gebhart/patrepeval huggingface dataset:
SAT-311 Role of SREBP in Regulation of Corticotroph Tumor ACTH Secretion and Cell Proliferation (2020)

Abstract Cushing Disease (CD) is a life-threatening condition with suboptimal medical treatment. To identify drugs that not only inhibit ACTH secretion to attain eucortisolemia but also inhibit tumor growth, we conducted a high throughput screen employing a novel “gain of signal” ACTH AlphaLISA assay. From a kinase inhibitor library containing 430 compounds, we identified the dual PI3K/HDAC inhibitor, CUDC-907, as a potent inhibitor of both in vitro and in vivo corticotroph tumor ACTH secretion and growth. By stepwise comparison of CUDC-907 with mono-functional PI3K and HDAC inhibitors, we demonstrated that CUDC-907 exerts its inhibitory effect on ACTH secretion primarily through its inhibition of HDAC activity at the POMC transcriptional level; while PI3K-mediated inhibition of corticotroph cell viability further contributes to reduced ACTH secretion. We also used RNA-seq to characterize the global transcriptiome changes associated with CUDC-907 treatment. Hierarchical clustering showed that 1432 differentially expressed genes (DEGs, p≤0.05 and fold-change≥1.5) were altered by CUDC-907 treatment in comparison to the vehicle-treated control cells. Gene ontology (GO) analysis of 456 downregulated and 976 upregulated DEGs revealed that the most enriched biological processes were cholesterol biosynthesis (GO:0006695, p=1.977e-17) and the type I interferon signaling pathway (GO: 0060337, p=4.928e-7) respectively. Further analysis demonstrated downregulation of the membrane-bound transcription factor sterol regulatory element binding proteins (SREBPs). Downregulation of SREBP-2 by CUDC-907 as well as the several other target enzymes in the cholesterol biosynthesis and uptake pathway including IDI2, NSDHL, MVD, and HMGCR, was confirmed by real-time PCR. To further characterize a role for SREBP-2 in regulation of corticotroph tumor ACTH secretion and proliferation, we employed siRNA targeting endogenous SREBP-2 (SREBP-2 mRNA, Control vs. siRNA 1±0.03 vs. 0.6±0.08, p&amp;lt;0.05), and demonstrated that knockdown of SREBP-2 not only inhibited POMC mRNA expression (POMC mRNA, 1±0.03 vs. 0.7±0.01, p&amp;lt;0.01), and ACTH secretion (ACTH (ng/mL) 29±0.4 vs. 23±0.3, p&amp;lt;0.005), but also suppressed cell proliferation (Relative Proliferation Rate, 1±0.01 vs. 0.7±0.01, p&amp;lt;0.005). This was further confirmed by overexpression of cleaved mature SREBP-2, which led to increased POMC expression and cell proliferation. We demonstrate for the first time the role of the SREBP-mediated cholesterol biosynthesis pathway in regulation of corticotroph tumor POMC regulation and growth. Our studies identify SREBP and cholesterol biosynthesis as a therapeutic target in CD.
Safety Evaluation of Vaccine Adjuvants (2006)

This chapter contains sections titled: Introduction General Considerations Mechanisms behind Adjuvant Side Effects Safety Aspects of Adjuvants Used in Practical Vaccination Safety Requirements for Future Adjuvants Assays for Testing Adjuvant Safety Conclusions Acknowledgments References
Programming model alternatives for disconnected business applications (2006)

In connected environments, various programming models exist to facilitate the development of business applications with critical properties such as persistence, data sharing, transactions, and security. In disconnected environments, the programming models must address other issues as well, such as how to merge the work performed while disconnected from other concurrent work. Among existing programming models, a transparent model that uses a method-replay approach is particularly promising. A comparison of programming model semantics suggests that method replay is superior to other approaches. We evaluate via three criteria: conflict footprint size, client-server application divergence, and transactional semantics.
Abstract 5512: Mechanisms of inhibition of cancer cell growth and metastasis by novel small molecule compounds. (2013)

