gebhart/patrepeval huggingface dataset:
CDK9 Inhibition Reverses Resistance to ABT-199 (GDC-0199) By Down-Regulating MCL-1 (2014)

Abstract All authors are employees of AbbVie and participated in the design, conduct, and interpretation of these studies. AbbVie and Genentech provided financial support for these studies and participated in the review and approval of this publication. The BCL-2-selective inhibitor ABT-199 has demonstrated efficacy in numerous preclinical models of hematologic malignancies without causing thrombocytopenia, a dose-limiting toxicity associated with the BCL-2/BCL-XL inhibitor navitoclax (Souers et al. 2013. Nat. Med. 19, 202-208). ABT-199 has also demonstrated clinical activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL) (Seymour et al. 2014. J. Clin. Oncol. 32, 448s; Davids et al. 2014. J. Clin. Oncol. 32, 544s). Despite these encouraging early clinical data, some subjects do not respond to ABT-199 or progress while on treatment. Pre-clinical models indicate that both intrinsic and acquired resistance may be a consequence of MCL-1 expression. Consequently, we have explored potent and selective small molecule inhibitors of CDK9, a kinase known to maintain the expression of MCL-1 through its role in p-TEFb-mediated transcription. Inhibition of CDK9 resulted in the rapid loss in RNA polymerase II phosphorylation (Serine 5) and MCL-1 expression that was closely followed by the induction of apoptosis in MCL-1-dependent cell lines, a cellular response that could be rescued by overexpression of BCL-2. Substantial synergy was observed between CDK9 inhibitors and ABT-199 in a number of hematologic cell lines with intrinsic or acquired resistance to ABT-199. Direct inhibition of MCL-1 with the small molecule BH3 mimetic A-1210477 was also highly synergistic with ABT-199, further validating the utility of co-inhibiting MCL-1 and BCL-2 function simultaneously in ABT-199 resistant tumors. Importantly, the CDK9 inhibitor-ABT-199 combination was well tolerated in vivo and demonstrated efficacy superior to either agent alone in xenograft models of non-Hodgkin’s lymphoma (NHL) and acute myelogenous leukemia (AML). These data indicate that CDK9 inhibitors may be highly efficacious when used in combination with ABT-199 for the treatment of hematologic malignancies. Disclosures Chen: Abbvie: Employment, Equity Ownership. Jin:Abbvie: Employment, Equity Ownership. Tapang:abbvie: Employment, Equity Ownership. Tahir:abbvie: Employment, Equity Ownership. Smith:abbvie: Employment, Equity Ownership. Xue:abbvie: Employment, Equity Ownership. Zhang:abbvie: Employment, Equity Ownership. Gao:abbvie: Employment, Equity Ownership. Tong:abbvie: Employment, Equity Ownership. Clark:abbvie: Employment, Equity Ownership. Ricker:abbvie: Employment, Equity Ownership. Penning:abbvie: Employment, Equity Ownership. Albert:abbvie: Employment, Equity Ownership. Phillips:abbvie: Employment, Equity Ownership. Souers:abbvie: Employment, Equity Ownership. Leverson:abbvie: Employment, Equity Ownership.
Wireless Orbiter Hang-Angle Inclinometer System (2011)

A document describes a system to reliably gather the hang-angle inclination of the orbiter. The system comprises a wireless handheld master station (which contains the main station software) and a wireless remote station (which contains the inclinometer sensors, the RF transceivers, and the remote station software). The remote station is designed to provide redundancy to the system. It includes two RF transceivers, two power-management boards, and four inclinometer sensors.
Reversible Electrowetting of Vertically Aligned Superhydrophobic Carbon Nanofibers (2006)

Reversible electrostatically induced wetting (electrowetting) of vertically aligned superhydrophobic carbon nanofibers has been investigated. Carbon nanofibers on a 5 x 5 microm pitch were grown on Si substrates, electrically insulated with a conformal dielectric, and hydrophobized with fluoropolymer. This nanostructured scaffold exhibited superhydrophobic behavior for saline (theta approximately 160 degrees). Electrowetting induced a contact angle reduction to theta approximately 100 degrees. Competitive two-liquid (dodecane/saline) electrowetting exhibited reversibility on the same nanostructured scaffold. Without applied bias, ultra-fine-point tip (approximately 25 nm radius) nanofibers result in effectively zero capacitance with the overlying saline layer. Complete electrowetting of the substrate is confirmed as capacitance values increase by several orders of magnitude with increased wetting. These results demonstrate the applicability of reversible electrowetting on nanostructured scaffolds and use of nanofabricated structures that can be integrated with various micro- and nanoelectronic technologies.
In Vitro Characterization of L-Type Calcium Channels and Their Contribution to Firing Behavior in Invertebrate Respiratory Neurons (2005)

