Non-local modulation of the energy cascade in broad-band forced turbulence

Classically, large-scale forced turbulence is characterized by a transfer of energy from large to small scales via nonlinear interactions. We have investigated the changes in this energy transfer process in broad-band forced turbulence where an additional perturbation of flow at smaller scales is introduced. The modulation of the energy dynamics via the introduction of forcing at smaller scales occurs not only in the forced region but also in a broad range of length-scales outside the forced bands due to non-local triad interactions. Broad-band forcing changes the energy distribution and energy transfer function in a characteristic manner leading to a significant modulation of the turbulence. We studied the changes in this transfer of energy when changing the strength and location of the small-scale forcing support. The energy content in the larger scales was observed to decrease, while the energy transport power for scales in between the large and small scale forcing regions was enhanced. This was investigated further in terms of the detailed transfer function between the triad contributions and observing the long-time statistics of the flow. The energy is transferred toward smaller scales not only by wavenumbers of similar size as in the case of large-scale forced turbulence, but by a much wider extent of scales that can be externally controlled.Comment: submitted to Phys. Rev. E, 15 pages, 18 figures, uses revtex4.cl

Huge decreases in the risk of breast cancer relapse over the last three decades

Introduction The aim of this study was to evaluate local and systemic breast cancer control by comparing the risk of relapse in breast cancer patients in 2003–2004 with that in 1972–1979 and in 1980–1986. Methods About 8,570 women diagnosed with invasive breast cancer in 2003–2004 were selected from the population-based Netherlands Cancer Registry and compared with 133 patients treated in 1972–1979 and 174 in 1980–1986. Five-year risk of relapse was calculated by the Kaplan–Meier method. Cox-proportional hazard models were applied to adjust for tumour size, nodal status and age at diagnosis. Results Patients diagnosed in 2003–2004 had smaller tumours and a less advanced nodal stage than patients diagnosed in 1972–1986. In 1972–1979, 1980–1986 and 2003–2004, treatment included mastectomy in 94%, 72% and 47%; postmastectomy radiotherapy in 75%, 70% and 30%; chemotherapy in 9%, 14% and 37% and hormonal therapy in 3%, 3% and 42% of patients, respectively. Five-year risk of locoregional and distant recurrence decreased from 37% and 34% to 15%, respectively. The 5-year risk of second primary breast cancer did not differ and was 1%, 4% and 2%, respectively. The improved relapse-free survival in patients diagnosed in 2003–2004 as compared with 1972–1979 hardly changed after adjustment (HR = 0.38, 95% CI = 0.28–0.52). Conclusion Over the last decades, local breast cancer therapies have become less rigorous, whereas systemic therapy use has increased. Simultaneously, the risk of breast cancer relapse has tremendously decreased. Future novel therapies may lead to such small additional decreases in relapse rates, while the long-term side effects in breast cancer survivors will increas

Distributed utterances

I propose an apparatus for handling intrasentential change in context. The standard approach has problems with sentences with multiple occurrences of the same demonstrative or indexical. My proposal involves the idea that contexts can be complex. Complex contexts are built out of (“simple”) Kaplanian contexts by ordered n-tupling. With these we can revise the clauses of Kaplan’s Logic of Demonstratives so that each part of a sentence is taken in a different component of a complex context. I consider other applications of the framework: to agentially distributed utterances (ones made partly by one speaker and partly by another); to an account of scare-quoting; and to an account of a binding-like phenomenon that avoids what Kit Fine calls “the antinomy of the variable.

LAPW frozen-phonon calculation, shell model lattice dynamics and specific-heat measurement of SnO

An ab-initio Linear Augmented Plane-Wave (LAPW) calculation of the zone-centered phonon frequencies of SnO has been performed. E$_g$ symmetry has been ascribed to the mode observed at 113 cm$^{-1}$ in Raman measurements, discarding a previous B$_{1g}$ assignement. The other phonon modes measured by Raman spectroscopy are also well reproduced. A new shell-model has also been developed, that gives good agreement of the zone-centered frequencies compared to the measured data and the LAPW results. Specific heat measurements have been performed between 5 K and 110 K. Computation of the specific heat and the M\"{o}ssbauer recoilless fraction with the improved shell-model shows a good agreement with the experimental data as a function of temperature.Comment: 11 pages, 1 figure. to appear in Phys. Rev. B (November 1999

Inferring biological networks with output kernel trees

International audienc

Double p52Shc/p46Shc Rat Knockout Demonstrates Severe Gait Abnormalities Accompanied by Dilated Cardiomyopathy

