gebhart/patrepeval huggingface dataset:
Abstract 645: Preclinical efficacy of AZD8055, an ATP-competitive mammalian target of rapamycin (mTOR) kinase inhibitor, in vitro in clear cell renal cell carcinoma (RCC) (2011)

Abstract Inhibitors of the mTORC1 complex such as the rapamycin analogues temsirolimus and everolimus are approved by the FDA for treatment of advanced renal cell carcinoma. However, objective responses with these agents are infrequent and clinical benefits transient, with the majority of patients eventually developing progressive disease and dying from metastatic disease. Dual mTORC1/2 inhibitors may overcome some of the limitations of rapamycin analogues by suppressing the feedback activation of AKT induced by mTORC1 inhibition. In this study, we investigated the in vitro efficacy of AZD8055, a potent inhibitor of both mTORC1 and mTORC2, in clear cell RCC utilizing 2 von Hippel Lindau (VHL) null clear cell kidney cancer cell lines, UOK139 and UOK140. AZD8055 strongly suppressed mTORC2 signaling in RCC and at concentrations ranging from 50nM-250nM, downregulated pAKTs473 and pmTORs2481 in a concentration-dependent fashion. Phosphorylation of AKTt308 was also diminished in both cell lines at these concentrations. In contrast, rapamycin did not significantly inhibit either mTORC2 signaling or AKTt308 phosphorylation. Both AZD8055 and rapamycin were able to downregulate the mTORC1 substrate pS6; however, only AZD8055 was effective in downregulating p4E-BP1, a critical component of cap-dependent translation that is regulated by mTORC1. The vast majority of clear cell renal tumors are characterized by inactivation of the VHL tumor suppressor gene due to mutation or promoter hypermethylation. One well characterized consequence of VHL inactivation is upregulation of hypoxia inducible factor-2α (HIF-2α), an important mediator of both tumorigenesis and neo-angiogenesis in clear cell RCC. While HIF expression is dependent on mTOR activity, it has been reported that mTORC1 inhibition does not reliably suppress HIF-2α expression; we show that treatment with AZD8055 resulted in significant downregulation of HIF-2α levels in both UOK139 and UOK140, an effect that may be mediated by mTORC2 inhibition. AZD8055 exhibited potent in vitro antitumor activity against clear cell RCC, with an IC50 of 100-150nM in the MTT assay; rapamycin had minimal antitumor activity at these concentrations (IC50 not reached at 10uM). These data demonstrate that AZD8055 is a potent inhibitor of mTORC2 and a more effective inhibitor of downstream mTORC1 targets than rapamycin. Simultaneous mTORC1/2 kinase inhibition may be superior to selective mTORC1 inhibition, and is worthy of clinical evaluation in clear cell RCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 645. doi:10.1158/1538-7445.AM2011-645
Crystal Engineering and Organometallic Architecture (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCrystal Engineering and Organometallic ArchitectureDario Braga, Fabrizia Grepioni, and Gautam R. DesirajuView Author Information Dipartimento di Chimica G. Ciamician, Università di Bologna, Via Selmi 2, 40126 Bologna, Italy, and School of Chemistry, University of Hyderabad, PO Central University, Hyderabad 500 046, India Cite this: Chem. Rev. 1998, 98, 4, 1375–1406Publication Date (Web):May 14, 1998Publication History Received16 June 1997Revised24 February 1998Published online14 May 1998Published inissue 1 June 1998https://pubs.acs.org/doi/10.1021/cr960091bhttps://doi.org/10.1021/cr960091bresearch-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views3720Altmetric-Citations1019LEARN 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 SUBJECTS:Crystal structure,Crystals,Ligands,Metals,Noncovalent interactions Get e-Alerts
Prostatic complications of testosterone replacement therapy (1989)

