Three-particle templates for boosted Higgs

We explore the ability of three-particle templates to distinguish color neutral objects from QCD background. This method is particularly useful to identify the standard model Higgs, as well as other massive neutral particles. Simple cut-based analysis in the overlap distributions of the signal and background is shown to provide a significant rejection power. By combining with other discriminating variables, such as planar flow, and several variables that depend on the partonic template, three-particle templates are used to characterize the influence of gluon emission and color flow in collider events. The performance of the method is discussed for the case of a highly boosted Higgs in association with a leptonically-decaying W boson.Comment: 32 pages, 13 figures. v2: Acknowledgments added, typos fixed. v3: added comparison to filtering method, minor correction and acknowledgment added. The version to appear in Phys. Rev.

Toward condition monitoring of damper windings in synchronous motors via EMD analysis

(c) 2012 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] Failures in damper windings of synchronous machines operating in real facilities have been recently reported by several authors and companies. These windings are crucial elements of synchronous motors and generators, playing an important role in the asynchronous startup of these machines as well as in their stability during load transients. However, the diagnosis of failures in such elements has barely been studied in the literature. This paper presents a method to diagnose the condition of damper bars in synchronous motors. It is based on the capture of the stator current of the machine during a direct startup and its further analysis in order to track the characteristic transient evolution of a particular fault-related component in the time-frequency map. The fact that the damper only carries significant current during the startup and little or no current, when the machine operates in steady state, makes this transient-based approach specially suited for the detection of such failure. The Hilbert-Huang transform (based on the empirical mode decomposition method) is proposed as a signal-processing tool. Simulation and experimental results on laboratory synchronous machines prove the validity of the approach for condition monitoring of such windings. © 2012 IEEE.This work was supported by the Spanish Ministerio de Ciencia e Innovacion (MICINN) in the framework of the VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica 2008-2011. (Programa Nacional de proyectos de Investigacion Fundamental, project reference DPI2011-23740). Paper no. TEC-00443-2011.Antonino-Daviu, J.; Riera-Guasp, M.; Pons Llinares, J.; Roger-Folch, J.; Perez, R.; Charlton-Perez, C. (2012). Toward condition monitoring of damper windings in synchronous motors via EMD analysis. IEEE Transactions on Energy Conversion. 27(2):432-439. https://doi.org/10.1109/TEC.2012.2190292S43243927

Red de evaluación de cultivares de soja para el Noroeste Argentino: resultados de la campaña 2013/2014

La Estación Experimental Agroindustrial Obispo Colombres (EEAOC) nuevamente coordinó el desarrollo y evaluación de la Red de Evaluación de Cultivares de Soja para el Noroeste Argentino (NOA). Como en campañas anteriores, el Programa Granos de la EEAOC fue el responsable de coordinar los ensayos que, desde hace 17 campañas agrícolas, se vienen realizando ininterrumpidamente. El objetivo de esta red es evaluar el comportamiento agronómico de las variedades de soja que se encuentran disponibles comercialmente. La información que se obtiene resulta de utilidad para los productores de la región, constituyendo además una importante herramienta para la elección de los materiales a implantar en la siguiente campaña agrícola. Es necesario destacar la colaboración y el aporte que realizan productores, asesores, empresas privadas y técnicos del medio. La contribución que ellos vienen brindando desde el inicio de las evaluaciones resulta fundamental para el desarrollo y la continuidad en el tiempo de la Red de Evaluación de Cultivares de Soja.Fil: Devani, Mario R.. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Ledesma, Fernando. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Sanchez, José R.. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Perez, Daniela R.. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Gonzalez, Victoria. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; ArgentinaFil: Ploper, Leonardo Daniel. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentina; ArgentinaFil: Coronel, Norma B.. Gobierno de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial Obispo Colombres; Argentin

Discovery of Small-Molecule Modulators of the Sonic Hedgehog Pathway

The Hedgehog signaling pathway is involved in the development of multicellular organisms and, when deregulated, can contribute to certain cancers, among other diseases. The molecular characterization of the pathway, which has been enabled by small-molecule probes targeting its components, remains incomplete. Here, we report the discovery of two potent, small-molecule inhibitors of the Sonic Hedgehog (Shh) pathway, BRD50837 and BRD9526. Both compounds exhibit stereochemistry-based structure–activity relationships, a feature suggestive of a specific and selective interaction of the compounds with as-yet-unknown cellular target(s) and made possible by the strategy used to synthesize them as members of a stereochemically and skeletally diverse screening collection. The mechanism-of-action of these compounds in some ways shares similarities to that of cyclopamine, a commonly used pathway inhibitor. Yet, in other ways their mechanism-of-action is strikingly distinct. We hope that these novel compounds will be useful probes of this complex signaling pathway

Ultrasound intensification of Ferrochelatase extraction from pork liver as a strategy to improve ZINC-protoporphyrin formation

