gebhart/patrepeval huggingface dataset:
Modulation of Melphalan Resistance in Glioma Cells with a Peripheral Benzodiazepine Receptor Ligand−Melphalan Conjugate (1997)

Peripheral benzodiazepine receptors (PBRs) are located on the outer membrane of mitochondria, and their density is increased in brain tumors. Thus, they may serve as a unique intracellular and selective target for antineoplastic agents. A PBR ligand-melphalan conjugate (PBR-MEL) was synthesized and evaluated for cytotoxicity and affinity for PBRs. PBR-MEL (9) (i.e., 670 amu) was synthesized by coupling of two key intermediates: 4-[bis(2-chloroethyl)-amino]-L-phenylalanine ethyl ester trifluoroacetate (6) and 1-(3'-carboxylpropyl)-7-chloro-1,3- dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one (8). On the basis of receptor-binding displacement assays in rat brain and glioma cells, 9 had appreciable binding affinity and displaced a prototypical PBR ligand, Ro 5-4864, with IC50 values between 289 and 390 nM. 9 displayed differential cytotoxicity to a variety of rat and human brain tumor cell lines. In some of the cell lines tested including rat and human melphalan-resistant cell lines, 9 demonstrated appreciable cytotoxicity with IC50 values in the micromolar range, lower than that of melphalan alone. The enhanced activity of 9 may reflect increased membrane permeability, increased intracellular retention, or modulation of melphalan's mechanisms of resistance. The combined data support additional studies to determine how 9 may modulate melphalan resistance, its mechanisms of action, and if target selectivity can be achieved in in vivo glioma models.
Human epididymal secreted protein CD52 on ejaculated spermatozoa: correlations with semen characteristics and the effect of its antibody (1997)

CD52 is a glycosylphosphatidylinositol-anchored glycoprotein secreted by the epididymis where it is incorporated into sperm membranes. The antigen is common to spermatozoa and lymphocytes, and its role is not known. Quantitative analysis using immunostaining with the monoclonal antibody CAMPATH-1G and flow cytometry indicated positive signals from approximately 80% of viable, washed ejaculated spermatozoa. Staining intensity increased after capacitation overnight, and decreased after short incubation with high density lipoprotein. After incubation of Percoll-washed spermatozoa with CAMPATH-1G, motility was reduced from 83 to 74% after 5 min and from 73 to 52% after 3.5 h. Swimming velocities were reduced by approximately 30% and linearity by 15% in 5 min, but no further decreases were observed over 3.5 h. After 20 min incubation with the antibody, cell viability was decreased by 10 and 20% in freshly washed and capacitated spermatozoa respectively. Comparison of fertile and infertile patients revealed no difference in the percentages of immunostained spermatozoa or in staining intensity and there were no differences in sperm labelling between normozoospermia and teratozoospermia. Compared with normozoospermia, percentages of stained spermatozoa were lower by 20 and 27% in asthenozoospermia and oligozoospermia respectively, whereas staining intensity in asthenozoospermia was less than half that in oligozoospermia. The correlation of percentages of stained spermatozoa with percentages of motile cells suggests the involvement of epididymal CD52 in the maturation of sperm function.
Exome sequencing: Dual role as a discovery and diagnostic tool (2011)

Recent developments in high-throughput sequence capture methods and next-generation sequencing technologies have now made exome sequencing a viable approach to elucidate the genetic basis of Mendelian disorders with hitherto unknown etiology. In addition, exome sequencing is increasingly being employed as a diagnostic tool for specific genetic diseases, particularly in the context of those disorders characterized by significant genetic and phenotypic heterogeneity, for example, Charcot-Marie-Tooth disease and congenital disorders of glycosylation. Such disorders are challenging to interrogate with conventional polymerase chain reaction-Sanger sequencing methods, because of the inherent difficulty in prioritizing candidate genes for diagnostic testing. Here, we explore the value of exome sequencing as a diagnostic tool and discuss whether exome sequencing can come to serve a dual role in diagnosis and discovery. We summarize the current status of exome sequencing, the technical challenges facing it, and its adaptation to diagnostics, and make recommendations for the use of exome sequencing as a routine diagnostic tool. Finally, we discuss pertinent ethical concerns, such as the use of exome sequencing data, originally generated in a diagnostic context, in research investigations.
Expression of GD2 ganglioside by untreated primary human neuroblastomas. (1986)