Abstract The molecular complexity of cancers and therapy-associated side effects often limit effectiveness of many therapies, and warrant development of new agents for specific molecular targets while minimizing the off-target effects. Thus, our goal is to develop novel, safer and effective anti-cancer therapies on the basis of cell growth and survival inhibiting functions of an apoptosis regulatory protein, termed CARP-1. CARP-1 was identified by us as a novel target of select chemotherapy (adriamycin, etoposide, or Iressa)-dependent human breast cancer cell growth suppression. By conducting the high-throughput screening of chemical libraries, we identified a number of novel, small molecule compounds called CARP-1 Functional Mimetics (CFMs). MTT assay results showed that CFMs, as well as quinazoline analogues of CFMs, inhibited growth of a variety of cancer cells, including the drug-resistant breast cancer cell line MDA-MB 468, without affecting growth of immortalized mammary epithelial cells. Results of MTT assay indicated also that CFM-4 (1(2-chlorobenzyl)-5′-phenyl-3′H-spiro[indoline-3,2′-[1,3,4]thiadiazol]-2-one) was the most potent one. CFMs suppressed cancer cell growth in part by stimulating CARP-1 levels and promoting cell cycle arrest and apoptosis. RT-PCR assay results revealed that CFM-4 induced the extrinsic pathway of apoptosis via upregulation of TRAIL receptors, caspase-8 and caspase-3 which can then cleave multiple cellular proteins, leading to cancer cell death. Cancer-related deaths are often due to spread of cancers to other organ sites (metastasis) that involves invasion and movement of cancer cells through the nearby normal tissue and the lymph and blood vessels to reach other tissues to form secondary tumors. Here we also demonstrate that CFMs impact biological properties of cancer cells by inhibiting their movement and invasion through the membranes coated with the extra-cellular matrix. CFMs also inhibited abilities of cancer cells to grow as colonies in soft-agar. These proof-of-concept studies suggest that CFMs could induce cancer cell apoptosis and effectively inhibit migration and tumor-forming abilities of cancer cells. Thus CFMs or their analogues have potential as anti-cancer agents to target cancer cell proliferation, survival, migration, invasion and metastasis, and provide a strong basis for their development as anti-cancer agents. Citation Format: Abdelkader E. Ashour, Vino T. Cheryan, Shazia Jamal, Ahmed M. Alafeefy, Khairy M. Zoheir, Adel R. Abdallah, Arun K. Rishi. Mechanisms of inhibition of cancer cell growth and metastasis by novel small molecule compounds. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5512. doi:10.1158/1538-7445.AM2013-5512
CarbonTag: A Browser-Based Method for Approximating Energy Consumption of Online Ads (2022)

Energy is today the most critical environmental challenge. The amount of carbon emissions contributing to climate change is significantly influenced by both the production and consumption of energy. Measuring and reducing the energy consumption of services is a crucial step toward reducing adverse environmental effects caused by carbon emissions. Millions of websites rely on online advertisements to generate revenue, with most websites earning most or all of their revenues from ads. As a result, hundreds of billions of online ads are delivered daily to internet users to be rendered in their browsers. Both the delivery and rendering of each ad consume energy. This study investigates how much energy online ads use in the rendering process and offers a way for predicting it as part of rendering the ad. To the best of the authors' knowledge, this is the first study to calculate the energy usage of single advertisements in the rendering process. Our research further introduces different levels of consumption by which online ads can be classified based on energy efficiency. This classification will allow advertisers to add energy efficiency metrics and optimize campaigns towards consuming less possible.
Injecting Humidified and Heated Air to Meet Peak Power Demands (2000)

