109 research outputs found
Inhibition of the norepinephrine transporter by χ-conotoxin dendrimers.
Peptide dendrimers are a novel class of macromolecules of emerging interest with the potential of delayed renal clearance due to their molecular size and enhanced activity due to the multivalency effect. In this work, an active analogue of the disulfide-rich χ-conotoxin χ-MrIA (χ-MrIA), a norepinephrine reuptake (norepinephrine transporter) inhibitor, was grafted onto a polylysine dendron. Dendron decoration was achieved by employing copper-catalyzed alkyne-azide cycloaddition with azido-PEG chain-modified χ-MrIA analogues, leading to homogenous 4-mer and 8-mer χ-MrIA dendrimers with molecular weights ranging from 8 to 22 kDa. These dendrimers were investigated for their impact on peptide secondary structure, in vitro functional activity, and potential anti-allodynia in vivo. NMR studies showed that the χ-MrIA tertiary structure was maintained in the χ-MrIA dendrimers. In a functional norepinephrine transporter reuptake assay, χ-MrIA dendrimers showed slightly increased potency relative to the azido-PEGylated χ-MrIA analogues with similar potency to the parent peptide. In contrast to χ-MrIA, no anti-allodynic action was observed when the χ-MrIA dendrimers were administered intrathecally in a rat model of neuropathic pain, suggesting that the larger dendrimer structures are unable to diffuse through the spinal column tissue and reach the norepinephrine transporter.NHMRC Grants: 1045964 & 107211
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The effect of asymmetries on stock index return value-at-risk estimates
It is widely accepted that equity return volatility increases more following negative shocks rather than positive shocks. However, much of value-at-risk (VaR) analysis relies on the assumption that returns are normally distributed (a symmetric distribution). This article considers the effect of asymmetries on the evaluation and accuracy of VaR by comparing estimates based on various models
Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium
Background: Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk. Methods and Results: We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥ 1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤ 1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026). Conclusion: Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings
Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV
We report a measurement of the longitudinal double-spin asymmetry A_LL and
the differential cross section for inclusive Pi0 production at midrapidity in
polarized proton collisions at sqrt(s) = 200 GeV. The cross section was
measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be
in good agreement with a next-to-leading order perturbative QCD calculation.
The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T <
11 GeV/c and excludes a maximal positive gluon polarization in the proton. The
mean transverse momentum fraction of Pi0's in their parent jets was found to be
around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC
Longitudinal scaling property of the charge balance function in Au + Au collisions at 200 GeV
We present measurements of the charge balance function, from the charged
particles, for diverse pseudorapidity and transverse momentum ranges in Au + Au
collisions at 200 GeV using the STAR detector at RHIC. We observe that the
balance function is boost-invariant within the pseudorapidity coverage [-1.3,
1.3]. The balance function properly scaled by the width of the observed
pseudorapidity window does not depend on the position or size of the
pseudorapidity window. This scaling property also holds for particles in
different transverse momentum ranges. In addition, we find that the width of
the balance function decreases monotonically with increasing transverse
momentum for all centrality classes.Comment: 6 pages, 3 figure
Energy and system size dependence of \phi meson production in Cu+Cu and Au+Au collisions
We study the beam-energy and system-size dependence of \phi meson production
(using the hadronic decay mode \phi -- K+K-) by comparing the new results from
Cu+Cu collisions and previously reported Au+Au collisions at \sqrt{s_NN} = 62.4
and 200 GeV measured in the STAR experiment at RHIC. Data presented are from
mid-rapidity (|y|<0.5) for 0.4 < pT < 5 GeV/c. At a given beam energy, the
transverse momentum distributions for \phi mesons are observed to be similar in
yield and shape for Cu+Cu and Au+Au colliding systems with similar average
numbers of participating nucleons. The \phi meson yields in nucleus-nucleus
collisions, normalised by the average number of participating nucleons, are
found to be enhanced relative to those from p+p collisions with a different
trend compared to strange baryons. The enhancement for \phi mesons is observed
to be higher at \sqrt{s_NN} = 200 GeV compared to 62.4 GeV. These observations
for the produced \phi(s\bar{s}) mesons clearly suggest that, at these collision
energies, the source of enhancement of strange hadrons is related to the
formation of a dense partonic medium in high energy nucleus-nucleus collisions
and cannot be alone due to canonical suppression of their production in smaller
systems.Comment: 20 pages and 5 figure
Measurement of the Bottom contribution to non-photonic electron production in collisions at =200 GeV
The contribution of meson decays to non-photonic electrons, which are
mainly produced by the semi-leptonic decays of heavy flavor mesons, in
collisions at 200 GeV has been measured using azimuthal
correlations between non-photonic electrons and hadrons. The extracted
decay contribution is approximately 50% at a transverse momentum of GeV/. These measurements constrain the nuclear modification factor for
electrons from and meson decays. The result indicates that meson
production in heavy ion collisions is also suppressed at high .Comment: 6 pages, 4 figures, accepted by PR
System size dependence of associated yields in hadron-triggered jets
We present results on the system size dependence of high transverse momentum
di-hadron correlations at = 200 GeV as measured by STAR at
RHIC. Measurements in d+Au, Cu+Cu and Au+Au collisions reveal similar jet-like
correlation yields at small angular separation (,
) for all systems and centralities. Previous measurements have
shown that the away-side yield is suppressed in heavy-ion collisions. We
present measurements of the away-side suppression as a function of transverse
momentum and centrality in Cu+Cu and Au+Au collisions. The suppression is found
to be similar in Cu+Cu and Au+Au collisions at a similar number of
participants. The results are compared to theoretical calculations based on the
parton quenching model and the modified fragmentation model. The observed
differences between data and theory indicate that the correlated yields
presented here will provide important constraints on medium density profile and
energy loss model parameters.Comment: 12 pages, 5 figure
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