Detectors for the James Webb Space Telescope Near-Infrared Spectrograph I: Readout Mode, Noise Model, and Calibration Considerations

We describe how the James Webb Space Telescope (JWST) Near-Infrared Spectrograph's (NIRSpec's) detectors will be read out, and present a model of how noise scales with the number of multiple non-destructive reads sampling-up-the-ramp. We believe that this noise model, which is validated using real and simulated test data, is applicable to most astronomical near-infrared instruments. We describe some non-ideal behaviors that have been observed in engineering grade NIRSpec detectors, and demonstrate that they are unlikely to affect NIRSpec sensitivity, operations, or calibration. These include a HAWAII-2RG reset anomaly and random telegraph noise (RTN). Using real test data, we show that the reset anomaly is: (1) very nearly noiseless and (2) can be easily calibrated out. Likewise, we show that large-amplitude RTN affects only a small and fixed population of pixels. It can therefore be tracked using standard pixel operability maps.Comment: 55 pages, 10 figure

Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Enjoyment of the shopping experience:impact on customers’ repatronage intentions and gender influence

In this paper the authors investigate enjoyment of the shopping experience, its influence on consumers’ intention to repatronise a regional shopping centre and the effect of gender differences on shopping enjoyment. Four dimensions of shopping enjoyment are proposed and a 16-item measure is developed to assess 536 consumer perceptions of the shopping experience across five counties in the United Kingdom. Findings indicate that shopping experience enjoyment has a significant positive influence upon customers’ repatronage intentions. Furthermore, men are found to have a stronger relationship of enjoyment with repatronage than women. The implications of these results are discussed, together with managerial implications, study limitations, and future research directions

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial

Funded by Asthma UK grant number 09/ 36

mTORC1-mediated translational elongation limits intestinal tumour initiation and growth.

Inactivation of APC is a strongly predisposing event in the development of colorectal cancer, prompting the search for vulnerabilities specific to cells that have lost APC function. Signalling through the mTOR pathway is known to be required for epithelial cell proliferation and tumour growth, and the current paradigm suggests that a critical function of mTOR activity is to upregulate translational initiation through phosphorylation of 4EBP1 (refs 6, 7). This model predicts that the mTOR inhibitor rapamycin, which does not efficiently inhibit 4EBP1 (ref. 8), would be ineffective in limiting cancer progression in APC-deficient lesions. Here we show in mice that mTOR complex 1 (mTORC1) activity is absolutely required for the proliferation of Apc-deficient (but not wild-type) enterocytes, revealing an unexpected opportunity for therapeutic intervention. Although APC-deficient cells show the expected increases in protein synthesis, our study reveals that it is translation elongation, and not initiation, which is the rate-limiting component. Mechanistically, mTORC1-mediated inhibition of eEF2 kinase is required for the proliferation of APC-deficient cells. Importantly, treatment of established APC-deficient adenomas with rapamycin (which can target eEF2 through the mTORC1-S6K-eEF2K axis) causes tumour cells to undergo growth arrest and differentiation. Taken together, our data suggest that inhibition of translation elongation using existing, clinically approved drugs, such as the rapalogs, would provide clear therapeutic benefit for patients at high risk of developing colorectal cancer