Primary neuroblastomas obtained before therapy from 36 patients were studied to determine the frequency of tumors expressing a specific glycosphingolipid, GD2 ganglioside. Total tissue gangliosides were purified by a new partition method, quantitated, and analyzed by high-performance thin-layer chromatography. All 36 neuroblastoma tumors, representing all clinical stages, contained GD2 ganglioside. The mean relative and absolute concentrations of GD2 were substantial (12% of the total tissue gangliosides and 50 nmol/g of tissue) and were independent of the clinical stage of the tumor. In contrast, 6 samples of related but more differentiated tumors (ganglioneuroblastoma and ganglioneuroma) had little or no detectable GD2 (less than or equal to 1.5% of total gangliosides and less than or equal to 4 nmol/g of tissue). These results suggest that GD2 is a sensitive marker for neuroblastoma tissue and may be an excellent target antigen for immunotherapy of this tumor.
Collagen VI deficiency induces early onset myopathy in the mouse: an animal model for Bethlem myopathy (1998)

To gain insight into the function of type VI collagen, the col6a1 gene was inactivated by targeted gene disruption in the mouse. The homozygous mutants lacked collagen VI in the tissues and showed histological features of myopathy such as fiber necrosis and phagocytosis and a pronounced variation in the fiber diameter. Muscles also showed signs of stimulated regeneration of fibers. Necrotic fibers were particularly frequent in the diaphragm at all ages examined. Similar, although milder, alterations were detected in heterozygous mutant mice, indicating haploinsufficiency of the col6a1 gene function. The data led us to conclude that collagen VI is necessary for maintenance of the integrity of muscle fibers and that the col6a1 -deficient mouse can be considered an animal model of Bethlem myopathy.
Modular Synthesis of Cyclic Peptidomimetics Inspired by γ-Turns (2005)

[reaction: see text] A series of peptidomimetics based on a gamma-turn motif were synthesized using a modular approach, in which N-protected piperidones were reacted with a selection of 2-hydroxyalkyl azides derived from common l-amino acids. Hydrolysis of the initially formed iminium ethers afforded the targeted series of substituted 1,4-diazepin-5-ones.
Inhibition of IκB Kinase by a New Class of Retinoid-Related Anticancer Agents That Induce Apoptosis (2003)

The transcription factor NF-kappaB is overexpressed or constitutively activated in many cancer cells, where it induces expression of antiapoptotic genes correlating with resistance to anticancer therapies. Small molecules that inhibit the NF-kappaB signaling pathway could therefore be used to induce apoptosis in NF-kappaB-overexpressing tumors and potentially serve as anticancer agents. We found that retinoid antagonist MX781 inhibited the activation of NF-kappaB-dependent transcriptional activity in different tumor cell lines. MX781 was able to completely inhibit tumor necrosis factor alpha-mediated activation of IkappaB kinase (IKK), the upstream regulator of NF-kappaB. Inhibition of IKK activity resulted from direct binding of MX781 to the kinase, as demonstrated by in vitro inhibition studies. Two other molecules, MX3350-1 and CD2325, which are retinoic acid receptor gamma-selective agonists, were capable of inhibiting IKK in vitro, although they exerted variable inhibition of IKK and NF-kappaB activities in intact cells in a cell type-specific manner. However, N-(4-hydroxyphenyl)-retinamide, another apoptosis-inducing retinoid, and retinoic acid as well as other nonapoptotic retinoids did not inhibit IKK. Inhibition of IKK by the retinoid-related compounds and other small molecules correlated with reduced cell proliferation and increased apoptosis. Reduced cell viability was also observed after overexpression of an IKKbeta kinase-dead mutant or the IkappaBalpha superrepressor. The induction of apoptosis by the retinoid-related molecules that inhibited IKK was dependent on caspase activity but independent of the retinoid receptors. Thus, the presence of an excess of retinoic acid or a retinoid antagonist did not prevent the inhibition of IKK activation by MX781 and CD2325, indicating a retinoid receptor-independent mechanism of action.
Microwave Characterization of Josephson Junction Arrays: Implementing a Low Loss Superinductance (2012)

