A Geometric Approach to Massive p-form Duality

Massive theories of abelian p-forms are quantized in a generalized path-representation that leads to a description of the phase space in terms of a pair of dual non-local operators analogous to the Wilson Loop and the 't Hooft disorder operators. Special atention is devoted to the study of the duality between the Topologically Massive and the Self-Dual models in 2+1 dimensions. It is shown that these models share a geometric representation in which just one non local operator suffices to describe the observables.Comment: 26 pages, LaTeX. The discussion about the equivalence between the Proca model and two seldual models, with opposite spins, was eliminated. Typos correcte

Effect of Calcium Carbonate Residues from Cement Industries on the Phenolic Composition and Yield of Shiraz Grapes

Phenolic compounds are secondary metabolites synthesised in response to biotic or abiotic stress in plants.  This stress-induced increase in phenolic compound concentrations is generally activated by internal levels of abscisic acid (ABA). The exogenous application of ABA or calcium chloride on grapevines is also known to increase grape yield and alter the phenolic composition of grapes. Residues of cement industries such as calcium carbonates (CaCO3) are a safe environmental source of calcium that could be used to induce the synthesis of phenolic compounds and act as a yield promoter in grapes and other crops. Consequently, the objective of this study was to evaluate the effect of cement industries’ CaCO3 residues (CaCO3R) on the yield and concentration of phenolic compounds in Shiraz grapes. Thirteen phenolic compounds were identified and quantified by HPLC-DAD. Malvidin-3-O-glucoside was the major anthocyanin found inShiraz grapes, and its concentration increased by more than 200% in CaCO3R-treated vines. Similarly, the concentration of cinnamic acid, the main precursor of phenolic compounds, increased by more than 900%in grapes treated with CaCO3 residues at harvest time. Finally, catechin, epicatechin and procyanidin B1 and B2 increased significantly at harvest time in CaCO3R-treated grapes relative to the controls. In general, it was found that foliar application of CaCO3 residues from the cement industry at véraison induced an increase in yield, and in the concentration and composition of phenolic compounds in grapes

¿cómo responder a nuestras preguntas de investigación de forma específica y no morir en el intento? Parte X: ¿dónde y cómo busco información científica fiable y de calidad?

Indexación: Scopus.¿Cómo responder a nuestras preguntas de investigación de forma específica y no morir en el intento? Parte X: ¿Dónde y cómo busco información científica fiable y de calidad? How to answer our research questions specifically and not die trying? Part X: where and how do i look for reliable and quality scientific information?https://www.resed.es/como-responder-a-nuestras-preguntas-de-investigacion-de-forma-especifica-y-no-morir-en-el-intento-parte-x-donde-y-como-busco-informacion-cientifica-fiable-y-de-calidad937?AspxAutoDetectCookieSupport=

The wonderful complexity of the Mira AB system

We have mapped the CO(3-2) line emission around the Mira AB system at 0.5 resolution using the Atacama Large Millimeter/submillimeter Array (ALMA). The CO map shows amazing complexity. The circumstellar gas has been shaped by different dynamical actors during the evolution of the system and several morphological components can be identified. The companion is marginally resolved in continuum emission and is currently at 0.487$\pm$0.006 separation. In the main line component, centered on the stellar velocity, spiral arcs around Mira A are found. The spiral appears to be relatively flat and oriented in the orbital plane. An accretion wake behind the companion is clearly visible and the projected arc separation is of order 5''. In the blue wing of the line emission, offset from the main line, several large ($\sim$5-10''), opposing arcs are found. We tentatively suggest that this structure is created by the wind of Mira B blowing a bubble in the expanding envelope of Mira A.Comment: Letter accepted in A&

3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental Feedback from Film Dosimetry.

A model based on a specific phantom, called QuAArC, has been designed for the evaluation of planning and verification systems of complex radiotherapy treatments, such as volumetric modulated arc therapy (VMAT). This model uses the high accuracy provided by the Monte Carlo (MC) simulation of log files and allows the experimental feedback from the high spatial resolution of films hosted in QuAArC. This cylindrical phantom was specifically designed to host films rolled at different radial distances able to take into account the entrance fluence and the 3D dose distribution. Ionization chamber measurements are also included in the feedback process for absolute dose considerations. In this way, automated MC simulation of treatment log files is implemented to calculate the actual delivery geometries, while the monitor units are experimentally adjusted to reconstruct the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck clinical cases, previously planned with Monaco and Pinnacle treatment planning systems and verified with two different commercial systems (Delta4 and COMPASS), were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measure- ments (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary discre- tization level of the log file for dose calculation and the potential mismatching between calculated control points and detection grid in the verification process were discussed. Besides the effect of dose calculation accuracy of the analytic algorithm implemented in treatment planning systems for a dynamic technique, it was discussed the importance of the detection density level and its location in VMAT specific phantom to obtain a more reliable DVH in the patient CT. The proposed model also showed enough robustness and efficiency to be considered as a pre-treatment VMAT verification system.Ministerio de Ciencia y Tecnología SAF2011- 27116; IPT-2011-1480-900000

