Analysis of Surface Charge Effects and Edge Fringing Capacitance in Planar GaAs and GaN Schottky Barrier Diodes

[EN]In this article, by means of a 2-D ensemble Monte Carlo simulator, the Schottky barrier diodes (SBDs) with realistic geometries based on GaAs and GaN are studied as promising devices for increasing the high-frequency performance- and power-handling capability of frequency mixers and multipliers. The nonlinearity of the capacitance–voltage (C–V) characteristic is the most important parameter for optimizing the performance of SBDs as frequencymultipliers. The small size of the diodes used for ultrahigh-frequency applications makes the value of its intrinsic capacitance to deviate from the ideal one due to fringing effects. We have observed that the value of the edge capacitancewell into reverse bias does not depend on the applied voltage. We define an edge-effect parameter beta, which, interestingly, is affected by the presence or absence of surface charges at the semiconductor–dielectric interface, sigma . Two physical models have been considered: a fixed sigma related to a surface potential Vs constant surface-charge model (CCM) and a self-consistent model in which the local value of sigma is dynamically evaluated depending on the surrounding electron density self-consistent surface-charge model (SCCM). Using the CCM, we obtain that beta depends on the depth of the depletion region Ws created by the surface charges, nearly irrespectively of the epilayer doping or semiconductor type. The more realistic SCCM indicates that, at low frequencies, when the surface charges are able to follow the variations of the applied voltage, the value of beta approaches the one obtained without surface charges,while the high-frequency value (the significant one) is smaller.Spanish MINECO and FEDER under Project TEC2017-83910-R and Junta de Castilla y León and FEDER under Project SA254P18

Analysis of nonharmonic oscillations in Schottky diodes

[EN]We investigate damped nonharmonic oscillations at terahertz frequencies observed in the current response of Schottky diodes simulated with the Monte Carlo method under applied signals of a few hundred GHz. From Monte Carlo simulations of different diode structures, two kinds of nonharmonic oscillations have been identified. The first kind of oscillations is due to the coupling of the nonlinear performance of the Schottky junction with the inertial motion of the carriers in the non-depleted region of the epilayer. The second kind of oscillations is due to the modulation of the n+–n junction when high electric fields are induced in the non-depleted region of the epilayer. These oscillations constitute a promising mechanism for THz signal generation.ROOTHz (FP7-243845

Electrostatic screening, acidic pH and macromolecular crowding increase the self-assembly efficiency of the minute virus of mice capsid in vitro

The hollow protein capsids from a number of different viruses are being considered for multiple biomedical or nanotechnological applications. In order to improve the applied potential of a given viral capsid as a nanocarrier or nanocontainer, specific conditions must be found for achieving its faithful and efficient assembly in vitro. The small size, adequate physical properties and specialized biological functions of the capsids of parvoviruses such as the minute virus of mice (MVM) make them excellent choices as nanocarriers and nanocontainers. In this study we analyzed the effects of protein concentration, macromolecular crowding, temperature, pH, ionic strength, or a combination of some of those variables on the fidelity and efficiency of self-assembly of the MVM capsid in vitro. The results revealed that the in vitro reassembly of the MVM capsid is an efficient and faithful process. Under some conditions, up to ~40% of the starting virus capsids were reassembled in vitro as free, non aggregated, correctly assembled particles. These results open up the possibility of encapsidating different compounds in VP2-only capsids of MVM during its reassembly in vitro, and encourage the use of virus-like particles of MVM as nanocontainersThis research was funded by grants from MICINN/FEDER EU (Spain, RTI2018-096635-B-100 and PID2021-126973OB-I00) to M.G.M. and by an institutional grant from Fundación Ramón Arece

Analysis of noise spectra in GaAs and GaN Schottky barrier diodes

The Monte Carlo method is applied in this paper to characterize the noise spectra of GaAs and GaN Schottky barrier diodes operating under static and time varying conditions. We show the influence of the structure of the diode and working regimes on the noise spectrum of the diodes. Besides, the paper evaluates the capabilities of published analytical models to describe the noise spectra in Schottky diodes under time varying conditions. This is a further step towards the development of a design tool that integrates both the electrical response and the intrinsic noise generated in the devices.ROOTHz (FP7-243845

Technological Parameters and Edge Fringing Capacitance in GaN Schottky Barrier Diodes: Monte Carlo Simulations

