Epigenetics and chromatin remodeling play a role in lung disease

Epigenetics is defined as heritable changes that affect gene expression without altering the DNA sequence. Epigenetic regulation of gene expression is facilitated through different mechanisms such as DNA methylation, histone modifications and RNA-associated silencing by small non-coding RNAs. All these mechanisms are crucial for normal development, differentiation and tissue-specific gene expression. These three systems interact and stabilize one another and can initiate and sustain epigenetic silencing, thus determining heritable changes in gene expression. Histone acetylation regulates diverse cellular functions including inflammatory gene expression, DNA repair and cell proliferation. Transcriptional coactivators possess intrinsic histone acetyltransferase activity and this activity drives inflammatory gene expression. Eleven classical histone deacetylases (HDACs) act to regulate the expression of distinct subsets of inflammatory/immune genes. Thus, loss of HDAC activity or the presence of HDAC inhibitors can further enhance inflammatory gene expression by producing a gene-specific change in HAT activity. For example, HDAC2 expression and activity are reduced in lung macrophages, biopsy specimens, and blood cells from patients with severe asthma and smoking asthmatics, as well as in patients with chronic obstructive pulmonary disease (COPD). This may account, at least in part, for the enhanced inflammation and reduced steroid responsiveness seen in these patients. Other proteins, particularly transcription factors, are also acetylated and are targets for deacetylation by HDACs and sirtuins, a related family of 7 predominantly protein deacetylases. Thus the acetylation/deacetylation status of NF-κB and the glucocorticoid receptor can also affect the overall expression pattern of inflammatory genes and regulate the inflammatory response. Understanding and targeting specific enzymes involved in this process might lead to new therapeutic agents, particularly in situations in which current anti-inflammatory therapies are suboptimal

Atmospheric refraction effects on baseline error in satellite laser ranging systems

Because of the mathematical complexities involved in exact analyses of baseline errors, it is not easy to isolate atmospheric refraction effects; however, by making certain simplifying assumptions about the ranging system geometry, relatively simple expressions can be derived which relate the baseline errors directly to the refraction errors. The results indicate that even in the absence of other errors, the baseline error for intercontinental baselines can be more than an order of magnitude larger than the refraction error

Performance Evaluation of Sparse Matrix Multiplication Kernels on Intel Xeon Phi

Intel Xeon Phi is a recently released high-performance coprocessor which features 61 cores each supporting 4 hardware threads with 512-bit wide SIMD registers achieving a peak theoretical performance of 1Tflop/s in double precision. Many scientific applications involve operations on large sparse matrices such as linear solvers, eigensolver, and graph mining algorithms. The core of most of these applications involves the multiplication of a large, sparse matrix with a dense vector (SpMV). In this paper, we investigate the performance of the Xeon Phi coprocessor for SpMV. We first provide a comprehensive introduction to this new architecture and analyze its peak performance with a number of micro benchmarks. Although the design of a Xeon Phi core is not much different than those of the cores in modern processors, its large number of cores and hyperthreading capability allow many application to saturate the available memory bandwidth, which is not the case for many cutting-edge processors. Yet, our performance studies show that it is the memory latency not the bandwidth which creates a bottleneck for SpMV on this architecture. Finally, our experiments show that Xeon Phi's sparse kernel performance is very promising and even better than that of cutting-edge general purpose processors and GPUs

Infinite Divisibility in Euclidean Quantum Mechanics

In simple -- but selected -- quantum systems, the probability distribution determined by the ground state wave function is infinitely divisible. Like all simple quantum systems, the Euclidean temporal extension leads to a system that involves a stochastic variable and which can be characterized by a probability distribution on continuous paths. The restriction of the latter distribution to sharp time expectations recovers the infinitely divisible behavior of the ground state probability distribution, and the question is raised whether or not the temporally extended probability distribution retains the property of being infinitely divisible. A similar question extended to a quantum field theory relates to whether or not such systems would have nontrivial scattering behavior.Comment: 17 pages, no figure

New approximations for the cone of copositive matrices and its dual

We provide convergent hierarchies for the cone C of copositive matrices and its dual, the cone of completely positive matrices. In both cases the corresponding hierarchy consists of nested spectrahedra and provide outer (resp. inner) approximations for C (resp. for its dual), thus complementing previous inner (resp. outer) approximations for C (for the dual). In particular, both inner and outer approximations have a very simple interpretation. Finally, extension to K-copositivity and K-complete positivity for a closed convex cone K, is straightforward.Comment: 8

Analysis of short pulse laser altimetry data obtained over horizontal path

Recent pulsed measurements of atmospheric delay obtained by ranging to the more realistic targets including a simulated ocean target and an extended plate target are discussed. These measurements are used to estimate the expected timing accuracy of a correlation receiver system. The experimental work was conducted using a pulsed two color laser altimeter

Exosomes and Exosomal miRNA in Respiratory Diseases

Exosomes are nanosized vesicles released from every cell in the body including those in the respiratory tract and lungs. They are found in most body fluids and contain a number of different biomolecules including proteins, lipids, and both mRNA and noncoding RNAs. Since they can release their contents, particularly miRNAs, to both neighboring and distal cells, they are considered important in cell-cell communication. Recent evidence has shown their possible importance in the pathogenesis of several pulmonary diseases. The differential expression of exosomes and of exosomal miRNAs in disease has driven their promise as biomarkers of disease enabling noninvasive clinical diagnosis in addition to their use as therapeutic tools. In this review, we summarize recent advances in this area as applicable to pulmonary diseases

Higgs bosons of a supersymmetric E6E_6 model at the Large Hadron Collider

It is found that CP symmetry may be explicitly broken in the Higgs sector of a supersymmetric $E_6$ model with two extra neutral gauge bosons at the one-loop level. The phenomenology of the model, the Higgs sector in particular, is studied for a reasonable parameter space of the model, in the presence of explicit CP violation at the one-loop level. At least one of the neutral Higgs bosons of the model might be produced via the $WW$ fusion process at the Large Hadron Collider.Comment: 23 pages, 5 figures, JHE

Duration and breaks in sedentary behaviour: Accelerometer data from 1566 community-dwelling older men (British Regional Heart Study)

Background: Sedentary behaviours are increasingly recognised as raising risk of CVD events, diabetes and mortality, independently of physical activity (PA) levels. However, little is known about patterns of sedentary behaviour in older adults. Methods: Cross sectional study of 1566/3137 (50% response) men aged 71-91 years from a UK population-based cohort study. Men wore a GT3x accelerometer over the hip for one week in 2010-11. Mean daily minutes of SB, % of day in sedentary behaviours, sedentary bouts and breaks were calculated and summarized by health and demographic characteristics. Results: 1403 ambulatory men aged 78.4 years (SD 4.6 years) with ≥600 minutes of accelerometer wear on ≥3 days had complete data on covariables. Men spent on average 618 minutes (SD=83), or 72% of their day in sedentary behaviours (<100 counts/minute). On average men accumulated 72 spells of sedentary behaviours per day, with 7 breaks in each sedentary hour. Men had on average 5.1 sedentary bouts of ≥30 minutes, which accounted for 43% of sedentary time, and 1.4 bouts of ≥60 minutes, which accounted for 19% of daily sedentary time. Men who were over 80 years old, obese, depressed and had multiple chronic conditions accumulated more sedentary time and spent more time in longer sedentary bouts. Conclusions: Older men spend nearly three quarters of their day in sedentary behaviours, mostly accumulated in short bouts, although bouts lasting ≥30 minutes accounted for nearly half of the sedentary time each day. Men with medical risk factors were more likely to also display sedentary behaviour