gebhart/patrepeval huggingface dataset:
Antitumor Agents. 250. Design and Synthesis of New Curcumin Analogues as Potential Anti-Prostate Cancer Agents (2006)

In a continuing study of curcumin analogues as potential drug candidates to treat prostate cancer at both androgen-dependent and androgen-refractory stages, we designed and synthesized over 40 new analogues classified into four series: monophenyl analogues (series A), heterocycle-containing analogues (series B), analogues bearing various substituents on the phenyl rings (series C), and analogues with various linkers (series D). These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells, seven only against LNCaP, and one solely against PC-3. This study established an advanced structure-activity relationship (SAR), and these correlations will guide the further design of new curcumin analogues with better anti-prostate cancer activity.
Microstructural Observations on Gallium Nitride Light-Emitting Diodes (1974)

Microstructural observations, utilizing optical microscopy, scanning electron microscopy, and transmission electron microscopy, were made on gallium nitride metal/insulator/n‐type semiconductor (m‐i‐n) light‐emitting diodes. The films from which the diodes were fabricated were grown by heteroepitaxial chemical vapor deposition on sapphire substrates, and consisted of an undoped n‐layer and a Mg‐doped i‐layer; a metal contact was subsequently placed on the surface of the i‐layer forming an m‐i and an n‐i junction. Significant observations include the following: optical microscopy and scanning electron microscopy show a faceted surface of the layers and the existence of cell boundaries; the cell boundaries result from the coalescence of the individual crystallites formed on the substrate in the early stages of growth; x‐ray Laue patterns consist of spots that are slightly diffuse, indicating that the cells are only slightly misoriented with respect to their adjoining cells; light emission occurs as a pattern of small discrete spots and this pattern of spots correlates with the faceted structure of the film; the light emanates from the cathode regions (the i‐n junction with forward bias and the m‐i junction with reverse bias); steep electrical potential gradients (∼105 V/cm), measured using line scan techniques in the scanning electron microscope, occur at the m‐i and the n‐i junctions. The observations are consistent with an impact ionization model for light emission.
SARA ATRP or SET-LRP. End of controversy? (2014)

A debate has proceeded in the literature regarding the mechanism of reversible-deactivation radical polymerization in the presence of Cu0. The two proposed models are supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) and single electron transfer living radical polymerization (SET-LRP). In SARA ATRP, CuI is the major activator of alkyl halides, Cu0 is a supplemental activator and reducing agent of excess CuII through comproportionation, and disproportionation is negligible. In contrast, in SET-LRP, Cu0 is the major activator, CuI does not activate alkyl halides but instead undergoes instantaneous disproportionation. In this article we present a body of experimental and theoretical data, which supports the SARA ATRP mechanism and disagrees with the SET-LRP mechanism.
Expression of von Willebrand factor, an endothelial cell marker, is up-regulated by angiogenesis factors: A potential method for objective assessment of tumor angiogenesis (2000)

von Willebrand factor (vWF), a glycoprotein produced uniquely by endothelial cells and megakaryocytes, is routinely used to identify vessels in tissue sections. Vessel density in tumor specimens, as determined by immuno-histochemical staining for vWF or other endothelial cell markers, is a negative prognostic factor for many solid tumors. vWF is heterogeneously distributed throughout the vasculature, transcriptional control in response to the tissue microenvironment being responsible for local variations in endothelial cell levels of vWF. Here, we report that fibroblast growth factor-2 and vascular endothelial growth factor, potent angiogenesis inducers expressed in a variety of tumors, up-regulate expression of vWF mRNA and protein in cultured endothelial cells with a synergistic effect. Our data support the measurement of vWF mRNA in tumors to detect activated endothelium or angiogenesis. For this purpose, we developed a semi-quantitative RT-PCR for vWF mRNA. Preliminary results obtained with specimens from colon carcinoma and the corresponding normal colonic mucosa showed higher vWF mRNA levels in most tumors than in their normal counterparts. The differences in vWF mRNA levels were much larger than the differences in vessel counts between a tumor and the corresponding normal mucosa, indicating that high vWF mRNA levels in tumors may indeed be an early sign of activation of the endothelium. The rapidity, objectivity, sensitivity and specificity of this technique make it suitable for routine clinical application to identify aggressive, highly angiogenic tumors.
Salivary lysozyme, lactoferrin and peroxidases: antibacterial effects on cariogenic bacteria and clinical applications in preventive dentistry. (1991)

