Submanifolds with boundary and Stokes' Theorem in Heisenberg groups

We introduce and study the notion of $C^1_\mathbb{H}$-regular submanifold with boundary in sub-Riemannian Heisenberg groups. As an application, we prove a version of Stokes' Theorem for $C^1_\mathbb{H}$-regular submanifolds with boundary that takes into account Rumin's complex of differential forms in Heisenberg groups.Comment: 30 page

Help! I need somebody! Multidisciplinary support forworkers in the economic crisis

La actual crisis económica está causando dificultades a una gran cantidad de trabajadores en diferentes campos, y ahora, muchos de ellos, se encuentran necesitando ayuda. La pregunta es cómo apoyarles de manera eficaz, sobre todo teniendo en cuenta la amplia gama de condiciones, problemas, enfermedades, y temores que experimentan en relación a la situación económica. Desde esta perspectiva, un factor crítico de éxito se puede identificar en la naturaleza multidisciplinar de la intervención. De hecho, la ayuda no puede ser sólo psicológica: también existe la necesidad de apoyo jurídico, económico, social y médico. El psicólogo, dentro de este marco, desempeña un papel fundamental: no sólo el de prestar ayuda psicológica, sino también el de la coordinación de los otros profesionales con el fin de producir un servicio integrado que sea aceptable, comprensible y útil para los trabajadores en busca de apoyo. Este artículo examina la experiencia del Centro de asistencia multidisciplinar creado en el área de Padova, Italia, para la asistencia a los trabajadores que experimentan dificultades relacionadas con la crisis. Este centro fue creado en 2010 después de una serie de suicidios que podrían estar relacionados con el trabajo, y contribuyó a ayudar a más de 150 trabajadores. Se procede a examinar y discutir sus metodologías, procedimientos y resultados.The current economic crisis is causing difficulties to a vast amount of workers in different fields, and many of them now find themselves in need of help. The question is how to effectively support them, especially considering the wide range of conditions, problems, diseases, and fears that they experience in relation to the contingent economic situation. In this perspective, one critical success factor can be identified in the multidisciplinary natureof the intervention. In fact the help cannot be just psychological: there is also the need of legal, economic, social and medical support. The psychologist, in this perspective, has a pivotal role: not only the one of giving psychological aid, but also the one of coordinating the other professionals in order to produce an integrated service that is acceptable, understandable and useful for the workers seeking support. This paper examines the experience of the multidisciplinary help center created in the area of Padova, Italy, for the assistance to workers experiencing difficulties related to the crisis. This center was established in 2010 after a series of suicides that could be related to work, and contributed to help more than 150 workers. Its methodologies, procedures and results are examined and discussed.peerReviewe

Characterization of the interaction of African swine fever virus with monocytes and derived macrophage subsets.

Abstract African swine fever (ASF) is a devastating disease for which there is no vaccine available. The ASF virus (ASFV) primarily infects cells of the myeloid lineage and this tropism is thought to be crucial for disease pathogenesis. A detailed in vitro characterization of the interactions of a virulent Sardinian isolate (22653/14) and a tissue culture adapted avirulent strain (BA71V) of ASFV with porcine monocytes, un-activated (moMΦ), classically (moM1) and alternatively (moM2) activated monocyte-derived macrophages was conducted in an attempt to better understand this relationship. Using a multiplicity-of-infection (MOI) of 1, both viruses were able to infect monocytes and macrophage subsets, but BA71V presented a reduced ability to infect moM1 compared to 22653/14, with higher expression of early compared to late proteins. Using an MOI of 0.01, only 22653/14 was able to replicate in all the macrophage subsets, with initially lowest in moM1 and moM2. No differences were observed in the expression of CD163 between ASFV infected and uninfected bystander cells. ASFV down-regulated CD16 expression but did not modulate MHC class II levels in monocytes and macrophage subsets. BA71V-infected but not 22653/14-infected moMΦ and moM2 presented with a reduced expression of MHC class I compared to the mock-infected controls. Higher levels of IL-18, IL1-β and IL-1α were released from moM1 after infection with BA71V compared to 22653/14 or mock-infected control. These results revealed differences between these ASFV strains, suggesting that virulent isolates have evolved mechanisms to counteract activated macrophages responses, promoting their survival, dissemination in the host and so ASF pathogenesis

A simplified genomic profiling approach predicts outcome in metastatic colorectal cancer

The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on TP53 and/or RAS genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of TP53/RAS, the expected response is much worse compared to patients with exclusive TP53/RAS mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy

Old World megadroughts and pluvials during the Common Era

Climate model projections suggest widespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other “Old World” climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the “Old World Drought Atlas” (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era. The OWDA matches historical accounts of severe drought and wetness with a spatial completeness not previously available. In addition, megadroughts reconstructed over north-central Europe in the 11th and mid-15th centuries reinforce other evidence from North America and Asia that droughts were more severe, extensive, and prolonged over Northern Hemisphere land areas before the 20th century, with an inadequate understanding of their causes. The OWDA provides new data to determine the causes of Old World drought and wetness and attribute past climate variability to forced and/or internal variability

