The spectral variability of FSRQs

The optical variability of 29 flat spectrum radio quasars in SDSS Stripe 82 region are investigated by using DR7 released multi-epoch data. All FSRQs show variations with overall amplitude ranging from 0.24 mag to 3.46 mag in different sources. About half of FSRQs show a bluer-when-brighter trend, which is commonly observed for blazars. However, only one source shows a redder-when-brighter trend, which implies it is rare in FSRQs. In this source, the thermal emission may likely be responsible for the spectral behavior.Comment: 4 pages, 1 figure, to be published in Journal of Astrophysics and Astronomy, as a proceeding paper of the conference "Multiwavelength Variability of Blazars", Guangzhou, China, September 22-24, 201

Aerothermodynamic Analysis of a Reentry Brazilian Satellite

This work deals with a computational investigation on the small ballistic reentry Brazilian vehicle SARA (acronyms for SAt\'elite de Reentrada Atmosf\'erica). Hypersonic flows over the vehicle SARA at zero-degree angle of attack in a chemical equilibrium and thermal non-equilibrium are modeled by the Direct Simulation Monte Carlo (DSMC) method, which has become the main technique for studying complex multidimensional rarefied flows, and that properly accounts for the non-equilibrium aspects of the flows. The emphasis of this paper is to examine the behavior of the primary properties during the high altitude portion of SARA reentry. In this way, velocity, density, pressure and temperature field are investigated for altitudes of 100, 95, 90, 85 and 80 km. In addition, comparisons based on geometry are made between axisymmetric and planar two-dimensional configurations. Some significant differences between these configurations were noted on the flowfield structure in the reentry trajectory. The analysis showed that the flow disturbances have different influence on velocity, density, pressure and temperature along the stagnation streamline ahead of the capsule nose. It was found that the stagnation region is a thermally stressed zone. It was also found that the stagnation region is a zone of strong compression, high wall pressure. Wall pressure distributions are compared with those of available experimental data and good agreement is found along the spherical nose for the altitude range investigated.Comment: The paper will be published in Vol. 42 of the Brazilian Journal of Physic

Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects

Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAIL DR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAIL DR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments. © 2013 Macmillan Publishers Limited All rights reserved

Yukawa Textures From Heterotic Stability Walls

A holomorphic vector bundle on a Calabi-Yau threefold, X, with h^{1,1}(X)>1 can have regions of its Kahler cone where it is slope-stable, that is, where the four-dimensional theory is N=1 supersymmetric, bounded by "walls of stability". On these walls the bundle becomes poly-stable, decomposing into a direct sum, and the low energy gauge group is enhanced by at least one anomalous U(1) gauge factor. In this paper, we show that these additional symmetries can strongly constrain the superpotential in the stable region, leading to non-trivial textures of Yukawa interactions and restrictions on allowed masses for vector-like pairs of matter multiplets. The Yukawa textures exhibit a hierarchy; large couplings arise on the stability wall and some suppressed interactions "grow back" off the wall, where the extended U(1) symmetries are spontaneously broken. A number of explicit examples are presented involving both one and two stability walls, with different decompositions of the bundle structure group. A three family standard-like model with no vector-like pairs is given as an example of a class of SU(4) bundles that has a naturally heavy third quark/lepton family. Finally, we present the complete set of Yukawa textures that can arise for any holomorphic bundle with one stability wall where the structure group breaks into two factors.Comment: 53 pages, 4 figures and 13 table

A ground-based near-infrared emission spectrum of the exoplanet HD 189733b

Detection of molecules using infrared spectroscopy probes the conditions and compositions of exoplanet atmospheres. Water (H2O), methane (CH4), carbon dioxide (CO2), and carbon monoxide (CO) have been detected in two hot Jupiters. These previous results relied on space-based telescopes that do not provide spectroscopic capability in the 2.4 - 5.2 micron spectral region. Here we report ground-based observations of the dayside emission spectrum for HD 189733b between 2.0-2.4 micron and 3.1-4.1 micron, where we find a bright emission feature. Where overlap with space-based instruments exists, our results are in excellent agreement with previous measurements. A feature at ~3.25 micron is unexpected and difficult to explain with models that assume local thermodynamic equilibrium (LTE) conditions at the 1 bar to 1 x 10-6 bar pressures typically sampled by infrared measurements. The most likely explanation for this feature is that it arises from non-LTE emission from CH4, similar to what is seen in the atmospheres of planets in our own Solar System. These results suggest that non-LTE effects may need to be considered when interpreting measurements of strongly irradiated exoplanets.Comment: 12 pages, 2 figures, published in Natur

Chain-store pricing and the structure of retail markets

This paper examines competition between chain-stores and independent retailers in the UK retail opticians' market. We demonstrate that the pricing policy adopted by chain-stores can determine the impact their entry has on independent retailers. Crucially, in this market the chain-store retailers set an identical national price across all local markets. Our results suggest that this pricing strategy lessens the detrimental effect competition from chain-stores has on independent retailers

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size

The uptake and effect of a mailed multi-modal colon cancer screening intervention: A pilot controlled trial

Abstract Background We sought to determine whether a multi-modal intervention, which included mailing a patient reminder with a colon cancer decision aid to patients and system changes allowing direct access to scheduling screening tests through standing orders, would be an effective and efficient means of promoting colon cancer screening in primary care practice. Methods We conducted a controlled trial comparing the proportion of intervention patients who received colon cancer screening with wait list controls at one practice site. The intervention was a mailed package that included a letter from their primary care physician, a colon cancer screening decision aid, and instructions for obtaining each screening test without an office visit so that patients could access screening tests directly. Major outcomes were screening test completion and cost per additional patient screened. Results In the intervention group, 15% (20/137) were screened versus 4% (4/100) in the control group (difference 11%; (95%; CI 3%;18% p = 0.01). The cost per additional patient screened was estimated to be $94. Conclusion A multi-modal intervention, which included mailing a patient reminder with a colon cancer decision aid to patients and system changes allowing patients direct access to schedule screening tests, increased colon cancer screening test completion in a subset of patients within a single academic practice. Although the uptake of the decision aid was low, the cost was also modest, suggesting that this method could be a viable approach to colon cancer screening

Geographical classifications to guide rural health policy in Australia

The Australian Government's recent decision to replace the Rural Remote and Metropolitan Area (RRMA) classification with the Australian Standard Geographical Classification - Remoteness Areas (ASGC-RA) system highlights the ongoing significance of geographical classifications for rural health policy, particularly in relation to improving the rural health workforce supply. None of the existing classifications, including the government's preferred choice, were designed specifically to guide health resource allocation, and all exhibit strong weaknesses when applied as such. Continuing reliance on these classifications as policy tools will continue to result in inappropriate health program resource distribution. Purely 'geographical' classifications alone cannot capture all relevant aspects of rural health service provision within a single measure. Moreover, because many subjective decisions (such as the choice of algorithm and breakdown of groupings) influence a classification's impact and acceptance from its users, policy-makers need to specify explicitly the purpose and role of their different programs as the basis for developing and implementing appropriate decision tools such as 'rural-urban' classifications. Failure to do so will continue to limit the effectiveness that current rural health support and incentive programs can have in achieving their objective of improving the provision of health care services to rural populations though affirmative action programs