Bridging Proper Orthogonal Decomposition methods and augmented Newton-Krylov algorithms: an adaptive model order reduction for highly nonlinear mechanical problems

This article describes a bridge between POD-based model order reduction techniques and the classical Newton/Krylov solvers. This bridge is used to derive an efficient algorithm to correct, "on-the-fly", the reduced order modelling of highly nonlinear problems undergoing strong topological changes. Damage initiation problems are addressed and tackle via a corrected hyperreduction method. It is shown that the relevancy of reduced order model can be significantly improved with reasonable additional costs when using this algorithm, even when strong topological changes are involved

Nudging and boosting children's restaurant menus for healthier food choice: A blinded quasi-randomized controlled trial in a real life setting.

Background: Restaurants are ideal settings for implementing food interventions targeted at children. Studies with adults suggest that changes to the physical menu can lead to healthier food choices; online studies with parents indicate that specific menu designs facilitate healthier choices. However, it is unknown whether applying well-established nudging and boosting methods to children’s menus also increases their choice of healthier meals in a real-world restaurant setting. Methods: The effects of two versions of a restaurant menu on the frequency of choosing a healthy meal (newly created, healthy target dish) were tested in a blinded quasi-randomized controlled trial. The menu in the control condition contained all dishes (including the healthy target dish) in a standardized format. The intervention menu included nudging (e.g. comic character, fun attractive name for the dish) and boosting elements (e.g. information on low calorie density) next to the healthy target dish. Over five months, the control and intervention menus were switched every two weeks and records were made of how often the healthy target dish was ordered. Results: In total, 607 orders were made from the children’s restaurant menu (57% from the intervention menu). During the intervention phase, 4.2% of all ordered dishes from the children’s menu were the healthy target dish, during the control phase, 4.4% of orders were for the target dish (p=.896). Conclusions: Contrary to our hypothesis, a modified children’s menu did not lead to a significant increase in the number of orders for a healthy dish compared with a neutral control menu. Importantly, given that parents and children often choose the child’s dish together, particularly boosting methods that focus on social processes and joint decision making could be promising to increase children’s frequency of healthy food choices in restaurants

Targeting ER-mitochondria signaling as a therapeutic target for frontotemporal dementia and related amyotrophic lateral sclerosis

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two major neurodegenerative diseases. FTD is the second most common cause of dementia and ALS is the most common form of motor neuron disease. These diseases are now known to be linked. There are no cures or effective treatments for FTD or ALS and so new targets for therapeutic intervention are required but this is hampered by the large number of physiological processes that are damaged in FTD/ALS. Many of these damaged functions are now known to be regulated by signaling between the endoplasmic reticulum (ER) and mitochondria. This signaling is mediated by “tethering” proteins that serve to recruit ER to mitochondria. One tether strongly associated with FTD/ALS involves an interaction between the ER protein VAPB and the mitochondrial protein PTPIP51. Recent studies have shown that ER-mitochondria signaling is damaged in FTD/ALS and that this involves breaking of the VAPB-PTPIP51 tethers. Correcting disrupted tethering may therefore correct many other downstream damaged features of FTD/ALS. Here, we review progress on this topic with particular emphasis on targeting of the VAPB-PTPIP51 tethers as a new drug target.</p

PMV Junior – HERSIL

Con la finalidad de hacer un análisis más específico de los productos de la marca, el desarrollo del trabajo se centrará en uno de los productos estrella de Hersil, PVM Junior. PVM Junior son las siglas para proteínas, vitaminas y minerales. El nombre resalta las principales características del producto. Es un complemento nutricional que brinda las proteínas, vitaminas y minerales necesarios para cubrir los requerimientos diarios de micro y macronutrientes y maximizar el crecimiento y desarrollo del niño en las etapas en las que necesita de un alto requerimiento nutricional. Asimismo, es extensible pues existe el PVM para adultos. Es distintivo pues en comparación con sus competidores es el único nombre con las siglas de sus beneficios. Además, el nombre es corto y fácil de recordar y pronunciar

The PTPIP51 coiled-coil domain is important in VAPB binding, formation of ER-mitochondria contacts and IP3 receptor delivery of Ca2+ to mitochondria

Signaling between the endoplasmic reticulum (ER) and mitochondria regulates a number of fundamental physiological processes. This signaling involves close physical contacts between the two organelles that are mediated by the VAPB-PTPIP51 ″tethering” proteins. The VAPB-PTPIP51 tethers facilitate inositol 1,4,5-trisphosphate (IP3) receptor delivery of Ca 2+ from ER to mitochondria. Damage to the tethers is seen in Alzheimer’s disease, Parkinson’s disease and frontotemporal dementia with related amyotrophic lateral sclerosis (FTD/ALS). Understanding the mechanisms that regulate the VAPB‐PTPIP51 interaction thus represents an important area of research. Recent studies suggest that an FFAT motif in PTPIP51 is key to its binding to VAPB but this work relies on in vitro studies with short peptides. Cellular studies to support this notion with full-length proteins are lacking. Here we address this issue. Immunoprecipitation assays from transfected cells revealed that deletion of the PTPIP51 FFAT motif has little effect on VAPB binding. However, mutation and deletion of a nearby coiled-coil domain markedly affect this binding. Using electron microscopy, we then show that deletion of the coiled-coil domain but not the FFAT motif abrogates the effect of PTPIP51 on ER-mitochondria contacts. Finally, we show that deletion of the coiled-coil domain but not the FFAT motif abrogates the effect of PTPIP51 on the IP3 receptor-mediated delivery of Ca 2+ to mitochondria. Thus, the coiled-coil domain is essential for PTPIP51 ER-mitochondria signaling functions. </p

