gebhart/patrepeval huggingface dataset:
THE GENETICIST'S APPROACH TO COMPLEX DISEASE (1996)

Many studies are in progress worldwide to elucidate the genetics of complex diseases. Nevertheless, few articles are available that provide the scientific rationale and give guidelines for such ambitious endeavours. We describe the methodology and background necessary to study the genetics of complex disease and discuss how to analyze the data. We also provide a table of some ongoing studies. In particular, we wish to emphasize the analysis of intermediate, heritable, quantitative traits as a means of dissecting the genetic basis of a complex trait.
A wasp venom mastoparan‐induced polyphosphoinositide breakdown in rat peritoneal mast cells (1985)

The phospholipid metabolism of rat peritoneal mast cells stimulated with mastoparan, a secretagogue purified from wasp venom, was investigated. Mastoparan at 20 micrograms/ml caused a rapid secretion of histamine. Mastoparan induced a transient decrease of phosphatidylinositol 4,5-biphosphate on 32P labeling and generation of a water-soluble degradation product, inositol trisphosphate on [3H]inositol labeling, suggesting the activation of phospholipase C upon stimulation.
Surface Grafted Sulfobetaine Polymers via Atom Transfer Radical Polymerization as Superlow Fouling Coatings (2006)

One of the sulfobetaine methacrylate (SBMA) monomers, N-(3-sulfopropyl)-N-(methacryloxyethyl)-N,N-dimethylammonium betaine, was polymerized onto initiator-covered gold surfaces using atom transfer radical polymerization (ATRP) to form uniform polymer brushes. Self-assembled monolayers (SAMs) with ATRP initiators were characterized by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The thickness of grafted poly(SBMA) films was measured by ellipsometry. Fibrinogen adsorption on poly(SBMA) grafted surfaces was measured with a surface plasmon resonance (SPR) sensor. Two approaches were compared to graft ATRP initiators onto gold surfaces for surface polymerization and subsequent protein adsorption on these polymer grafted surfaces. The first was to prepare a SAM from omega-mercaptoundecyl bromoisobutyrate onto a gold surface. Superlow fouling surfaces with well-controlled poly(SBMA) brushes were achieved using this approach (e.g., fibrinogen adsorption <0.3 ng/cm2). The second approach was to react bromoisobutyryl bromide with a hydroxyl-terminated SAM on a gold surface. Although protein adsorption decreased as the density of surface initiators increased, the surface prepared using the second approach was not able to achieve as low protein adsorption as the first approach. Key parameters to achieve superlow fouling surfaces were studied and discussed.
GPU‐Based Nonlinear Ray Tracing (2004)

Abstract In this paper, we present a mapping of nonlinear ray tracing to the GPU which avoids any data transfer back to main memory. The rendering process consists of the following parts: ray setup according to the camera parameters, ray integration, ray‐object intersection, and local illumination. Bent rays are approximated by polygonal lines that are represented by textures. Ray integration is based on an iterative numerical solution of ordinary differential equations whose initial values are determined during ray setup. To improve the rendering performance, we propose acceleration techniques such as early ray termination and adaptive ray integration. Finally, we discuss a variety of applications that range from the visualization of dynamical systems to the general relativistic visualization in astrophysics and the rendering of the continuous refraction in media with varying density. Categories and Subject Descriptors (according to ACM CCS): I.3.3 [Computer Graphics]: Picture/Image Generation I.3.7 [Computer Graphics]: Three‐Dimensional Graphics and Realism
Context-Aware Machine to Machine Communications in Cellular Networks (2013)

Cellular network based Machine-to-Machine (M2M) communications have been growing rapidly in recent years, being used in a wide range of services such as security, metering, health, remote control, ...
Factor H–related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation (2009)

Homozygous deletion of a 84-kb genomic fragment in human chromosome 1 that encompasses the CFHR1 and CFHR3 genes represents a risk factor for hemolytic uremic syndrome (HUS) but has a protective effect in age-related macular degeneration (AMD). Here we identify CFHR1 as a novel inhibitor of the complement pathway that blocks C5 convertase activity and interferes with C5b surface deposition and MAC formation. This activity is distinct from complement factor H, and apparently factor H and CFHR1 control complement activation in a sequential manner. As both proteins bind to the same or similar sites at the cellular surfaces, the gain of CFHR1 activity presumably is at the expense of CFH-mediated function (inhibition of the C3 convertase). In HUS, the absence of CFHR1 may result in reduced inhibition of terminal complex formation and in reduced protection of endothelial cells upon complement attack. These findings provide new insights into complement regulation on the cell surface and biosurfaces and likely define the role of CFHR1 in human diseases.
Phase III Multinational, Randomized, Double-Blind, Placebo-Controlled Study of Tivantinib (ARQ 197) Plus Erlotinib Versus Erlotinib Alone in Previously Treated Patients With Locally Advanced or Metastatic Nonsquamous Non–Small-Cell Lung Cancer (2015)