The method for combustion turbine (CT) power augmentation denoted as CTHAI, (HAI is an acronym for Humidified Air Injection) allows production of additional megawatt-hours (MWH) at low cost during peak demand periods by injecting externally compressed, humidified, and heated air into a CT upstream of the combustors. Energy Storage and Power Consultants (ESPC) and Parsons Infrastructure Group (Parsons) conducted a study for Tennessee Valley Authority (TVA) on the power augmentation of the new PG7121EA combustion turbine by implementing the CTHAI concept. Results of the study demonstrated significant power augmentation and heat rate reduction over the whole range of ambient temperatures, and it was shown to be the most effective at high ambient temperature conditions when reduction in normal unit output is severe (References 1 and 2). Following these developments, TVA, after exhaustive evaluations and analyses of the CTHAI power augmentation technology and other competitive power augmentation options, decided to demonstrate this concept on one of their operating PG7661 gas turbines at the Colbert Power Plant.
MRI Characteristics of Globus Pallidus Infarcts in Isolated Methylmalonic Acidemia (2014)

The staged pattern of globus pallidus infarcts in isolated methylmalonic acidemia suggests a nonuniform, regionally specific cellular susceptibility to metabolic injury, even for patients having milder biochemical phenotypes. In support of this hypothesis, the delineation of lacunar infarcts in the pars reticulata of the substantia nigra, a tissue functionally and histologically identical to the globus pallidus interna, supports the concept of cell-specific pathology.
Orbitofrontal response to drug-related stimuli after heroin administration (2014)

The compulsion to seek and use heroin is frequently driven by stress and craving during drug-cue exposure. Although previous neuroimaging studies have indicated that craving is mediated by increased prefrontal cortex activity, it remains unknown how heroin administration modulates the prefrontal cortex response. This study examines the acute effects of heroin on brain function in heroin-maintained patients. Using a crossover, double-blind, placebo-controlled design, 27 heroin-maintained patients performed functional magnetic resonance imaging 20 minutes after the administration of heroin or placebo (saline) while drug-related and neutral stimuli were presented. Images were processed and analysed with statistical parametric mapping. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Region of interest analyses showed a drug-related cue-associated blood-oxygen-level-dependent activation in the orbitofrontal cortex (OFC) in heroin-dependent patients during both treatment conditions (heroin and placebo). This activation of the OFC was significantly higher after heroin than after placebo administration. These findings may indicate the importance of OFC activity for impulse control and decision-making after regular heroin administration and may emphasize the benefit of the heroin-assisted treatment in heroin dependence.
Initial Evaluation of 11C-DPA-713, a Novel TSPO PET Ligand, in Humans (2009)

Studies in patient populations will help determine whether (11)C-DPA-713 provides better sensitivity for evaluating increased TSPO expression. This initial study in humans shows that (11)C-DPA-713 is a promising ligand for evaluating TSPO binding with PET.
Cover Picture: Differential Protein Assembly on Micropatterned Surfaces with Tailored Molecular and Surface Multivalency (ChemBioChem 9/2006) (2006)

The cover picture shows surface‐plasmon images of a chelator density array on a gold surface, which was employed for differential protein assembly. These arrays were generated by piezo‐dispensing ethanolic thiol solutions into a hydrophobic grid obtained by microcontact printing of an eicosane thiol. By mixing an oligo(ethylene glycol)‐terminated matrix thiol with different concentrations of mono‐ and bivalent chelator thiols, the density of the chelator group was varied in different array elements. The combination of different molecular multivalencies with density‐dependent surface multivalencies yielded differential binding affinities of histidine‐tagged proteins to different array elements. Thus, selective elution with a competitor was achieved from array elements with low binding affinity, which could be subsequently refilled with a different protein. This strategy opens new perspectives for dissection and assembly of multiple protein complexes combined with real‐time, unlabeled detection. Further details can be found in the article by J. Piehler et al. on p. 1325 ff.
Evaluation of Sensitivity on a Capacitive Fingerprint Sensor LSI with a Grounded Wall Structure (2002)

