Ionization via Chaos Assisted Tunneling

A simple example of quantum transport in a classically chaotic system is studied. It consists in a single state lying on a regular island (a stable primary resonance island) which may tunnel into a chaotic sea and further escape to infinity via chaotic diffusion. The specific system is realistic : it is the hydrogen atom exposed to either linearly or circularly polarized microwaves. We show that the combination of tunneling followed by chaotic diffusion leads to peculiar statistical fluctuation properties of the energy and the ionization rate, especially to enhanced fluctuations compared to the purely chaotic case. An appropriate random matrix model, whose predictions are analytically derived, describes accurately these statistical properties.Comment: 30 pages, 11 figures, RevTeX and postscript, Physical Review E in pres

Computational Analysis of Whole-Genome Differential Allelic Expression Data in Human

Allelic imbalance (AI) is a phenomenon where the two alleles of a given gene are expressed at different levels in a given cell, either because of epigenetic inactivation of one of the two alleles, or because of genetic variation in regulatory regions. Recently, Bing et al. have described the use of genotyping arrays to assay AI at a high resolution (∼750,000 SNPs across the autosomes). In this paper, we investigate computational approaches to analyze this data and identify genomic regions with AI in an unbiased and robust statistical manner. We propose two families of approaches: (i) a statistical approach based on z-score computations, and (ii) a family of machine learning approaches based on Hidden Markov Models. Each method is evaluated using previously published experimental data sets as well as with permutation testing. When applied to whole genome data from 53 HapMap samples, our approaches reveal that allelic imbalance is widespread (most expressed genes show evidence of AI in at least one of our 53 samples) and that most AI regions in a given individual are also found in at least a few other individuals. While many AI regions identified in the genome correspond to known protein-coding transcripts, others overlap with recently discovered long non-coding RNAs. We also observe that genomic regions with AI not only include complete transcripts with consistent differential expression levels, but also more complex patterns of allelic expression such as alternative promoters and alternative 3′ end. The approaches developed not only shed light on the incidence and mechanisms of allelic expression, but will also help towards mapping the genetic causes of allelic expression and identify cases where this variation may be linked to diseases

Genomic Islands as a Marker to Differentiate between Clinical and Environmental Burkholderia pseudomallei

Burkholderia pseudomallei, as a saprophytic bacterium that can cause a severe sepsis disease named melioidosis, has preserved several extra genes in its genome for survival. The sequenced genome of the organism showed high diversity contributed mainly from genomic islands (GIs). Comparative genome hybridization (CGH) of 3 clinical and 2 environmental isolates, using whole genome microarrays based on B. pseudomallei K96243 genes, revealed a difference in the presence of genomic islands between clinical and environmental isolates. The largest GI, GI8, of B. pseudomallei was observed as a 2 sub-GI named GIs8.1 and 8.2 with distinguishable %GC content and unequal presence in the genome. GIs8.1, 8.2 and 15 were found to be more common in clinical isolates. A new GI, GI16c, was detected on chromosome 2. Presences of GIs8.1, 8.2, 15 and 16c were evaluated in 70 environmental and 64 clinical isolates using PCR assays. A combination of GIs8.1 and 16c (positivity of either GI) was detected in 70% of clinical isolates and 11.4% of environmental isolates (P<0.001). Using BALB/c mice model, no significant difference of time to mortality was observed between K96243 isolate and three isolates without GIs under evaluation (P>0.05). Some virulence genes located in the absent GIs and the difference of GIs seems to contribute less to bacterial virulence. The PCR detection of 2 GIs could be used as a cost effective and rapid tool to detect potentially virulent isolates that were contaminated in soil

On the price of morals in markets: an empirical study of the Swedish AP-Funds and the Norwegian Government Pension Fund

This study empirically analyses the exclusion of companies from investors’ investment universe due to a company’s business model (sector-based exclusion) or due to a company’s violations of international norms (normbased exclusion). We conduct a time-series analysis of the performance implications of the exclusion decisions of two leading Nordic investors, Norway’s Government Pension Fund-Global (GPFG) and Sweden’s AP-funds. We find that their portfolios of excluded companies do not generate an abnormal return relative to the funds’ benchmark index. While the exclusion portfolios show higher risk than the respective benchmark, this difference is only statistically significant for the case of GPFG. These findings suggest that the exclusion of the companies generally does not harm funds’ performance. We interpret these findings as indicative that with exclusionary screening, as practiced by the sample funds, asset owners can meet the ethical objectives of their beneficiaries without compromising financial returns

