gebhart/patrepeval huggingface dataset:
The FDA Critical Path Initiative and Its Influence on New Drug Development (2008)

Societal expectations about drug safety and efficacy are rising while productivity in the pharmaceutical industry is falling. In 2004, the US Food and Drug Administration introduced the Critical Path Initiative with the intent of modernizing drug development by incorporating recent scientific advances, such as genomics and advanced imaging technologies, into the process. An important part of the initiative is the use of public-private partnerships and consortia to accomplish the needed research. This article explicates the reasoning behind the Critical Path Initiative and discusses examples of successful consortia.
C-kit gene mutation in human gastrointestinal stromal tumors (2004)

C-kit gene mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs and can help to differentiate GISTs from other mesenchymal tumors of gastrointestinal tract, such as smooth muscle tumors, schwannomas, etc.
Ephrin-As Cooperate With EphA4 to Promote Trunk Neural Crest Migration (2002)

Trunk neural crest cells delaminate from the dorsal neural tube and migrate on two distinct pathways: a dorsolateral route, between the ectoderm and somites,and a ventromedial route, through the somitic mesoderm. Neural crest cells that migrate ventromedially travel in a segmental manner through rostral half-somites, avoiding caudal halves. Recent studies demonstrate that various molecular cues guide the migration of neural crest cells, primarily by serving as inhibitors to premature pathway entry orby preventing neural crest from entering inappropriate territories. Trajectories of migrating trunk neural crest are well organized and generally linear in nature, suggesting that positive, migration-promoting factors may be responsible for this organized cell behavior. However, the identity of these factors and their function are not well understood. Here we examine the expression of members of the EphA subclass of receptor tyrosine kinases and ephrins using RT-PCR and immunocytochemistry. Neural crest cells express ephrins and EphA4 at distinct stages during their migration. In functional analyses, addition of ephrin-A2-, ephrin-A5-, and EphA4-Fc disrupted the segmental organization of trunk neural crest migration in explants: neural crest cells entered rostral and caudal halves of somites. Finally, to test the specific effects of these factors on cell behavior, neural crest cells were exposed in vitro to substrate-bound EphA and ephrin-As. Surprisingly, neural crest cells avoided ephrin-A2 or ephrin-A5 substrates; this avoidance was abolished by the addition of EphA4. Together, these data suggest that ephrin-As and EphA4 cooperate to positively promote the migration of neural crest cells through rostral half somites in vivo.
Irritable bowel syndrome: Relations with functional, mental, and somatoform disorders (2014)

This review describes the conceptual and clinical relations between irritable bowel syndrome (IBS), other functional, somatoform, and mental disorders, and points to appropriate future conceptualizations. IBS is considered to be a functional somatic syndrome (FSS) with a considerable symptom overlap with other FSSs like chronic fatigue syndrome or fibromyalgia syndrome. IBS patients show an increased prevalence of psychiatric symptoms and disorders, especially depression and anxiety. IBS is largely congruent with the concepts of somatoform and somatic symptom disorders. Roughly 50% of IBS patients complain of gastrointestinal symptoms only and have no psychiatric comorbidity. IBS concepts, treatment approaches, as well as health care structures should acknowledge its variability and multidimensionality by: (1) awareness of additional extraintestinal and psychobehavioral symptoms in patients with IBS; (2) general and collaborative care rather than specialist and separated care; and (3) implementation of "interface disorders" to abandon the dualistic classification of purely organic or purely mental disorders.
Vinylation and the Formation of Acylals (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTVinylation and the Formation of AcylalsCharles D. Hurd, Robert Roach, and C. W. HuffmanCite this: J. Am. Chem. Soc. 1956, 78, 1, 104–106Publication Date (Print):January 1, 1956Publication History Published online1 May 2002Published inissue 1 January 1956https://pubs.acs.org/doi/10.1021/ja01582a031https://doi.org/10.1021/ja01582a031research-articleACS PublicationsRequest reuse permissionsArticle Views240Altmetric-Citations10LEARN 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
Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy (2016)