[EN]Schottky barrier diodes (SBDs) with realistic geometries have been studied by means of a 2-D ensemble Monte Carlo simulator. The non-linearity of the Capacitance-Voltage (C-V) characteristic is the most important parameter for optimizing SBDs as frequency multipliers. In this paper, by changing the values of several technological parameters, we analyze their influence on the edge fringing capacitance in a GaN SBD. We have found that the parameters related with the dielectric used for the passivation and the lateral extension of the epilayer significantly affect the fringing capacitance, thus increasing the value of the total capacitance above the ideal one.Spanish MINECO and FEDER under Project TEC2017-83910-R and Junta de Castilla y León and FEDER under Project SA254P1

S-Nitrosation of E3 Ubiquitin Ligase Complex Components Regulates Hormonal Signalings in Arabidopsis

E3 ubiquitin ligases mediate the last step of the ubiquitination pathway in the ubiquitin-proteasome system (UPS). By targeting transcriptional regulators for their turnover, E3s play a crucial role in every aspect of plant biology. In plants, SKP1/CULLIN1/F-BOX PROTEIN (SCF)-type E3 ubiquitin ligases are essential for the perception and signaling of several key hormones including auxins and jasmonates (JAs). F-box proteins, TRANSPORT INHIBITOR RESPONSE 1 (TIR1) and CORONATINE INSENSITIVE 1 (COI1), bind directly transcriptional repressors AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) and JASMONATE ZIM-DOMAIN (JAZ) in auxin- and JAs-depending manner, respectively, which permits the perception of the hormones and transcriptional activation of signaling pathways. Redox modification of proteins mainly by S-nitrosation of cysteines (Cys) residues via nitric oxide (NO) has emerged as a valued regulatory mechanism in physiological processes requiring its rapid and versatile integration. Previously, we demonstrated that TIR1 and Arabidopsis thaliana SKP1 (ASK1) are targets of S-nitrosation, and these NO-dependent posttranslational modifications enhance protein-protein interactions and positively regulate SCFTIR1 complex assembly and expression of auxin response genes. In this work, we confirmed S-nitrosation of Cys140 in TIR1, which was associated in planta to auxin-dependent developmental and stress-associated responses. In addition, we provide evidence on the modulation of the SCFCOI1 complex by different S-nitrosation events. We demonstrated that S-nitrosation of ASK1 Cys118 enhanced ASK1-COI1 protein-protein interaction. Overexpression of non-nitrosable ask1 mutant protein impaired the activation of JA-responsive genes mediated by SCFCOI1 illustrating the functional relevance of this redox-mediated regulation in planta. In silico analysis positions COI1 as a promising S-nitrosation target, and demonstrated that plants treated with methyl JA (MeJA) or S-nitrosocysteine (NO-Cys, S-nitrosation agent) develop shared responses at a genome-wide level. The regulation of SCF components involved in hormonal perception by S-nitrosation may represent a key strategy to determine the precise time and site-dependent activation of each hormonal signaling pathway and highlights NO as a pivotal molecular player in these scenarios.Fil: Terrile, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Tebez, Nuria Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Colman, Silvana Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Mateos, Julieta Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Morato López, Esperanza. CENTRO DE BIOLOGIA MOLECULAR SEVERO OCHOA (CBMSO) ; UNIVERSIDAD AUTONOMA DE MADRID;Fil: Sánchez López, Nuria. CENTRO DE BIOLOGIA MOLECULAR SEVERO OCHOA (CBMSO) ; UNIVERSIDAD AUTONOMA DE MADRID;Fil: Izquierdo Álvarez, Alicia. No especifíca;Fil: Marina, Anabel. CENTRO DE BIOLOGIA MOLECULAR SEVERO OCHOA (CBMSO) ; UNIVERSIDAD AUTONOMA DE MADRID;Fil: Calderón Villalobos, Luz Irina A.. Donald Danforth Plant Science Center; Estados UnidosFil: Estelle, Mark. No especifíca;Fil: Martínez Ruiz, Antonio. No especifíca;Fil: Fiol, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Casalongue, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Iglesias, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Magneto-mechanical system to reproduce and quantify complex strain patterns in biological materials

