gebhart/patrepeval huggingface dataset:
Adaptive enrichment designs for clinical trials (2013)

Modern medicine has graduated from broad spectrum treatments to targeted therapeutics. New drugs recognize the recently discovered heterogeneity of many diseases previously considered to be fairly homogeneous. These treatments attack specific genetic pathways which are only dysregulated in some smaller subset of patients with the disease. Often this subset is only rudimentarily understood until well into large-scale clinical trials. As such, standard practice has been to enroll a broad range of patients and run post hoc subset analysis to determine those who may particularly benefit. This unnecessarily exposes many patients to hazardous side effects, and may vastly decrease the efficiency of the trial (especially if only a small subset of patients benefit). In this manuscript, we propose a class of adaptive enrichment designs that allow the eligibility criteria of a trial to be adaptively updated during the trial, restricting entry to patients likely to benefit from the new treatment. We show that our designs both preserve the type 1 error, and in a variety of cases provide a substantial increase in power.
Passage retrieval based on language models (2002)

Previous research has shown that passage-level evidence can bring added benefits to document retrieval when documents are long or span different subject areas. Recent developments in language modeling approach to IR provided a new effective alternative to traditional retrieval models. These two streams of research motivate us to examine the use of passages in a language model framework. This paper reports on experiments using passages in a simple language model and a relevance model, and compares the results with document-based retrieval. Results from the INQUERY search engine, which is not based on a language modeling approach, are also given for comparison. Test data include two heterogeneous and one homogeneous document collections. Our experiments show that passage retrieval is feasible in the language modeling context, and more importantly, it can provide more reliable performance than retrieval based on full documents.
Replication and Predictive Value of SNPs Associated with Melanoma and Pigmentation Traits in a Southern European Case-Control Study (2013)

Overall, our study has validated genetic variants that are likely to contribute to melanoma susceptibility in the Greek population.
The osteotome technique: Part 3--Less invasive methods of elevating the sinus floor. (1994)

Previous articles in The Compendium (February 1994, April 1994) described the features of the osteotome technique. In the initial article, a procedure that uses osteotomes to elevate the floor of the sinus, called the osteotome sinus floor elevation (OSFE), was mentioned. This article provides details and case reports on the OSFE. An enhanced version of the OSFE in which bone is added to the osteotomy will also be presented. The author concludes that the OSFE and the bone-added OSFE techniques are suitable means of altering the floor of the sinus so that in many patients, longer implants can be inserted in a less invasive manner.
Induction and isolation of tumor antigen-specific CD4+ T lymphocytes using sorting signal directed MHC class-II expression (2013)

Meeting abstracts The adoptive transfer of tumor-antigen specific CD8+ T lymphocytes has shown highly promising but somewhat limited benefit in tumor immunotherapy. The poor objective clinical efficacy observed in early studies has been overcome partly by integration of patient preconditioning and
The Investment Climate for the Informal Economy : A Case of Durban, South Africa (2003)

This investment climate of South Africa's informal economy is investigated with special focus on the regulatory environment (taxes and laws), institutions, services (training, financial services and insurance, access to markets), and access to infrastructure and protection from crime. Durban, South Africa's third largest city, is ahead of other cities in responding to the growth of informal work and has been proactive in seeking out ways of creatively supporting informal enterprises.
High-Efficiency Induction of Neural Conversion in Human ESCs and Human Induced Pluripotent Stem Cells with a Single Chemical Inhibitor of Transforming Growth Factor Beta Superfamily Receptors (2010)