Many antimicrobial agents in human saliva are known to have bacteriostatic or bactericidal effects on cariogenic bacteria, in particular against Streptococcus mutans. Studies have usually been conducted with purified agents (proteins) in vitro. Very little proof exists to show that they also affect oral cariogenic flora in vivo. Recent studies have shown that some salivary systems can act synergistically against Streptococcus mutans. Such synergistic antibacterial activity is likely to exist in the human mouth. Attempts to enhance the anticariogenic properties of saliva have been made by adding antimicrobial proteins such as peroxidase, lactoferrin and lysozyme to oral health products. Although clinical evidence is still limited, the idea of using such antimicrobial agents--"natural antibiotics"--rather than synthetic agents against cariogenic bacteria seems promising.
Vision-based autonomous landing system for unmanned aerial vehicle: A survey (2014)

Recently, there has been growing interest in developing unmanned aircraft system (UAS) based on visual sensors. During the whole autonomous assignment, the landing procedure is one of the most dangerous and challenging process. For most of unmanned aircraft vehicle, visual sensors are the basic equipment, which are also widely used during the landing maneuver. This paper first presents the main research groups involved in the development of vision-based autonomous landing systems. Then it discusses the detail of each algorithms and systems in different categories. The goal of this paper is to review the state-of-the-art vision-based autonomous landing methods that captures all milestones and seminal works. These algorithms and systems are classified into different categories. Finally, the paper highlights challenges in this research field.
Cytomegalovirus in autoimmunity: T cell crossreactivity to viral antigen and autoantigen glutamic acid decarboxylase (2001)

Antigens of pathogenic microbes that mimic autoantigens are thought to be responsible for the activation of autoreactive T cells. Viral infections have been associated with the development of the neuroendocrine autoimmune diseases type 1 diabetes and stiff-man syndrome, but the mechanism is unknown. These diseases share glutamic acid decarboxylase (GAD65) as a major autoantigen. We screened synthetic peptide libraries dedicated to bind to HLA-DR3, which predisposes to both diseases, using clonal CD4(+) T cells reactive to GAD65 isolated from a prediabetic stiff-man syndrome patient. Here we show that these GAD65-specific T cells crossreact with a peptide of the human cytomegalovirus (hCMV) major DNA-binding protein. This peptide was identified after database searching with a recognition pattern that had been deduced from the library studies. Furthermore, we showed that hCMV-derived epitope can be naturally processed by dendritic cells and recognized by GAD65 reactive T cells. Thus, hCMV may be involved in the loss of T cell tolerance to autoantigen GAD65 by a mechanism of molecular mimicry leading to autoimmunity.
Lessons Learned from Animal Models of Inherited Bleeding Disorders. (2014)

Advances in treatment of hemophilia and von Willebrand disease (VWD) depend heavily on the availability of well-characterized animal models. These animals faithfully recapitulate the severe bleeding phenotype that occurs in humans with these inherited bleeding disorders. Research in these animal models represents important early and intermediate steps of translational research aimed at addressing current limitations in treatment such as the development of inhibitory antibodies to coagulation factors VIII and IX (FVIII, FIX) or von Willebrand factor (VWF), the life-long need for frequent venous access, the expense of therapy, and the ongoing need for improved ex vivo coagulation assays and in vivo methods for assessing hemostasis. The primary strengths of research that utilizes these highly relevant animal models include the development of better and safer treatments for hemophilia and VWD. Careful consideration of the strengths and limitations of the specific models is essential for optimizing chances for successful translation of advances to clinical medicine that benefits humans and animals.
Developmental roles of the BMP1/TLD metalloproteinases (2006)