We have measured the plasma resonances of an array of Josephson junctions in the regime E(J)>>E(C), up to the ninth harmonic by incorporating it as part of a resonator capacitively coupled to a coplanar waveguide. From the characteristics of the resonances, we infer the successful implementation of a superinductance, an electrical element with a nondissipative impedance greater than the resistance quantum [R(Q)=h/(2e)(2) is approximately equal to 6.5 kΩ] at microwave frequencies. Such an element is crucial for preserving the quantum coherence in circuits exploiting large fluctuations of the superconducting phase. Our results show internal losses less than 20 ppm, self-resonant frequencies greater than 10 GHz, and phase-slip rates less than 1 mHz, enabling direct application of such arrays for quantum information and metrology. Arrays with a loop geometry also demonstrate a new manifestation of flux quantization in a dispersive analog of the Little-Parks effect.
Asymmetric synthesis of chiral sulfoxides. II. Intramolecular oxygen to nitrogen sulfinyl migration (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric synthesis of chiral sulfoxides. II. Intramolecular oxygen to nitrogen sulfinyl migrationFred. Wudl and Thomas B. K. LeeCite this: J. Am. Chem. Soc. 1973, 95, 19, 6349–6358Publication Date (Print):September 1, 1973Publication History Published online1 May 2002Published inissue 1 September 1973https://pubs.acs.org/doi/10.1021/ja00800a031https://doi.org/10.1021/ja00800a031research-articleACS PublicationsRequest reuse permissionsArticle Views451Altmetric-Citations73LEARN 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
A Survey of Available Corpora For Building Data-Driven Dialogue Systems: The Journal Version (2018)

During the past decade, several areas of speech and language understanding have witnessed substantial breakthroughs from the use of data-driven models. In the area of dialogue systems, the trend is less obvious, and most practical systems are still built through significant engineering and expert knowledge. Nevertheless, several recent results suggest that data-driven approaches are feasible and quite promising. To facilitate research in this area, we have carried out a wide survey of publicly available datasets suitable for data-driven learning of dialogue systems. We discuss important characteristics of these datasets, how they can be used to learn diverse dialogue strategies, and their other potential uses. We also examine methods for transfer learning between datasets and the use of external knowledge. Finally, we discuss appropriate choice of evaluation metrics for the learning objective.
Signal alignment for two-cell CR networks (2013)