Chemical compounds have emerged as powerful tools for modulating ESC functions and deriving induced pluripotent stem cells (iPSCs), but documentation of compound-induced efficient directed differentiation in human ESCs (hESCs) and human iPSC (hiPSCs) is limited. By screening a collection of chemical compounds, we identified compound C (also denoted as dorsomorphin), a protein kinase inhibitor, as a potent regulator of hESC and hiPSC fate decisions. Compound C suppresses mesoderm, endoderm, and trophoectoderm differentiation and induces rapid and high-efficiency neural conversion in both hESCs and hiPSCs, 88.7% and 70.4%, respectively. Interestingly, compound C is ineffective in inducing neural conversion in mouse ESCs (mESCs). Large-scale kinase assay revealed that compound C targets at least seven transforming growth factor beta (TGF-β) superfamily receptors, including both type I and type II receptors, and thereby blocks both the Activin and bone morphogenesis protein (BMP) signaling pathways in hESCs. Dual inhibition of Activin and BMP signaling accounts for the effects of compound C on hESC differentiation and neural conversion. We also identified muscle segment homeobox gene 2 (MSX2) as a downstream target gene of compound C and a key signaling intermediate of the BMP pathway in hESCs. Our findings provide a single-step cost-effective method for efficient derivation of neural progenitor cells in adherent culture from human pluripotent stem cells. Therefore, it will be uniquely suitable for the production of neural progenitor cells in large scale and should facilitate the use of stem cells in drug screening and regenerative medicine and study of early human neural development.
Use of aza-Cope rearrangement-Mannich cyclization reactions to achieve a general entry to Melodinus and Aspidosperma alkaloids. Stereocontrolled total syntheses of (.+-.)-deoxoapodine, (.+-.)-meloscine, and (.+-.)-epimeloscine and a formal synthesis of (.+-.)-1-acetylaspidoalbidine (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUse of aza-Cope rearrangement-Mannich cyclization reactions to achieve a general entry to Melodinus and Aspidosperma alkaloids. Stereocontrolled total syntheses of (.+-.)-deoxoapodine, (.+-.)-meloscine, and (.+-.)-epimeloscine and a formal synthesis of (.+-.)-1-acetylaspidoalbidineLarry E. Overman, Graeme M. Robertson, and Albert J. RobichaudCite this: J. Am. Chem. Soc. 1991, 113, 7, 2598–2610Publication Date (Print):March 1, 1991Publication History Published online1 May 2002Published inissue 1 March 1991https://pubs.acs.org/doi/10.1021/ja00007a038https://doi.org/10.1021/ja00007a038research-articleACS PublicationsRequest reuse permissionsArticle Views2991Altmetric-Citations111LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Additional Minor Diterpene Glycosides from Stevia rebaudiana Bertoni (2013)

Two additional novel minor diterpene glycosides were isolated from the commercial extract of the leaves of Stevia rebaudiana Bertoni. The structures of the new compounds were identified as 13-{β-D-glucopyranosyl-(1 → 2)-O-[β-D-glucopyranosyl-(1 → 3)-β-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {β-D-xylopyranosyl-(1 → 2)-O-[β-D-glucopyranosyl-(1 → 3)]-O-β-D-glucupyranosyl-ester} (1), and 13-{β-D-6-deoxy-glucopyranosyl-(1 → 2)-O-[β-D-glucopyranosyl-(1 → 3)-β-D-glucopyranosyl-oxy} ent-kaur-16-en-19-oic acid {β-D-glucopyranosyl-(1 → 2)-O-[β-D-glucopyranosyl-(1 → 3)-β-D-gluco-pyranosyl-ester} (2), on the basis of extensive 1D (1H- and 13C-) 2D NMR (COSY, HSQC and HMBC) and MS spectroscopic data as well as chemical studies.
The optimal logic depth per pipeline stage is 6 to 8 FO4 inverter delays (2002)

Microprocessor clock frequency has improved by nearly 40% annually over the past decade. This improvement has been provided, in equal measure, by smaller technologies and deeper pipelines. From our study of the SPEC 2000 benchmarks, we find that for a high-performance architecture implemented in 100nm technology, the optimal clock period is approximately 8 fan-out-of-four (FO4) inverter delays for integer benchmarks, comprised of 6 FO4 of useful work and an overhead of about 2 FO4. The optimal clock period for floating-point benchmarks is 6 FO4. We find these optimal points to be insensitive to latch and clock skew overheads. Our study indicates that further pipelining can at best improve performance of integer programs by a factor of 2 over current designs. At these high clock frequencies it will be difficult to design the instruction issue window to operate in a single cycle. Consequently, we propose and evaluate a high-frequency design called a segmented instruction window.
Determination of myo‐inositol phosphates in food samples by flow injection‐capillary zone electrophoresis (2003)

A capillary electrophoresis (CE) method with indirect photometric detection was developed to identify and quantify myo-inositol phosphates in food samples. A flow-injection (FI) system including a micro-column containing anionic exchange resin was used for the solid-phase extraction of the myo-inositol phosphates with a view to their preconcentration. The FI system was automatically coupled to CE equipment via a mechanical interface. The overall analysis time was shortened by incorporating an FI system for myo-inositol hexakisphosphate monitoring. The limit of detection for myo-inositol phosphates as determined by FI-CE ranged from 11 to 26 micromol/L and the coefficient of variation from 3.9 to 5.0%. On the other hand, the limit of detection and coefficient of variation for myo-inositol hexakisphosphate as monitored by the FI system were 75 micromol/L and 2.9%, respectively. The proposed method was successfully applied to a variety of food samples with recoveries ranging from 96.0 to 107.7% and the precision from 3.9 to 7.9%. Based on the results, the content of myo-inositol hexakisphosphate in nuts was two or three times higher than that in legumes.
Ligand and protein kinase C downmodulate the colony-stimulating factor 1 receptor by independent mechanisms. (1989)