Somatic mutations in the epidermal growth factor receptor (EGFR) gene are present in approximately 20% (in Caucasians) to 40% (in East Asians) of adenocarcinomas of the lung. Targeted therapy for these lung cancers has been established based on evidence regarding mainly common mutations; that is, exon 19 deletions (Del19) and L858R. EGFR-tyrosine kinase inhibitors (TKI), gefitinib, erlotinib or afatinib showed high objective response rates (ORR) of approximately 60%. Several studies suggested that Del19 might be more sensitive to EGFR-TKI than L858R. On the other hand, it has been difficult to establish evidence for other less common mutations, accounting for 12% of all EGFR mutations, because there are many variants and many studies have excluded patients with these uncommon mutations. However, recent studies revealed that these rare genotypes could be targetable if appropriate TKI are selected. For example, G719X (X denotes A, S, C and so on), Del18, E709K, insertions in exon 19 (Ins19), S768I or L861Q showed moderate sensitivities to gefitinib or erlotinb with ORR of 30%-50%. However, afatinib appeared to be especially effective for these tumors. Although Ins20s (except for insFQEA) have been regarded as resistant mutations, osimertinib may be effective for rare subtypes of them and nazartinib (EGF816) is promising for the majority of them. For the further development of targeted therapy in all EGFR mutations, it is important to precisely detect targetable mutations, to select the most appropriate TKI for each mutation, and to continue investigating in vitro studies and collecting clinical data on even rare mutations.
Milieux hyperbasiques: préparation de carbanions en α d'amides N,N-disubstitués. Synthèse de β- et γ-hydroxyamides et de γ-butyrolactones (1977)

The α anions of N,N-disubstituted carboxamides can be conveniently prepared by treatment with "activated" lithium dialkylamides in HMPT. They react with aldehydes and ketones and lead to β-hydroxyamides; furthermore the ring opening of epoxides affords γ-hydroxyamides which may be cyclized in situ to γ-butyrolactones
Protein Identification and Analysis Tools on the ExPASy Server (2005)

Protein identification and analysis software performs a central role in the investigation of proteins from two-dimensional (2-D) gels and mass spectrometry. For protein identification, the user matches certain empirically acquired information against a protein database to define a protein as already known or as novel. For protein analysis, information in protein databases can be used to predict certain properties about a protein, which can be useful for its empirical investigation. The two processes are thus complementary. Although there are numerous programs available for those applications, we have developed a set of original tools with a few main goals in mind. Specifically, these are:
Human papillomavirus DNA and P16INK4Aexpression in concurrent esophageal and gastric cardia cancers (2010)

HPV16 as a correlated risk factor may play an important role in the development of ESCC and GCA. P16(INK4A) may be a screening index in the HPV-associated carcinoma of gastric cardia.
Intravenous Sildenafil Is a Potent Pulmonary Vasodilator in Children With Congenital Heart Disease (2003)

Intravenous sildenafil is as effective as inhaled NO as a pulmonary vasodilator in children with congenital heart disease. Although clinically insignificant in this study, increased intrapulmonary shunting with sildenafil may be disadvantageous in some patients after CHD surgery.
Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes (2018)

Xerostomia (dry mouth) is the most common side effect of radiation therapy in patients with head and neck cancer and causes difficulty speaking and swallowing. Since aldehyde dehydrogenase 3A1 (ALDH3A1) is highly expressed in mouse salivary stem/progenitor cells (SSPCs), we sought to determine the role of ALDH3A1 in SSPCs using genetic loss-of-function and pharmacologic gain-of-function studies. Using DarkZone dye to measure intracellular aldehydes, we observed higher aldehyde accumulation in irradiated <i>Aldh3a1</i><sup><i>-/-</i></sup> adult murine salisphere cells and in situ in whole murine embryonic salivary glands enriched in SSPCs compared with wild-type glands. To identify a safe ALDH3A1 activator for potential clinical testing, we screened a traditional Chinese medicine library and isolated d-limonene, commonly used as a food-flavoring agent, as a single constituent activator. ALDH3A1 activation by d-limonene significantly reduced aldehyde accumulation in SSPCs and whole embryonic glands, increased sphere-forming ability, decreased apoptosis, and improved submandibular gland structure and function in vivo after radiation. A phase 0 study in patients with salivary gland tumors showed effective delivery of d-limonene into human salivary glands following daily oral dosing. Given its safety and bioavailability, d-limonene may be a good clinical candidate for mitigating xerostomia in patients with head and neck cancer receiving radiation therapy.
Ex vitro composite plants: an inexpensive, rapid method for root biology (2005)