The ubiquitously expressed adaptor protein Shc exists in three isoforms p46Shc, p52Shc, and p66Shc, which execute distinctly different actions in cells. The role of p46Shc is insufficiently studied, and the purpose of this study was to further investigate its functional significance. We developed unique rat mutants lacking p52Shc and p46Shc isoforms (p52Shc/46Shc-KO) and carried out histological analysis of skeletal and cardiac muscle of parental and genetically modified rats with impaired gait. p52Shc/46Shc-KO rats demonstrate severe functional abnormalities associated with impaired gait. Our analysis of p52Shc/46Shc-KO rat axons and myelin sheets in cross-sections of the sciatic nerve revealed the presence of significant anomalies. Based on the lack of skeletal muscle fiber atrophy and the presence of sciatic nerve abnormalities, we suggest that the impaired gait in p52Shc/46Shc-KO rats might be due to the sensory feedback from active muscle to the brain locomotor centers. The lack of dystrophin in some heart muscle fibers reflects damage due to dilated cardiomyopathy. Since rats with only p52Shc knockout do not display the phenotype of p52Shc/p46Shc-KO, abnormal locomotion is likely to be caused by p46Shc deletion. Our data suggest a previously unknown role of 46Shc actions and signaling in regulation of gait

Interleukin-27 Is Essential for Type 1 Diabetes Development and Sjögren Syndrome-like Inflammation.

Human genetic studies implicate interleukin-27 (IL-27) in the pathogenesis of type 1 diabetes (T1D), but the underlying mechanisms remain largely unexplored. To further define the role of IL-27 in T1D, we generated non-obese diabetic (NOD) mice deficient in IL-27 or IL-27Rα. In contrast to wild-type NOD mice, both NOD.Il27-/- and NOD.Il27ra-/- strains are completely resistant to T1D. IL-27 from myeloid cells and IL-27 signaling in T cells are critical for T1D development. IL-27 directly alters the balance of regulatory T cells (Tregs) and T helper 1 (Th1) cells in pancreatic islets, which in turn modulates the diabetogenic activity of CD8 T cells. IL-27 also directly enhances the effector function of CD8 T cells within pancreatic islets. In addition to T1D, IL-27 signaling in T cells is also required for lacrimal and salivary gland inflammation in NOD mice. Our study reveals that IL-27 contributes to autoimmunity in NOD mice through multiple mechanisms and provides substantial evidence to support its pathogenic role in human T1D

Meson exchange currents in electromagnetic one-nucleon emission

The role of meson exchange currents (MEC) in electron- and photon-induced one-nucleon emission processes is studied in a nonrelativistic model including correlations and final state interactions. The nuclear current is the sum of a one-body and of a two-body part. The two-body current includes pion seagull, pion-in-flight and the isobar current contributions. Numerical results are presented for the exclusive 16O(e,e'p)15N and 16O(\gamma,p)15N reactions. MEC effects are in general rather small in (e,e'p), while in (\gamma,p) they are always large and important to obtain a consistent description of (e,e'p) and (\gamma,p) data, with the same spectroscopic factors. The calculated (\gamma,p) cross sections are sensitive to short-range correlations at high values of the recoil momentum, where MEC effects are larger and overwhelm the contribution of correlations.Comment: 9 pages, 6 figure

Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability

Background and aims: Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. Methods: Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. Results: Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. Conclusion: We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes

Three decades of advancements in osteoarthritis research: insights from transcriptomic, proteomic, and metabolomic studies.

Osteoarthritis (OA) is a complex disease involving contributions from both local joint tissues and systemic sources. Patient characteristics, encompassing sociodemographic and clinical variables, are intricately linked with OA rendering its understanding challenging. Technological advancements have allowed for a comprehensive analysis of transcripts, proteomes and metabolomes in OA tissues/fluids through omic analyses. The objective of this review is to highlight the advancements achieved by omic studies in enhancing our understanding of OA pathogenesis over the last three decades. We conducted an extensive literature search focusing on transcriptomics, proteomics and metabolomics within the context of OA. Specifically, we explore how these technologies have identified individual transcripts, proteins, and metabolites, as well as distinctive endotype signatures from various body tissues or fluids of OA patients, including insights at the single-cell level, to advance our understanding of this highly complex disease. Omic studies reveal the description of numerous individual molecules and molecular patterns within OA-associated tissues and fluids. This includes the identification of specific cell (sub)types and associated pathways that contribute to disease mechanisms. However, there remains a necessity to further advance these technologies to delineate the spatial organization of cellular subtypes and molecular patterns within OA-afflicted tissues. Leveraging a multi-omics approach that integrates datasets from diverse molecular detection technologies, combined with patients' clinical and sociodemographic features, and molecular and regulatory networks, holds promise for identifying unique patient endophenotypes. This holistic approach can illuminate the heterogeneity among OA patients and, in turn, facilitate the development of tailored therapeutic interventions