The turnover of the colony-stimulating factor 1 receptor (CSF-1R), the c-fms proto-oncogene product, is accelerated by ligand binding or by activators of protein kinase C (PKC), such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). The mechanisms of ligand- and TPA-induced downmodulation were shown to differ by the following criteria. First, in cells in which PKC was downmodulated, CSF-1R reexpressed at the cell surface remained sensitive to ligand but was refractory to TPA-induced degradation. Second, a kinase-defective receptor containing a methionine-for-lysine substitution at amino acid 616 at its ATP-binding site failed to undergo ligand-induced downmodulation but remained responsive to TPA. Following CSF-1 stimulation, no intermediates of receptor degradation could be immunoprecipitated with polyvalent antisera to CSF-1R. In contrast, TPA induced specific proteolytic cleavage of the receptor near its transmembrane segment, resulting in the release of the extracellular ligand-binding domain from the cell and the generation of an intracellular fragment containing the kinase domain. Two-dimensional phosphopeptide mapping demonstrated no new sites of phosphorylation in response to TPA in either the residual intact receptor or the intracellular proteolytic fragment. Therefore, PKC appears not to trigger downmodulation by directly phosphorylating the receptor but, rather, activates a protease which recognizes CSF-1R as a substrate.
Synthesis of 4''-Deoxy Motilides: Identification of a Potent and Orally Active Prokinetic Drug Candidate (1995)

As an approach to discovering highly potent motilides with oral activity, novel 4"-deoxy derivatives of 8,9-anhydroerythromycin 6,9-hemiacetal were designed, synthesized, and evaluated for their gastrointestinal prokinetic activities. These compounds were orders of magnitude more potent than their 4"-hydroxy analogs in inducing smooth muscle contractions in an in vitro rabbit duodenal assay. Removal of the 12-hydroxy group, which was aimed at improving oral bioavailability, also afforded further potentiation in in vitro activity, leading to the identification of 8,9-anhydro-4"-deoxy-3'-N-desmethyl-3'-N-ethylerythromycin B 6,9-hemiacetal (ABT-229) as a potential prokinetic drug. ABT-229 was > 300,000 times more potent than erythromycin in vitro and had 39% oral bioavailability in dog compared to its 4",12-dihydroxy congener (EM-523), which was only 400 times more potent than erythromycin and had relatively low (1.4%) oral bioavailability.
30 Years of Membrane Technology for Gas Separation (2013)

Membrane technology applied to the separation of gaseous mixtures competes with conventional unit operations (e.g., distillation, absorption, adsorption) on the basis of overall economics, safety, environmental and technical aspects. Since the first industrial installations for hydrogen separation in the early eighties, significant improvements in membrane quality have been achieved in air separation as well as in CO2 separation. However, beside the improvement in the materials as well as in membrane module design, an important point is represented by a correct engineering of these separation processes. The recovery of high value co-products from different industrial streams (e.g. organic vapours from off-gas streams, helium from natural gas) is an interesting application, which created a new market for gas separation membranes, coupling environmental and economic benefits. The opportunity to integrate membrane operations in ongoing production cycles for taking advantage from their peculiar characteristics has been proved as a viable approach. In this ambit, membrane systems in appropriate ranges of operating conditions meet the main requirements such as purity, productivity, energy demand of specific industrial processes. A critical discussion about the role of membrane material and engineering aspects is given. Finally, this work intends to give a brief overview of the development of the membrane technology for gas separation in the last 30 years, addressing open problems and strategies proposed in applications of industrial interest.
Fit and diverse (2012)

We introduce set evolution as a means for creative 3D shape modeling, where an initial population of 3D models is evolved to produce generations of novel shapes. Part of the evolving set is presented to a user as a shape gallery to offer modeling suggestions. User preferences define the fitness for the evolution so that over time, the shape population will mainly consist of individuals with good fitness. However, to inspire the user's creativity, we must also keep the evolving set diverse. Hence the evolution is " fit and diverse ", drawing motivation from evolution theory. We introduce a novel part crossover operator which works at the finer-level part structures of the shapes, leading to significant variations and thus increased diversity in the evolved shape structures. Diversity is also achieved by explicitly compromising the fitness scores on a portion of the evolving population. We demonstrate the effectiveness of set evolution on man-made shapes. We show that selecting only models with high fitness leads to an elite population with low diversity. By keeping the population fit and diverse, the evolution can generate inspiring, and sometimes unexpected, shapes.
Identification of a Varicella-Zoster Virus Origin of DNA Replication and Its Activation by Herpes Simplex Virus Type 1 Gene Products (1986)

