Autophagy: A cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress

The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia-reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found to be key regulators of autophagy. Autophagy involved the upregulation of BECN1, LC3A, Atg7, Atg5 and Atg 12 during hypoxia and H-R. Autophagy was seen to occur within the mitochondria of the hepatocyte and inhibition of autophagy resulted in the lowering a mitochondrial membrane potential and onset of cell death. Autophagic responses were primarily observed in the large peri-venular (PV) hepatocyte subpopulation. Inhibition of autophagy, using 3-methyladenine, increased apoptosis during H-R. Specifically, PV human hepatocytes were more susceptible to apoptosis after inhibition of autophagy. These findings show for the first time that during oxidative stress autophagy serves as a cell survival mechanism for primary human hepatocytes

Index Theorem and Overlap Formalism with Naive and Minimally Doubled Fermions

We present a theoretical foundation for the Index theorem in naive and minimally doubled lattice fermions by studying the spectral flow of a Hermitean version of Dirac operators. We utilize the point splitting method to implement flavored mass terms, which play an important role in constructing proper Hermitean operators. We show the spectral flow correctly detects the index of the would-be zero modes which is determined by gauge field topology. Using the flavored mass terms, we present new types of overlap fermions from the naive fermion kernels, with a number of flavors that depends on the choice of the mass terms. We succeed to obtain a single-flavor naive overlap fermion which maintains hypercubic symmetry.Comment: 27 pages, 17 figures; references added, version accepted in JHE

Generating the Best Stacking Sequence Table for the Design of Blended Composite Structures

In order to improve the ability of a large-scale light-weight composite structure to carry tensile or compressive loads, stiffeners are added to the structure. The stiffeners divide the structure into several smaller panels. For a composite structure to be manufacturable, it is necessary that plies are continuous in multiple adjacent panels. To be able to prescribe a manufacturable design, an optimization algorithm can be coupled with a reference table for the stacking sequences (SST). As long as the ply stacks are selected from the SST, it is guaranteed that the design is manufacturable and all strength related guidelines associated with the design of composite structures are satisfied. An SST is made only based on strength related guidelines. Therefore, there exist a large number of possibilities for SSTs. Minimized mass is a typical goal in the design of aircraft structures. Different SSTs result in different values for the minimized mass. Thus it is crucial to perform optimization based on the SST which results in the lowest mass. This paper aims to introduce an approach to generate a unique SST resulting in the lowest mass. The proposed method is applied to the optimization problem of a stiffened composite structure resembling the skin of an aircraft wing box

Numerical properties of staggered quarks with a taste-dependent mass term

The numerical properties of staggered Dirac operators with a taste-dependent mass term proposed by Adams [1,2] and by Hoelbling [3] are compared with those of ordinary staggered and Wilson Dirac operators. In the free limit and on (quenched) interacting configurations, we consider their topological properties, their spectrum, and the resulting pion mass. Although we also consider the spectral structure, topological properties, locality, and computational cost of an overlap operator with a staggered kernel, we call attention to the possibility of using the Adams and Hoelbling operators without the overlap construction. In particular, the Hoelbling operator could be used to simulate two degenerate flavors without additive mass renormalization, and thus without fine-tuning in the chiral limit.Comment: 14 pages, 9 figures. V2: published version; important note added regarding Hoelbling fermions, otherwise minor change

Single and two-particle energy gaps across the disorder-driven superconductor-insulator transition

The competition between superconductivity and localization raises profound questions in condensed matter physics. In spite of decades of research, the mechanism of the superconductor-insulator transition (SIT) and the nature of the insulator are not understood. We use quantum Monte Carlo simulations that treat, on an equal footing, inhomogeneous amplitude variations and phase fluctuations, a major advance over previous theories. We gain new microscopic insights and make testable predictions for local spectroscopic probes. The energy gap in the density of states survives across the transition, but coherence peaks exist only in the superconductor. A characteristic pseudogap persists above the critical disorder and critical temperature, in contrast to conventional theories. Surprisingly, the insulator has a two-particle gap scale that vanishes at the SIT, despite a robust single-particle gap.Comment: 7 pages, 5 figures (plus supplement with 4 pages, 5 figures

Social marketing and healthy eating : Findings from young people in Greece

This document is the Accepted Manuscript version. The final publication is available at Springer via http://dx.doi.org/10.1007/s12208-013-0112-xGreece has high rates of obesity and non-communicable diseases owing to poor dietary choices. This research provides lessons for social marketing to tackle the severe nutrition-related problems in this country by obtaining insight into the eating behaviour of young adults aged 18–23. Also, the main behavioural theories used to inform the research are critically discussed. The research was conducted in Athens. Nine focus groups with young adults from eight educational institutions were conducted and fifty-nine participants’ views towards eating habits, healthy eating and the factors that affect their food choices were explored. The study found that the participants adopted unhealthier nutritional habits after enrolment. Motivations for healthy eating were good health, appearance and psychological consequences, while barriers included lack of time, fast-food availability and taste, peer pressure, lack of knowledge and lack of family support. Participants reported lack of supportive environments when deciding on food choices. Based on the findings, recommendations about the development of the basic 4Ps of the marketing mix, as well as of a fifth P, for Policy are proposedPeer reviewe

Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

On the effect of resonances in composite Higgs phenomenology

We consider a generic composite Higgs model based on the coset SO(5)/SO(4) and study its phenomenology beyond the leading low-energy effective lagrangian approximation. Our basic goal is to introduce in a controllable and simple way the lowest-lying, possibly narrow, resonances that may exist is such models. We do so by proposing a criterion that we call partial UV completion. We characterize the simplest cases, corresponding respectively to a scalar in either singlet or tensor representation of SO(4) and to vectors in the adjoint of SO(4). We study the impact of these resonances on the signals associated to high-energy vector boson scattering, pointing out for each resonance the characteristic patterns of depletion and enhancement with respect to the leading-order chiral lagrangian. En route we derive the O(p^4) general chiral lagrangian and discuss its peculiar accidental and approximate symmetries.Comment: v3: a few typos corrected. Conclusions unchange