Antisense Oligonucleotide Rescue of Deep-Intronic Variants Activating Pseudoexons in the 6-Pyruvoyl-Tetrahydropterin Synthase Gene

We report two new 6-pyruvoyl-tetrahydropterin synthase splicing variants identified through genomic sequencing and transcript analysis in a patient with tetrahydrobiopterin deficiency, presenting with hyperphenylalaninemia and monoamine neurotransmitter deficiency. Variant c.243 + 3A>G causes exon 4 skipping. The deep-intronic c.164-672C>T variant creates a potential 5' splice site that leads to the inclusion of four overlapping pseudoexons, corresponding to exonizations of an antisense short interspersed nuclear element AluSq repeat sequence. Two of the identified pseudoexons have been reported previously, activated by different deep-intronic variants, and were also detected at residual levels in control cells. Interestingly, the predominant pseudoexon is nearly identical to a disease causing activated pseudoexon in the F8 gene, with the same 3' and 5' splice sites. Splice switching antisense oligonucleotides (SSOs) were designed to hybridize with splice sites and/or predicted binding sites for regulatory splice factors. Different SSOs corrected the aberrant pseudoexon inclusion, both in minigenes and in fibroblasts from patients carrying the new variant c.164-672C>T or the previously described c.164-716A>T. With SSO treatment PTPS protein was recovered, illustrating the therapeutic potential of the approach, for patients with different pseudoexon activating variants in the region. In addition, the natural presence of pseudoexons in the wild type context suggests the possibility of applying the antisense strategy in patients with hypomorphic PTS variants with the purpose of upregulating their expression to increase overall protein and activity

Aplicaciones de enmiendas orgánicas y microorganismos para optimizar parámetros del suelo y rendimiento del nogal pecanero

El cultivo de nogal pecanero en el estado de Chihuahua es una actividad en crecimiento. Las zonas donde se cultiva el nogal presentan una serie de problemas, como son falta de agua, alta salinidad y alto contenido de sodio, baja nutrición en los suelos, bajo contenido de materia orgánica, entre otras, lo que provoca una disminución de la producción de nuez pecanera. El objetivo del presente estudio fue evaluar las aplicaciones al suelo de enmiendas cálcicas, orgánicas y microorganismos para los componentes del rendimiento y contenido de macronutrientes en el nogal pecanero. Los factores que se aplicaron y que influyeron en todas las variables de respuesta de los componentes de rendimiento y contenido de macronutrientes son: Ca/CaCO3 75.0 y 147.4 kg ha-1, Hongos Micorrízicos 20.7 y 17.2 kg ha-1, Humus Liquida (Hu_Liq) 750 y 1083.1 L ha-1, Humus Solida (Hu_sol) 1671.2 y 1632.6 kg ha-1. Las variables de respuesta que se evaluaron y fueron las más importantes para los componentes del rendimiento son: porcentaje de nuez comestible, nueces por kilogramo y peso promedio de nuez. Mientras que para el contenido de macronutrientes del suelo en nogal fueron: calcio/porcentaje de saturación de bases, calcio/(potasio+magnesio) y sodio

Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia

This is the peer reviewed version of the following article: Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia. Human Mutation (2020): 25 April, which has been published in final form at [https://doi.org/10.1002/humu.24026. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThe variants identified in this study are openly available at http://www.lovd.nl/ with reference numbers 0000644164, 0000645396, 0000644166, and 0000405673Biallelic variants of the gene DNAJC12, which encodes a cochaperone, were recently described in patients with hyperphenylalaninemia (HPA). This paper reports the retrospective genetic analysis of a cohort of unsolved cases of HPA. Biallelic variants of DNAJC12 were identified in 20 patients (generally neurologically asymptomatic) previously diagnosed with phenylalanine hydroxylase (PAH) deficiency (phenylketonuria [PKU]). Further, mutations of DNAJC12 were identified in four carriers of a pathogenic variant of PAH. The genetic spectrum of DNAJC12 in the present patients included four new variants, two intronic changes c.298‐2A>C and c.502+1G>C, presumably affecting the splicing process, and two exonic changes c.309G>T (p.Trp103Cys) and c.524G>A (p.Trp175Ter), classified as variants of unknown clinical significance (VUS). The variant p.Trp175Ter was detected in 83% of the mutant alleles, with 14 cases homozygous, and was present in 0.3% of a Spanish control population. Functional analysis indicated a significant reduction in PAH and its activity, reduced tyrosine hydroxylase stability, but no effect on tryptophan hydroxylase 2 stability, classifying the two VUS as pathogenic variants. Additionally, the effect of the overexpression of DNAJC12 on some destabilizing PAH mutations was examined and a mutation‐specific effect on stabilization was detected suggesting that the proteostasis network could be a genetic modifier of PAH deficiency and a potential target for developing mutation‐specific treatments for PKUThis work was funded by grant PI16/00573, B2017/BMD-3721, the Fundación Isabel Gemio and the Fundación La Caixa (LCF/PR/PR16/11110018), an institutional grant from the Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa, and the European Regional Development Fun