E + T was well tolerated and increased PFS but did not improve OS in the overall nonsquamous NSCLC population.
An Empirical Study of Spatial Attention Mechanisms in Deep Networks (2019)

Attention mechanisms have become a popular component in deep neural networks, yet there has been little examination of how different influencing factors and methods for computing attention from these factors affect performance. Toward a better general understanding of attention mechanisms, we present an empirical study that ablates various spatial attention elements within a generalized attention formulation, encompassing the dominant Transformer attention as well as the prevalent deformable convolution and dynamic convolution modules. Conducted on a variety of applications, the study yields significant findings about spatial attention in deep networks, some of which run counter to conventional understanding. For example, we find that the query and key content comparison in Transformer attention is negligible for self-attention, but vital for encoder-decoder attention. A proper combination of deformable convolution with key content only saliency achieves the best accuracy-efficiency tradeoff in self-attention. Our results suggest that there exists much room for improvement in the design of attention mechanisms.
Architecture and cell types of the adult subventricular zone: In search of the stem cells (1998)

Neural stem cells are maintained in the subventricular zone (SVZ) of the adult mammalian brain. Here, we review the cellular organization of this germinal layer and propose lineage relationships of the three main cell types found in this area. The majority of cells in the adult SVZ are migrating neuroblasts (type A cells) that continue to proliferate. These cells form an extensive network of tangentially oriented pathways throughout the lateral wall of the lateral ventricle. Type A cells move long distances through this network at high speeds by means of chain migration. Cells in the SVZ network enter the rostral migratory stream (RMS) and migrate anteriorly into the olfactory bulb, where they differentiate into interneurons. The chains of type A cells are ensheathed by slowly proliferating astrocytes (type B cells), the second most common cell type in this germinal layer. The most actively proliferating cells in the SVZ, type C, form small clusters dispersed throughout the network. These foci of proliferating type C cells are in close proximity to chains of type A cells. We discuss possible lineage relationships among these cells and hypothesize which are the neural stem cells in the adult SVZ. In addition, we suggest that interactions between type A, B, and C cells may regulate proliferation and initial differentiation within this germinal layer.
Identification of Trypanocidal Activity for Known Clinical Compounds Using a New Trypanosoma cruzi Hit-Discovery Screening Cascade (2016)

Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy. There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities. A key first step is the identification of compounds with anti-Trypanosoma cruzi activity from compound libraries. Here we describe a hit discovery screening cascade designed to specifically identify hits that have the appropriate anti-parasitic properties to warrant further development. The cascade consists of a primary imaging-based assay followed by newly developed and appropriately scaled secondary assays to predict the cidality and rate-of-kill of the compounds. Finally, we incorporated a cytochrome P450 CYP51 biochemical assay to remove compounds that owe their phenotypic response to inhibition of this enzyme. We report the use of the cascade in profiling two small libraries containing clinically tested compounds and identify Clemastine, Azelastine, Ifenprodil, Ziprasidone and Clofibrate as molecules having appropriate profiles. Analysis of clinical derived pharmacokinetic and toxicity data indicates that none of these are appropriate for repurposing but they may represent suitable start points for further optimisation for the treatment of Chagas disease.
Modern Arylation Methods (2009)

