Visualization of the flow distribution inside the piston displacement of a gamma-type stirling engine

The dynamics of the confined flow inside the piston displacement of a Gamma-type Stirling engine operating as a heat pump is experimentally analyzed. The diameter of the piston is 30 mm; 2 mm smaller than the internal diameter of the cold cylinder. As the piston performs its reciprocating motion, the gas leaks around the gap between the piston and the cylinder wall, generating a continuous pulsating motion. In the first part of the cycle air is introduced and compressed by the piston motion, and then the second part of the cycle starts by expanding the air and ejecting it from the assembly chamber. Experimental observations were carried out at frequencies in the range 100 to 300 rpm. The flow was visualized using a vertical laser beam plane oriented in the same axial direction of the piston’s motion. The particles used as trackers are water drops condensed on carbon dioxide microcrystals. Images were taken with a high speed video camera with a frame rate of 1000 fps. PIV techniques were implemented to identify the flow main structures. For analysis purposes, fixed phase averages of the velocity fields are required, due to the turbulent regime observed in this phenomena and its oscillatory nature. Based on experimental measurements it can be demonstrated that the average flow involved is not axisymmetric, although very interestingly, specific inlet and exit regions of the piston-cylinder gap were identified.Papers presented to the 12th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Costa de Sol, Spain on 11-13 July 2016

Theoretical and experimental study of polarization switching in longwavelength VCSELs subject to parallel optical injection

We report a theoretical and experimental analysis of the polarization switching found in a single-transverse mode VCSEL when subject to parallel optical injection. We have found a novel situation in which injection locking of the parallel polarization and excitation of the free-running orthogonal polarization of the VCSEL are simultaneously obtained. Analytical expressions for the power of both linear polarizations in the previous steady state are determined. We show that considering two linear polarization modes in a model of a VCSEL subject to parallel optical injection leads to simpler expressions than those found for a VCSEL with only a single linear polarization. We show that the power emitted in both linear polarizations depend linearly on the injected power. The stability region of this solution is measured in the plane injected power versus frequency detuning.This work has been funded by the Ministerio de Economía y Competitividad, Spain under project TEC2015-65212-C3-1-P and cofinanced by FEDER funds

A High-Fat Diet Modifies Brain Neurotransmitter Profile and Hippocampal Proteome and Morphology in an IUGR Pig Model

This research was funded by the Spanish Ministry of Economy and Competitivity (AGL2015-68463-C2-2-P to A.B. and projects AGL2013-48121-C3-R and AGL2016-79321-C2-1-R to A.G.-B.), cofunded by FEDER. N.Y. is recipient of a graduate student fellowship from the Spanish FPU National Program Grant (Ministry of Science, Innovation and Universities; number FPU17/01881). A.H.-M. is recipient of a graduate student fellowship from the Spanish FPI National Program Grant (Ministry of Science, Innovation and Universities; number BES-2017-080541).Intrauterine Growth Restriction (IUGR) hinders the correct growth of the fetus during pregnancy due to the lack of oxygen or nutrients. The developing fetus gives priority to brain development ("brain sparing"), but the risk exists of neurological and cognitive deficits at short or long term. On the other hand, diets rich in fat exert pernicious effects on brain function. Using a pig model of spontaneous IUGR, we have studied the effect on the adult of a long-term high-fat diet (HFD) on the neurotransmitter profile in several brain areas, and the morphology and the proteome of the hippocampus. Our hypothesis was that animals affected by IUGR (born with low birth weight) would present a different susceptibility to an HFD when they become adults, compared with normal birth-weight animals. Our results indicate that HFD affected the serotoninergic pathway, but it did not provoke relevant changes in the morphology of the hippocampus. Finally, the proteomic analysis revealed that, in some instances, NBW and LBW individuals respond to HFD in different ways. In particular, NBW animals presented changes in oxidative phosphorylation and the extracellular matrix, whereas LBW animals presented differences in RNA splicing, anterograde and retrograde transport and the mTOR pathway

