Stimați și dragi timișoreni

Dear Shim Shim, I hate this month, it's so miserable and even more so cos you passed on Halloween eve. I remember it all so vividly, your loss and Zeusy's

Contes de fées aux enfants - Dodo le mouton et le landau mystérieux.

Contes de fées aux enfants - Octo-Puce la pieuvre et Craby-la-Pince le crabe.

Affiches.
Vous pouvez commander des affiches de cette image en ligne.
De très petit à 76 x 102 centimètres, c'est à 30 x 40 pouces.
Prix d'USS 1.95 vers les USA $79.95.

Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. As a result of globally increasing risk factors including metabolic disorders, the incidence rates of HCC are still rising. However, the molecular hallmarks of HCC remain poorly understood. Neuropeptide Y (NPY) and NPY receptors represent a highly conserved, stress-activated system involved in diverse cancer-related hallmarks including aging and metabolic alterations, but its impact on liver cancer had been unclear. Here, we observed increased expression of NPY5 receptor (Y5R) in HCC, which correlated with tumor growth and survival. Furthermore, we found that its ligand NPY was secreted by peritumorous hepatocytes. Hepatocyte-derived NPY promoted HCC progression by Y5R activation. TGF-β1 was identified as a regulator of NPY in hepatocytes and induced Y5R in invasive cancer cells. Moreover, NPY conversion by dipeptidylpeptidase 4 (DPP4) augmented Y5R activation and function in liver cancer. The TGF-β/NPY/Y5R axis and DPP4 represent attractive therapeutic targets for controlling liver cancer progression.

BACKGROUND Neurofibroma/schwannoma hybrid nerve sheath tumors (N/S HNSTs) are neoplasms associated with larger nerves that occur sporadically and in the context of schwannomatosis or neurofibromatosis type 2 or 1. Clinical management of N/S HNSTs is challenging, especially for large tumors, and established systemic treatments are lacking.METHODS We used next-generation sequencing and array-based DNA methylation profiling to determine the clinically actionable genomic and epigenomic landscapes of N/S HNSTs.RESULTS Whole-exome sequencing within a precision oncology program identified an activating mutation (p.Asp769Tyr) in the catalytic domain of the ERBB2 receptor tyrosine kinase in a patient with schwannomatosis-associated N/S HNST, and targeted treatment with the small-molecule ERBB inhibitor lapatinib led to prolonged clinical benefit and a lasting radiographic and metabolic response. Analysis of a multicenter validation cohort revealed recurrent ERBB2 mutations (p.Leu755Ser, p.Asp769Tyr, p.Val777Leu) in N/S HNSTs occurring in patients who met diagnostic criteria for sporadic schwannomatosis (3 of 7 patients), but not in N/S HNSTs arising in the context of neurofibromatosis (6 patients) or outside a tumor syndrome (1 patient), and showed that ERBB2-mutant N/S HNSTs cluster in a distinct subgroup of peripheral nerve sheath tumors based on genome-wide DNA methylation patterns.CONCLUSION These findings uncover a key biological feature of N/S HNSTs that may have important diagnostic and therapeutic implications.FUNDING This work was supported by grant H021 from DKFZ-HIPO, the University Cancer Center Frankfurt, and the Frankfurt Research Funding Clinician Scientist Program.

Treating neuropathic pain is challenging and novel non–opioid-based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence, and in situ hybridization, we found that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element–binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights into its signaling pathways. CARTp is involved in many diseases including depression and reward and addiction; de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.

Regenerative pain medicine, which seeks to harness the body’s own reparative capacity, is rapidly emerging as a field within pain medicine and orthopedics. It is increasingly appreciated that common analgesic mechanisms for these treatments depend on neuroimmune modulation. In this Review, we discuss recent progress in mechanistic understanding of nociceptive sensitization in chronic pain with a focus on neuroimmune modulation. We also examine the spectrum of regenerative outcomes, including preclinical and clinical outcomes. We further distinguish the analgesic mechanisms of regenerative therapies from those of cellular replacement, creating a conceptual and mechanistic framework to evaluate future research on regenerative medicine.

The physical integrity of endothelial cells (ECs) lining the blood vessels regulates the inflammatory response. Both innate immunity and inflammatory disorders hinge on the EC-neutrophil interaction. Neutrophil binding, rolling, and migrating along and between ECs is associated with vascular permeability. In this issue of the JCI, Owen-Woods et al. tracked neutrophils in vivo in venules of mouse striated muscle and revealed how endothelial permeability can affect neutrophil trafficking. Strikingly, many neutrophils that migrated between EC junctions were able to rejoin the blood circulation. Further, the chemokine and neutrophil chemoattractant, CXCL1, drove this reverse transendothelial migration (rTEM). This paradigm-shifting study provides a mechanism for distal organ damage as well as an explanation for sepsis-associated acute respiratory distress syndrome.