L-type calcium channel activity has been associated with a number of cytoplasmic responses, including gene transcription and activation of calcium-dependent enzymes, yet their direct contribution to the electrical activities of neurons has remained largely unexplored. Here we report the cloning and functional characterization of a molluscan L-type calcium channel homologue, LCa(v)1, and investigate its role in coordinating neuronal firing patterns. The LCav1 channel exhibits many hallmarks of vertebrate L-type channels in that it is high-voltage activated, slowly inactivating, and dihydropyridine sensitive and displays calcium-dependent inactivation in recording solutions with standard EGTA concentrations. We show that despite comprising less than approximately 20% of the total whole cell current in identified Lymnaea respiratory network neurons, the L-type channels are essential for maintaining rhythmic action potential discharges without being involved in synaptic release. Our data therefore suggest an important role of L-type calcium channels in maintaining rhythmical pattern activity underlying breathing behavior in Lymnaea.
Investigation of the driver’s seat that displays future vehicle motion (2019)

Automated driving reduces the burden on the driver, however also makes it difficult for the driver to understand the current situation and predict the future movement of the vehicle. When the acceleration due to automated driving occurs without future prediction, the driver's anxiety and discomfort are increased compared to the case in manual driving. To facilitate the prediction of the future behavior of the vehicle by the driver, this paper aims to design and evaluate a haptic interface that actuates the vehicle seat. Our system displays to the driver the movement of the vehicle a few seconds in the future, which allows the driver to make predictions and preparations. Using a driving simulator, we compared the conditions where the movement of the car was displayed in advance for the length of different time. The subjective evaluation of the driver showed that the predictability of the behavior of the vehicle were significantly increased compared to the case without display. The experiment also showed that comfortable feeling significantly decreased if the preceding display is too early.
Cholecystokinin dipeptoid antagonists: design, synthesis, and anxiolytic profile of some novel CCK-A and CCK-B selective and mixed CCK-A/CCK-B antagonists (1993)

The design, synthesis, and structure-activity relationships (SAR) for the development of selective dipeptoid ligands for both of the cholecystokinin (CCK) receptor subtypes CCK-A and CCK-B are described. The SAR developed is used to design a ligand with equal nanomolar binding affinity for both the CCK-A and CCK-B receptors. Example compounds such as [1R-[1 alpha[R*(R*)],2 beta]]-4-[[2-[[3-(1H-indol-3-yl)- 2-methyl-2-[[[(2-methylcyclohexyl)oxy]carbonyl]amino]-1- oxopropyl]-amino]-1-phenylethyl]amino]-4-oxo-butanoic acid (24c), (1R-trans)-N-[alpha-methyl-N-[[(2-methylcyclohexyl)oxy] carbonyl]-D-tryptophyl]-L-3-(phenylmethyl)-beta-alanine (28i), and N-[alpha-methyl-N-[(tricyclo[3.3.1.1]dec-2-yloxy) carbonyl]-D-tryptophanyl]-L-3-(phenylmethyl)-beta-alanine (30m) are CCK-B selective compounds having CCK-B binding affinities of IC50 = 3.9, 0.34, and 0.15 nM with a CCK-A/CCK-B ratio of 464, 53, and 170, respectively. Other compounds such as (1R-trans)-N-[alpha-methyl-N-[[(2-methylcyclohexyl)oxy]carbonyl]- L-tryptophyl]-D-3-(phenylmethyl)-beta-alanine (281) and N-(alpha-methyl-N-[(tricyclo[3.3.1.1]dec-2-yloxy)carbonyl]-L - tryptophyl]-D-3-(phenylmethyl)-beta-alanine (30p) are CCK-A-selective compounds having CCK-A binding affinities of IC50 = 7.9 and 2.82 nM with a CCK-A/CCK-B ratio of 0.007 and 0.01, respectively. Further to these, (1S-trans)-N-[alpha-methyl-N-[[(2-methylcyclohexyl)oxy] carbonyl]-D-tryptophyl]-L-3-(phenylmethyl)-beta-alanine (28h) is a mixed CCK-A/CCK-B ligand with a CCK-A binding affinity of IC50 = 3.9 nM and a CCK-B binding affinity of IC50 = 4.2, producing a CCK-A/CCK-B ratio of unity. The CCK-B selective compounds are shown to be antagonists in electrophysiological tests on the rat ventromedial nucleus of the hypothalamus with an equilibrium constant (Ke) value of 2.8 nM for 30m and are also shown to be anxiolytic in the mouse ligh/dark box test with a minimum effective dose of 0.01 mg/kg, sc, for 30m. The CCK-A selective compounds are also shown to be competitive antagonists by the inhibition of CCK-8S-evoked amylase secretion from pancreatic acinar cells with a Ke value of 16 nM for 30p. In electrophysiological tests on the rat dorsal raphé (an area rich in CCK-A receptors) 30p had a Ke value of 12.8 nM. The mixed CCK-A/CCK-B compound 28h showed antagonistic properties in both CCK-A and CCK-B models; thus it inhibited CCK-8S-evoked amylase secretion from pancreatic acinar cells and is anxiolytic in the light/dark box paradigm.(ABSTRACT TRUNCATED AT 400 WORDS)
Rapid diagnosis of homocystinuria and other hypermethioninemias from newborns' blood spots by tandem mass spectrometry (1996)