In this paper, we study interference-free uplink transmission for two-cell multiple-antenna cognitive radio (CR) networks. We consider a scenario that the primary user (PU) transmission is based on orthogonal frequency-division multiplexing (OFDM) and the nullspace generated by the cyclic-prefix (CP) can be used for CR transmission using Vandermonde-subspace frequency division multiplexing (VFDM). Besides interference to the PU system, we will take intra- and inter-cell interference within CR networks into consideration. A signal alignment scheme will be developed to protect the PU transmission while aligning inter-cell interference into a lower dimensional-subspace. When the interference signals are perfectly aligned, the number of interference-free symbols that can be transmitted by the whole CR network will increase with the number of CR users. Numerical results show significant performance gain can be obtained by using the proposed scheme.
p-Hydroxyphenacyl Phototriggers: The Reactive Excited State of Phosphate Photorelease (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTp-Hydroxyphenacyl Phototriggers: The Reactive Excited State of Phosphate PhotoreleasePeter G. Conrad, Richard S. Givens, Bruno Hellrung, Cheruvallil S. Rajesh, Markus Ramseier, and Jakob WirzView Author Information Institut für Physikalische Chemie der Universität Basel Klingelbergstrasse 80, CH-4056 Basel, Switzerland Department of Chemistry, University of Kansas Lawrence, Kansas 66045 Cite this: J. Am. Chem. Soc. 2000, 122, 38, 9346–9347Publication Date (Web):September 9, 2000Publication History Received31 March 2000Revised11 July 2000Published online9 September 2000Published inissue 1 September 2000https://pubs.acs.org/doi/10.1021/ja001134fhttps://doi.org/10.1021/ja001134frapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views807Altmetric-Citations67LEARN 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:Ethyl groups,Ionization,Lithium iron phosphate,Phosphates,Quantum yield Get e-Alerts
Design, Synthesis, and Structure-Activity Relationship of Novel Dinucleotide Analogs as Agents against Herpes and Human Immunodeficiency Viruses (1995)

A new acyclic nucleoside phosphonate (13) containing an adenine moiety was synthesized, which acted as an excellent inhibitor of calf mucosal adenosine deaminase. This inhibitory property allows it to exert great synergistic effect on certain antiviral agents (e.g., ara-A, 37). Phosphonate 13 was not phosphorylated by the bovine brain guanylate kinase nor by 5-phosphoribosyl 1-pyrophosphate synthetase. Syntheses of biologically active nucleotide phosphonate 40 and its phosphonoamidate derivative 42 were accomplished, which showed remarkable activity against herpes viruses and exhibited low host cell toxicity. 3'-Azido-nucleoside phosphonate 20 and 3'-fluoronucleoside phosphonate 32, as well as the corresponding dinucleotide analogs 47 and 48, and their respective phosphonoamidates 53-56 were also synthesized as new compounds, among which phosphonoamidates 53-56 showed potent activity against human immunodeficiency virus. Phosphonoamidates 55 and 56 bearing a methyl D-alaninate moiety exhibited less cellular toxicity than 53 and 54 bearing a methyl L-alaninate moiety. Nucleotide phosphonate 40 as well as dinucleotide phosphonates 47 and 48 were found susceptible to degradation by phosphodiesterases. Their respective phosphonoamidates 42 and 53-56, however, were completely resistant to snake venom and spleen enzymes.
Systematic Review: Anti–Epidermal Growth Factor Receptor Treatment Effect Modification by KRAS Mutations in Advanced Colorectal Cancer (2011)

Agency for Healthcare Research and Quality.
Alkali metal reduction studies of cis- and trans-bicyclo[6.1.0]nona-2,4,6-trienes in liquid ammonia. Evidence for the high basicity of monohomocyclooctatetraene dianions (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlkali metal reduction studies of cis- and trans-bicyclo[6.1.0]nona-2,4,6-trienes in liquid ammonia. Evidence for the high basicity of monohomocyclooctatetraene dianionsSteven V. Ley and Leo A. PaquetteCite this: J. Am. Chem. Soc. 1974, 96, 21, 6670–6679Publication Date (Print):October 1, 1974Publication History Published online1 May 2002Published inissue 1 October 1974https://pubs.acs.org/doi/10.1021/ja00828a021https://doi.org/10.1021/ja00828a021research-articleACS PublicationsRequest reuse permissionsArticle Views265Altmetric-Citations17LEARN 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
Left atrial isolation: new technique for the treatment of supraventricular arrhythmias. (1980)

