First-principles method of propagation of tightly bound excitons: exciton band structure of LiF and verification with inelastic x-ray scattering

We propose a simple first-principles method to describe propagation of tightly bound excitons. By viewing the exciton as a composite object (an effective Frenkel exciton in Wannier orbitals), we define an exciton kinetic kernel to encapsulate the exciton propagation and decay for all binding energy. Applied to prototypical LiF, our approach produces three exciton bands, which we verified quantitatively via inelastic x-ray scattering. The proposed real-space picture is computationally inexpensive and thus enables study of the full exciton dynamics, even in the presence of surfaces and impurity scattering. It also provides intuitive understanding to facilitate practical exciton engineering in semiconductors, strongly correlated oxides, and their nanostructures.Comment: 5 pages, 4 figures. Accepted by PR

On the origin of non-monotonic doping dependence of the in-plane resistivity anisotropy in Ba(Fe1−xTx_{1-x}T_x)2_2As2_2, TT = Co, Ni and Cu

The in-plane resistivity anisotropy has been measured for detwinned single crystals of Ba(Fe$_{1-x}$Ni$_x$)$_2$As$_2$ and Ba(Fe$_{1-x}$Cu$_x$)$_2$As$_2$. The data reveal a non-monotonic doping dependence, similar to previous observations for Ba(Fe$_{1-x}$Co$_x$)$_2$As$_2$. Magnetotransport measurements of the parent compound reveal a non-linear Hall coefficient and a strong linear term in the transverse magnetoresistance. Both effects are rapidly suppressed with chemical substitution over a similar compositional range as the onset of the large in-plane resistivity anisotropy. It is suggested that the relatively small in-plane anisotropy of the parent compound in the spin density wave state is due to the presence of an isotropic, high mobility pocket of reconstructed Fermi surface. Progressive suppression of the contribution to the conductivity arising from this isotropic pocket with chemical substitution eventually reveals the underlying in-plane anisotropy associated with the remaining FS pockets.Comment: 12 pages, 9 figure

Using BEAM Software to Simulate the Introduction of On-Demand, Automated, and Electric Shuttles for Last Mile Connectivity in Santa Clara County

Despite growing interest in low-speed automated shuttles, pilot deployments have only just begun in a few places in the U.S., and there is a lack of studies that estimate the impacts of a widespread deployment of automated shuttles designed to supplement existing transit networks. This project estimated the potential impacts of automated shuttles based on a deployment scenario generated for a sample geographic area: Santa Clara County, California. The project identified sample deployment markets within Santa Clara County using a GIS screening exercise; tested the mode share changes of an automated shuttle deployment scenario using BEAM, an open-source beta software developed at the Lawrence Berkeley National Laboratory to run traffic simulations with MATSim; elaborated the model outputs within the R environment; and then estimated the related impacts. The main findings have been that the BEAM software, despite still being in its beta version, was able to model a scenario with the automated shuttle service: this report illustrates the potential of the software and the lessons learned. Regarding transportation aspects, the model estimated automated shuttle use throughout the county, with a higher rate of use in the downtown San José area. The shuttles would be preferred mainly by people who had been using gasoline-powered ride hail vehicles for A-to-B trips or going to the bus stop, as well as walking trips and a few car trips directed to public transport stops. As a result, the shuttles contributed to a small decrease in emissions of air pollutants, provided a competitive solution for short trips, and increased the overall use of the public transport system. The shuttles also presented a solution for short night trips—mainly between midnight and 2 am—when there are not many options for moving between points A and B. The conclusion is that the automated shuttle service is a good solution in certain contexts and can increase public transit ridership overall

Modified Weekly Cisplatin-Based Chemotherapy Is Acceptable in Postoperative Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer

Background. Triweekly cisplatin-based postoperative concurrent chemoradiotherapy (CCRT) has high intolerance and toxicities in locally advanced head and neck cancer (LAHNC). We evaluated the effect of a modified weekly cisplatin-based chemotherapy in postoperative CCRT. Methods. A total of 117 patients with LAHNC were enrolled between December 2007 and December 2012. Survival, compliance/adverse events, and independent prognostic factors were analyzed. Results. Median follow-up time was 30.0 (3.1–73.0) months. Most patients completed the entire course of postoperative CCRT (radiotherapy ≥ 60 Gy, 94.9%; ≥6 times weekly chemotherapy, 75.2%). Only 17.1% patients required hospital admission. The most common adverse effect was grade 3/4 mucositis (28.2%). No patient died due to protocol-related adverse effects. Multivariate analysis revealed the following independent prognostic factors: oropharyngeal cancer, extracapsular spread, and total radiation dose. Two-year progression-free survival and overall survival rates were 70.9% and 79.5%, respectively. Conclusion. Modified weekly cisplatin-based chemotherapy is an acceptable regimen in postoperative CCRT for LAHNC

Potential Role of Platelet-Derived Growth Factor Receptor Inhibition Using Imatinib in Combination with Docetaxel in the Treatment of Recurrent Non-small Cell Lung Cancer