We report a new method for the diagnosis of homocystinuria and other hypermethioninemias from dried blood spots on newborn screening cards, based on isotope-dilution tandem mass spectrometry. The mean concentration of methionine in 909 unaffected newborns was 19 micromol/L (CV 44%). The variability of results was reduced when the concentration of methionine was expressed relative to that of another amino acid in the same specimen. The mean ratio of methionine to leucine plus isoleucine for these same newborn blood spots was 0.16 (CV 25%). In newborn samples from a collection categorized by a Guthrie bacterial inhibition assay as true positive, unaffected, or falsely positive for hypermethioninemias, the ratio of methionine to leucine for each true-positive specimen was at least 2.5 times greater than for respective age-matched unaffected blood specimens. The ratio for falsely positive samples did not differ from that for unaffected blood samples. We predict that the ratio of methionine to leucine plus isoleucine determined by tandem mass spectrometry will successfully detect hypermethioninemias with very low rates for false positives and false negatives.
Inhibition of interferon-gamma-stimulated melanoma progression by targeting neuronal nitric oxide synthase (nNOS) (2022)

Interferon-gamma (IFN-γ) is shown to stimulate melanoma development and progression. However, the underlying mechanism has not been completely defined. Our study aimed to determine the role of neuronal nitric oxide synthase (nNOS)-mediated signaling in IFN-γ-stimulated melanoma progression and the anti-melanoma effects of novel nNOS inhibitors. Our study shows that IFN-γ markedly induced the expression levels of nNOS in melanoma cells associated with increased intracellular nitric oxide (NO) levels. Co-treatment with novel nNOS inhibitors effectively alleviated IFN-γ-activated STAT1/3. Further, reverse phase protein array (RPPA) analysis demonstrated that IFN-γ induced the expression of HIF1α, c-Myc, and programmed death-ligand 1 (PD-L1), in contrast to IFN-α. Blocking the nNOS-mediated signaling pathway using nNOS-selective inhibitors was shown to effectively diminish IFN-γ-induced PD-L1 expression in melanoma cells. Using a human melanoma xenograft mouse model, the in vivo studies revealed that IFN-γ increased tumor growth compared to control, which was inhibited by the co-administration of nNOS inhibitor MAC-3-190. Another nNOS inhibitor, HH044, was shown to effectively inhibit in vivo tumor growth and was associated with reduced PD-L1 expression levels in melanoma xenografts. Our study demonstrates the important role of nNOS-mediated NO signaling in IFN-γ-stimulated melanoma progression. Targeting nNOS using highly selective small molecular inhibitors is a unique and effective strategy to improve melanoma treatment.
Vector Multilevel Tone-Dependent Error Diffusion in the YyCxCz Color Space (2019)

