Electronic thermal conductivity of disordered metals

We calculate the thermal conductivity of interacting electrons in disordered metals. In our analysis we point out that the interaction affects thermal transport through two distinct mechanims, associated with quantum interference corrections and energy exchange of the quasi particles with the electromagnetic environment, respectively. The latter is seen to lead to a violation of the Wiedemann-Franz law. Our theory predicts a strong enhancement of the Lorenz ratio $\kappa /\sigma T$ over the value which is predicted by the Wiedemann-Franz law, when the electrons encounter a large environmental impedance.Comment: 4 page

Induction of Peripheral T Cell Tolerance by Antigen-Presenting B Cells. II. Chronic Antigen Presentation Overrules Antigen-Presenting B Cell Activation

Abstract Ag presentation in the absence of danger signals and Ag persistence are the inductive processes of peripheral T cell tolerization proposed so far. Nevertheless, it has never been definitively shown that chronic Ag presentation per se can induce T cell tolerance independent of the state of activation of APCs. In the present work, we investigated whether chronic Ag presentation by either resting or activated B cells can induce tolerance of peripheral Ag-specific T cells. We show that CD4+ T cells that re-encounter the Ag for a prolonged period, presented either by resting or activated Ag-presenting B cells, become nonfunctional and lose any autoimmune reactivity. Thus, when the main APCs are B cells, the major mechanism responsible for peripheral T cell tolerization is persistent Ag exposure, independent of the B cell activation state

Combining Theoretical and Experimental Techniques to Study Murine Heart Transplant Rejection

The quality of life of organ transplant recipients is compromised by complications associated with life-long immunosuppression, such as hypertension, diabetes, opportunistic infections, and cancer. Moreover, the absence of established tolerance to the transplanted tissues causes limited long-term graft survival rates. Thus, there is a great medical need to understand the complex immune system interactions that lead to transplant rejection so that novel and effective strategies of intervention that redirect the system toward transplant acceptance (while preserving overall immune competence) can be identified. This study implements a systems biology approach in which an experimentally based mathematical model is used to predict how alterations in the immune response influence the rejection of mouse heart transplants. Five stages of conventional mouse heart transplantation are modeled using a system of 13 ordinary differential equations that tracks populations of both innate and adaptive immunity as well as proxies for pro- and anti-inflammatory factors within the graft and a representative draining lymph node. The model correctly reproduces known experimental outcomes, such as indefinite survival of the graft in the absence of CD4(+) T cells and quick rejection in the absence of CD8(+) T cells. The model predicts that decreasing the translocation rate of effector cells from the lymph node to the graft delays transplant rejection. Increasing the starting number of quiescent regulatory T cells in the model yields a significant but somewhat limited protective effect on graft survival. Surprisingly, the model shows that a delayed appearance of alloreactive T cells has an impact on graft survival that does not correlate linearly with the time delay. This computational model represents one of the first comprehensive approaches toward simulating the many interacting components of the immune system. Despite some limitations, the model provides important suggestions of experimental investigations that could improve the understanding of rejection. Overall, the systems biology approach used here is a first step in predicting treatments and interventions that can induce transplant tolerance while preserving the capacity of the immune system to protect against legitimate pathogens

Evidence for non-linear quasiparticle tunneling between fractional quantum Hall edges

Remarkable nonlinearities in the differential tunneling conductance between fractional quantum Hall edge states at a constriction are observed in the weak-backscattering regime. In the $\nu$ = 1/3 state a peak develops as temperature is increased and its width is determined by the fractional charge. In the range $2/3 \le \nu \le 1/3$ this width displays a symmetric behavior around $\nu$ = 1/2. We discuss the consistency of these results with available theoretical predictions for inter-edge quasiparticle tunneling in the weak-backscattering regime

Cardiovascular Risk Evaluation through Heart Rate Variability (HRV) Analysis in Patients with Psoriasis before and after 12 Weeks of Etanercept Therapy: A Preliminary Prospective Study