This paper describes the sensitivity to capture fingerprint images on a capacitive fingerprint sensor LSI with a grounded (GND) wall structure. We investigated the sensing characteristics of the fingerprint sensor LSI with the GND wall structure in comparison with that of the conventional planar structure. For the analysis, we proposed circuit models based on the GND wall and the planar structure that take account of the finger's resistance, and calculated numerically the sensing characteristics. The analysis revealed that the resistance of the finger degrades the sensitivity and the GND wall structure provides a high sensitivity because it suppresses the finger's resistance. The experimental results confirmed that the proposed models are appropriate and clarified the effect of the GND wall structure on fingerprint images. Therefore, it is concluded that a fingerprint sensor LSI with the GND wall structure achieves a high sensitivity in capturing clear fingerprint images.
Micro-architectural optimization of a coarse-grained array based baseband processor (2010)

Software Defined Radios (SDR) has been introduced as the ultimate way to achieve the flexibility that is needed to cope with the many emerging wireless standards. A key challenge in the implementation of such radios for mobile terminals is meeting the performance and energy requirements. A suitable architecture template is the first requirement, but finding the optimal instance is as important. This paper shows that it is possible to half the power consumption of an already very energy efficient baseband processor by doing micro-architectural improvements. Overall a 2.6× improvement in energy efficiency and a 2.0× improvement in power consumption has been achieved, resulting in an average power consumption for the baseband processing of 108mW.
5-Amino-oxazepine and 5-Amino-thiazepine Compounds as β-Secretase Antagonists and Methods of Use (2012)

ADVERTISEMENT RETURN TO ISSUEPREVPatent HighlightNEXT5-Amino-oxazepine and 5-Amino-thiazepine Compounds as β-Secretase Antagonists and Methods of UsePatent HighlightBenjamin Blass*View Author Information Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, Pennsylvania 19140*Tel: 215-707-1085. E-mail: [email protected]Cite this: ACS Med. Chem. Lett. 2012, 3, 11, 873–874Publication Date (Web):October 29, 2012Publication History Published online29 October 2012Published inissue 8 November 2012https://pubs.acs.org/doi/10.1021/ml300323yhttps://doi.org/10.1021/ml300323yeditorialACS PublicationsCopyright © 2012 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views920Altmetric-Citations6LEARN 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 PDF (243 KB) Get e-AlertscloseSUBJECTS:Assays,Inhibitors,Nervous system diseases,Peptides and proteins Get e-Alerts
Transmission of Integrase Strand-Transfer Inhibitor Multidrug-Resistant HIV-1: Case Report and Response to Raltegravir-Containing Antiretroviral Therapy (2011)

We report the case of an integrase strand-transfer inhibitor (INI)-resistant and four-drug-class-resistant HIV-1 variant infecting an antiretroviral therapy-naive man. The virus harboured INI drug resistance substitutions (Q148H and G140S) along with multiple reverse transcriptase and protease inhibitor resistance mutations. This case illustrates an emerging need to consider the possibility of acquired INI resistance among newly diagnosed treatment-naive individuals harbouring multidrug-resistant HIV-1.
Data from Secreted CXCL1 Is a Potential Mediator and Marker of the Tumor Invasion of Bladder Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; The purpose of this study was to identify proteins that are potentially involved in the tumor invasion of bladder cancer.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We searched for the candidate proteins by comparing the profiles of secreted proteins among the poorly invasive human bladder carcinoma cell line RT112 and the highly invasive cell line T24. The proteins isolated from cell culture supernatants were identified by shotgun proteomics. We found that CXCL1 is related to the tumor invasion of bladder cancer cells. We also evaluated whether the amount of the chemokine CXCL1 in the urine would be a potential marker for predicting the existence of invasive bladder tumors.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Higher amount of CXCL1 was secreted from highly invasive bladder carcinoma cell lines and this chemokine modulated the invasive ability of those cells &lt;i&gt;in vitro&lt;/i&gt;. It was revealed that CXCL1 regulated the expression of matrix metalloproteinase-13 &lt;i&gt;in vitro&lt;/i&gt; and higher expression of CXCL1 was associated with higher pathologic stages in bladder cancer &lt;i&gt;in vivo&lt;/i&gt;. We also showed that urinary CXCL1 levels were significantly higher in patients with invasive bladder cancer (pT1-4) than those with noninvasive pTa tumors (&lt;i&gt;P&lt;/i&gt; = 0.0028) and normal control (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001). Finally, it was shown that CXCL1 was an independent factor for predicting the bladder cancer with invasive phenotype.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our results suggest that CXCL1 modulates the invasive abilities of bladder cancer cells and this chemokine may be a potential candidate of urinary biomarker for invasive bladder cancer and a possible therapeutic target for preventing tumor invasion.&lt;/p&gt;&lt;/div&gt;
Prepubertal Administration of Estradiol Valerate Disrupts Cyclicity and Leads to Cystic Ovarian Morphology during Adult Life in the Rat: Role of Sympathetic Innervation (2003)