Increased microvascular permeability to plasma proteins and neutrophil emigration are hallmarks of innate immunity and key features of numerous inflammatory disorders. Although neutrophils can promote microvascular leakage, the impact of vascular permeability on neutrophil trafficking is unknown. Here, through the application of confocal intravital microscopy, we report that vascular permeability–enhancing stimuli caused a significant frequency of neutrophil reverse transendothelial cell migration (rTEM). Furthermore, mice with a selective defect in microvascular permeability enhancement (VEC-Y685F-ki) showed reduced incidence of neutrophil rTEM. Mechanistically, elevated vascular leakage promoted movement of interstitial chemokines into the bloodstream, a response that supported abluminal-to-luminal neutrophil TEM. Through development of an in vivo cell labeling method we provide direct evidence for the systemic dissemination of rTEM neutrophils, and showed them to exhibit an activated phenotype and be capable of trafficking to the lungs where their presence was aligned with regions of vascular injury. Collectively, we demonstrate that increased microvascular leakage reverses the localization of directional cues across venular walls, thus causing neutrophils engaged in diapedesis to reenter the systemic circulation. This cascade of events offers a mechanism to explain how local tissue inflammation and vascular permeability can induce downstream pathological effects in remote organs, most notably in the lungs.

Erowid Exp108047

PSA Peugeot Citroën and IBM today announced a partnership to help various industries within the Internet of Things economy to analyze data to deliver new services from connected vehicles.

Today IBM and Eurobank announced the first cloud-based digital platform for online international commercial trading. Using IBM's industry-leading Digital Experience software, with advanced cloud capabilities and social offerings, Eurobank is uniting exporters and importers from around the globe to enhance international trade operations and increase transactions.

Fleury Medicina e Saúde es el primer socio de la unidad IBM Watson Health en Latinoamérica. Las dos compañías trabajaron juntas para testear y validar la solución Watson for Genomics en Brasil como una potencial herramienta, que provee información para ayudar en la toma de decisiones médicas. De este modo, la alianza busca avances que permitan aumentar la precisión en la medicina personalizada.

IBM (NYSE: IBM) et SAP SE (NYSE: SAP) annoncent aujourd’hui des projets communs pour accompagner leurs clients dans la modernisation de leurs systèmes et processus afin d’accélérer leur présence dans l’économie numérique. Les deux compagnies envisagent particulièrement d’innover ensemble pour créer de nouvelles solutions qui augmentent la valeur ajoutée du client en s’appuyant sur des extensions cognitives, des expériences client et utilisateur renforcées ainsi que des fonctionnalités sectorielles. Tout ceci doté de la SAP® Business Suite, du logiciel 4 SAP HANA® (SAP S/4HANA) et disponible sur site et dans le Cloud.

Les revendeurs internationaux observent une croissance significative pendant Thanksgiving et le Black Friday. IBM enregistre un engagement record dans son rapport annuel Holiday Readiness Clients

A l’occasion de VMworld® 2016, VMware, Inc. (NYSE : VMW) et IBM (NYSE : IBM) annoncent la disponibilité de services Cloud d’un genre nouveau, permettant aux entreprises de migrer rapidement et simplement des ressources informatiques d’entreprise vers le Cloud. Avec déjà plus de 500 clients concernés, le partenariat mondial entre IBM et VMware aide de plus en plus d’organisations à étendre leurs ressources informatiques existantes vers le Cloud en quelques minutes au lieu de plusieurs semaines ou mois.

Dans l’objectif d’une recherche permanente d’innovation et d’anticipation, cette alliance stratégique couvre le co-développement de nouvelles offres commerciales pour l’installation et la maintenance de systèmes informatiques, monétiques et d’objets connectés. Ce domaine représente un potentiel de marché dont la croissance est estimée à 12% par an.

La nouvelle plateforme URights s’appuie sur les solutions analytiques et cloud d’IBM pour mieux valoriser les droits des auteurs, compositeurs et éditeurs de musique

Dans le cadre de sa conférence InterConnect qui se tient à Las Vegas du 19 a 23 mars, à laquelle assistent 20 000 clients, développeurs et partenaires issus du monde entier, IBM annonce :

IBM, rejoint par plus de 100 partenaires commerciaux, lance le réseau IBM Digital Marketing dans le cloud et aide les directeurs marketing (CMO) et leurs équipes à intégrer plus rapidement et plus facilement de nouveaux services marketing, afin de mesurer et d’améliorer leur efficacité en temps réel.