Background The association between psoriasis and cardiovascular diseases is suggested by epidemiological studies. The sub-inflammatory systemic state that characterizes both psoriasis and atherosclerosis has been proposed as the link between these conditions; it cannot, however, explain the increased incidence of sudden cardiac death reported in young patients with severe psoriasis without common cardiovascular risk factors. In a previous study we reported higher levels of autonomic dysregulation in psoriatic patients, concluding that the prevalence of the sympathetic arm over the para-sympathetic one could increase cardiovascular risk. Objectives To assess the influence of etanercept, an anti-TNFα agent, on the autonomic cardiovascular regulation in young patients with moderate-to-severe psoriasis without cardiovascular risk factors. Methods Five-minute ECG recordings were collected at rest conditions before and after 12 weeks of therapy with etanercept in 19 young psoriatic patients without cardiovascular risk factors. The Cardiolab CE pocket PC ECG system was used for linear methods of heart rate variability (HRV) analysis. Results No significant change in HRV analysis parameters was apparent after 12 weeks of etanercept therapy. Conclusion Our data suggest that treatment with etanercept in patients with moderate-to-severe psoriasis doesn\u27t affect cardiovascular autonomic regulation, and subsequently the cardiovascular risk.</p

Inflammatory Microenvironment in Early Non-Small Cell Lung Cancer: Exploring the Predictive Value of Radiomics

Patient prognosis is a critical consideration in the treatment decision-making process. Conventionally, patient outcome is related to tumor characteristics, the cancer spread, and the patients’ conditions. However, unexplained differences in survival time are often observed, even among patients with similar clinical and molecular tumor traits. This study investigated how inflammatory radiomic features can correlate with evidence-based biological analyses to provide translated value in assessing clinical outcomes in patients with NSCLC. We analyzed a group of 15 patients with stage I NSCLC who showed extremely different OS outcomes despite apparently harboring the same tumor characteristics. We thus analyzed the inflammatory levels in their tumor microenvironment (TME) either biologically or radiologically, focusing our attention on the NLRP3 cancer-dependent inflammasome pathway. We determined an NLRP3-dependent peritumoral inflammatory status correlated with the outcome of NSCLC patients, with markedly increased OS in those patients with a low rate of NLRP3 activation. We consistently extracted specific radiomic signatures that perfectly discriminated patients’ inflammatory levels and, therefore, their clinical outcomes. We developed and validated a radiomic model unleashing quantitative inflammatory features from CT images with an excellent performance to predict the evolution pattern of NSCLC tumors for a personalized and accelerated patient management in a non-invasive way

Type-I Interferons Inhibit Interleukin-10 Signaling and Favor Type 1 Diabetes Development in Nonobese Diabetic Mice

Destruction of insulin-producing β-cells by autoreactive T lymphocytes leads to the development of type 1 diabetes. Type-I interferons (TI-IFN) and interleukin-10 (IL-10) have been connected with the pathophysiology of this disease; however, their interplay in the modulation of diabetogenic T cells remains unknown. We have discovered that TI-IFN cause a selective inhibition of IL-10 signaling in effector and regulatory T cells, altering their responses. This correlates with diabetes development in nonobese diabetic mice, where the inhibition is also spatially localized to T cells of pancreatic and mesenteric lymph nodes. IL-10 signaling inhibition is reversible and can be restored via blockade of TI-IFN/IFN-R interaction, paralleling with the resulting delay in diabetes onset and reduced severity. Overall, we propose a novel molecular link between TI-IFN and IL-10 signaling that helps better understand the complex dynamics of autoimmune diabetes development and reveals new strategies of intervention

ANGPT2 and NOS3 Polymorphisms and Clinical Outcome in Advanced Hepatocellular Carcinoma Patients Receiving Sorafenib