• The prostatic complications of testosterone replacement therapy have received little clinical attention. We describe three hypogonadal men who had prostatic disease (adenocarcinoma in two) detected in relation to such therapy. Literature review suggests that surveillance for early prostate cancer is appropriate during replacement therapy in men over the age of 50 years. We discuss the selective use of digital rectal examination, transrectal sonography, directed prostate biopsy, and prostate-specific antigen determinations before therapy and in subsequent follow-up in this age group of men during androgen replacement. (<i>Arch Intern Med</i>. 1989;149:2365-2366)
Rapid Detection of Shigella Species in Environmental Sewage by an Immunocapture PCR with Universal Primers (2002)

In the present study, we developed a quick, highly specific method for detection of Shigella species by combining immunocapturing of the bacteria and a universal primer PCR. The method drastically enhances test sensitivity, and it can be used not only for identification of Shigella species in the environment but also for rapid detection of other pathogens.
Virtual electrowetting channels: electronic liquid transport with continuous channel functionality (2010)

Reported is a new mechanism for electronic transport of liquid in virtual channels. These virtual channels are formed by application of voltage to an array of polymer posts. The posts are coated with a conducting electrode and hydrophobic dielectric, and thereby capable of electrowetting. Directional channel formation, as well as splitting and merging, is also demonstrated using specific arrangements of posts. The channel dimensions are approximately 20 microm in cross-section, are scalable, and at the threshold for channel formation the minimum transport speed is approximately 1 mm s(-1). The virtual electrowetting channels are further unique as they can retain any channel geometry even in the absence of voltage. With the addition of arrayed voltage controls, the virtual electrowetting channels have the potential to combine the advantages of programmable electrowetting and continuous channel functionality into a single lab-on-chip platform.
Connective Tissue Growth Factor (IGFBP-rP2) Expression and Regulation in Cultured Bovine Endothelial Cells (1999)

Media from large vessel endothelial cells (pulmonary artery, aorta) contained intact connective tissue growth factor (CTGF) and a dominant 19-kDa band. N-terminal analysis of the 19-kDa band showed sequence corresponding to CTGF amino acid 181-190, suggesting that the 19-kDa band represented a proteolytic fragment of CTGF. Intact CTGF was increased by cAMP but not by transforming growth factor- (TGF). CTGF messenger RNA (mRNA) was not changed by cAMP nor TGF. In two microvessel endothelial cells, mRNA was found at low levels by PCR and Northern analysis, but no CTGF protein was seen on Western analysis. In the microvessel cells, TGF increased and cAMP did not change CTGF mRNA levels, with neither
Evolution of a Complex T Cell Receptor Repertoire during Primary and Recall Bacterial Infection (1998)

The mechanisms underlying the genesis and maintenance of T cell memory remain unclear. In this study, we examined the evolution of a complex, antigen-specific T cell population during the transition from primary effector to memory T cells after Listeria monocytogenes infection. T cell populations specific for listeriolysin O (LLO)91-99, the immunodominant epitope recognized by H2-Kd-restricted T lymphocytes, were directly identified in immune spleens using tetrameric H2-Kd-epitope complexes. The T cell receptor (TCR) Vbeta repertoire of specific T cells was determined by direct, ex vivo staining with a panel of mAbs. We demonstrate that LLO91-99-specific, primary effector T cell populations have a diverse TCR Vbeta repertoire. Analyses of memory T cell populations demonstrated similar TCR diversity. Furthermore, experiments with individual mice demonstrated that primary effector and memory T cells have indistinguishable TCR repertoires. Remarkably, after reinfection with L. monocytogenes, LLO91-99-specific T cells have a narrower TCR repertoire than do primary effector or memory T cells. Thus, our studies show that the TCR repertoire of primary effector T lymphocytes is uniformly transmitted to memory T cells, whereas expansion of memory T cells is selective.
Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis (2010)

The effects of Runx2 in C4-2B/Rx2 dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is therefore an attractive target for the development of novel diagnostic, prognostic and therapeutic approaches to PCa management. Targeting Runx2 may prove more effective than focusing on its individual downstream genes and pathways.
Vanish: increasing data privacy with self-destructing data (2009)

