Quantum diffusion beyond slow-roll: implications for primordial black-hole production

Primordial black-holes (PBH) can be produced in single-field models of inflation with a quasi-inflection point in the potential. In these models, a large production of PBHs requires a deviation from the slow-roll (SR) trajectory. In turn, this SR violation can produce an exponential growth of quantum fluctuations. We study the back-reaction of these quantum modes on the inflationary dynamics using stochastic inflation in the Hamilton-Jacobi formalism. We develop a methodology to solve quantum diffusion beyond SR in terms of the statistical moments of the probability distribution. We apply these techniques to a toy model potential with a quasi-inflection point. We find that there is an enhancement of the power spectrum due to the dominance of the stochastic noise in the phase beyond SR. Moreover, non-Gaussian corrections become as well relevant with a large positive kurtosis. Altogether, this produces a significant boost of PBH production. We discuss how our results extend to other single-field models with similar dynamics. We conclude that the abundance of PBHs in this class of models should be revisited including quantum diffusion.Comment: 17+7 pages, 5 figures. Matches JCAP versio

Towards the most general scalar-tensor theories of gravity: a unified approach in the language of differential forms

We use a description based on differential forms to systematically explore the space of scalar-tensor theories of gravity. Within this formalism, we propose a basis for the scalar sector at the lowest order in derivatives of the field and in any number of dimensions. This minimal basis is used to construct a finite and closed set of Lagrangians describing general scalar-tensor theories invariant under Local Lorentz Transformations in a pseudo-Riemannian manifold, which contains ten physically distinct elements in four spacetime dimensions. Subsequently, we compute their corresponding equations of motion and find which combinations are at most second order in derivatives in four as well as arbitrary number of dimensions. By studying the possible exact forms (total derivatives) and algebraic relations between the basis components, we discover that there are only four Lagrangian combinations producing second order equations, which can be associated with Horndeski's theory. In this process, we identify a new second order Lagrangian, named kinetic Gauss-Bonnet, that was not previously considered in the literature. However, we show that its dynamics is already contained in Horndeski's theory. Finally, we provide a full classification of the relations between different second order theories. This allows us to clarify, for instance, the connection between different covariantizations of Galileons theory. In conclusion, our formulation affords great computational simplicity with a systematic structure. As a first step we focus on theories with second order equations of motion. However, this new formalism aims to facilitate advances towards unveiling the most general scalar-tensor theories.Comment: 28 pages, 1 figure, version published in PRD (minor changes

Intrinsically disordered inhibitor of glutamine synthetase is a functional protein with random-coil-like pKa values

The sequential action of glutamine synthetase (GS) and glutamate synthase (GOGAT) in cyanobacteria allows the incorporation of ammonium into carbon skeletons. In the cyanobacterium Synechocystis sp. PCC 6803, the activity of GS is modulated by the interaction with proteins, which include a 65-residue-long intrinsically disordered protein (IDP), the inactivating factor IF7. This interaction is regulated by the presence of charged residues in both IF7 and GS. To understand how charged amino acids can affect the binding of an IDP with its target and to provide clues on electrostatic interactions in disordered states of proteins, we measured the pKa values of all IF7 acidic groups (Glu32, Glu36, Glu38, Asp40, Asp58, and Ser65, the backbone C-terminus) at 100 mM NaCl concentration, by using NMR spectroscopy. We also obtained solution structures of IF7 through molecular dynamics simulation, validated them on the basis of previous experiments, and used them to obtain theoretical estimates of the pKa values. Titration values for the two Asp and three Glu residues of IF7 were similar to those reported for random-coil models, suggesting the lack of electrostatic interactions around these residues. Furthermore, our results suggest the presence of helical structure at the N-terminus of the protein and of conformational changes at acidic pH values. The overall experimental and in silico findings suggest that local interactions and conformational equilibria do not play a role in determining the electrostatic features of the acidic residues of IF7.Ministerio de Economía y Competitividad CTQ 2015-64445-R, BFU2013- 41712-P, BIO2016-75634PJunta de Andalucía BIO-284Generalitat Valenciana Prometeo 018/201

