Substructuring approach to the calculation of higher-order eigensensitivity

2012-2013 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

Double hadron leptoproduction in the nuclear medium

First measurement of double-hadron production in deep-inelastic scattering has been measured with the HERMES spectrometer at HERA using a 27.6 GeV positron beam with deuterium, nitrogen, krypton and xenon targets. The influence of the nuclear medium on the ratio of double-hadron to single-hadron yields has been investigated. Nuclear effects are clearly observed but with substantially smaller magnitude and reduced $A$-dependence compared to previously measured single-hadron multiplicity ratios. The data are in fair agreement with models based on partonic or pre-hadronic energy loss, while they seem to rule out a pure absorptive treatment of the final state interactions. Thus, the double-hadron ratio provides an additional tool for studying modifications of hadronization in nuclear matter

Evidence for a narrow |S|=1 baryon state at a mass of 1528 MeV in quasi-real photoproduction

Evidence for a narrow baryon state is found in quasi-real photoproduction on a deuterium target through the decay channel p K^0_S --> p pi^+ pi^-. A peak is observed in the p K^0_S invariant mass spectrum at 1528 +/- 2.6 (stat) +/-2.1 (syst) MeV. Depending on the background model,the naive statistical significance of the peak is 4--6 standard deviations and its width may be somewhat larger than the experimental resolution of sigma=4.3 -- 6.2 MeV. This state may be interpreted as the predicted S=+1 exotic Theta^{+}(uuddbar(s)) pentaquark baryon. No signal for an hypothetical Theta^{++} baryon was observed in the pK^+ invariant mass distribution. The absence of such a signal indicates that an isotensor Theta is excluded and an isovector Theta is unlikely.Comment: 8 pages, 4 figure

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Plasma brain natriuretic peptide as a surrogate marker for cardioembolic stroke

<p>Abstract</p> <p>Background</p> <p>Cardioembolic stroke generally results in more severe disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic stroke from non-cardioembolic stroke (atherothrombotic stroke and lacunar stroke). In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic stroke or non-cardioembolic stroke, and assessed the prediction factors of plasma brain natriuretic peptide and whether we could differentiate between stroke subtypes on the basis of plasma brain natriuretic peptide concentrations in addition to patient's clinical variables.</p> <p>Methods</p> <p>Our patient cohort consisted of 131 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005 to December 31, 2007. The mean age of patients (43 females, 88 males) was 69.6 ± 10.1 years. Sixty-two patients had cardioembolic stroke; the remaining 69 patients had non-cardioembolic stroke (including atherothrombotic stroke, lacunar stroke, or the other). Clinical variables and the plasma brain natriuretic peptide were evaluated in all patients.</p> <p>Results</p> <p>Plasma brain natriuretic peptide was linearly associated with atrial fibrillation, heart failure, chronic renal failure, and left atrial diameter, independently (F_4,126= 27.6, p < 0.0001; adjusted R²= 0.45). Furthermore, atrial fibrillation, mitral regurgitation, plasma brain natriuretic peptide (> 77 pg/ml), and left atrial diameter (> 36 mm) were statistically significant independent predictors of cardioembolic stroke in the multivariable setting (Χ²= 127.5, p < 0.001).</p> <p>Conclusion</p> <p>It was suggested that cardioembolic stroke was strongly predicted with atrial fibrillation and plasma brain natriuretic peptide. Plasma brain natriuretic peptide can be a surrogate marker for cardioembolic stroke.</p

Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells

IL-2 is the primary growth factor for promoting survival and proliferation of activated T cells that occurs following engagement of the Janus Kinase (JAK)1-3/and Signal Transducer and Activator of Transcription (STAT) 5 signaling pathway. STAT5 has two isoforms: STAT5A and STAT5B ( commonly referred to as STAT5) which, in T cells, play redundant roles transcribing cell cycle and survival genes. As such, inhibition of STAT5 by a variety of mechanisms can rapidly induce apoptosis in certain lymphoid tumor cells, suggesting that it and its target genes represent therapeutic targets to control certain lymphoid diseases. To search for these molecules we aligned IL-2 regulated genes detected by Affymetrix gene expression microarrays with the STAT5 cistrome identified by chip-on-ChIP analysis in an IL-2-dependent human leukemia cell line, Kit225. Select overlapping genes were then validated using qRT(2)PCR medium-throughput arrays in human PHA-activated PBMCs. Of 19 putative genes, one key regulator of T cell receptor signaling, PDE4B, was identified as a novel target, which was readily up-regulated at the protein level (3 h) in IL-2 stimulated, activated human PBMCs. Surprisingly, only purified CD8+ primary T-cells expressed PDE4B, but not CD4+ cells. Moreover, PDE4B was found to be highly expressed in CD4+ lymphoid cancer cells, which suggests that it may represent a physiological role unique to the CD8+ and lymphoid cancer cells and thus might represent a target for pharmaceutical intervention for certain lymphoid diseases