ARYLATION REACTIONS: A HISTORICAL PERSPECTIVE Structure and Bonding of Benzene Syntheses of Substituted (Hetero)Arenes, and the Contents of this Book METAL-CATALYZED COUPLING REACTIONS WITH ARYL CHLORIDES, TOSYLATES AND FLUORIDES Introduction Coupling Reactions of Aryl Chlorides Coupling Reactions Aryl Fluorides Coupling Reactions of Aryl Tosylates PALLADIUM-CATALYZED ARYLATIONS OF AMINES AND ALPHA-C-H ACIDIC COMPOUNDS Introduction Palladium-Catalyzed Arylations of Amines Palladium-Catalyzed Arylations of Alpha-C-H Acidic Compounds COPPER-CATALYZED ARYLATIONS OF AMINES AND ALCOHOLS WITH BORON-BASED ARYLATING REAGENTS Introduction Discovery and Development of a New O-H Bond Arylation Reaction: From Stoichiometric to Catalytic in Copper Mechanistic Considerations Miscellaneous Applications Development of a New N-H Bond Arylation Reaction Development of a New N-H Bond Arylation Reaction: Catalytic in Copper METAL-CATALYZED ARYLATIONS OF NONACTIVATED ALKYL (PSEUDO)HALIDES VIA CROSS-COUPLING REACTIONS Introduction Palladium-Catalyzed Arylations of Alkyl (Pseudo)Halides Nickel-Catalyzed Arylations of Alkyl (Pseudo)Halides Iron-Catalyzed Arylations of Alkyl (Pseudo)Halides Copper- and Cobalt-Catalyzed Arylations of Alkyl (Pseudo)Halides ARYLATION REACTIONS OF ALKYNES: THE SONOGASHIRA REACTION Introduction Palladium-Catalyzed Reactions: Ligands and Reaction Protocols Alternative Metal Catalysts Mechanism of the Sonogashira Reaction PALLADIUM-CATALYZED ARYLATION REACTIONS OF ALKENES (MIZOROKI-HECK REACTION AND RELATED PROCESSES) Introduction Mizoroki-Heck Arylations Reductive Mizoroki-Heck-Type Arylations Oxidative Mizoroki-Heck-Type Arylations MODERN ARYLATIONS OF CARBONYL COMPOUNDS Introduction Enantioselective Arylation of Aldehydes Enantioselective Arylation of Ketones Enantioselective Arylation of Imines Conjugate Asymmetric Arylation Tandem Processes Enantioselective Friedel-Crafts Arylation METAL-CATALYZED DIRECT ARYLATIONS (EXCLUDING PALLADIUM) Introduction Rhodium-Catalyzed Direct Arylations Ruthenium-Catalyzed Direct Arylations Iridium-, Copper- and Iron-Catalyzed Direct Arylations PALLADIUM-CATALYZED DIRECT ARYLATION REACTIONS Introduction Intermolecular Arylation of Functionalized Arenes Intramolecular Reaction of Haloaryl-Linked Arenes Intermolecular Arylation Reactions of Heteroaromatic Compounds MECHANISTIC ASPECTS OF TRANSITION METAL-CATALYZED DIRECT ARYLATION REACTIONS Introduction Palladium-Catalyzed Intramolecular Direct Arylation Intermolecular Metal-Catalyzed Direct Arylation of Arenes Metal-Catalyzed Heteroaryl-Aryl and Heteroaryl-Heteroaryl Bond Formation Direct Arylation via Metallacycles Cross-Dehydrogenative Couplings ARYLATION REACTIONS INVOLVING THE FORMATION OF ARYNES Introduction Generation of Arynes Electrophilic Coupling of Arynes Pericyclic Reactions of Arynes Transition Metal-Catalyzed Reactions Arynes RADICAL-BASED ARYLATION METHODS Introduction SRN1-Type Radical Arylations Homolytic Aromatic Substitutions Arylations Using Aryl Radicals PHOTOCHEMICAL ARYLATION REACTIONS Introduction Photochemical Formation of Aryl-C Bonds Photochemical Formation of Aryl-N Bonds
New Analogues of (E)-β-Farnesene with Insecticidal Activity and Binding Affinity to Aphid Odorant-Binding Proteins (2011)

(E)-β-farnesene is a strong and efficient alarm pheromone in most aphid species. However, applications in agriculture are prevented by its relatively high volatility, its susceptibility to oxidation and its complex and expensive synthesis. To develop novel compounds for aphid control, we have designed and synthesized analogues of (E)-β-farnesene, containing a pyrazole moiety present in several insecticides. Their structures have been confirmed by 1H NMR, elemental analysis, high-resolution mass spectroscopy and IR. Binding activities to three odorant-binding proteins (OBPs) of the pea aphid Acythosiphon pisum have been evaluated and correlated with their structures with reference to (E)-β-farnesene. Several derivatives were shown both to bind to A. pisum OBPs with a specificity similar to that of (E)-β-farnesene and to have aphicidal activity comparable to that of thiacloprid, a commercial insecticide. The compounds synthesized in this work represent new potential agents for aphid population control and provide guidelines to design analogues of (E)-β-farnesene endowed with both insecticidal and repellent activity for aphids.
Non-Peptide Angiotensin II Receptor Antagonists: Synthesis and Biological Activity of a Series of Novel 4,5-Dihydro-4-oxo-3H-imidazo[4,5-c]pyridine Derivatives (1994)