Today’s technical and legal landscape presents formidable challenges to personal data privacy. First, our increasing reliance on Web services causes personal data to be cached, copied, and archived by third parties, often without our knowledge or control. Second, the disclosure of private data has become commonplace due to carelessness, theft, or legal actions. Our research seeks to protect the privacy of past, archived data — such as copies of emails maintained by an email provider — against accidental, malicious, and legal attacks. Specifically, we wish to ensure that all copies of certain data become unreadable after a userspecified time, without any specific action on the part of a user, and even if an attacker obtains both a cached copy of that data and the user’s cryptographic keys and passwords. This paper presents Vanish, a system that meets this challenge through a novel integration of cryptographic techniques with global-scale, P2P, distributed hash tables (DHTs). We implemented a proof-of-concept Vanish prototype to use both the million-plus-node Vuze Bit-Torrent DHT and the restricted-membership OpenDHT. We evaluate experimentally and analytically the functionality, security, and performance properties of Vanish, demonstrating that it is practical to use and meets the privacy-preserving goals described above. We also describe two applications that we prototyped on Vanish: a Firefox plugin for Gmail and other Web sites and a Vanishing File application. 1
Imidazo[1,2-a]pyridines: Orally Active Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor (2012)

Advanced leads of an imidazopyridine series of positive allosteric modulators of the metabotropic glutamate 2 (mGlu2) receptor are reported. The optimization of in vitro ADMET and in vivo pharmacokinetic properties led to the identification of 27o. With good potency and selectivity for the mGlu2 receptor, 27o affected sleep-wake architecture in rats after oral treatment, which we have previously shown to be indicative of mGlu2 receptor-mediated central activity.
Mass Spectrometry of Polymers and Polymer Surfaces (2001)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMass Spectrometry of Polymers and Polymer SurfacesS. D. HantonView Author Information Air Products and Chemicals, Incorporated, Allentown, Pennsylvania 18195 Cite this: Chem. Rev. 2001, 101, 2, 527–570Publication Date (Web):January 27, 2001Publication History Received4 April 2000Published online27 January 2001Published inissue 1 February 2001https://doi.org/10.1021/cr9901081Copyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views8305Altmetric-Citations403LEARN 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 Read OnlinePDF (1 MB) Get e-AlertscloseSUBJECTS:Ions,Mass spectrometry,Materials,Oligomers,Polymers Get e-Alerts
Erythrocyte antioxidant enzymes in Parkinson's disease. (2005)

Results of the present study showed involvement of oxidative stress as one of the risk factors, which can initiate and/or promote neurodegeneration in PD and was correlated to the severity of the disease.
Allogeneic non-T spleen cells restore the responsiveness of normal T cell clones stimulated with antigen and chemically modified antigen-presenting cells. (1988)

Stimulation of IL-2-producing T cell clones with chemically modified APC and Ag induces a state of proliferative unresponsiveness, i.e., subsequent stimulation with normal APC and Ag fails to elicit IL-2 production. One possible effect of chemical modification on the APC is the destruction of its ability to provide costimulatory signals. To test this, various potential costimulators were added to T cells at the time of exposure to Ag and chemically modified APC. None of the cytokines tested, including IL-1, had a positive effect; however, addition of allogeneic spleen cells allowed a T cell proliferative response and prevented the induction of subsequent unresponsiveness. Fractionation of the spleen cells showed that low density B cells and macrophages were the best source of costimulatory activity. Allogeneic resting B cells provided some costimulatory activity and resting T cells, none at all. Attempts to mimic costimulatory signals with the phorbol ester PMA were only partially successful. PMA prevented the induction of T cell unresponsiveness but failed to allow T cell proliferation in response to Ag plus chemically modified APC. Our results suggest that IL-2 production by normal T cell clones is dependent not only on T cell receptor occupancy, but also on short range costimulatory signals that are provided to different degrees by various non-T accessory cells.
Predicting Peptide-Mediated Interactions on a Genome-Wide Scale (2015)

