1,361 research outputs found
Globally clustered chimera states in delay--coupled populations
We have identified the existence of globally clustered chimera states in
delay coupled oscillator populations and find that these states can breathe
periodically, aperiodically and become unstable depending upon the value of
coupling delay. We also find that the coupling delay induces frequency
suppression in the desynchronized group. We provide numerical evidence and
theoretical explanations for the above results and discuss possible
applications of the observed phenomena.Comment: Accepted in Phys. Rev. E as a Rapid Communicatio
Interferometry of direct photons in Pb+Pb collisions at 158 AGeV
We present final results from the WA98 experiment which provide first
measurements of Bose-Einstein correlations of direct photons in
ultrarelativistic heavy ion collisions. Invariant interferometric radii were
extracted in the range MeV/c and compared to interferometric
radii of charged pions. The yield of direct photons for MeV/c was
extracted from the correlation strength parameter and compared to the yield of
direct photons measured in WA98 at higher with the statistical
subtraction method, and to predictions of a fireball model.Comment: 4 pages, 3 figures, proceedings for Quark Matter 200
The Ratio of Ortho- to Para-H2 in Photodissociation Regions
We discuss the ratio of ortho- to para-H2 in photodissociation regions
(PDRs). We draw attention to an apparent confusion in the literature between
the ortho-to-para ratio of molecules in FUV-pumped vibrationally excited
states, and the H2 ortho-to-para abundance ratio. These ratios are not the same
because the process of FUV-pumping of fluorescent H2 emission in PDRs occurs
via optically thick absorption lines. Thus, gas with an equilibrium ratio of
ortho- to para-H2 equal to 3 will yield FUV-pumped vibrationally excited
ortho-to-para ratios smaller than 3, because the ortho-H2 pumping rates are
preferentially reduced by optical depth effects. Indeed, if the ortho and para
pumping lines are on the ``square root'' part of the curve-of-growth, then the
expected ratio of ortho and para vibrational line strengths is the square root
of 3, ~ 1.7, close to the typically observed value. Thus, contrary to what has
sometimes been stated in the literature, most previous measurements of the
ratio of ortho- to para-H2 in vibrationally excited states are entirely
consistent with a total ortho-to-para ratio of 3, the equilibrium value for
temperatures greater than 200 K. We present an analysis and several detailed
models which illustrate the relationship between the total ratios of ortho- to
para-H2 and the vibrationally excited ortho-to-para ratios in PDRs. Recent
Infrared Space Observatory (ISO) measurements of pure rotational and
vibrational H2 emissions from the PDR in the star-forming region S140 provide
strong observational support for our conclusions.Comment: 23 pages (including 5 figures), LaTeX, uses aaspp4.sty, accepted for
publication in Ap
Withaferin A Induces Proteasome-Dependent Degradation of Breast Cancer Susceptibility Gene 1 and Heat Shock Factor 1 Proteins in Breast Cancer Cells
This is the publisher's version, also available electronically from "http://www.hindawi.com".The purpose of this study was to examine the regulation of prosurvival factors heat shock factor 1 (HSF1) and breast cancer susceptibility gene 1 (BRCA1) by a natural withanolide withaferin A (WA) in triple negative breast cancer cell lines MDA-MB-231 and BT20. Western analysis was used to examine alternations in HSF1 and BRCA1 protein levels following WA treatment. A protein synthesis inhibitor cycloheximide and a proteasome inhibitor MG132 were used to investigate the mechanisms of HSF1 and BRCA1 regulation by WA. It was found that WA induced a dose-dependent decrease in HSF1 and BRCA1 protein levels. Further analysis showed that levels of HSF1 and BRCA1 proteins decreased rapidly after WA treatment, and this was attributed to WA-induced denaturation of HSF1 and BRCA1 proteins and subsequent degradation via proteasome-dependent, and protein-synthesis dependent mechanism. In summary, WA induces denaturation and proteasomal degradation of HSF1 and BRCA1 proteins. Further studies are warranted to examine the contribution of HSF1 and BRCA1 depletion to the anticancer effects of WA in breast cancer
Anti-proliferative withanolides from the Solanaceae: a structure-activity study
This is the publisher's version, also available electronically from "http://www.degruyter.com".As part of our search for bioactive compounds from plant biodiversity, 29 withanolides were recently isolated from three members of the Solanaceae: Physalis longifolia, Vassobia breviflora, and Withania somnifera. Six derivatives were prepared from these naturally occurring withanolides. All compounds were evaluated for in vitro antiproliferative activity against an array of cell lines [melanoma cell lines (B16F10, SKMEL28); human head and neck squamous cell carcinomas (HNSCC) cell lines (JMAR, MDA1986, DR081-1); breast cancer cell line (Hs578T), and non-malignant human cell line (MRC5)]. This led to the discovery of 15 withanolides, with IC50 values in the range of 0.067−17.4 μM, including withaferin A, withaferin A 4,27-diacetate, 27-O-glucopyranosylwithaferin A, withalongolide H, withalongolide C, withalongolide A, withalongolide A 4,27-diacetate, withalongolide A 4,19,27-triacetate, withalongolide B, withalongolide B 4-acetate, withalongolide B 4,19-diacetate, withalongolide D, withalongolide E, withalongolide G, and 2,3-dihydrowithaferin A 3-O-sulfate. In order to update the growing literature on withanolides and their activities, we summarized the distribution, structural types, and antiproliferative activities for all published withanolides to date. The structure–activity relationship analysis (SARA) confirmed the importance of the presence of a ∆2-1-oxo-functionality in ring A, a 5β,6β-epoxy or 5α-chloro-6β-hydroxy grouping in ring B, and nine-carbon side chain with a lactone moiety for cytotoxic activity. Conversely, the SARA indicated that the –OH or –OR groups at C-4, 7, 11, 12, 14, 15, 16, 17, 18, 19, 20, 23, 24, 27, and 28 were not contributors to the observed antiproliferative activity within the systems analyzed
