Channeling Effects in Direct Dark Matter Detectors

The channeling of the ion recoiling after a collision with a WIMP changes the ionization signal in direct detection experiments, producing a larger signal than otherwise expected. We give estimates of the fraction of channeled recoiling ions in NaI (Tl), Si and Ge crystals using analytic models produced since the 1960's and 70's to describe channeling and blocking effects. We find that the channeling fraction of recoiling lattice nuclei is smaller than that of ions that are injected into the crystal and that it is strongly temperature dependent.Comment: 8 pages, 12 figures, To appear in the Proceedings of the sixth International Workshop on the Dark Side of the Universe (DSU2010) Leon, Guanajuato, Mexico 1-6 June 201

Nitric oxide in the nucleus raphe magnus modulates cutaneous blood flow in rats during hypothermia

Objective(s): Nucleus Raphe Magnus (NRM) that is involved in the regulation of body temperature contains nitric oxide (NO) synthase. Considering the effect of NO on skin blood flow control, in this study, we assessed its thermoregulatory role within the raphe magnus. Materials and Methods: To this end, tail blood flow of male Wistar rats was measured by laser doppler following the induction of hypothermia. Results: Intra�NRM injection of SNP (exogenous NO donor, 0.1� 0.2 μl, 0.2 nM) increased the blood flow. Similarly, unilateral microinjection of glutamate (0.1� 0.2 μl, 2.3 nM) into the nucleus increased the blood flow. This effect of L�glutamate was reduced by prior intra NRM administration of NO synthase inhibitor NG�methyl�L�arginine or NG�nitro�L�arginine methyl ester (L�NAME, 0.1 μl, 100 nM). Conclusion: It is concluded that NO modulates the thermoregulatory response of NRM to hypothermia and may interact with excitatory amino acids in central skin blood flow regulation. © 2015, Mashhad University of Medical Sciences. All rights reserved

In vivo microscopic voxel-based morphometry with a brain template to characterize strain-specific structures in the mouse brain

Hundreds of inbred mouse strains are established for use in a broad spectrum of basic research fields, including genetics, neuroscience, immunology, and cancer. Inbred mice exhibit identical intra-strain genetics and divergent inter-strain phenotypes. The cognitive and behavioral divergences must be controlled by the variances of structure and function of their brains; however, the underlying morphological features of strain-to-strain difference remain obscure. Here, in vivo microscopic magnetic resonance imaging was optimized to image the mouse brains by using an isotropic resolution of 80 mum. Next, in vivo templates were created from the data from four major inbred mouse strains (C57Bl/6, BALB/cBy, C3H/He, and DBA/2). A strain-mixed brain template was also created, and the template was then employed to establish automatic voxel-based morphometry (VBM) for the mouse brain. The VBM assessment revealed strain-specific brain morphologies concerning the gray matter volume of the four strains, with a smaller volume in the primary visual cortex for the C3H/He strain, and a smaller volume in the primary auditory cortex and field CA1 of the hippocampus for the DBA/2 strain. These findings would contribute to the basis of for understanding morphological phenotype of the inbred mouse strain and may indicate a relationship between brain morphology and strain-specific cognition and behavior

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

Genetic Variants in Inflammation-Related Genes Are Associated with Radiation-Induced Toxicity Following Treatment for Non-Small Cell Lung Cancer

Treatment of non-small cell lung cancer (NSCLC) with radiotherapy or chemoradiotherapy is often accompanied by the development of esophagitis and pneumonitis. Identifying patients who might be at increased risk for normal tissue toxicity would help in determination of the optimal radiation dose to avoid these events. We profiled 59 single nucleotide polymorphisms (SNPs) from 37 inflammation-related genes in 173 NSCLC patients with stage IIIA/IIIB (dry) disease who were treated with definitive radiation or chemoradiation. For esophagitis risk, nine SNPs were associated with a 1.5- to 4-fold increase in risk, including three PTGS2 (COX2) variants: rs20417 (HR:1.93, 95% CI:1.10–3.39), rs5275 (HR:1.58, 95% CI:1.09–2.27), and rs689470 (HR:3.38, 95% CI:1.09–10.49). Significantly increased risk of pneumonitis was observed for patients with genetic variation in the proinflammatory genes IL1A, IL8, TNF, TNFRSF1B, and MIF. In contrast, NOS3:rs1799983 displayed a protective effect with a 45% reduction in pneumonitis risk (HR:0.55, 95% CI:0.31–0.96). Pneumonitis risk was also modulated by polymorphisms in anti-inflammatory genes, including genetic variation in IL13. rs20541 and rs180925 each resulted in increased risk (HR:2.95, 95% CI:1.14–7.63 and HR:3.23, 95% CI:1.03–10.18, respectively). The cumulative effect of these SNPs on risk was dose-dependent, as evidenced by a significantly increased risk of either toxicity with an increasing number of risk genotypes (P<0.001). These results suggest that genetic variations among inflammation pathway genes may modulate the development of radiation-induced toxicity and, ultimately, help in identifying patients who are at an increased likelihood for such events

Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial.