Surgical management of refractory ectopic supraventricular tachycardia arising in the left atrium requires cryoablation of the bundle of His and insertion of a permanent ventricular pacemaker. This study was designed to develop a technique to isolate the left atrium electrically from the remainder of the heart, so that an artificial pacemaking system would be unnecessary. Ten adult dogs were subjected to cardiopulmonary bypass and a standard left atriotomy was extended anteriorly across the mitral valve anulus between the right and left fibrous trigones. Posteriorly, the atriotomy was extended across the mitral valve anulus just to the left of the posterior crux and interatrial septum. The muscular interatrial fibers accompanying the coronary sinus were cryoablated at -60 degrees C for 2 minutes. Postoperatively, all animals remained in normal sinus rhythm. Rapid left atrial pacing did not affect the rate or rhythm of the remainder of the heart. Preliminary hemodynamic measurements suggest that loss of the synchronous left atrial "kick" does not significantly affect left ventricular preload, afterload, or cardiac output. This technique offers an alternative to the current surgical approach for management of refractory ectopic supraventricular tachycardia arising in the left atrium.
New and Emerging Proteomic Techniques (2006)

Leading researchers and innovators describe in step-by-step detail the latest techniques that promise to significantly impact the practice of proteomics, as well as its success in developing novel cli
Evaluation of Dust Palliatives for Unpaved Roads in Arid Climates (2006)

An evaluation of commercial and experimental dust palliatives was conducted to determine their effectiveness for mitigating fugitive dust on roads in arid climates. Several types of chemicals were tested including polymer emulsions, lignosulfonates, chloride salts, synthetic fluids, an asphalt emulsion, a polysaccharide solution, a polyacrylamide, and a guar gum. Each product was placed in an individual test section at a rate of 3.8L∕m2 using an admix construction method (grade/spray/till/compact/spray). Fourteen test sections were constructed and observed at 30-day intervals to monitor product performance. Data from both stationary and mobile particle collectors were analyzed to determine the ability of each product to suppress dust for extended periods. Several products are recommended for use on roads in arid climates as a result of this evaluation.
Acidic pH reduces VEGF-mediated endothelial cell responses by downregulation of VEGFR-2; relevance for anti-angiogenic therapies (2016)

Anti-angiogenic treatments targeting the vascular endothelial growth factor or its receptors have shown clinical benefits. However, impact on long-term survival remains limited. Solid tumors display an acidic microenvironment that profoundly influences their biology. Consequences of acidity on endothelial cells and anti-angiogenic therapies remain poorly characterized and hence are the focus of this study. We found that exposing endothelial cells to acidic extracellular pH resulted in reduced cell proliferation and migration. Also, whereas VEGF increased endothelial cell proliferation and survival at pH 7.4, it had no effect at pH 6.4. Furthermore, in acidic conditions, stimulation of endothelial cells with VEGF did not result in activation of downstream signaling pathways such as AKT. At a molecular level, acidity significantly decreased the expression of VEGFR-2 by endothelial cells. Consequently, anti-angiogenic therapies that target VEGFR-2 such as sunitinib and sorafenib failed to block endothelial cell proliferation in acidic conditions. In vivo, neutralizing tumor acidity with sodium bicarbonate increased the percentage of endothelial cells expressing VEGFR-2 in tumor xenografts. Furthermore, combining sodium bicarbonate with sunitinib provided stronger anti-cancer activity than either treatment alone. Histological analysis showed that sunitinib had a stronger anti-angiogenic effect when combined with sodium bicarbonate. Overall, our results show that endothelial cells prosper independently of VEGF in acidic conditions partly as a consequence of decreased VEGFR-2 expression. They further suggest that strategies aiming to raise intratumoral pH can improve the efficacy of anti-VEGF treatments.
Enzyme linked immunosorbent assay (ELISA) for the detection of antibodies to porcine cytomegalovirus. (1982)

The ELISA and indirect immunofluorescence test were compared on 56 porcine sera which were tested for antibodies to porcine cytomegalovirus. Viral antigens were prepared in cells of a pig fallopian tube line. The ELISA was found to be a sensitive reproducible and practical test to measure specific antibodies to this infection.