Data-Efficient Iterative Training of Gaussian Approximation Potentials: Application to Surface Structure Determination of Rutile IrO<sub>2</sub> and RuO<sub>2</sub>
Machine-learning interatomic potentials like Gaussian Approximation Potentials (GAPs) constitute a powerful class of surrogate models to computationally involved first-principles calculations. At similar predictive quality but significantly reduced cost, they could leverage otherwise barely tractable extensive sampling as in global surface structure determination (SSD). This efficiency is jeopardized though, if an a priori unknown structural and chemical search space as in SSD requires an excessive number of first-principles data for the GAP training.To this end, we present a general and data-efficient iterative training protocol that blends the creation of new training data with the actual surface exploration process. Demonstrating this protocol with the SSD of low-index facets of rutile IrO2 and RuO2 , the involved simulated annealing on the basis of the refining GAP identifies a number of unknown terminations even in the restricted sub-space of (1×1) surface unit-cells. Especially in an O-poor environment, some of these, then metal-rich terminations, are thermodynamically most stable and are reminiscent of complexions as discussed for complex ceramic materials
A novel RET inhibitor with potent efficacy against medullary thyroid cancer in vivo
Background
Most medullary thyroid carcinomas (MTC) recur or progress despite optimal surgical resection. Current targeted-therapies show promise but lack durable efficacy and tolerability. The purpose of this study was to build upon previous in vitro work and evaluate Withaferin A (WA), a novel RET inhibitor, in a metastatic murine model of MTC.
Methods
5 million DRO-81-1 human MTC-cells injected in the left posterior neck of Nu/Nu mice uniformly generated metastases to the liver, spleen, and/or lungs. Treatment with WA (8mg/kg/day i.p.×21 days) was started for tumors >100 mm3. Endpoints were survival, tumor>1500 mm3, decreased bodyweight, or body score (all measured thrice weekly).
Results
All controls (saline; n=5) died or deteriorated from metastatic disease by 7 weeks post injection. All treated animals were alive,(WA; n=5), having tumor regression and growth-delay without toxicity or weight-loss at 6 wks post treatment; p<0.01. Tumor cells treated with WA demonstrated inhibition of total and phospho-RET levels by Western-Blot analysis in a dose-dependent manner (almost complete inhibition with 5uM WA treatment) as well as potent inhibition of phospho-ERK and phospho-AKT levels.
Conclusions
Withaferin A is a novel natural-product RET-inhibitor with efficacy in a metastatic murine model of MTC. Further long-term efficacy/toxicity studies are warranted to evaluate this compound for clinical translation
Probabilistic tractography in the ventrolateral thalamic nucleus: cerebellar and pallidal connections
The ventrolateral thalamic nucleus (VL), as part of the ‘motor thalamus’, is main relay station of cerebellar and pallidal projections. It comprises anterior (VLa) and posterior (VLpd and VLpv) subnuclei. Though the fibre architecture of cerebellar and pallidal projections to of the VL nucleus has already been focus in a numerous amount of in vitro studies mainly in animals, probabilistic tractography now offers the possibility of an in vivo comparison in healthy humans. In this study we performed a (a) qualitative and (b) quantitative examination of VL-cerebellar and VL-pallidal pathways and compared the probability distributions between both projection fields in the VL after an (I) atlas-based and (II) manual-based segmentation procedure. Both procedures led to high congruent results of cerebellar and pallidal connectivity distributions: the maximum of pallidal projections was located in anterior and medial parts of the VL nucleus, whereas cerebellar connectivity was more located in lateral and posterior parts. The median connectivity for cerebellar connections in both approaches (manual and atlas-based segmentation) was VLa > VLpv > VLpd, whereas the pallidal median connectivity was VLa ~ VLpv > VLpd in the atlas-based approach and VLpv > VLa > VLpd in the manual approach.Peer reviewe
Can woodland caribou and the forest industry coexist: The Ontario scene
Ontario is in the process of developing a strategy to improve the likelihood of woodland caribou (Rangifer tarandus caribou) and the forest industry coexisting in the province. This strategy is described within a set of proposed Timber Management Guidelines for the Provision of Woodland Caribou Habitat. The proposed guidelines advocate managing for large blocks of suitable winter habitat across caribou range, large cutovers to regenerate caribou winter habitat and the protection of traditional calving areas and travel routes. Summer habitat will be provided by the resulting mosaic. The forest industry can provide a sustainable supply of woodland caribou habitat that was traditionally maintained by wildfire
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