A series of novel non-peptide angiotensin II receptor antagonists containing a 2,3,5-trisubstituted 4,5-dihydro-4-oxo-3H-imidazo[4,5-c]pyridine was prepared via several synthetic routes. Their affinity for angiotensin II receptors was established in a binding assay experiment and in an isolated-organ test. Molecules with small alkyl groups at C-2 and the (methylbiphenylyl)tetrazole moiety at N-3 were the preferred compounds with affinities and potencies in the nanomolar range. Variations at the N-5 position modulate the activity. Substitution at N-5 with various benzyl groups led to derivatives with in vitro potencies in the nanomolar range, which were equivalent to those of losartan in these assays. Replacement of the N-5 hydrogen with acetic acid esters or, in particular, acetamides gave molecules with increased activity. The most potent was 2-butyl-4,5-dihydro-4-oxo-3-[[2'-(1H-tetrazol-5-yl)-4- biphenylyl]methyl]-3H-imidazo[4,5-c]pyridine-5- (N,N-diethylacetamide) (14u), which is superior to L-158,809 in vitro. Two prototypes were selected as their potassium salts for in vivo testing as antihypertensives. Compounds 14a (EMD 61,650) and 14q (EMD 66,684) reduced blood pressure dose dependently in spontaneously hypertensive rats when administered iv. In this assay, acetamide 14q is superior to losartan.
[Treatment of Diphyllobothrium latum and Taenia saginata infections with aminosidine (author's transl)]. (1979)

Recently, it has been known that the aminosidine has marked anthelmintic efficacy against tapeworm. In this investigation, aminosidine was used for treating 14 cases with Ciphyllobothrium latum infection and 5 cases with Taenia saginata infection. Aminosidine was administered orally in a single dose of 50 mg/kg, followed by a purge after the treatment. Fourteen patients with D. latum infection and 5 patients with T. saginata infection expelled long strobila in all cases. Although only 7 scolices of 18 worms of D. latum were found in the stool and no scolex of T. saginata was found, follow-up examination for a long period showed no evidence of remaining infection with one exception of D. latum. Mild nausea, vomiting and abdominal pain were observed in only one of 19 cases given aminosidine. But in the other 18 cases, no side effects were encountered. It was concluded that aminosidine is safe, effective therapeutic agent for the treatment of cestodiasis in man.
Improved muscle healing through enhanced regeneration and reduced fibrosis in myostatin-null mice (2005)

Numerous stimulatory growth factors that can influence muscle regeneration are known. Recently, it has been demonstrated that neutralization of muscle growth inhibitory factors, such as myostatin (Mstn; also known as growth differentiation factor 8, Gdf8), also leads to increased muscle regeneration in mdx mice that are known to have cycles of degeneration. However, the precise mechanism by which Mstn regulates muscle regeneration has not yet been fully determined. To investigate the role of Mstn in adult skeletal muscle regeneration, wild-type and myostatin-null (Mstn-/-) mice were injured with notexin. Forty-eight hours after injury, accelerated migration and enhanced accretion of myogenic cells (MyoD1+) and macrophages (Mac-1+) was observed at the site of regeneration in Mstn-/- muscle as compared with wild-type muscle. Inflammatory cell numbers decreased more rapidly in the Mstn-/- muscle, indicating that the whole process of inflammatory cell response is accelerated in Mstn-/- mice. Consistent with this result, the addition of recombinant Mstn reduced the activation of satellite cells (SCs) and chemotactic movements of both myoblasts and macrophages ex vivo. Examination of regenerated muscle (28 days after injury) also revealed that Mstn-/- mice showed increased expression of decorin mRNA, reduced fibrosis and improved healing as compared with wild-type mice. On the basis of these results, we propose that Mstn negatively regulates muscle regeneration not only by controlling SC activation but also by regulating the migration of myoblasts and macrophages to the site of injury. Thus, antagonists of Mstn could potentially be useful as pharmacological agents for the treatment of disorders of overt degeneration and regeneration.
Unimpeded Permeation of Water Through Helium-Leak–Tight Graphene-Based Membranes (2012)