Biological cells and tissues are continuously subjected to mechanical stress and strain cues from their surrounding substrate. How these forces modulate cell and tissue behavior is a major question in mechanobiology. To conduct studies under controlled varying physiological strain scenarios, a new virtually-assisted experimental system is proposed allowing for non-invasive and real-time control of complex deformation modes within the substrates. This approach is based on the use of extremely soft magneto-active polymers, which mimic the stiffness of biological materials. Thus, the system enables the untethered control of biological substrates providing reversible mechanical changes and controlling heterogeneous patterns. Motivated on a deep magneto-mechanical characterization across scales, a multi-physics and multi-scale in silico framework was developed to guide the experimental stimulation setup. The versatility and viability of the system have been demonstrated through its ability to reproduce complex mechanical scenarios simulating local strain patterns in brain tissue during a head impact, and its capability to transmit physiologically relevant mechanical forces to dermal fibroblasts. The proposed framework opens the way to understanding the mechanobiological processes that occur during complex and dynamic deformation states, e.g., in traumatic brain injury, pathological skin scarring or fibrotic heart remodeling during myocardial infarction.The authors thank Denis Wirtz (Johns Hopkins University) and Jean-Christophe Olivo-Marin (Institute Pasteur) for relevant discussion. The authors acknowledge support from the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Program (Grant agreement No. 947723, project: 4D-BIOMAP), and from Programa de Apoyo a la Realizacion de Proyectos Interdiscisplinares de I+D para Jovenes Investigadores de la Universidad Carlos III de Madrid and Comunidad de Madrid (project: BIOMASKIN). MAMM and CGC acknowledges support from the Ministerio de Ciencia, Innovacion y Universidades, Spain (FPU19/03874 and FPU20/01459) and DGG acknowledges support from the Talent Attraction grant (CM 2018 - 2018-T2/IND-9992) from the Comunidad de Madrid

In vivo murine model of acquired resistance in myeloma reveals differential mechanisms for lenalidomide and pomalidomide in combination with dexamethasone

The development of resistance to therapy is unavoidable in the history of multiple myeloma patients. Therefore, the study of its characteristics and mechanisms is critical in the search for novel therapeutic approaches to overcome it. This effort is hampered by the absence of appropriate preclinical models, especially those mimicking acquired resistance. Here we present an in vivo model of acquired resistance based on the continuous treatment of mice bearing subcutaneous MM1S plasmacytomas. Xenografts acquired resistance to two generations of immunomodulatory drugs (IMiDs; lenalidomide and pomalidomide) in combination with dexamethasone, that was reversible after a wash-out period. Furthermore, lenalidomide-dexamethasone (LD) or pomalidomide-dexamethasone (PD) did not display cross-resistance, which could be due to the differential requirements of the key target Cereblon and its substrates Aiolos and Ikaros observed in cells resistant to each combination. Differential gene expression profiles of LD and PD could also explain the absence of cross-resistance. Onset of resistance to both combinations was accompanied by upregulation of the mitogen-activated protein kinaseextracellular signal-regulated kinase (ERK) kinase (MEK)ERK pathway and addition of selumetinib, a small-molecule MEK inhibitor, could resensitize resistant cells. Our results provide insights into the mechanisms of acquired resistance to LD and PD combinations and offer possible therapeutic approaches to addressing IMiD resistance in the clinic.Peer Reviewe

MM, SARS-CoV-2 infection, and inpatient mortality

There is limited information on the characteristics, pre-admission prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with coronavirus disease 2019 (COVID-19). This retrospective case series investigated characteristics and outcomes of 167 MM patients hospitalized with COVID-19 reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in Spain between March 1 and April 30, 2020. Outcomes were compared with a randomly selected contemporary cohort of 167 age-/sex-matched non-cancer patients with COVID-19 admitted at 6 participating hospitals. Common demographic, clinical, laboratory, treatment, and outcome variables were collected; specific disease status and treatment data were collected for MM patients. Among the MM and non-cancer patients, median age was 71 years and 57% of patients were male in each series, and 75% and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77% and 89% of patients and critical in 8% and 4%, respectively. Supplemental oxygen was required by 47% and 55% of MM and non-cancer patients, respectively, and 21%/9% vs 8%/6% required non-invasive/invasive ventilation. Inpatient mortality was 34% and 23% in MM and non-cancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors of inpatient mortality on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.This study was supported by PETHEMA FoundationN

Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2

Most public health measures to contain the COVID-19 pandemic are based on preventing the pathogen spread, and the use of oral antiseptics has been proposed as a strategy to reduce transmission risk. The aim of this manuscript is to test the efficacy of mouthwashes to reduce salivary viral load in vivo. This is a multi-centre, blinded, parallel-group, placebo-controlled randomised clinical trial that tests the effect of four mouthwashes (cetylpyridinium chloride, chlorhexidine, povidone-iodine and hydrogen peroxide) in SARS-CoV-2 salivary load measured by qPCR at baseline and 30, 60 and 120 min after the mouthrinse. A fifth group of patients used distilled water mouthrinse as a control. Eighty-four participants were recruited and divided into 12-15 per group. There were no statistically significant changes in salivary viral load after the use of the different mouthwashes. Although oral antiseptics have shown virucidal effects in vitro, our data show that salivary viral load in COVID-19 patients was not affected by the tested treatments. This could reflect that those mouthwashes are not effective in vivo, or that viral particles are not infective but viral RNA is still detected by PCR. Viral infectivity studies after the use of mouthwashes are therefore required