The astacin family (M12A) of the metzincin subclan MA(M) of metalloproteinases has been detected in developing and mature individuals of species that range from hydra to humans. Functions of this family of metalloproteinase vary from digestive degradation of polypeptides, to biosynthetic processing of extracellular proteins, to activation of growth factors. This review will focus on a small subgroup of the astacin family; the bone morphogenetic protein 1 (BMP1)/Tolloid (TLD)-like metalloproteinases. In vertebrates, the BMP1/TLD-like metalloproteinases play key roles in regulating formation of the extracellular matrix (ECM) via biosynthetic processing of various precursor proteins into mature functional enzymes, structural proteins, and proteins involved in initiating mineralization of the ECM of hard tissues. Roles in ECM formation include: processing of the C-propeptides of procollagens types I-III, to yield the major fibrous components of vertebrate ECM; proteolytic activation of the enzyme lysyl oxidase, necessary to formation of covalent cross-links in collagen and elastic fibers; processing of NH2-terminal globular domains and C-propeptides of types V and XI procollagen chains to yield monomers that are incorporated into and control the diameters of collagen type I and II fibrils, respectively; processing of precursors for laminin 5 and collagen type VII, both of which are involved in securing epidermis to underlying dermis; and maturation of small leucine-rich proteoglycans. The BMP1/TLD-related metalloproteinases are also capable of activating the vertebrate transforming growth factor-beta (TGF-beta)-like "chalones" growth differentiation factor 8 (GDF8, also known as myostatin), and GDF11 (also known as BMP11), involved in negative feedback inhibition of muscle and neural tissue growth, respectively; by freeing them from noncovalent latent complexes with their cleaved prodomains. BMP1/TLD-like proteinases also liberate the vertebrate TGF-beta-like morphogens BMP2 and 4 and their invertebrate ortholog decapentaplegic, from latent complexes with the vertebrate extracellular antagonist chordin and its invertebrate ortholog short gastrulation (SOG), respectively. The result is formation of the BMP signaling gradients that form the dorsal-ventral axis in embryogenesis. Thus, BMP1/TLD-like proteinases appear to be key to regulating and orchestrating formation of the ECM and signaling by various TGF-beta-like proteins in morphogenetic and homeostatic events.
Automatic feedback using past queries (1997)

The effect of using paat queries to improve automatic query expansion was examined in the TREC environment. Automatic feedback of documents identified from similar past queries was compared with standard top-document feedback and with no feedback. A new query similarity metric was used based on comparing result lists and using probability of relevance. Our top-document feedback method showed small improvements over no feedback method consistent with past studies. On recall-precision and average precision measures, past query feedback yielded performance superior to that of top-document feedback. The past query feedback method also lends itself to tunable thresholds such that better performance can be obtained by automatically deciding when, and when not, to apply the expansion. Automatic past-query feedback actually improved top document precision in this experiment.
To build a synapse: signaling pathways in neuromuscular junction assembly (2010)

Synapses, as fundamental units of the neural circuitry, enable complex behaviors. The neuromuscular junction (NMJ) is a synapse type that forms between motoneurons and skeletal muscle fibers and that exhibits a high degree of subcellular specialization. Aided by genetic techniques and suitable animal models, studies in the past decade have brought significant progress in identifying NMJ components and assembly mechanisms. This review highlights recent advances in the study of NMJ development, focusing on signaling pathways that are activated by diffusible cues, which shed light on synaptogenesis in the brain and contribute to a better understanding of muscular dystrophy.
Phosphorylation of the Insulin Receptor in Permeabilized Adipocytes Is Coupled to a Rapid Dephosphorylation Reaction (1989)