Factores de riesgo cardiovascular en pacientes ancianos diabéticos que acuden a urgencias

Comunicación en formato cartel con defensa oralOBJETIVO: Son escasas las evidencias clínicas disponibles sobre los factores de riesgo cardiovascular en los pacientes ancianos diabéticos. Nuestro objetivo fue determinar los principales factores de riesgo cardiovasculares de los pacientes diabéticos ancianos en urgencias. MATERIAL Y MÉTODOS: Diseño, ámbito de realización y marco o nivel de atención sanitaria, criterios de selección, número de sujetos incluidos, número de sujetos que responden y abandonos, intervenciones (si procede), variables y métodos de evaluación de la respuesta. Análisis estadístico, limitaciones, aspectos ético-legales. Estudio descriptivo observacional, retrospectivo, transversal y quasiexperimental en pacientes diabéticos ≥65 años de ambos géneros que acudieron a urgencias durante 1 año. Criterios inclusión: tratamiento hipoglucemiante, HbA1c >6,5% durante el año previo, sin comorbilidades graves. RESULTADOS: Se han incluido 146 pacientes diabéticos tipo 2, 39,7% hombres,76,4±7,2 años. Un 24,2% presentó síndromes geriátricos, 93,2% presentó comorbilidades asociadas, 22,6% presentó afectación renal, 89% utilizaba normoglucemiantes orales (hombres 91,4% >mujeres 86,4%): Biguanidas 78,8%, IDPP-4 22,5%, sulfonilureas 2ª-generación 18,5%. El 61% tratado con metformina 850 mg, seguido de gliclazida 30 mg 13% y metformina 1 g 11%. Tratamientos para comorbilidades más usados: Antihipertensivos 88,40%, normocolesterolemiantes 58,90%, antiagregantes 56,80%, benzodiacepinas 45,90%, calcioantagonistas 37,7%, betabloqueantes adrenérgicos 37%, antidepresivos 26,70% y opiáceos 24%. CONCLUSION: Ser mujer, tener mayor edad, más comorbilidades y de ellas hipertensión arterial y fibrilación auricular se relacionó con el mayor número de ictus isquémicos y el mayor tiempo de evolución del accidente isquémico transitorio. La prevalencia de reacciones adversas a medicamentos fue el doble en las mujeres que en los hombres y mayor en los pacientes menores de 80 años.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

Gonadotropin-primed immature rats (GPIR) constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG) synthesis indomethacin (INDO) and a progesterone (P) receptor (PR) antagonist (RU486). Immature Wistar rats were primed with equine chorionic gonadotropin (eCG) at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG) 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC) was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age

El desarrollo y análisis de ECOEs mejoró las habilidades de comunicación, aprendizaje y evaluación de los estudiantes de Farmacología en el Grado de Podología.