In this paper, we present a tone-dependent fast error diffusion algorithm for color images, in which the quantizer is based on a simulated linearized printer space and the filter weight function depends on the ratio of the luminance of the current pixel to the maximum luminance value. The pixels are processed according to a serpentine scan instead of the classic raster scan. We compare the results of our algorithm to those achieved using the fixed Floyd-Steinberg weights and processing the image according to a raster scan ordering.
Data Cleansing Techniques for Large Enterprise Datasets (2011)

Data quality improvement is an important aspect of enterprise data management. Data characteristics can change with customers, with domain and geography making data quality improvement a challenging task. Data quality improvement is often an iterative process which mainly involves writing a set of data quality rules for standardization and elimination of duplicates that are present within the data. Existing data cleansing tools require a fair amount of customization whenever moving from one customer to another and from one domain to another. In this paper, we present a data quality improvement tool which helps the data quality practitioner by showing the characteristics of the entities present in the data. The tool identifies the variants and synonyms of a given entity present in the data which is an important task for writing data quality rules for standardizing the data. We present a ripple down rule framework for maintaining data quality rules which helps in reducing the services effort for adding new rules. We also present a typical workflow of the data quality improvement process and show the usefulness of the tool at each step. We also present some experimental results and discussions on the usefulness of the tools for reducing services effort in a data quality improvement.
Open-Source Potentiostat for Wireless Electrochemical Detection with Smartphones (2018)

This paper describes the design and characterization of an open-source "universal wireless electrochemical detector" (UWED). This detector interfaces with a smartphone (or a tablet) using "Bluetooth Low Energy" protocol; the smartphone provides (i) a user interface for receiving the experimental parameters from the user and visualizing the result in real time, and (ii) a proxy for storing, processing, and transmitting the data and experimental protocols. This approach simplifies the design, and decreases both the size and the cost of the hardware; it also makes the UWED adaptable to different types of analyses by simple modification of the software. The UWED can perform the most common electroanalytical techniques of potentiometry, chronoamperometry, cyclic voltammetry, and square wave voltammetry, with results closely comparable to benchtop commercial potentiostats. Although the operating ranges of electrical current and voltage of the UWED (±1.5 V, ±180 μA) are more limited than most benchtop commercial potentiostats, its functional range is sufficient for most electrochemical analyses in aqueous solutions. Because the UWED is simple, small in size, assembled from inexpensive components, and completely wireless, it offers new opportunities for the development of affordable diagnostics, sensors, and wearable devices.
Nuclear magnetic resonance studies of the solution chemistry of metal complexes. 21. The complexation of zinc by glycylhistidine and alanylhistidine peptides (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNuclear magnetic resonance studies of the solution chemistry of metal complexes. 21. The complexation of zinc by glycylhistidine and alanylhistidine peptidesDallas L. Rabenstein, Susan A. Daignault, Anvarhusein A. Isab, Alan P. Arnold, and Mohamed M. ShoukryCite this: J. Am. Chem. Soc. 1985, 107, 23, 6435–6439Publication Date (Print):November 1, 1985Publication History Published online1 May 2002Published inissue 1 November 1985https://pubs.acs.org/doi/10.1021/ja00309a001https://doi.org/10.1021/ja00309a001research-articleACS PublicationsRequest reuse permissionsArticle Views157Altmetric-Citations76LEARN 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
in prostate cancer. Analysis in radical prostatectomy specimens and needle biopsies (2004)