Role of Seroalbumin in the Cytotoxicity of cis-Dichloro Pt(II) Complexes with (N^N)-Donor Ligands Bearing Functionalized Tails

Given the potent anticancer properties of cisdiamminedichloroplatinum( II) and knowing its mode of action, we synthesized four new cis-[PtCl2(N^N)] organoplatinum complexes, two with N-substituted pbi ligands (pbiR = 1-R-2-(2-pyridyl)benzimidazole) (namely, 1 and 2) and two more with 4,4′-disubstituted bpy ligands (bpy = 2,2′-bipyridine) (namely, 3 and 4). We explored their cytotoxicity and ability to bind to deoxyguanosine monophosphate (dGMP), DNA, and albumin models. By 1H NMR and UV−vis spectroscopies, circular dichroism, agarose gel electrophoresis, differential scanning calorimetry measurements, and density functional theory calculations, we verified that only 3 can form aquacomplex species after dimethyl sulfoxide solvation; surprisingly, 1, 2, and 3 can bind covalently to DNA, whereas 4 can form a noncovalent complex. Interestingly, only complexes 1 and 4 exhibit good cytotoxicity against human ovarian carcinoma (HeLa) cell line, whereas 2 and 3 are inactive. Although lung carcinoma (A549) cells are more resistant to the four platinum complexes than HeLa cells, when the protein concentration in the extracellular media is lower, the cytotoxicity becomes substantially enhanced. By native electrophoresis of bovine seroalbumin (BSA) and inductively coupled plasma mass spectrometry uptake studies we bear out, on one hand, that 2 and 3 can interact strongly with BSA and its cellular uptake is negligible and, on the other hand, that 1 and 4 can interact with BSA only weakly, its cellular uptake being higher by several orders. These results point up the important role of the protein binding features on their biological activity and cellular uptake of cis-“PtCl2” derivatives. Our results are valuable in the future rational design of new platinum complexes with improved biological properties, as they expose the importance not only of their DNA binding abilities but also of additional factors such as protein binding.La Caixa Foundation (LCF/PR/PR12/11070003), Ministerio de Economía y Competitividad-FEDER (CTQ2014-58812-C2-2- R, CTQ2014-58812-C2-1-R, and CTQ2015-70371-REDT), Consejería de Educación−Junta de Castilla y León-FEDER (BU042U16), Spain

Different profiles of immune reconstitution in children and adults with HIV-infection after highly active antiretroviral therapy

BACKGROUND: Recent advances in characterizing the immune recovery of HIV-1-infected people have highlighted the importance of the thymus for peripheral T-cell diversity and function. The aim of this study was to investigate differences in immune reconstitution profiles after highly active antiretroviral therapy (HAART) between HIV-children and adults. METHODS: HIV patients were grouped according to their previous clinical and immunological status: 9 HIV-Reconstituting-adults (HIV-Rec-adults) and 10 HIV-Reconstituting-children (HIV-Rec-children) on HAART with viral load (VL) ≤400 copies/ml and CD4(+ )≥500 cells/μL at least during 6 months before the study and CD4(+ )≤300 cells/μL anytime before. Fifteen healthy-adults and 20 healthy-children (control subjects) were used to calculate Z-score values to unify value scales between children and adults to make them comparable. RESULTS: HIV-Rec-children had higher T-cell receptor excision circles (TREC) and lower interleukin (IL)-7 levels than HIV-Rec-adults (p < 0.05). When we analyzed Z-score values, HIV-Rec-children had higher TREC Z-score levels (p = 0.03) than HIV-Rec-adults but similar IL-7 Z-score levels. Regarding T-cell subsets, HIV-Rec-children had higher naïve CD4(+ )(CD4(+)CD45RA (hi+)CD27(+)), naïve CD8(+ )(CD8(+)CD45RA (hi+)CD27(+)), and memory CD8(+ )(CD8(+)CD45RO(+)) cells/μl than HIV-Rec-adults, but similar memory CD4(+ )(CD4(+)CD45RO(+)) counts. HIV-Rec-children had lower naïve CD8(+ )Z-score values than HIV-Rec-adults (p = 0.05). CONCLUSION: Our data suggest that HIV-Rec-children had better thymic function than HIV-Rec-adults and this fact affects the peripheral T-cell subsets. Thus, T-cell recovery after HAART in HIV-Rec-adults could be the consequence of antigen-independent peripheral T-cell expansion while in HIV-Rec-children thymic output could play a predominant role in immune reconstitution