We describe a method to predict protein-protein interactions (PPIs) formed between structured domains and short peptide motifs. We take an integrative approach based on consensus patterns of known motifs in databases, structures of domain-motif complexes from the PDB and various sources of non-structural evidence. We combine this set of clues using a Bayesian classifier that reports the likelihood of an interaction and obtain significantly improved prediction performance when compared to individual sources of evidence and to previously reported algorithms. Our Bayesian approach was integrated into PrePPI, a structure-based PPI prediction method that, so far, has been limited to interactions formed between two structured domains. Around 80,000 new domain-motif mediated interactions were predicted, thus enhancing PrePPI's coverage of the human protein interactome.
Pigment dispersion in frog melanophores can be induced by a phorbol ester or stimulation of a recombinant receptor that activates phospholipase C. (1993)

Pigment dispersion in frog melanophores is classically mediated by receptors that activate protein kinase A via an elevation of intracellular cyclic AMP. Here, 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, is found to induce pigment dispersion. To demonstrate that an increase in cAMP is not required for the melanosome movement, a murine bombesin receptor was expressed in the melanophores. When these cells were treated with bombesin, they accumulated intracellular inositol phosphates but not cAMP and dispersed their pigment. Four agonists, one partial agonist, and two antagonists for the bombesin receptor were compared for their ability to induce or block bombesin-induced pigment dispersion. In all cases, the degree of pigment dispersion followed simple equilibrium reactions. The resulting dose-response curves allowed for the determination of the effective concentration for half-maximal pigment dispersion (EC50) or half-maximal inhibition of bombesin-stimulated pigment dispersion (IC50) for the peptides. As the pigment dispersion assay can rapidly evaluate chemicals for their effects on receptors that activate phospholipase C via a functional assay, it has potential utility for investigations of ligand-receptor interactions and for massive drug screening.
Ammonothermal Synthesis of Cubic Gallium Nitride (1999)

Cubic gallium nitride (zinc blende type) was formed by reactions of Ga, gallium iodides, and gallium imide−iodides in supercritical ammonia under acidic conditions above 250 °C. Solvothermal transport and recrystallization of c-GaN occurred above 440 °C.
Which Left Ventricular Function Is Impaired Earlier in the Evolution of Diabetic Cardiomyopathy?: An echocardiographic study of young type I diabetic patients (1994)

Our findings indicate that myocardial damage in patients with diabetes affects diastolic function before systolic function. The intentional assessment of diastolic function is advisable for early detection of LV dysfunction before clinical symptoms appear, with follow-up to detect further deterioration of cardiac status.
Noncompetitive Immunoassay of Small Analytes at the Femtomolar Level by Affinity Probe Capillary Electrophoresis:  Direct Analysis of Digoxin Using a Uniform-Labeled scFv Immunoreagent (2000)

A general method for noncompetitive immunoassay of small analytes using affinity probe capillary electrophoresis (APCE) is demonstrated using digoxin as a model analyte. A uniform immunoreagent was prepared from a single-chain antibody (scFv) gene specific for digoxin. Site-directed mutagenesis introduced a unique cysteine residue for uniform labeling with a thiol-reactive fluorochrome. After expression in E. coli, the scFv was purified by immobilized metal affinity chromatography (IMAC) using an added C-terminal 6-histidine sequence. The protein was renatured and labeled while immobilized on the IMAC resin. After 0.02-microm filtration to remove microaggregates, the resulting reagent was highly uniform and stable at -12 degrees C for at least 1 year. Three formats of APCE using the scFv reagent were explored. A "mix-and-inject" assay optimized for low detection limits demonstrated analysis of 10 pM digoxin in aqueous standard solutions in 10 min. A rapid mix-and-inject format in a short capillary allowed detection of 1 nM digoxin in 1 min. Digoxin samples in serum and urine were injected directly after 10-fold dilution. In combination with solid-phase extraction, 400 fM digoxin was detected in 1 mL of serum. Including solid-phase extraction, reproducibility was within 2.5%, and the linear range was 3 orders of magnitude. The strategy adopted in this paper should be of general use in the low-level analysis of small analytes.
PP.13.12 (2015)