We have identified and characterized an origin of DNA replication in the genome of the human herpesvirus, varicella-zoster virus (VZV). This origin of replication (VZV ORIS) is located within the major inverted repeats in a position equivalent to that occupied by one of the herpes simplex virus type 1 (HSV-1) replication origins. Products encoded by both VZV and HSV-1 activate cloned copies of VZV ORIs, generating high molecular weight molecules consisting of tandem duplications of the input plasmid. The VZV ORIS region contains a tract of alternating A and T residues located at the centre of symmetry of an almost perfect palindrome of 45 bp, and the use of plasmid deletion mutants has demonstrated that this tract is an important functional element of the origin. Two sequences common to the VZV ORIS region and the regions specifying the two HSV-1 origins (ORIS, located within the TRS/IRS regions, and ORIL, located within the UL region) were identified and these may represent important recognition sites. One is an 11 bp sequence (CGTTCGCACTT), and the other is represented by the tract of alternating A and T residues. VZV does not appear to contain an origin of replication in a position equivalent to that of HSV-1 ORIL.
Tissue Transglutaminase Regulates Matrix Metalloproteinase-2 in Ovarian Cancer by Modulating cAMP-response Element-binding Protein Activity (2009)

Tissue transglutaminase 2 (TG2) is overexpressed in epithelial ovarian cancer (EOC) and promotes intraperitoneal metastasis. How TG2 facilitates the spread of EOC is unknown. Here, we show that TG2 regulates the expression and function of matrix metalloproteinase-2 (MMP-2), a critical mediator of tissue invasiveness. TG2 knockdown down-regulates MMP-2 protein and mRNA expression in SKOV3, IGROV-1, MDA-MB-436, and PC-3 cancer cells. TG2 knockdown or inhibition of TG2 activity using KCC009 decreases MMP-2 gelatinase activity in cancer cells. MMP-2 expression and function are regulated by TG2 at transcriptional level, as demonstrated by quantitative PCR and reporter assays. We used bioinformatics and chromatin immunoprecipitation to identify a CREB binding site in the MMP-2 promoter. Binding of CREB to the MMP-2 promoter was diminished in cells that expressed decreased TG2 levels. TG2 knockdown decreased CREB phosphorylation, and CREB knockdown decreased MMP-2 expression. The effect of TG2 on CREB activity and MMP-2 transcription is mediated by TG2-dependent degradation of protein phosphatase 2 (PP2A-alpha). We show that PP2A-alpha complexes with and is targeted for degradation by TG2. In addition to their related in vitro expression levels, TG2 and MMP-2 expression were significantly correlated in vivo, as shown by concordant immunostaining in peritoneal xenografts and in human ovarian tumors. The capacity of TG2 to regulate MMP-2 expression in vitro and in vivo identifies a mechanism that may facilitate tissue invasion and the spread of EOC. The demonstration that TG2 induced degradation of PP2A-alpha activates CREB, and thereby increases MMP-2 transcription, provides novel mechanistic insight into the pro- metastatic function of TG2.
Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception (2019)

In humans, gamma-band oscillations in the primary somatosensory cortex (S1) correlate with subjective pain perception. However, functional contributions to pain and the nature of underlying circuits are unclear. Here we report that gamma oscillations, but not other rhythms, are specifically strengthened independently of any motor component in the S1 cortex of mice during nociception. Moreover, mice with inflammatory pain show elevated resting gamma and alpha activity and increased gamma power in response to sub-threshold stimuli, in association with behavioral nociceptive hypersensitivity. Inducing gamma oscillations via optogenetic activation of parvalbumin-expressing inhibitory interneurons in the S1 cortex enhances nociceptive sensitivity and induces aversive avoidance behavior. Activity mapping identified a network of prefrontal cortical and subcortical centers whilst morphological tracing and pharmacological studies demonstrate the requirement of descending serotonergic facilitatory pathways in these pain-related behaviors. This study thus describes a mechanistic framework for modulation of pain by specific activity patterns in the S1 cortex.
Synthesis and antiviral properties of 1-adamantylguanidine. A modified method for preparing tert-alkylguanidines (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and antiviral properties of 1-adamantylguanidine. A modified method for preparing tert-alkylguanidinesH. W. Geluk, J. Schut, and J. L. M. A. SchlatmannCite this: J. Med. Chem. 1969, 12, 4, 712–715Publication Date (Print):July 1, 1969Publication History Published online1 May 2002Published inissue 1 July 1969https://pubs.acs.org/doi/10.1021/jm00304a045https://doi.org/10.1021/jm00304a045research-articleACS PublicationsRequest reuse permissionsArticle Views240Altmetric-Citations19LEARN 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