Comunicación a congresoEl desarrollo y análisis de ECOEs mejoró las habilidades de comunicación, aprendizaje y evaluación de los estudiantes de Farmacología en el Grado de Podología. Bellido Estevez I, Blanco Reina E, Bellido Estevez MV, García Arnés JA, Gómez Luque A. Dep. Farmacología. Facultad de Medicina. IBIMA. S. de Anestesia. Hospitales Regional Carlos Haya y Virgen de la Victoria. Universidad de Málaga. Mlaga, España. Antecedentes/Objetivos: La enseñanza inversa facilita el aprendizaje activo. Las evaluaciones clínicas objetivas estructuradas (ECOEs) son herramientas evaluativas, multipropósito, versátiles, usadas para evaluar en el entorno clínico. Nuestro objetivo fue evaluar el impacto del desarrollo y análisis ECOEs en el aprendizaje de la farmacología. Métodos: Estudio prospectivo a lo largo de 5 años en el que los estudiantes de Farmacología del Grado de Podología desarrollaron y analizaron ECOEs usando técnicas de enseñanza inversa. Cada grupo (5 estudiantes máximo) analizó a lo largo de 1 semana una ECOE filmada y desarrollada por otros alumnos, preparó un resumen de los elementos correctos e incorrectos relacionados con eventos clínicos, usos de medicamentos y comportamientos de las personas. Cada grupo presentó sus resultados al resto de la clase, contestaron a las preguntas de sus compañeros y posteriormente a una encuesta de satisfacción. Resultados/Discusión: Fueron incluidos 405 estudiantes, 65,2% mujeres, 20±5,3 años. Los estudiantes dedicaron 13,4±5,4 h a analizar las ECOEs. El porcentaje de estudiantes satisfechos con esta forma de estudiar farmacología fue del 96,5%. Esta actividad incrementó el porcentaje de éxito en la evaluación final en las preguntas relacionadas con las ECOEs un 18,5% y en las no relacionadas un 10,1%. Conclusión: El desarrollo y análisis de ECOEs mejoró los conocimientos sobre el uso de medicamentos, habilidades de comunicación y evaluación de los estudiantes de Farmacología del Grado de Podología.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Efficient proton acceleration from a 3 TW table-top laser interacting with submicrometric mass-produced solid targets

[EN] Thin layer membranes with controllable features and material arrangements are often used as target materials for laser driven particle accelerators. Reduced cost, large scale fabrication of such membranes with high reproducibility, and good stability are central for the efficient production of proton beams. These characteristics are of growing importance in the context of advanced laser light sources where increased repetition rates boost the need for consumable targets with design and properties adjusted to study the different phenomena arising in ultra-intense laser-plasma interaction. Wepresent the fabrication of sub-micrometric thin-layer gold or aluminum membranes in a silicon wafer frame by using nano/micro-electro-mechanical-system (N/MEMS) processing which are suitable for rapid patterning and machining of many samples at the same time and allowing for high-throughput production of targets for laser-driven acceleration. Obtained targets were tested for laserproton acceleration through the Target Normal Sheath Acceleration mechanism (TNSA) in a series of experiments carried out on a purpose-made table-top Ti:Sa running at 3 TW peak power and 10 Hz diode pump rate with a contrast over ASE of 10(8)The authors highly appreciate the collaboration of Radosys (Budapest) which provided CR-39 detector material, etching bath, and readout equipment. This project has been financed by the Spanish Ministry for Economy and Competitiveness within the Retos-Colaboracion 2015 initiative, ref. RTC-2015-3278-1. P Mur has received a grant of the Garantia Juvenil 2015 program. This work has made use of the Spanish ICTS Network MICRONANOFABS partially supported by MEINCOM.Zaffino, R.; Seimetz, M.; Ruiz-De La Cruz, A.; Sánchez, I.; Mur, P.; Quirión, D.; Bellido-Millán, PJ.... (2018). Efficient proton acceleration from a 3 TW table-top laser interacting with submicrometric mass-produced solid targets. Journal of Physics Communications. 2(4):1-6. https://doi.org/10.1088/2399-6528/aabc25S1624Borghesi, M., Campbell, D. H., Schiavi, A., Haines, M. G., Willi, O., MacKinnon, A. J., … Bulanov, S. (2002). Electric field detection in laser-plasma interaction experiments via the proton imaging technique. Physics of Plasmas, 9(5), 2214-2220. doi:10.1063/1.1459457Ledingham, K., Bolton, P., Shikazono, N., & Ma, C.-M. (2014). Towards Laser Driven Hadron Cancer Radiotherapy: A Review of Progress. Applied Sciences, 4(3), 402-443. doi:10.3390/app4030402Spindloe, C., Arthur, G., Hall, F., Tomlinson, S., Potter, R., Kar, S., … Tolley, M. K. (2016). High volume fabrication of laser targets using MEMS techniques. Journal of Physics: Conference Series, 713, 012002. doi:10.1088/1742-6596/713/1/012002Schomburg, W. K. (2011). Thin Films. RWTHedition, 9-20. doi:10.1007/978-3-642-19489-4_4Bellido, P., Lera, R., Seimetz, M., Cruz, A. R. la, Torres-Peirò, S., Galán, M., … Benlloch, J. M. (2017). Characterization of protons accelerated from a 3 TW table-top laser system. Journal of Instrumentation, 12(05), T05001-T05001. doi:10.1088/1748-0221/12/05/t05001Mayer, M. (1999). SIMNRA, a simulation program for the analysis of NRA, RBS and ERDA. AIP Conference Proceedings. doi:10.1063/1.59188Ceccotti, T., Lévy, A., Popescu, H., Réau, F., D’Oliveira, P., Monot, P., … Martin, P. (2007). Proton Acceleration with High-Intensity Ultrahigh-Contrast Laser Pulses. Physical Review Letters, 99(18). doi:10.1103/physrevlett.99.185002Dollar, F., Reed, S. A., Matsuoka, T., Bulanov, S. S., Chvykov, V., Kalintchenko, G., … Maksimchuk, A. (2013). High-intensity laser-driven proton acceleration enhancement from hydrogen containing ultrathin targets. Applied Physics Letters, 103(14), 141117. doi:10.1063/1.4824361Neely, D., Foster, P., Robinson, A., Lindau, F., Lundh, O., Persson, A., … McKenna, P. (2006). Enhanced proton beams from ultrathin targets driven by high contrast laser pulses. Applied Physics Letters, 89(2), 021502. doi:10.1063/1.2220011Green, J. S., Carroll, D. C., Brenner, C., Dromey, B., Foster, P. S., Kar, S., … Zepf, M. (2010). Enhanced proton flux in the MeV range by defocused laser irradiation. New Journal of Physics, 12(8), 085012. doi:10.1088/1367-2630/12/8/085012Giuffrida, L., Svensson, K., Psikal, J., Dalui, M., Ekerfelt, H., Gallardo Gonzalez, I., … Margarone, D. (2017). Manipulation of laser-accelerated proton beam profiles by nanostructured and microstructured targets. Physical Review Accelerators and Beams, 20(8). doi:10.1103/physrevaccelbeams.20.08130