Administration of estradiol valerate (EV) to adult rats leads to anovulation and cystic ovarian morphology. Sympathetic ovarian nerve denervation (SONX) overcomes this disruption. In this study, we determined whether EV administration to juvenile rats prevents achievement of reproductive competence, disrupts cyclicity, and whether this programming is facilitated via activation of the sympathetic nerve input to the ovary. Prepubertal rats were administered 2 mg EV in corn oil or corn oil alone. One half of the animals from each group underwent SONX on d 71 of life. Rats were euthanized on d 91 for determination of serum gonadotropins, progesterone, Delta4 androstenedione, and estradiol concentrations, ovarian norepinephrine (NE), and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) activities and ovarian dynamics. Results revealed that EV administration during juvenile period advanced pubertal onset, suppressed circulating LH, FSH, and Delta4 androstenedione, increased ovarian NE, estradiol, and 3beta-HSD activities, disrupted ovarian dynamics evidenced as absent corpus luteum and presence of ovarian cysts and culminated in anovulation. SONX restored cyclicity in these animals, normalized LH, estradiol, ovarian 3beta-HSD activities, and ovarian dynamics as evidenced by the disappearance of ovarian cysts and appearance of corpus luteum and restored corpus luteum function. These findings provide evidence that EV exposure during juvenile life leads to long-lasting deleterious reproductive consequences via activation of the sympathetic ovarian nerve.
Recognition and treatment of bladder outlet obstruction after sling surgery. (2004)

At the University of Pittsburgh School of Medicine, our experience with urethrolysis over the past several years offered a unique opportunity to assess outcomes after delayed time to urethrolysis. We observed a highly suggestive association between prolonged time to urethrolysis and a greater likelihood of persistent bladder dysfunction. If this observation is corroborated by other studies, it would be prudent to lower our threshold of clinical suspicion to detect bladder outlet obstruction. Videourodynamics testing can be invaluable for making the distinction between outlet obstruction versus de novo urge incontinence. Here, we briefly review the literature on urethrolysis and present the urethrolysis technique utilized at our institution. The article concludes with several challenging and controversial clinical judgment questions asked ofDr Leng by Dr Chancellor.
Resolution Enhancement of UWB Time-Reversal Microwave Imaging in Dispersive Environments (2021)

Time Reversal (TR) techniques allow optimal re- focusing of ultrawideband (UWB) electromagnetic waves in complex propagation environments, due to the invariance of the wave equations. Propagation of electromagnetic waves through dispersive or lossy media breaks this invariance. Consequently, such media degrade the refocusing ability of TR techniques. In this work, we propose a novel algorithm for the enhancement of the UWB TR microwave imaging resolution in dispersive environments. The presented algorithm takes into account the frequency-dependent complex permittivity of the propagation medium across the entire bandwidth of the UWB pulse. Using this complex permittivity, it models the medium-, time-, and frequency- dependent attenuation in the wavelet domain to create inverse filters which compensate for the effects of the attenuation. This is the first algorithm that constructs inverse filters in the wavelet domain using the complex permittivity of the dispersive propagation medium across the entire bandwidth, rather than at a center frequency, of the excitation pulse. We also introduce a smart scaling concept to minimize undesired noise amplification. We apply the proposed method to a practical scenario and exhibit enhancement in the resolution of UWB microwave TR imaging of a simulated brain tumor inside the digital human phantom (DHP).