Risk factors and myocardial infarction in patients with obstructive sleep apnea: impact of β2-adrenergic receptor polymorphisms

BACKGROUND: The increased sympathetic nervous activity in patients with obstructive sleep apnea (OSA) is largely responsible for the high prevalence of arterial hypertension, and it is suggested to adversely affect triglyceride and high-density lipoprotein (HDL) cholesterol levels in these patients. The functionally relevant polymorphisms of the β2-adrenergic receptor (Arg-47Cys/Arg16Gly and Gln27Glu) have been shown to exert modifying effects on these risk factors in previous studies, but results are inconsistent. METHODS: We investigated a group of 429 patients (55 ± 10.7 years; 361 men, 68 women) with moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI) 29.1 ± 23.1/h) and, on average, a high cardiovascular risk profile (body mass index 31.1 ± 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2% of patients). We typed the β2-adrenergic receptor polymorphisms and investigated the five most frequent haplotypes for their modifying effects on OSA-induced changes in blood pressure, heart rate, and lipid levels. The prevalence of cardiovascular risk factors and coronary heart disease (n = 55, 12.8%) and survived myocardial infarction (n = 27, 6.3%) were compared between the genotypes and haplotypes. RESULTS: Multivariate linear/logistic regressions revealed a significant and independent (from BMI, age, sex, presence of diabetes, use of antidiabetic, lipid-lowering, and antihypertensive medication) influence of AHI on daytime systolic and diastolic blood pressure, heart rate, prevalence of hypertension, and triglyceride and HDL levels. The β2-adrenergic receptor genotypes and haplotypes showed no modifying effects on these relationships or on the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for all three polymorphisms, heterozygous carriers had a significantly lower relative risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR) = 0.32, P = 0.012; Arg16Gly: n = 197, OR = 0.39, P = 0.031; Gln27Glu: OR = 0.37, P = 0.023). Carriers of the most frequent haplotype (n = 113) (haplotype 1; heterozygous for all three polymorphisms) showed a five-fold lower prevalence of survived myocardial infarction (OR = 0.21, P = 0.023). CONCLUSION: Our study showed no significant modifying effect of the functionally relevant β2-adrenergic receptor polymorphisms on OSA-induced blood pressure, heart rate, or lipid changes. Nevertheless, heterozygosity of these polymorphisms is associated with a lower prevalence of survived myocardial infarction in this group with, on average, a high cardiovascular risk profile

Synthetic RGDS peptide attenuates lipopolysaccharide-induced pulmonary inflammation by inhibiting integrin signaled MAP kinase pathways

<p>Abstract</p> <p>Background</p> <p>Synthetic peptides containing the RGD sequence inhibit integrin-related functions in different cell systems. Here, we investigated the effects of synthetic Arg-Gly-Asp-Ser (RGDS) peptide on key inflammatory responses to intratracheal (<it>i.t.</it>) lipopolysaccharide (LPS) treatment and on the integrin signaled mitogen-activated protein (MAP) kinase pathway during the development of acute lung injury.</p> <p>Methods</p> <p>Saline or LPS (1.5 mg/kg) was administered <it>i.t. </it>with or without a single dose of RGDS (1, 2.5, or 5 mg/kg, i.p.), anti-α_vor anti-β₃mAb (5 mg/kg, i.p.). Mice were sacrificed 4 or 24 h post-LPS.</p> <p>Results</p> <p>A pretreatment with RGDS inhibited LPS-induced increases in neutrophil and macrophage numbers, total protein levels and TNF-α and MIP-2 levels, and matrix metalloproteinase-9 activity in bronchoalveolar lavage (BAL) fluid at 4 or 24 h post-LPS treatment. RGDS inhibited LPS-induced phosphorylation of focal adhesion kinase and MAP kinases, including ERK, JNK, and p38 MAP kinase, in lung tissue. Importantly, the inhibition of the inflammatory responses and the kinase pathways were still evident when this peptide was administered 2 h after LPS treatment. Similarly, a blocking antibody against integrin α_vsignificantly inhibited LPS-induced inflammatory cell migration into the lung, protein accumulation and proinflammatory mediator production in BAL fluid, at 4 or 24 h post-LPS. Anti-β₃also inhibited all LPS-induced inflammatory responses, except the accumulation of BAL protein at 24 h post-LPS.</p> <p>Conclusion</p> <p>These results suggest that RGDS with high specificity for α_vintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury.</p