[EN] The enzyme Ferrochelatase (FeCH), which is naturally present in pork liver, catalyses the formation of Zincprotoporphyrin (ZnPP), a natural pigment responsible for the typical color of dry-cured Italian Parma ham. The aim of this study was to evaluate the feasibility of using high power ultrasound in continuous and pulsed modes to intensify the extraction of the enzyme FeCH from pork liver. US application during FeCH extraction led to an improved enzymatic activity and further increase in the formation of ZnPP. The optimal condition tested was that of 1 min in continuous US application, in which time the enzymatic activity increased by 33.3 % compared to conventional extraction (30 min). Pulsed US application required 5 min treatments to observe a significant intensification effect. Therefore, ultrasound is a potentially feasible technique as it increases the catalytic activity of FeCH and saves time compared to the conventional extraction methodThe authors acknowledge the financial support from the "Ministerio de Economia y Competitividad (MINECO) and Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria (INIA)" in Spain (Project RTA2017-00024-C04-03). The authors acknowledge the contribution of the undergraduate student Jose V. Pedrero-Gonzalez to the experimental work.Abril-Gisbert, B.; Sanchez-Torres, E.; Bou, R.; Garcia-Perez, J.; Benedito Fort, JJ. (2021). Ultrasound intensification of Ferrochelatase extraction from pork liver as a strategy to improve ZINC-protoporphyrin formation. Ultrasonics Sonochemistry. 78:1-7. https://doi.org/10.1016/j.ultsonch.2021.105703S177

Benzo-fused Lactams from a Diversity-oriented Synthesis (DOS) Library as Inhibitors of Scavenger Receptor BI (SR-BI)-mediated Lipid Uptake

We report a new series of 8-membered benzo-fused lactams that inhibit cellular lipid uptake from HDL particles mediated by Scavenger Receptor, Class B, Type I (SR-BI). The series was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR), measuring the transfer of the fluorescent lipid DiI from HDL particles to CHO cells overexpressing SR-BI. The series is part of a previously reported diversity-oriented synthesis (DOS) library prepared via a build-couple-pair approach. Detailed structure–activity relationship (SAR) studies were performed with a selection of the original library, as well as additional analogs prepared via solution phase synthesis. These studies demonstrate that the orientation of the substituents on the aliphatic ring have a critical effect on activity. Additionally, a lipophilic group is required at the western end of the molecule, and a northern hydroxyl group and a southern sulfonamide substituent also proved to be optimal. Compound 2p was found to possess a superior combination of potency (av IC50 = 0.10 μM) and solubility (79 μM in PBS), and it was designated as probe ML312

Evidence that heparin but not hirudin reduces PAI-1 expression in cultured human endothelial cells

Heparin and other antithrombotic drugs besides their anticoagulant action could have a profibrinolytic effect. We have analyzed the effect of unfractionated heparin (UFH) and hirudin on PAI-1 gene expression in human umbilical vein endothelial cells (HUVEC). Cells were stimulated with UFH (1 and 10 IU/ml) and hirudin (20 and 100 TIU/ml). Samples were obtained before and 2, 6, and 24 hours after stimulation. mRNA analysis was conducted by reverse transcription followed by polymerase chain reaction, and PAI-1 antigen was determined by ELISA. Addition of UFH (10 IU/ml) to HUVEC resulted in a decrease of PAI-1 mRNA at 6 hours (40% reduction) and 24 hours (60% reduction) and PAI-1 antigen. Hirudin, however, did not modify significantly the PAI-1 mRNA nor the inhibitor secretion. The addition of UFH (10 or 100 IU/ml) to endotoxin-stimulated HUVEC also reduced the increased PAI-1 mRNA and antigen secretion (45%), whereas no effect could be observed with hirudin. Our results suggest that UFH, but not hirudin, by reducing the endothelial expression of PAI-1 might have a profibrinolytic effect

Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients.

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0-∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.)

Discovery of Bisamide-heterocycles as Inhibitors of Scavenger Receptor BI (SR-BI)-mediated Lipid Uptake

A new series of potent inhibitors of cellular lipid uptake from HDL particles mediated by scavenger receptor, class B, type I (SR-BI) was identified. The series was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) that measured the transfer of the fluorescent lipid DiI from HDL particles to CHO cells overexpressing SR-BI. The series is characterized by a linear peptidomimetic scaffold with two adjacent amide groups, as well as an aryl-substituted heterocycle. Analogs of the initial hit were rapidly prepared via Ugi 4-component reaction, and select enantiopure compounds were prepared via a stepwise sequence. Structure–activity relationship (SAR) studies suggest an oxygenated arene is preferred at the western end of the molecule, as well as highly lipophilic substituents on the central and eastern nitrogens. Compound 5e, with (R)-stereochemistry at the central carbon, was designated as probe ML279. Mechanistic studies indicate that ML279 stabilizes the interaction of HDL particles with SR-BI, and its effect is reversible. It shows good potency (IC50 = 17 nM), is non-toxic, plasma stable, and has improved solubility over our alternative probe ML278