Introduction:Platelet-derived growth factor receptor (PDGFR) is expressed in lung cancer and is involved in angiogenesis. Preclinical models demonstrated that imatinib (Im) regulates angiogenesis through PDGFR inhibition and enhances efficacy of chemotherapy. Hypothesis: We hypothesized that Im plus docetaxel (D) would have a synergistic effect detectable by an increase in response rate in patients with recurrent non-small cell lung cancer (NSCLC).Methods:A phase II trial to evaluate Im in combination with D in patients with recurrent NSCLC was conducted. The primary end point was response rate, using a Simon two-stage design. Eligible patients had measurable disease and no more than two chemotherapy regimens. D was given at 30 mg/m2/wk intravenously ×3 every 4 weeks and oral Im at 600 mg daily for four cycles. Patients required two cycles to be evaluable for response. Nonprogressors after four cycles continued with Im maintenance until progression or for a total of 12 months.Results:Twenty-three patients were enrolled in the first stage. Toxicity was mainly nonhematologic. We observed one partial response (5.5%), four stable disease (22.2%), and 13 progressed (72.2%). Median time to progression was 1.9 months, and median overall survival was 6.1 months. Two patients who went on Im maintenance had time to progression of 7.78 months and 15.8 months.Conclusion:Im in combination with D did not achieve its primary objective of improving response rate in patients with recurrent NSCLC. An increased understanding of the complex PDGFR pathway in lung cancer and alternative strategies to inhibit it are needed

Vigilin interacts with signal peptide peptidase.

BACKGROUND: Signal peptide peptidase (SPP), a member of the presenilin-like intra-membrane cleaving aspartyl protease family, migrates on Blue Native (BN) gels as 100 kDa, 200 kDa and 450 kDa species. SPP has recently been implicated in other non-proteolytic functions such as retro-translocation of MHC Class I molecules and binding of misfolded proteins in the endoplasmic reticulum (ER). These high molecular weight SPP complexes might contain additional proteins that regulate the proteolytic activity of SPP or support its non-catalytic functions. RESULTS: In this study, an unbiased iTRAQ-labeling mass spectrometry approach was used to identify SPP-interacting proteins. We found that vigilin, a ubiquitous multi-KH domain containing cytoplasmic protein involved in RNA binding and protein translation control, selectively enriched with SPP. Vigilin interacted with SPP and both proteins co-localized in restricted intracellular domains near the ER, biochemically co-fractionated and were part of the same 450 kDa complex on BN gels. However, vigilin does not alter the protease activity of SPP, suggesting that the SPP-vigilin interaction might be involved in the non-proteolytic functions of SPP. CONCLUSIONS: We have identified and validated vigilin as a novel interacting partner of SPP that could play an important role in the non-proteolytic functions of SPP. This data adds further weight to the idea that intramembrane-cleaving aspartyl proteases, such as presenilin and SPPs, could have other functions besides the proteolysis of short membrane stubs.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Metabolism of Low-Dose Inorganic Arsenic in a Central European Population: Influence of Sex and Genetic Polymorphisms

BACKGROUND: There is a wide variation in susceptibility to health effects of arsenic, which, in part, may be due to differences in arsenic metabolism. Arsenic is metabolized by reduction and methylation reactions, catalyzed by reductases and methyltransferases. OBJECTIVES: Our goal in this study was to elucidate the influence of various demographic and genetic factors on the metabolism of arsenic. METHODS: We studied 415 individuals from Hungary, Romania, and Slovakia by measuring arsenic metabolites in urine using liquid chromatography with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). We performed genotyping of arsenic (+III) methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), and methylene-tetrahydrofolate reductase (MTHFR). RESULTS: The results show that the M287T (T-->C) polymorphism in the AS3MT gene, the A222V (C-->T) polymorphism in the MTHFR gene, body mass index, and sex are major factors that influence arsenic metabolism in this population, with a median of 8.0 microg/L arsenic in urine. Females C) polymorphism in the AS3MT gene on the methylation capacity was much more pronounced in men than in women. CONCLUSIONS: The factors investigated explained almost 20% of the variation seen in the metabolism of arsenic among men and only around 4% of the variation among women. The rest of the variation is probably explained by other methyltransferases backing up the methylation of arsenic

Evaluation of prognostic factors and the role of chemotherapy in unfavorable carcinoma of unknown primary site: a 10-year cohort study

<p>Abstract</p> <p>Background</p> <p>Carcinoma of unknown primary site (CUP) has a poor prognosis and the prognostic factors in these patients are not well established. Furthermore, there are no selection criteria for patients who should benefit from chemotherapy.</p> <p>Methods</p> <p>The medical records of 179 CUP patients who were treated at Taipei Veterans General Hospital from 2000 to 2009 were reviewed. Factors associated with survival were determined by Kaplan-Meier analysis. Differences between the groups with and without palliative chemotherapy were analyzed.</p> <p>Results</p> <p>Univariate analysis revealed multiple prognostic factors, including performance status, lung metastasis, number of metastatic organs, serum albumin, corrected serum calcium, lactate dehydrogenase (LDH), sodium, and cholesterol levels, palliative chemotherapy, and white blood cell and lymphocyte counts. Multivariate analysis showed that performance status < 2, serum albumin level ≥ 3.5 g/dl, corrected serum calcium level < 10.7 mg/dl, single metastatic organ, and palliative chemotherapy were independent factors of better prognosis. Patients with better performance status, higher serum albumin, and lower serum LDH levels had significantly greater benefit from palliative chemotherapy.</p> <p>Conclusions</p> <p>Certain patients with unfavorable CUP will have better survival. Identification of patients with unfavorable CUP who could benefit from palliative chemotherapy warrants future prospective studies.</p

Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane

Vesicle fusion is executed via formation of an Ω-shaped structure (Ω-profile), followed by closure (kiss-and-run) or merging of the Ω-profile into the plasma membrane (full fusion). Although Ω-profile closure limits release but recycles vesicles economically, Ω-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Ω-profile merging is mediated is poorly understood in endocrine cells and neurons containing small ∼30–300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Ω-profile merging by providing sufficient plasma membrane tension to shrink the Ω-profile in neuroendocrine chromaffin cells containing ∼300 nm vesicles. Actin-directed compounds also induce Ω-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Ω-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Ω-profile merging