Decreased Functional Diversity and Biological Pest Control in Conventional Compared to Organic Crop Fields

Organic farming is one of the most successful agri-environmental schemes, as humans benefit from high quality food, farmers from higher prices for their products and it often successfully protects biodiversity. However there is little knowledge if organic farming also increases ecosystem services like pest control. We assessed 30 triticale fields (15 organic vs. 15 conventional) and recorded vascular plants, pollinators, aphids and their predators. Further, five conventional fields which were treated with insecticides were compared with 10 non-treated conventional fields. Organic fields had five times higher plant species richness and about twenty times higher pollinator species richness compared to conventional fields. Abundance of pollinators was even more than one-hundred times higher on organic fields. In contrast, the abundance of cereal aphids was five times lower in organic fields, while predator abundances were three times higher and predator-prey ratios twenty times higher in organic fields, indicating a significantly higher potential for biological pest control in organic fields. Insecticide treatment in conventional fields had only a short-term effect on aphid densities while later in the season aphid abundances were even higher and predator abundances lower in treated compared to untreated conventional fields. Our data indicate that insecticide treatment kept aphid predators at low abundances throughout the season, thereby significantly reducing top-down control of aphid populations. Plant and pollinator species richness as well as predator abundances and predator-prey ratios were higher at field edges compared to field centres, highlighting the importance of field edges for ecosystem services. In conclusion organic farming increases biodiversity, including important functional groups like plants, pollinators and predators which enhance natural pest control. Preventative insecticide application in conventional fields has only short-term effects on aphid densities but long-term negative effects on biological pest control. Therefore conventional farmers should restrict insecticide applications to situations where thresholds for pest densities are reached

DNA Demethylation and USF Regulate the Meiosis-Specific Expression of the Mouse Miwi

Miwi, a member of the Argonaute family, is required for initiating spermiogenesis; however, the mechanisms that regulate the expression of the Miwi gene remain unknown. By mutation analysis and transgenic models, we identified a 303 bp proximal promoter region of the mouse Miwi gene, which controls specific expression from midpachytene spermatocytes to round spermatids during meiosis. We characterized the binding sites of transcription factors NF-Y (Nuclear Factor Y) and USF (Upstream Stimulatory Factor) within the core promoter and found that both factors specifically bind to and activate the Miwi promoter. Methylation profiling of three CpG islands within the proximal promoter reveals a markedly inverse correlation between the methylation status of the CpG islands and germ cell type–specific expression of Miwi. CpG methylation at the USF–binding site within the E2 box in the promoter inhibits the binding of USF. Transgenic Miwi-EGFP and endogenous Miwi reveal a subcellular co-localization pattern in the germ cells of the Miwi-EGFP transgenic mouse. Furthermore, the DNA methylation profile of the Miwi promoter–driven transgene is consistent with that of the endogenous Miwi promoter, indicating that Miwi transgene is epigenetically modified through methylation in vivo to ensure its spatio-temporal expression. Our findings suggest that USF controls Miwi expression from midpachytene spermatocytes to round spermatids through methylation-mediated regulation. This work identifies an epigenetic regulation mechanism for the spatio-temporal expression of mouse Miwi during spermatogenesis

MicroRNA expression as risk biomarker of breast cancer metastasis : a pilot retrospective case-cohort study

Background: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further the understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development. Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n = 29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n = 35) consisted of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. MicroRNA profiling was performed and biomarkers related to metastatic were identified independent of clinical stage. Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. Results: MiRNA expression profiling identified several miRNAs that were both specific and shared across all clinical stages (p <= 0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were deregulated in metastatic cases of CSI and CSII. Furthermore, metastatic miRNAs shared across all clinical stages did not present high sensitivity and specificity when compared to specific-CS miRNAs. Between them, hsa-miR-183 was the most significative of CSII, which miRNAs combination for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs. Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.We thank the Researcher Support Center of Barretos Cancer Hospital, especially the statistician Zanardo C. for assisting in the statistical analysis.This study received financial support from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (Fapesp, Proc: 10/ 16796-0, Sao Paulo, Brazil)