Phosphorylation and dephosphorylation of the insulin receptor were examined in permeabilized rat adipocytes using pulse-chase techniques. Maximum insulin-dependent phosphorylation during a 2-min labeling period with 75 microM [gamma-32P]ATP was attained at 10(-6)-10(-7) M insulin with a small effect at 10(-9) M. The reaction utilized either Mn2+ or Mg2+, but insulin-dependent phosphorylation was 11-fold greater with Mn2+. In the absence of insulin, phosphorylation was 6-fold greater with Mn2+. With either cation, insulin (10(-7) M) was a potent stimulator of receptor phosphorylation with 5- and 8-fold increases above control levels in the presence of Mg2+ and Mn2+, respectively. Phosphorylation of the insulin receptor reached an apparent steady state within 30 s at 37 degrees C under all conditions. By phosphoamino acid analysis, all insulin- and Mn2+-dependent phosphorylation in the 95-kDa subunit of the insulin receptor was phosphotyrosine. A small amount of phosphoserine was detected, but it was not affected by either insulin or Mn2+. Dephosphorylation of the insulin receptor was examined by "chasing" labeled ATP after 2 min with a 40-fold excess of unlabeled ATP. Maximum dephosphorylation was reached in 2 min under all conditions. Insulin had no effect on the dephosphorylation reaction. The labile fraction of Mn2+-dependent phosphoreceptor dephosphorylated to one-half of its initial level in approximately 21 s at 37 degrees C. Vanadate, a potent phosphotyrosine phosphatase inhibitor, inhibited dephosphorylation of this phosphoreceptor by 25%. When vanadate was present during the 2-min labeling period, phosphorylation of control, and insulin-dependent receptor was increased by 50%. In summary, rapid "in vitro" autophosphorylation of the insulin receptor is coupled to an equally rapid dephosphorylation reaction in permeabilized adipocytes. This suggests that phosphorylation of the insulin receptor is a dynamic, rapidly reversible, insulin-dependent response in target cells and is consistent with it being involved in insulin signal transduction and insulin action.
Regenerative Urinary Bladder Augmentation Using Small Intestinal Submucosa: Urodynamic and Histopathologic Assessment in Long-term Canine Bladder augmentations (1996)

Small intestinal submucosa acts as a scaffold for bladder augmentation through regeneration and could be a potential option for bladder reconstruction.
Duobinary transmitter with low intersymbol interference (1998)

A duobinary transmitter employing two-level electrical drive signals for the modulator, exhibits negligible penalties for transmitting 2/sup 7/-1 as well as 2/sup 31/-1 pseudorandom bit sequences (PRBS's). Previous implementations of duobinary transmitters have relied on driving the modulator with three-level electrical signals, which are very susceptible to distortion in saturated amplifiers. The logic operation necessary for generating an optical duobinary signal is carried out in the dual-drive Mach-Zehnder modulator.
Effect of Topical Applications of Budesonide and Azelastine on Nasal Symptoms, Eosinophil Count and Mediator Release in Atopic Patients after Nasal Allergen Challenge during the Pollen Season (1997)

We studied the activity of a topical form of a corticosteroid (budesonide) and an antihistamine (azelastine) in the treatment of seasonal allergic rhinitis by including an assessment of mediator concentrations and the percentage of eosinophils in the nasal secretions before and after the treatment. Nasal allergen challenge (NAC) during the season was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction. The study compared in a randomized way (2 parallel groups) the effect of budesonide (Rhinocort Aqua) and azelastine (Allergodil nasal spray) in a group of 14 patients during the pollen season. The study showed that azelastine significantly reduced sneezing, total nasal resistance and increased nasal airflow even when significant increases in histamine, tryptase and leukotriene C4 (LTC4) concentrations in nasal secretions were evidenced immediately after NAC. Budesonide showed a strong (p<0.05) decrease in infiltration and activation of eosinophils, and on tryptase and LTC4 release after NAC. These effects (not for LTC4) lasted at least for 1 week after therapy. Azelastine is a powerful topical antihistamine, while budesonide appears to be a potent long-acting anti-inflammatory agent.
El almacenamiento de energía eléctrica (2011)