Plant transformation technology is frequently the rate-limiting step in gene function analysis in non-model plants. An important tool for root biologists is the Agrobacterium rhizogenes-derived composite plant, which has made possible genetic analyses in a wide variety of transformation recalcitrant dicotyledonous plants. The novel, rapid and inexpensive ex vitro method for producing composite plants described in this report represents a significant advance over existing composite plant induction protocols, which rely on expensive and time-consuming in vitro conditions. The utility of the new system is validated by expression and RNAi silencing of GFP in transgenic roots of composite plants, and is bolstered further by experimental disruption, via RNAi silencing, of endogenous plant resistance to the plant parasitic nematode Meloidogyne incognita in transgenic roots of Lycopersicon esculentum cv. Motelle composite plants. Critical parameters of the method are described and discussed herein.
Minimizing Paste Content in Concrete Using Limestone Powders - Demonstration Mixtures (2016)

In recent years, there has been great interest in reducing the cement content of concrete, due to the high energy and carbon dioxide footprints of cement production. There are numerous (waste) materials that can be substituted for cement in the concrete mixture proportions, including fly ash, slag, silica fume, metakaolin, waste glass, etc. However, a more abundant material substitute would be limestone powder, created from the same limestone that is currently heavily employed in cement production as the primary source of calcium oxide. This technical note presents an approach to replacing not only cement powder, but effectively cement paste consisting of the cement and water, with appropriately sized limestone powder(s). Such an approach effectively extends the conventional utilization of centimeter-sized coarse aggregates (rocks) and millimeter-sized fine aggregates (sand) that occupy between 65 % and 75 % of the volume of a concrete structure to include micro-aggregates ranging between about 1 m and 100 m in size.
DIRECT AND INVERSE SOLUTIONS OF GEODESICS ON THE ELLIPSOID WITH APPLICATION OF NESTED EQUATIONS (1975)

AbstractThis paper gives compact formulae for the direct and inverse solutions of geodesics of any length. Existing formulae have been recast for efficient programming to conserve space and reduce execution time. The main feature of the new formulae is the use of nested equations for elliptic terms. Both solutions are iterative.
Dual-function semiconducting polymer devices: Light-emitting and photodetecting diodes (1994)

Thin film devices made with poly[2-methoxy-5-(2′-ethyl-hexyloxy)-1,4-phenylene vinylene], MEH-PPV, are known to be efficient light-emitting diodes. The same devices, under reverse bias, exhibit excellent sensitivity as photodiodes. Thus the polymer tunnel diode is a dual-function device. For the Ca/MEH-PPV/ITO (indium/tin oxide) layered structure, the external quantum efficiency for electroluminescence is ≊1% photons/electron (forward bias ≳2.5 V). The same device is sensitive as a photodiode: The dc sensitivity (−10 V, reverse bias) is 9×10−2 A/W (at ∼1-μW/cm2 input) corresponding to a quantum yield of more than 20% electrons/photon.
Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression (1993)

