancer lesions. However, in the past and more recently, some histological investigations suggested that both antigens and genome of hepatitis B (HBV) and hepatitis C (HCV) viruses, two pathogens with well-known high liver tropism and pro-oncogenic properties may be detected also in extra-hepatic tissues, such as pancreas. In addition, some epidemiological articles have suggested that HBV and HCV might be involved even in pancreatic carcinogenesis. Here we review the results of available reports, evaluating the possible association between HBV or/HCV infections and risk of pancreatic cancer development as well as to discuss the limiting factors of these researches.
p16INK4a reporter mice reveal age-promoting effects of environmental toxicants (2020)

While murine-based systems to identify cancer-promoting agents (carcinogens) are established, models to identify compounds that promote aging (gerontogens) have not been described. For this purpose, we exploited the transcription of p16INK4a, which rises dynamically with aging and correlates with age-associated disease. Activation of p16INK4a was visualized in vivo using a murine strain that harbors a knockin of the luciferase gene into the Cdkn2a locus (p16LUC mice). We exposed p16LUC mice to candidate gerontogens, including arsenic, high-fat diet, UV light, and cigarette smoke and serially imaged animals to monitor senescence induction. We show that exposure to a high-fat diet did not accelerate p16INK4a expression, whereas arsenic modestly augmented, and cigarette smoke and UV light potently augmented, activation of p16INK4a-mediated senescence. This work provides a toxicological platform to study mammalian aging and suggests agents that directly damage DNA promote molecular aging.
Disentangling different types of El Niño episodes by evolving climate network analysis (2013)

Complex network theory provides a powerful toolbox for studying the structure of statistical interrelationships between multiple time series in various scientific disciplines. In this work, we apply the recently proposed climate network approach for characterizing the evolving correlation structure of the Earth's climate system based on reanalysis data of surface air temperatures. We provide a detailed study on the temporal variability of several global climate network characteristics. Based on a simple conceptual view on red climate networks (i.e., networks with a comparably low number of edges), we give a thorough interpretation of our evolving climate network characteristics, which allows a functional discrimination between recently recognized different types of El Niño episodes. Our analysis provides deep insights into the Earth's climate system, particularly its global response to strong volcanic eruptions and large-scale impacts of different phases of the El Niño Southern Oscillation (ENSO).
Dual Binding Mode of a Novel Series of DHODH Inhibitors (2006)

Human dihydroorotate dehydrogenase (DHODH) represents an important target for the treatment of hyperproliferative and inflammatory diseases. In the cell DHODH catalyzes the rate-limiting step of the de novo pyrimidine biosynthesis. DHODH inhibition results in beneficial immunosuppressant and antiproliferative effects in diseases such as rheumatoid arthritis. Here, we present high-resolution X-ray structures of human DHODH in complex with a novel class of low molecular weight compounds that inhibit the enzyme in the nanomolar range. Some compounds showed an interesting dual binding mode within the same cocrystal strongly depending on the nature of chemical substitution. Measured in vitro activity data correlated with the prevailing mode of binding and explained the observed structure-activity relationship. Additionally, the X-ray data confirmed the competitive nature of the inhibitors toward the putative ubiquinone binding site and will guide structure-based design and synthesis of molecules with higher activity.
Adaptive decision fusion for unequiprobable sources (1997)

An optimal decision rule has been derived by Chair and Varshney (1986) for fusing decisions based on the Bayesian criterion. However, to implement such a rule, the miss probability PM and the probability of false alarm PF for each local detector must be known, and these are not readily available in practice. To circumvent this situation, an adaptive fusion system for equiprobable sources has been developed. The system is extended to unequiprobable sources; thus its practicality is enhanced. An adaptive fusion model using the fusion result as a supervisor to estimate the PM and PF is introduced. The fusion results are classified as ‘reliable’ and ‘unreliable’. Reliable results are used as a reference to update the weights in the fusion centre. Unreliable results are discarded. The convergence and error analysis of the system are demonstrated theoretically and by simulations. The paper concludes with simulation results that conform to the analysis.
Chloride channel expression in cultured human fetal RPE cells: response to oxidative stress. (2000)

RT-PCR results confirmed the presence of ClC-5 mRNA, and a full-length clone encoding ClC-3 was isolated from a cDNA library for RPE 28 SV4 cells. Specific staining for CFTR and several ClC channels was detected by immunocytochemistry. Whole-cell chloride currents (under conditions of symmetrical chloride concentrations) averaged 16.9 +/- 3.4 pA/pF (at +100 mV; n = 8), showed outward rectification, and had an anion permeability sequence of Cl(-) > I(-) > cyclamate. Currents were stimulated by cAMP cocktail (250 microM cAMP, 100 microM IBMX, and 25 microM forskolin) and were inhibited by 1 mM DIDS. The oxidative agent hydrogen peroxide (100 microM) decreased the current by 34% +/- 10% (n = 4). CONCLUSIONS. These findings suggest that RPE 28 SV4 cells possess regulated chloride channels including CFTR and members of the ClC chloride channel family. The inhibition of chloride currents by H(2)O(2) suggests that this cell line may be advantageous for studies of chloride channel modulation by oxidative stress.