Cambios en la legislación laboral peruana a raíz de la emergencia sanitaria por el Covid-19

Debido al contexto actual en el que nos encontramos y las medidas dictadas por el Gobierno para frenar el contagio, muchas empresas han debido adaptarse a distintas regulaciones para sus actividades y en muchos casos frenar sus operaciones

Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases

Signaling between the endoplasmic reticulum (ER) and mitochondria regulates many of the seemingly disparate physiological functions that are damaged in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). A number of studies have now demonstrated that ER-mitochondria signaling is perturbed in these diseases and there is evidence that this may be a driving mechanism in disease onset and progression. VAPB and PTPIP51 are ER-mitochondria tethering proteins; VAPB is an ER protein and PTPIP51 is an outer mitochondrial membrane protein and the two proteins interact to enable inter-organelle signaling. The VAPB-PTPIP51 interaction is disrupted in Alzheimer's disease, Parkinson's disease, FTD and ALS. Here we review the roles of VAPB and PTPIP51 in ER-mitochondria signaling and the mechanisms by which neurodegenerative disease insults may disrupt the VAPB-PTPIP51 interaction.</p

Fibroblast Nox2 (NADPH Oxidase-2) Regulates ANG II (Angiotensin II)–Induced Vascular Remodeling and Hypertension via Paracrine Signaling to Vascular Smooth Muscle Cells

OBJECTIVE:The superoxide-generating Nox2 (NADPH oxidase-2) is expressed in multiple cell types. Previous studies demonstrated distinct roles for cardiomyocyte, endothelial cell, and leukocyte cell Nox2 in ANG II (angiotensin II)–induced cardiovascular remodeling. However, the in vivo role of fibroblast Nox2 remains unclear.APPROACH AND RESULTS:We developed a novel mouse model with inducible fibroblast-specific deficiency of Nox2 (fibroblast-specific Nox2 knockout or Fibro-Nox2KO mice) and investigated the responses to chronic ANG II stimulation. Fibro-Nox2KO mice showed no differences in basal blood pressure or vessel wall morphology, but the hypertensive response to ANG II infusion (1.1 mg/[kg·day] for 14 days) was substantially reduced as compared to control Nox2-Flox littermates. This was accompanied by a significant attenuation of aortic and resistance vessel remodeling. The conditioned medium of ANG II–stimulated primary fibroblasts induced a significant increase in vascular smooth muscle cell growth, which was inhibited by the short hairpin RNA (shRNA)-mediated knockdown of fibroblast Nox2. Mass spectrometric analysis of the secretome of ANG II–treated primary fibroblasts identified GDF6 (growth differentiation factor 6) as a potential growth factor that may be involved in these effects. Recombinant GDF6 induced a concentration-dependent increase in vascular smooth muscle cell growth while chronic ANG II infusion in vivo significantly increased aortic GDF6 protein levels in control mice but not Fibro-Nox2KO animals. Finally, silencing GDF6 in fibroblasts prevented the induction of vascular smooth muscle cell growth by fibroblast-conditioned media in vitro.CONCLUSIONS:These results indicate that fibroblast Nox2 plays a crucial role in the development of ANG II–induced vascular remodeling and hypertension in vivo. Mechanistically, fibroblast Nox2 may regulate paracrine signaling to medial vascular smooth muscle cells via factors, such as GDF6

La importancia del uso de energías renovables en centros comerciales en Lima

"No podemos seguir quemando carbón en nuestras centrales eléctricas. El carbón también es un recurso finito. Debemos encontrar alternativas, y es una mejor idea encontrar alternativas antes de esperar hasta que nos quedemos sin carbón" dijo Elon Musk (CEO de SpaceX, SolarCity y Tesla). En los últimos años, la problemática sobre la contaminación viene cobrando más importancia, distintas personalidades e instituciones en todo el mundo vienen alzando la voz sobre este tema y están buscando soluciones para poder contrarrestar esta inminente catástrofe. Es aquí donde el significado de energía renovable cobra sentido, estas son energías las cuales provienen de fuentes naturales inagotables como el agua, el viento y el sol. Estas energías tienen diferentes tipos entre los cuales están: la energía eólica, hidráulica, solar, geotérmica, mareomotriz, undimotriz y la biomasa o el biogás. En el siguiente trabajo se hablará sobre como en el Perú el uso de estas energías sigue siendo escaso, ya que a pesar de que se ha tratado de impulsar su uso, esto no se ha logrado concretar. Podemos ver también, que Lima es la octava ciudad con mayor contaminación de América Latina y que el 73.6% de energía que se utiliza en el país proviene de yacimientos fósiles y minerales. Esto genera controversia, debido a que en los últimos años se ha tratado de impulsar este tipo de energía sin éxito alguno. Las razones de esta situación son la falta de incentivos fiscales en estos proyectos, la desinformación que hay sobre el uso de estas fuentes de energías y el poco apoyo del Estado. Conceptuamos que, para lograr el uso de estas fuentes de energías en el Perú, es necesario analizar las políticas que se vienen utilizando en distintos países. Por ejemplo, exigir una cuota necesaria del uso de estas energías en los proyectos y la aplicación de impuestos para proyectos que utilicen fuentes de energías tradicionales. Por otro lado, es necesario que el Estado realice financiamiento a este tipo de proyectos y capacitaciones para informar sobre los beneficios de utilizar estas fuentes de energía