The nicotinic cholinergic antagonist alpha-bungarotoxin (alpha-BT) binds throughout the rat hippocampal formation. The binding is displaceable by d-tubocurarine. The most heavily labeled cells are GABA-containing interneurons in the dentate and in Ammon's horn. These neurons have several different morphologies and contain several neuropeptides. alpha-BT-labeled interneurons in the dentate are small cells between the granular and molecular layers that often contain neuropeptide Y. alpha-BT-labeled interneurons in CA1 are medium-sized interneurons, occasionally found in stratum pyramidale, but more often found in stratum radiatum and stratum lacunosum moleculare. These neurons often contain cholecystokinin. The largest alpha-BT-labeled interneurons are found in CA3, in both stratum radiatum and stratum lucidum. These neurons are multipolar and frequently are autofluorescent. They often contain somatostatin or cholecystokinin. These large interneurons have been found to receive medial septal innervation and may also have projections that provide inhibitory feedback directly to the medial septal nucleus. The cholinergic innervation of the hippocampus from the medial septal nucleus is under the trophic regulation of NGF and brain-derived neurotrophic factor, even in adult life. Expression of mRNA for both these factors is increased in CA3 and the dentate after intraventricular administration of alpha-BT, but not after administration of the muscarinic antagonist atropine. alpha-BT-sensitive cholinergic receptors on inhibitory interneurons may be critical to medial septal regulation of the hippocampal activity, including the habituation of response to sensory input.
Outer membrane biogenesis in Escherichia coli, Neisseria meningitidis, and Helicobacter pylori: paradigm deviations in H. pylori (2012)

The bacterial pathogen Helicobacter pylori is capable of colonizing the gastric mucosa of the human stomach using a variety of factors associated with or secreted from its outer membrane (OM). Lipopolysaccharide (LPS) and numerous OM proteins have been shown to be involved in adhesion and immune stimulation/evasion. Many of these factors are essential for colonization and/or pathogenesis in a variety of animal models. Despite this wide array of potential targets present on the bacterial surface, the ability of H. pylori to vary its OM profile limits the effectiveness of vaccines or therapeutics that target any single one of these components. However, it has become evident that the proteins comprising the complexes that transport the majority of these molecules to the OM are highly conserved and often essential. The field of membrane biogenesis has progressed remarkably in the last few years, and the possibility now exists for targeting the mechanisms by which β-barrel proteins, lipoproteins, and LPS are transported to the OM, resulting in loss of bacterial fitness and significant altering of membrane permeability. In this review, the OM transport machinery for LPS, lipoproteins, and outer membrane proteins (OMPs) are discussed. While the principal investigations of these transport mechanisms have been conducted in Escherichia coli and Neisseria meningitidis, here these systems will be presented in the genetic context of ε proteobacteria. Bioinformatic analysis reveals that minimalist genomes, such as that of Helicobacter pylori, offer insight into the smallest number of components required for these essential pathways to function. Interestingly, in the majority of ε proteobacteria, while the inner and OM associated apparatus of LPS, lipoprotein, and OMP transport pathways appear to all be intact, most of the components associated with the periplasmic compartment are either missing or are almost unrecognizable when compared to their E. coli counterparts. Eventual targeting of these pathways would have the net effect of severely limiting the delivery/transport of components to the OM and preventing the bacterium's ability to infect its human host.
Direct gene transfer into human cultured cells facilitated by laser micropuncture of the cell membrane. (1987)

The selective alteration of the cellular genome by laser microbeam irradiation has been extensively applied in cell biology. We report here the use of the third harmonic (355 nm) of an yttrium-aluminum garnet laser to facilitate the direct transfer of the neo gene into cultured human HT1080-6TG cells. The resultant transformants were selected in medium containing an aminoglycoside antibiotic, G418. Integration of the neo gene into individual human chromosomes and expression of the gene were demonstrated by Southern blot analyses, microcell-mediated chromosome transfer, and chromosome analyses. The stability of the integrated neo gene in the transformants was shown by a comparative growth assay in selective and nonselective media. Transformation and incorporation of the neo gene into the host genome occurred at a frequency of 8 X 10(-4)-3 X 10(-3). This method appears to be 100-fold more efficient than the standard calcium phosphate-mediated method of DNA transfer.
Synthesis and investigation of the configurational stability of some dimethylammonium borate salts (2000)