Wafer-scale fabrication of target arrays for stable generation of proton beams by laser-plasma interaction

[EN] Large-scale fabrication of targets for laser-driven acceleration of ion beams is a prerequisite to establish suitable applications, and to keep up with the challenge of increasing repetition rate of currently available high-power lasers. Here we present manufacturing and test results of large arrays of solid targets for TNSA laser-driven ion acceleration. By applying micro-electro-mechanical-system (MEMS) based methods allowing for parallel processing of thousands of targets on a single Si wafer, sub-micrometric, thin-layer metallic membranes were fabricated by combining photolithography, physical and chemical vapor deposition, selective etching, and Si micromachining. These structures were characterized by using optical and atomic force microscopy. Their performance for the production of laser-driven proton beams was tested on a purpose-made table-top Ti:Sapphire laser system running at 3 TW peak power with a contrast over ASE of 108. We have performed several test series achieving maximum proton energy values around 2 MeV.This work has made use of the Spanish ICTS Network MICRONANOFABS partially supported by MEINCOM. This project has been financed by the Spanish Ministry for Economy and Competitiveness within the Retos- Colaboración 2015 initiative, ref. RTC-2015-3278-1. P. Mur has received a grant of the Garantía Juvenil 2015 program.Zaffino, R.; Seimetz, M.; Ruiz-De La Cruz, A.; Sánchez, I.; Mur, P.; Bellido-Millán, PJ.; Lera, R.... (2018). Wafer-scale fabrication of target arrays for stable generation of proton beams by laser-plasma interaction. Journal of Physics: Conference Series (Online). 1079. https://doi.org/10.1088/1742-6596/1079/1/012007S0120071079Abedi, S., Dorranian, D., Abari, M. E., & Shokri, B. (2011). Relativistic effects in the interaction of high intensity ultra-short laser pulse with collisional underdense plasma. Physics of Plasmas, 18(9), 093108. doi:10.1063/1.3633529Antici, P., Fuchs, J., d’ Humières, E., Lefebvre, E., Borghesi, M., Brambrink, E., … Pépin, H. (2007). Energetic protons generated by ultrahigh contrast laser pulses interacting with ultrathin targets. Physics of Plasmas, 14(3), 030701. doi:10.1063/1.2480610Ceccotti, T., Lévy, A., Popescu, H., Réau, F., D’Oliveira, P., Monot, P., … Martin, P. (2007). Proton Acceleration with High-Intensity Ultrahigh-Contrast Laser Pulses. Physical Review Letters, 99(18). doi:10.1103/physrevlett.99.18500