Nonlinear dynamics induced by optical injection in optical frequency combs generated by gain-switching of laser diodes

We present experiments and numerical simulations of optical frequency combs generated by gain-switching a single mode laser diode when subject to optical injection. Our analysis focuses on the combs with a frequency separation fR in the GHz range. We present experimental maps in the parameter space spanned by the detuning and the strength of the optical injection that identify the boundaries between regions with different dynamical states. A rich variety of nonlinear behaviors including injection-locked, unlocked and irregular combs are observed and analyzed. The dynamical state corresponding to an injection locked comb, PN, is characterized by an optical phase oscillation with a well defined amplitude in such a way that repeats or changes in 2? with an N/f R period, where N is a natural number. Different regions of locked combs with a tongue shape around detuning values given by multiples of f R appear in the maps. P1 and P2 are the most widespread locked states for large values of the modulation amplitude. As this amplitude decreases a much larger variety of PN states with large values of N appear in small area regions of the map. Our numerical simulations are in very good agreement with experimental results.This work was supported by the Ministerio de Economía y Competitividad of Spain under Grants RTI2018-094118-B-C21 and RTI2018-094118-B-C22, and by Comunidad de Madrid, European Structural Funds (P2018/NMT-4326) and APOYO-JOVENES-KXHJ8C-16-VCKM78

MKK6 deficiency promotes cardiac dysfunction through MKK3-p38γ/δ-mTOR hyperactivation.

Stress-activated p38 kinases control a plethora of functions, and their dysregulation has been linked to the development of steatosis, obesity, immune disorders, and cancer. Therefore, they have been identified as potential targets for novel therapeutic strategies. There are four p38 family members (p38α, p38β, p38γ, and p38δ) that are activated by MKK3 and MKK6. Here, we demonstrate that lack of MKK6 reduces the lifespan in mice. Longitudinal study of cardiac function in MKK6 KO mice showed that young mice develop cardiac hypertrophy which progresses to cardiac dilatation and fibrosis with age. Mechanistically, lack of MKK6 blunts p38α activation while causing MKK3-p38γ/δ hyperphosphorylation and increased mammalian target of rapamycin (mTOR) signaling, resulting in cardiac hypertrophy. Cardiac hypertrophy in MKK6 KO mice is reverted by knocking out either p38γ or p38δ or by inhibiting the mTOR pathway with rapamycin. In conclusion, we have identified a key role for the MKK3/6-p38γ/δ pathway in the development of cardiac hypertrophy, which has important implications for the clinical use of p38α inhibitors in the long-term treatment since they might result in cardiotoxicity.We thank S Bartlett and F Chanut for English editing. We are grateful to RJ Davis, A Padmanabhan, M Costa and C López-Otín for critical reading of the manuscript. We thank Dr. RJ Davis for the MKK3 and MKK6 KO animals and Dr. Erwin F Wagner for the p38α flox mice. We thank AC Silva (ana@anasilva illustrations.com) for help with figure editing and design. This work was funded by a CNIC Intramural Project Severo Ochoa (Expediente 12–2016 IGP) to GS and JJ and PID2019-104399RB-I00 funded by MCIN/AEI/10.13039/501100011033 to GS. BGT was a fellow of FPI Severo Ochoa CNIC Program (SVP-2013-067639) and is an American Heart Association Postdoctoral Fellow (18POST34080175). RRB is a fellow of the FPU Program (FPU17/03847). The following grants provided additional funding: GS is granted by funds from European Regional Development Fund (ERDF): EFSD/Lilly European Diabetes Research Programme Dr Sabio, Fundación AECC PROYE19047SABI and Comunidad de Madrid IMMUNOTHERCAN-CM B2017/BMD-3733; US National Heart, Lung, and Blood Institute (R01 Grant HL122352), Fondos FEDER, Madrid, Spain, and Fundación Bancaria “La Caixa (project HR19/52160013); Fundación La Marató TV3: Ayudas a la investigación en enfermedades raras 2020 (LA MARATO-2020); and Instituto de Salud Carlos III to JJ. IN was funded by EFSD/Lilly grants (2017 and 2019), the CNIC IPP FP7 Marie Curie Programme (PCOFUND-2012–600396), EFSD Rising Star award (2019), JDC-2018-Incorporación (MIN/JDC1802). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC FoundationS