Endocannabinoid Tone Regulates Human Sebocyte Biology

We have previously shown that endocannabinoids (eCBs)(e.g., anandamide) are involved in the maintenance of homeostatic sebaceous lipid production inhuman sebaceous glands and thateCB treatment dramatically increases sebaceous lipid production. Here, we aimed to investigate the expression of the major eCB synthesizing and degrading enzymes and to study the effects of eCB uptake inhibitors on human SZ95 sebocytes, thus exploring the role of the putative eCB membrane transporter, which has been hypothesized to facilitate the cellular uptake and subsequent degradation of eCBs. We found that the major eCB synthesizing (N-acyl phosphatidylethanolaminespecific phospholipase D, and diacylglycerol lipase-a and -b) and degrading (fatty acid amide hydrolase, monoacylglycerol lipase) enzymes are expressed in SZ95 sebocytes and also in sebaceous glands (except for diacylglycerol lipase-a, the staining of whichwas dubious in histological preparations). eCB uptake-inhibitionwith VDM11 induced amoderate increase insebaceous lipid production and also elevated the levels of variouseCBs and related acylethanolamides. Finally, we found that VDM11 was able to interfere with the proinflammatory action of the TLR4 activator lipopolysaccharide. Collectively, our data suggest that inhibition of eCB uptake exerts anti-inflammatory actions and elevates both sebaceous lipid production and eCB levels; thus, these inhibitors might be beneficial in cutaneous inflammatory conditions accompanied by dry skin

Tree rings reveal globally coherent signature of cosmogenic radiocarbon events in 774 and 993 CE

This study was funded by the WSL-internal COSMIC project (5233.00148.001.01), the ETHZ (Laboratory of Ion Beam Physics), the Swiss National Science Foundation (SNF Grant 200021L_157187/1), and as the Czech Republic Grant Agency project no. 17-22102s.Though tree-ring chronologies are annually resolved, their dating has never been independently validated at the global scale. Moreover, it is unknown if atmospheric radiocarbon enrichment events of cosmogenic origin leave spatiotemporally consistent fingerprints. Here we measure the 14C content in 484 individual tree rings formed in the periods 770–780 and 990–1000 CE. Distinct 14C excursions starting in the boreal summer of 774 and the boreal spring of 993 ensure the precise dating of 44 tree-ring records from five continents. We also identify a meridional decline of 11-year mean atmospheric radiocarbon concentrations across both hemispheres. Corroborated by historical eye-witness accounts of red auroras, our results suggest a global exposure to strong solar proton radiation. To improve understanding of the return frequency and intensity of past cosmic events, which is particularly important for assessing the potential threat of space weather on our society, further annually resolved 14C measurements are needed.Publisher PDFPeer reviewe

Help! I need somebody! Multidisciplinary support forworkers in the economic crisis

La actual crisis económica está causando dificultades a una gran cantidad de trabajadores en diferentes campos, y ahora, muchos de ellos, se encuentran necesitando ayuda. La pregunta es cómo apoyarles de manera eficaz, sobre todo teniendo en cuenta la amplia gama de condiciones, problemas, enfermedades, y temores que experimentan en relación a la situación económica. Desde esta perspectiva, un factor crítico de éxito se puede identificar en la naturaleza multidisciplinar de la intervención. De hecho, la ayuda no puede ser sólo psicológica: también existe la necesidad de apoyo jurídico, económico, social y médico. El psicólogo, dentro de este marco, desempeña un papel fundamental: no sólo el de prestar ayuda psicológica, sino también el de la coordinación de los otros profesionales con el fin de producir un servicio integrado que sea aceptable, comprensible y útil para los trabajadores en busca de apoyo. Este artículo examina la experiencia del Centro de asistencia multidisciplinar creado en el área de Padova, Italia, para la asistencia a los trabajadores que experimentan dificultades relacionadas con la crisis. Este centro fue creado en 2010 después de una serie de suicidios que podrían estar relacionados con el trabajo, y contribuyó a ayudar a más de 150 trabajadores. Se procede a examinar y discutir sus metodologías, procedimientos y resultados.The current economic crisis is causing difficulties to a vast amount of workers in different fields, and many of them now find themselves in need of help. The question is how to effectively support them, especially considering the wide range of conditions, problems, diseases, and fears that they experience in relation to the contingent economic situation. In this perspective, one critical success factor can be identified in the multidisciplinary natureof the intervention. In fact the help cannot be just psychological: there is also the need of legal, economic, social and medical support. The psychologist, in this perspective, has a pivotal role: not only the one of giving psychological aid, but also the one of coordinating the other professionals in order to produce an integrated service that is acceptable, understandable and useful for the workers seeking support. This paper examines the experience of the multidisciplinary help center created in the area of Padova, Italy, for the assistance to workers experiencing difficulties related to the crisis. This center was established in 2010 after a series of suicides that could be related to work, and contributed to help more than 150 workers. Its methodologies, procedures and results are examined and discussed.peerReviewe