The extreme variability of prostate cancer im- plies latent disease with missing clinical symptoms in some cases. Tumor suppressors PTEN (phosphatase and tensin homolog deleted on chromosome ten) and p27 kip1 are frequently mutated in various human cancers. PTEN negatively influences cell growth and induces apoptosis, while p27 kip1 binds to cyclin-E-Cdk2 and counteracts mi- tosis. This study investigated the expression of PTEN and p27 kip1 in prostatectomies and needle biopsies in order to determine whether protein localization or expression lev- els are correlated with tumor grade and whether PTEN and p27 kip1 expression in biopsies are valuable predictive tumor markers. Analysis of PTEN demonstrated that weak expression levels were significantly more prevalent in high-grade tumors. Analysis of p27 kip1 revealed that high- grade tumors had a higher percentage of cytoplasmic lo- calization of the protein than low-grade tumors, where nuclear localization was more frequent. Furthermore, this study indicated a positive association between PTEN and p27 kip1 levels. An increase of high-grade tumors corre- sponded to a progressive loss of both tumor suppressors in needle biopsies and prostatectomies. p27 kip1 and PTEN did not show a higher predictive accuracy of the tumor grade in the surgical specimen than the Gleason score. However, p27 kip1 had the same predictive value as the Gleason score in needle biopsies. Keywords PTEN/MMAC1 · p27 kip1 · Immunohistochemistry · Prostatic carcinoma · Needle biopsy
Preface: International Symposium on Computational Electrochemistry (2007)

Computational methods and approaches play an increasingly important role in various areas of electrochemistry, but this fact still does not find a proper reflection in the structure of electrochemical societies, nor in the calendar of international conferences or symposia. Meetings devoted to computation in electrochemistry are rare, and they are focused on specific application areas. The present symposium has been organized with the aim to bring together computationally oriented electrochemists working in diverse application areas, in order to overcome communication barriers and expose common aspects of their work. The placement of the symposium within the ICCMSE has been dictated by the intention to uncover and reinforce links between Computational Electrochemistry and Computational Science and Engineering.
Recent Trends and Observations in the Design of High-Quality Screening Collections (2011)

The design of a high-quality screening collection is of utmost importance for the early drug-discovery process and provides, in combination with high-quality assay systems, the foundation of future discoveries. Herein, we review recent trends and observations to successfully expand the access to bioactive chemical space, including the feedback from hit assessment interviews of high-throughput screening campaigns; recent successes with chemogenomics target family approaches, the identification of new relevant target/domain families, diversity-oriented synthesis and new emerging compound classes, and non-classical approaches, such as fragment-based screening and DNA-encoded chemical libraries. The role of in silico library design approaches are emphasized.
Cell-substratum interactions mediate oncogene-induced phenotype of lung cancer cells. (1996)

In vivo and in vitro studies have linked small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cells along a differentiation continuum. The transition of a SCLC toward a NSCLC phenotype is modeled in culture by the simultaneous overexpression of myc and ras genes in cultured SCLC cells. A major phenotypic distinction between SCLC and NSCLC in culture is that SCLC cells usually grow in floating aggregates, whereas NSCLC cells and myc- plus ras-expressing SCLC cells grow as adherent spreading monolayers like other epithelial cells. The present studies examine how myc, ras, cell aggregation, and attachment to laminin may interact to modulate transitions between the SCLC and NSCLC phenotypes. We find that myc-expressing SCLC cells, which normally grow as anchorage-independent cells in plastic flasks, will adhere to laminin and exhibit an epithelial morphology. In this setting, the cells express both NSCLC and SCLC markers, thus resembling a tumor type previously termed NSCLC with neuroendocrine features. Anchorage-dependent SCLC cells simultaneously expressing the myc family and an exogenous ras oncogene move further toward the NSCLC phenotype than the above myc-expressing cells. However, forced suspension of such cells restores the expression of neuroendocrine SCLC features. These studies indicate that cell environment, as much as gene expression events, profoundly affects aspects of the SCLC cell phenotype.
Adding Depth to Cartoons Using Sparse Depth (In)equalities (2010)

Abstract This paper presents a novel interactive approach for adding depth information into hand‐drawn cartoon images and animations. In comparison to previous depth assignment techniques our solution requires minimal user effort and enables creation of consistent pop‐ups in a matter of seconds. Inspired by perceptual studies we formulate a custom tailored optimization framework that tries to mimic the way that a human reconstructs depth information from a single image. Its key advantage is that it completely avoids inputs requiring knowledge of absolute depth and instead uses a set of sparse depth (in)equalities that are much easier to specify. Since these constraints lead to a solution based on quadratic programming that is time consuming to evaluate we propose a simple approximative algorithm yielding similar results with much lower computational overhead. We demonstrate its usefulness in the context of a cartoon animation production pipeline including applications such as enhancement, registration, composition, 3D modelling and stereoscopic display.