Synthetic lethal activity of benzophenanthridine alkaloids from Zanthoxylum coco against BRCA1-deficientcancer cells

Several plants from South America show strong antitumoral properties based on anti-proliferative and/or pro-apoptotic activities. In this work we aimed to identify selective cytotoxic compounds that target BRCA1-deficient cancer cells by Synthetic Lethality (SL) induction. Using a high-throughput screening technology developed in our laboratory, we analyzed a collection of extracts from 46 native plant species from Argentina using a wide dose-response scheme. A highly selective SL-induction capacity was found in an alkaloidal extract from Zanthoxylum coco (Fam. Rutaceae). Bio-guided fractionation coupled to HPLC led to the identification of active benzophenanthridine alkaloids. The most potent SL activity was found with the compound oxynitidine, which showed a remarkably low relative abundance in the active fractions. Further validation experiments were performed using the commercially available and closely related analog nitidine, which showed SL-induction activity against various BRCA1-deficient cell lines with different genetic backgrounds, even in the nanomolar range. Exploration of the underlying mechanism of action using BRCA1-KO cells revealed AKT and topoisomerases as the potential targets responsible of nitidine-triggered SL-induction. Taken together, our findings expose an unforeseen therapeutic activity of alkaloids from Zanthoxylum-spp. that position them as novel lead molecules for drug discovery.Fil: García, Iris Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas. Universidad Católica de Córdoba. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas; ArgentinaFil: Pansa, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas. Universidad Católica de Córdoba. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pacciaroni, Adriana del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: García, Manuela Emila. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Gonzalez, Maria Laura. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: Oberti, Juan Carlos María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Carpinella, Maria Cecilia. Universidad Católica de Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Recursos Naturales y Sustentabilidad José Sanchez Labrador S. J.; ArgentinaFil: Barboza, Gloria Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Nicotra, Viviana Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Soria, Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Outcomes of abdominal wall reconstruction in patients with the combination of complex midline and lateral incisional hernias.

Background The best treatment for the combined defects of midline and lateral incisional hernia is not known. The aim of our multicenter study was to evaluate the operative and patient-reported outcomes using a modified posterior component separation in patients who present with the combination of midline and lateral incisional hernia. Methods We identified patients from a prospective, multicenter database who underwent operative repairs of a midline and lateral incisional hernia at 4 centers with minimum 2-year follow-up. Hernias were divided into a main hernia based on the larger size and associated abdominal wall hernias. Outcomes reported were short- and long-term complications, including recurrence, pain, and bulging. Quality of life was assessed with the European Registry for Abdominal Wall Hernias Quality of Life score. Results Fifty-eight patients were identified. Almost 70% of patients presented with a midline defect as the main incisional hernia. The operative technique was a transversus abdominis release in 26 patients (45%), a modification of transversus abdominis release 27 (47%), a reverse transversus abdominis release in 3 (5%), and a primary, lateral retromuscular preperitoneal approach in 2 (3%). Surgical site occurrences occurred in 22 patients (38%), with only 8 patients (14%) requiring procedural intervention. During a mean follow-up of 30.1 ± 14.4 months, 2 (3%) cases of recurrence were diagnosed and required reoperation. There were also 4 (7%) patients with asymptomatic but visible bulging. The European Registry for Abdominal Wall Hernias Quality of Life score showed a statistically significant decrease in the 3 domains (pain, restriction, and cosmetic) in the postoperative score compared with the preoperative score. Conclusion The different techniques of posterior component separation in the treatment of combined midline and lateral incisional hernia show acceptable results, despite the associated high complexity. Patient-reported outcomes after measurement of the European Registry for Abdominal Wall Hernias Quality of Life score demonstrated a clinically important improvement in quality of life and pain.post-print2.323 K