BACKGROUND: Concurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer. METHODS: The CONVERT trial was an open-label, phase 3, randomised superiority trial. We enrolled adult patients (aged ≥18 years) who had cytologically or histologically confirmed limited-stage small-cell lung cancer, Eastern Cooperative Oncology Group performance status of 0-2, and adequate pulmonary function. Patients were recruited from 73 centres in eight countries. Patients were randomly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin-etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups). The allocation method used was minimisation with a random element, stratified by institution, planned number of chemotherapy cycles, and performance status. Treatment group assignments were not masked. The primary endpoint was overall survival, defined as time from randomisation until death from any cause, analysed by modified intention-to-treat. A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen. The study is registered with ClinicalTrials.gov (NCT00433563) and is currently in follow-up. FINDINGS: Between April 7, 2008, and Nov 29, 2013, 547 patients were enrolled and randomly assigned to receive twice-daily concurrent chemoradiotherapy (274 patients) or once-daily concurrent chemoradiotherapy (273 patients). Four patients (one in the twice-daily group and three in the once-daily group) did not return their case report forms and were lost to follow-up; these patients were not included in our analyses. At a median follow-up of 45 months (IQR 35-58), median overall survival was 30 months (95% CI 24-34) in the twice-daily group versus 25 months (21-31) in the once-daily group (hazard ratio for death in the once daily group 1·18 [95% CI 0·95-1·45]; p=0·14). 2-year overall survival was 56% (95% CI 50-62) in the twice-daily group and 51% (45-57) in the once-daily group (absolute difference between the treatment groups 5·3% [95% CI -3·2% to 13·7%]). The most common grade 3-4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia (197 [74%] of 266 patients in the twice-daily group vs 170 [65%] of 263 in the once-daily group). Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiotherapy (129 [49%] vs 101 [38%]; p=0·05). In patients assessed for radiotherapy toxicity, was no difference in grade 3-4 oesophagitis between the groups (47 [19%] of 254 patients in the twice-daily group vs 47 [19%] of 246 in the once-daily group; p=0·85) and grade 3-4 radiation pneumonitis (4 [3%] of 254 vs 4 [2%] of 246; p=0·70). 11 patients died from treatment-related causes (three in the twice-daily group and eight in the once-daily group). INTERPRETATION: Survival outcomes did not differ between twice-daily and once-daily concurrent chemoradiotherapy in patients with limited-stage small-cell lung cancer, and toxicity was similar and lower than expected with both regimens. Since the trial was designed to show superiority of once-daily radiotherapy and was not powered to show equivalence, the implication is that twice-daily radiotherapy should continue to be considered the standard of care in this setting. FUNDING: Cancer Research UK (Clinical Trials Awards and Advisory Committee), French Ministry of Health, Canadian Cancer Society Research Institute, European Organisation for Research and Treatment of Cancer (Cancer Research Fund, Lung Cancer, and Radiation Oncology Groups)

In vitro evaluation of modified surface microhardness measurement, focus variation 3D microscopy and contact stylus profilometry to assess enamel surface loss after erosive-abrasive challenges

The aim of the study was to compare surface loss values after erosion-abrasion cycles obtained with modified surface microhardness measurement (mSMH), focus variation 3D microscopy (FVM) and contact stylus profilometry (CSP). We cut human molars into buccal and lingual halves, embedded them in resin and ground 200 μm of enamel away. The resulting surfaces were polished. To maintain a reference area, we applied Block-Out resin to partly cover the enamel surface. The samples were incubated in artificial saliva (37°C; 1 h), then rinsed in deionized water (10 s) and dried with oil-free air (5 s). We immersed the specimens individually in 30 mL citric acid (1%, pH 3.6) for 2 min (25°C, 70 rpm dynamic conditions) before brushing them (50 strokes, 200 g) in an automatic brushing machine with toothpaste-slurry. We calculated the surface loss as per mSMH, by re-measuring the length of the same six indentations made before the abrasive challenge. The experiment consisted of five experimental groups that received between 2 and 10 erosion-abrasion cycles. Each group contained 15 specimens and samples in groups 1, 2, 3, 4 and 5 underwent a total of 2, 4, 6, 8 and 10 cycles, respectively. The resin was removed from the reference area in one piece under 10× magnification and the FVM and CSP were performed. Agreement between the methods was calculated with the intraclass correlation coefficient (ICC) and depicted in Bland-Altman plots. All methods presented a linear pattern of surface loss measurements throughout the experiment, leading overall to a strong, statistically significant correlation between the methods (ICC = 0.85; p<0.001). So, despite the different surface loss values, all methods presented consistent results for surface loss measurement