Permeation through nanometer pores is important in the design of materials for filtration and separation techniques and because of unusual fundamental behavior arising at the molecular scale. We found that submicrometer-thick membranes made from graphene oxide can be completely impermeable to liquids, vapors, and gases, including helium, but these membranes allow unimpeded permeation of water (H(2)O permeates through the membranes at least 10(10) times faster than He). We attribute these seemingly incompatible observations to a low-friction flow of a monolayer of water through two-dimensional capillaries formed by closely spaced graphene sheets. Diffusion of other molecules is blocked by reversible narrowing of the capillaries in low humidity and/or by their clogging with water.
Tumor selective replication of Newcastle disease virus: Association with defects of tumor cells in antiviral defence (2006)

To investigate tumor-selective viral replication, we compared several tumorigenic human cell lines to nontumorigenic human cells from the blood for the sensitivity to become infected by a recombinant lentogenic strain of Newcastle Disease Virus (NDV) with incorporated transgene EGFP (NDFL-EGFP). Although fluorescence signals in nontumorigenic cells were only weak or missing completely, a massive and long-lasting transgene-expression was observed in all tumor cell lines. The majority of tumor cells (50-95%) could be infected, and viral replication was associated with an increase in the cell surface density of viral antigens. To clarify the underlying mechanism of the observed difference in virus susceptibility we examined the kinetics of interferon-induced antiviral enzymes because NDV is a strong type-I interferon inducer. This analysis revealed several defects of tumor cells in their antiviral defence responses: They showed no response to UV-inactivated NDV, whereas nontumorigenic cells reacted with induction of high-levels of the antiviral enzymes PKR and MxA. Upon coincubation with live NDV, tumor cells showed a delayed response in the increased expression of the antiviral enzymes in comparison with PBMC. In nontumorigenic cells the replication cycle of NDV stopped after the production of positive-strand RNA, while tumor cells continued in the replication cycle and copied viral genomes 10-50 hr after infection. These results can explain the tumor selective replication behavior of this interesting antineoplastic virus.
Attachment of mycoplasmas to erythrocytes: a model to study mycoplasma attachment to the epithelium of the host respiratory tract. (1981)

Mycoplasma pneumoniae, M. gallisepticum and M. pulmonis are pathogens of the respiratory tract. Their adherence to the host tissue is a prerequisite for manifestation of the disease. The attachment occurs between membrane components of the mycoplasmas and the host cells. In the attachment of M. pneumoniae and M. gallisepticum, binding sites of a protein nature of the mycoplasma membranes interact primarily with sialic acid residues of sialoglycoproteins of the host cell membranes. The latter was clearly indicated in studies on the pathogenic strain of M. pneumoniae and its nonpathogenic nonhemadsorbing mutants, and by the assessment of the direct binding of glycophorin [the major sialoglycoprotein of human red blood cells (RBC)] and other sialoglycoproteins to M. pneumoniae and M. gallisepticum. The components involved in the interaction of M. pulmonis with the host cells are not as well characterized, since the attachment is not affected by proteolytic treatment of the mycoplasmas, nor by removal of sialic acid residues from the host cell membranes. The attachment of the mycoplasmas to the host cells also occurs with nonviable organisms and can, in addition, by reproduced by isolated membranes. The binding sites of M. pneumoniae and M. gallisepticum were partially purified by affinity chromatography, using the high affinity of the binding sites for glycophorin. By this procedure the membranes were solubilized with detergents and chromatographed through glycophorin attached to Sepharose 4B as an affinity matrix. The binding sites retained the high affinity for glycophorin and bound to RBC membranes. Are the binding sites distributed throughout the membrane? Since the binding of the mycoplasma is via a polar structure (the tip or bleb), one may suggest that these structures harbor them. Experimental evidence for their distribution is being sought.
Synthesis of a titaniumsilicoaluminate isomorphous to zeolite beta and its application as a catalyst for the selective oxidation of large organic molecules (1992)

M. A. Camblor, A. Corma, A. Martínez and J. Pérez-Pariente, J. Chem. Soc., Chem. Commun., 1992, 589 DOI: 10.1039/C39920000589