Two borate salts, dimethylammonium bis[3-isopropylbenzene-1,2-diolato(2−)-O,O′]borate and dimethylammonium 3,3′′-ethylenebis(3′-methylbiphenyl-2,2′-diolato(2−)-O,O′)borate, were synthesised from the corresponding catechol and tetraphenol respectively. The configurational stability of these salts was determined by variable temperature 1H NMR spectroscopy; the activation energies for the racemisation process were determined to be 85 and 79 kJ mol−1 respectively. Mechanisms are proposed to explain the configurational instability observed.
Active Damping for Three-Phase PWM Rectifiers With High-Order Line-Side Filters (2008)

Active rectifiers interfacing the grid have gained much attention in recent years due to their current control capability that enables the application to exchange a certain range of power at the benefit of low harmonic distortion compared to line commutated converters. Moreover, the amount of active and reactive powers can be arbitrarily chosen within certain limits. These limits as well as the degree of harmonic attenuation is determined by the line-side filter. This paper basically focuses on the current control of active rectifiers incorporating a line-side filter of first- up to third-order degree. Thus, it treats both the current-source converter (CSC) as well as the voltage-source converter (VSC). The basic models of the plant are derived for each case, and important dualities are pointed out. As a conclusion, a recipe for the controller design of particularly CSCs with LC filters and VSCs with LCL filters is proposed.
A Theoretically Grounded Application of Dropout in Recurrent Neural Networks (2015)

Recurrent neural networks (RNNs) stand at the forefront of many recent developments in deep learning. Yet a major difficulty with these models is their tendency to overfit, with dropout shown to fail when applied to recurrent layers. Recent results at the intersection of Bayesian modelling and deep learning offer a Bayesian interpretation of common deep learning techniques such as dropout. This grounding of dropout in approximate Bayesian inference suggests an extension of the theoretical results, offering insights into the use of dropout with RNN models. We apply this new variational inference based dropout technique in LSTM and GRU models, assessing it on language modelling and sentiment analysis tasks. The new approach outperforms existing techniques, and to the best of our knowledge improves on the single model state-of-the-art in language modelling with the Penn Treebank (73.4 test perplexity). This extends our arsenal of variational tools in deep learning.
The Business Cycle, Investment, and a Wayward M2: A Midyear Review (1992)

A summary of the June 12, 1992 meeting of the Fourth District Economists' Roundtable, at which 22 panelists concurred that steady and moderate growth in the economy can be expected through late 1993; includes discussions on business fixed investment, monetary growth, and business cycle theory.
Regulation of Escherichia coli K-12 hexuronate system genes: exu regulon (1980)

Two types of Escherichia coli K-12 regulatory mutants, partially or totally negative for the induction of the five catabolic enzymes (uronic isomerase, uxaC; altronate oxidized nicotinamide adenine dinucleotide: uxaB; mannonate hydrolyase, uxuA) and the transport system (exuT) of the hexuronate-inducible pathway, were isolated and analyzed enzymatically. Hexuronate-catabolizing revertants of the negative mutants showed a constitutive synthesis for some or all of these enzymes. Negative and constitutive mutations were localized in the same genetic locus, called exuR, and the following order for the markers situated between the min 65 and 68 was determined: argG--exuR--exuT--uxaC--uxaA--tolC. The enzymatic characterization of the pleiotropic negative and constitutive mutants of the exuR gene suggests that the exuR regulatory gene product exerts a specific and total control on the three exuT, uszB, and uxaC-uxaA operons of the galacturonate pathway and a partial control on the uxuA-uxuB operon of the glucuronate pathway. The analysis of diploid strains conatining both the wild type and a negative or constitutive allele of the exuR gene, as well as the analysis of thermosensitive mutants of the exuR gene, was in agreement with a negative regulatory mechanism for the control of the hexuronate system.