Results of a combined monolithic crystal and an array of ASICs controlled SiPMs

[EN] In this work we present the energy and spatial resolutions we have obtained for a γ ray detector based on a monolithic LYSO crystal coupled to an array of 256 SiPMs. Two crystal configurations of the same trapezoidal shape have been tried. In one approach all surfaces were black painted but the exit one facing the photosensor array which was polished. The other approach included a retroreflector (RR) layer coupled to the entrance face of the crystal powering the amount of transmitted light to the photosensors. Two coupling media between the scintillator and the SiPM array were used, namely direct coupling by means of optical grease and coupling through an array of light guides. Since the same operational voltage was supplied to the entire array, it was needed to equalize their gains before feeding their signals to the Data Acquisition system. Such a job was performed by means of 4 scalable Application Specific Circuits (ASICs). An energy resolution of about 24.4% has been achieved for the direct coupling with the RR layer together with a spatial resolution of approximately 2.9 mm at the detector center. With the light guides coupling the effects of image compression at the edges are significantly minimized, but worsening the energy resolution to about 33.1% with a spatial resolution nearing 4 mm at the detector center. & 2013 Elsevier B.V. All rights reserved.cknowledgments This work was supported by the Centre for Industrial Technological Development co-funded by FEDER through the Technology Fund (DREAM Project, IDI-20110718), the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (IþDþI) under Grant no. FIS2010-21216-CO2-01 and the Valencian Local Government under Grant PROMETEO 2008/114Conde Castellanos, PE.; González Martínez, AJ.; Hernández Hernández, L.; Bellido, P.; Iborra Carreres, A.; Crespo Navarro, E.; Moliner Martínez, L.... (2014). Results of a combined monolithic crystal and an array of ASICs controlled SiPMs. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 734:132-136. https://doi.org/10.1016/j.nima.2013.08.079S13213673

Tracking the antibody immunome in sporadic colorectal cancer by using antigen self-assembled protein arrays

© 2021 by the authors.Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for the grants: FIS PI14/01538, FIS PI17/01930 and CB16/12/00400. We also acknowledge Fondos FEDER (EU) “Una manera de hacer Europa” and Junta Castilla-León (COVID19 grant COV20EDU/00187). Fundación Solórzano FS/38-2017. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023, of the PE I + D + I 2017-2020, funded by ISCIII and FEDER. CNPq-National Council for Scientific and Technological Development (Brazil) (306258/2019-6) and FAPERJ-Foundation for Research Support of Rio de Janeiro State for the financial support (E-26/201.670/2017 and 210.379/2018). M. González-González is supported by MINECOPTA2019-017870-I.A. Landeira-Viñuela is supported by VIII Centenario-USAL PhD Program. P.J.-V. is supported by JCYL PhD Program and scholarship JCYL-EDU/601/2020. P.D. and E.B. are supported by a JCYL-EDU/346/2013 Ph.D. scholarship