Objective: Atherosclerosis and hypertension are commonly observed in patients and strongly associated with increased mortality. Recently, we have shown that chronic Ang-(1–7) treatment acting through the Mas receptor improves vascular dysfunction in atherosclerotic apolipoprotein E-deficient (apoE-/-) mice. To test whether the G-protein-coupled Mas receptors plays also role in the development of atherosclerosis and abdominal aortic aneurysm (AAA), we generated apoE/Mas receptor deficient (apoE-/-/Mas-/-). Design and method: ApoE-/- and apoE-/-/Mas-/- mice fed on a lipid-rich Western diet were treated via osmotic minipumps with either saline or Ang-(1–7) (82 μg•kg(-1) •h(-1)) for 6 weeks. Aortae were stained with red oil and quantified for atherosclerosis. To better recognize the meaning of Mas receptors in the formation of AAA, both mice were infused with angiotensin II (AngII) (1000 ng/kg/min) for 4 weeks. Maximal external abdominal aortic diameter was measured by ultrasound in vivo and ex vivo on formalin fixed tissues. Results: Atherosclerosis was significantly increased in apoE-/-/Mas-/- mice compared to apoE-/- (relative lesion area of the aortic arch: 38.7 ± 3.0 vs. 25.4 ± 2.0%; P < 0.01; specific lesion area 11.7 ± 0.9 vs. 8.1 ± 1.0 mm2 P < 0.01). In contrast, chronic Ang-(1–7) infusion significantly attenuates atherosclerotic leasions in apoe-/- (apoE-/-/ vs. apoE-/- + Ang-(1–7): 25.4 ± 2.0 vs. 11.1 ± 2.6% P < 0.01 and 8.1 ± 1.0 vs. 3.1 ± 0.8 mm2 P < 0.01) but not in apoE-/-/Mas-/- mice (apoE-/-/Mas-/- vs. apoE-/-/Mas-/ + Ang-(1–7): 38.7 ± 3.0 vs. 38.0 ± 14.2% and 11.7 ± 0.9 vs. 11.4 ± 5.0 mm2). During chronic Ang II infusion, the incidence of AAA was increased in apoE-/-/Mas-/- compared to the apoE-/- mice (75% vs. 45% n = 8–11). Moreover, the maximal external abdominal aortic diameter was significantly larger in Ang II treated apoE-/-/Mas-/- mice compared to Ang II treated apoE-/- mice (2.24 ± 0.22 mm vs. 1.51 ± 0.17 mm; P < 0.05). Interestingly, blood pressures and cardiac hypertrophy did not differ during chronic AngII infusions in apoE-/- and apoE-/-/Mas-/- mice suggesting that the incidence and the extend of AAA seemed to be blood pressure independent. Conclusions: These findings indicate an important role for the Mas receptors in the progress of atherosclerosis and AAAs. Chronic Ang-(1–7) infusion stimulates the Mas receptor and attenuates atherosclerosis. Further research is required to investigate the underlying mechanisms and the specific cell type responsible for these findings.
Biochemical Targets of the Isoflavone Genistein in Tumor Cell Lines (1995)

Dietary intake of soy is associated with a decreased risk of both hormone-dependent and hormone-independent cancers. It has been proposed that genistein, the predominant isoflavone in soy foods, is responsible for this effect. In this review, the potential mechanisms of action of genistein at the cellular level are critically examined to determine which are physiologically relevant. We concluded that (i) only those mechanisms requiring genistein concentrations below 5 micrograms/ml (18 microM) should be considered, and (ii) more emphasis should be placed on the effects of genistein on events in normal cells or those from the early stages of the cancer process.
Modulated Inflammation by Injection of High-Mobility Group Box 1 Recovers Post-Infarction Chronically Failing Heart (2008)

HMGB1 injection modulated the local inflammation in the postinfarction chronically failing myocardium, particularly via reducing the accumulation of dendritic cells. This modulated inflammation resulted in attenuated fibrosis and cardiomyocyte hypertrophy, which thereby improved global cardiac function. These data suggest that HMGB1 may be valuable for the chronic heart failure treatment.