Molecular and life-history effects of a natural toxin on herbivorous and non-target soil arthropods

Natural toxins, such as isothiocyanate (ITC), are harmful secondary metabolites produced by plants. Many natural toxins occur in commercial crops, yet their possible negative repercussions on especially non-target soil organisms are largely unknown. This study examined life-history and gene transcriptional responses to 2-phenylethyl ITC on two soil arthropod species: Folsomia candida and Protaphorura fimata. To that end the standardized ISO guideline for ecotoxicological tests and a microarray for F. candida were used. The dissipation of 2-phenylethyl ITC in natural soil was investigated using GC-MS/MS for quantification. Half-lives, tested at four concentration levels in natural soil, were on average 16 h with biodegradation as the plausible main removal process. Regardless, toxic effects on reproduction were shown for F. candida and P. fimata, with EC50 values of around 11.5 nmol/g soil illustrating the toxic character of this compound. Gene expression profiles revealed the importance of fatty acid metabolism at low exposure concentrations (EC10), which is associated with the lipophilic nature of 2-phenylethyl ITC. At higher concentrations (EC50) gene expression became more ubiquitous with over-expression of especially stress-related genes and sugar metabolism. The regulation of a gene encoding a precursor of follistatin, furthermore, implied the inhibition of reproduction and may be an important molecular target that can be linked to the observed adverse effect of life-history traits

Terfenadine induces apoptosis and autophagy in melanoma cells through ROS-dependent and -independent mechanisms

Previously we found that terfenadine, an H1 histamine receptor antagonist, acts as a potent apoptosis inducer in melanoma cells through modulation of Ca2+ homeostasis. In this report, focusing our attention on the apoptotic mechanisms activated by terfenadine, we show that this drug can potentially activate distinct intrinsic signaling pathways depending on culture conditions. Serum-deprived conditions enhance the cytotoxic effect of terfenadine and caspase-4 and -2 are activated upstream of caspase-9. Moreover, although we found an increase in ROS levels, the apoptosis was ROS independent. Conversely, terfenadine treatment in complete medium induced ROS-dependent apoptosis. Caspase-4, -2, and -9 were simultaneously activated and p73 and Noxa induction were involved. ROS inhibition prevented p73 and Noxa expression but not p53 and p21 expression, suggesting a role for Noxa in p53-independent apoptosis in melanoma cells. Finally, we found that terfenadine induced autophagy, that can promote apoptosis. These findings demonstrate the great potential of terfenadine to kill melanoma cells through different cellular signaling pathways and could contribute to define new therapeutic strategies in melanoma

TIAF1 self-aggregation in peritumor capsule formation, spontaneous activation of SMAD-responsive promoter in p53-deficient environment, and cell death

Self-aggregation of transforming growth factor β (TGF-β)1-induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid β (Aβ) for causing neurodegeneration. Here, we determined that overexpressed TIAF1 exhibits as aggregates together with Smad4 and Aβ in the cancer stroma and peritumor capsules of solid tumors. Also, TIAF1/Aβ aggregates are shown on the interface between brain neural cells and the metastatic cancer cell mass. TIAF1 is upregulated in developing tumors, but may disappear in established metastatic cancer cells. Growing neuroblastoma cells on the extracellular matrices from other cancer cell types induced production of aggregated TIAF1 and Aβ. In vitro induction of TIAF1 self-association upregulated the expression of tumor suppressors Smad4 and WW domain-containing oxidoreductase (WOX1 or WWOX), and WOX1 in turn increased the TIAF1 expression. TIAF1/Smad4 interaction further enhanced Aβ formation. TIAF1 is known to suppress SMAD-regulated promoter activation. Intriguingly, without p53, self-aggregating TIAF1 spontaneously activated the SMAD-regulated promoter. TIAF1 was essential for p53-, WOX1- and dominant-negative JNK1-induced cell death. TIAF1, p53 and WOX1 acted synergistically in suppressing anchorage-independent growth, blocking cell migration and causing apoptosis. Together, TIAF1 shows an aggregation-dependent control of tumor progression and metastasis, and regulation of cell death