Sorafenib represents the standard of care for advanced hepatocellular carcinoma (HCC), even though a large number of patients have reported limited ecacy. The aim of the present study was to evaluate the prognostic value of single-nucleotide polymorphisms on angiopoietin-2 (ANGPT2) and endothelial-derived nitric oxide synthase (NOS3) genes in 135 patients with advanced HCC receiving sorafenib. Eight ANGPT2 polymorphisms were analyzed by direct sequencing in relation to overall survival (OS) and progression-free survival (PFS). In univariate analysis, ANGPT2rs55633437 and NOS3 rs2070744 were associated with OS and PFS. In particular, patients with ANGPT2rs55633437 TT/GT genotypes had significantly lower median OS (4.66 vs. 15.5 months, hazard ratio (HR) 4.86, 95% CI 2.73\u20138.67, p &lt; 0.001) and PFS (1.58 vs. 6.27 months, HR 4.79, 95% CI 2.73\u20138.35, p &lt; 0.001) than those homozygous for the G allele. Moreover, patients with NOS3 rs2070744 TC/CC genotypes had significantly higher median OS (15.6 vs. 9.1 months, HR 0.65, 95% CI 0.44\u20130.97; p = 0.036) and PFS (7.03 vs. 3.5 months, HR 0.43, 95% CI 0.30\u20130.63; p &lt; 0.001) than patients homozygous for the T allele. Multivariate analysis confirmed these polymorphisms as independent prognostic factors. Our results suggest that ANGPT2rs55633437 and NOS3 rs2070744 polymorphisms could identify a subset of HCC patients more resistant to sorafenib

Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis

Contacts between organelles create microdomains that play major roles in regulating key intracellular activities and signaling pathways, but whether they also regulate systemic functions remains unknown. Here, we report the ultrastructural organization and dynamics of the inter-organellar contact established by sheets of curved rough endoplasmic reticulum closely wrapped around the mitochondria (wrappER). To elucidate the in vivo function of this contact, mouse liver fractions enriched in wrappER-associated mitochondria are analyzed by transcriptomics, proteomics, and lipidomics. The biochemical signature of the wrappER points to a role in the biogenesis of very-low-density lipoproteins (VLDL). Altering wrappER-mitochondria contacts curtails VLDL secretion and increases hepatic fatty acids, lipid droplets, and neutral lipid content. Conversely, acute liver-specific ablation of Mttp, the most upstream regulator of VLDL biogenesis, recapitulates this hepatic dyslipidemia phenotype and promotes remodeling of the wrappER-mitochondria contact. The discovery that liver wrappER-mitochondria contacts participate in VLDL biology suggests an involvement of inter-organelle contacts in systemic lipid homeostasis.Fil: Anastasia, Irene. Laval University; Canadá. Brain Research Center; CanadáFil: Ilacqua, Nicolò. Laval University; Canadá. Brain Research Center; CanadáFil: Raimondi, Andrea. San Raffaele Scientific Institute; ItaliaFil: Lemieux, Philippe. Brain Research Center; CanadáFil: Ghandehari-Alavijeh, Rana. Brain Research Center; CanadáFil: Faure, Guilhem. Broad Institute of MIT and Harvard; Estados Unidos. National Center For Biotechnology Information; Estados UnidosFil: Mekhedov, Sergei L.. National Center For Biotechnology Information ; Estados UnidosFil: Williams, Kevin J.. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Caicci, Federico. Università di Padova; ItaliaFil: Valle, Giorgio. Università di Padova; ItaliaFil: Giacomello, Marta. Università di Padova; ItaliaFil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentina. University of Alberta; CanadáFil: Lehner, Richard. University of Alberta; CanadáFil: Miksis, Michael J.. Northwestern University; Estados UnidosFil: Toth, Katalin. University of Ottawa; CanadáFil: de Aguiar Vallim, Thomas Q.. University of California at Los Angeles. School of Medicine; Estados UnidosFil: Koonin, Eugene V.. National Center For Biotechnology Information ; Estados UnidosFil: Scorrano, Luca. Università di Padova; ItaliaFil: Pellegrini, Luca. Laval University; Canad