espanolEl almacenamiento de electricidad constituye una potente herramienta para la operacion del sistema a la hora de maximizar la integracion en el sistema electrico de la generacion procedente de energias renovables. En este articulo se repasan las principales tecnologias de almacenamiento disponibles, sus distintas funcionalidades dentro de la cadena de suministro electrico y en especial aquellas relacionadas con la operacion del sistema. Finalmente se plantea la necesidad de abrir el debate sobre la regulacion del almacenamiento y se aportan algunas consideraciones bajo el prisma de maxima seguridad y eficiencia para el conjunto del sistema. EnglishElectricity storage is a powerful tool for the system operation when maximizing the integration of renewable energy sources production into the power system. This article gives a review of the main available storage technologies as well as its different functionalities across the power supply chain, especially those linked with system operation. Finally the article discusses about the need to open a debate on storage regulation contributing with some remarks under the prism of maximum security of supply and efficiency for the whole system.
Herpes simplex virus type 1 DNA polymerase (1989)

Acyclovir triphosphate (ACVTP) was a substrate for herpes simplex virus type 1 (HSV-1) DNA polymerase and was rapidly incorporated into a synthetic template-primer designed to accept either dGTP or ACVTP followed by dCTP. HSV-1 DNA polymerase was not inactivated by ACVTP, nor was the template-primer with a 3'-terminal acyclovir monophosphate moiety a potent inhibitor. Potent inhibition of HSV-1 DNA polymerase was observed upon binding of the next deoxynucleoside 5'-triphosphate coded by the template subsequent to the incorporation of acyclovir monophosphate into the 3'-end of the primer. The Ki for the dissociation of dCTP (the "next nucleotide") from this dead-end complex was 76 nM. In contrast, the Km for dCTP as a substrate for incorporation into a template-primer containing dGMP in place of acyclovir monophosphate at the 3'-primer terminus was 2.6 microM. The structural requirements for effective binding of the next nucleotide revealed that the order of potency of inhibition of a series of analogs was: dCTP much greater than arabinosyl-CTP greater than 2'-3'-dideoxy-CTP much greater than CTP, dCMP, dCMP + PPi. In the presence of the next required deoxynucleotide (dCTP), high concentrations of dGTP compete with ACVTP for binding and thus retard the formation of the dead-end complex. This results in a first-order loss of enzyme activity indistinguishable from that expected for a mechanism-based inactivator. The reversibility of the dead-end complex was demonstrated by steady-state kinetic analysis, analytical gel filtration, and by rapid gel filtration through Sephadex G-25. Studies indicated that potent, reversible inhibition by ACVTP and the next required deoxynucleoside 5'-triphosphate also occurred when poly(dC)-oligo(dG) or activated calf thymus DNA were used as the template-primer.
Memory Profiling using Hardware Counters (2003)

Although memory performance is often a limiting factor in application performance, most tools only show performance data relating to the instructions in the program, not to its data. In this paper, we describe a technique for directly measuring the memory profile of an application. We describe the tools and their user model, and then discuss a particular code, the MCFbenchmark from SPEC CPU 2000. We show performance data for the data structures and elements, and discuss the use of the data to improve program performance. Finally, we discuss extensions to the work to provide feedback to the compiler for prefetching and to generate additional reports from the data.
Comparison of Rhesus and Cynomolgus macaques as an authentic model for COVID-19 (2020)

ABSTRACT A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques, resembling the mild clinical cases of COVID-19 in humans. Immune responses against SARS-CoV-2 were also similar in both species and equivalent to those reported in milder infections and convalescent human patients. Importantly, we have devised a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the optimal study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of novel and repurposed interventions against SARS-CoV-2. Accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks.
Incremental Light Bundle Adjustment (2012)

Presented at the Ninth Conference on 23rd British Machine Vision Conference (BMVC 2012), 3-7 September 2012, Guildford, Surrey, UK.