Calibration of a photomultiplier array spectrometer

A systematic approach to the calibration of a photomultiplier array spectrometer is presented. Through this approach, incident light radiance derivation is made by recognizing and tracing gain characteristics for each photomultiplier tube

Ifitm3 Limits the Severity of Acute Influenza in Mice

Interferon-induced transmembrane (IFITM) proteins are a family of viral restriction factors that inhibit the entry processes of several pathogenic viruses, including influenza A virus (IAV), in vitro. Here we report that IAV-infected knockout mice lacking the Ifitm locus on chromosome 7 exhibited accelerated disease progression, greater mortality, and higher pulmonary and systemic viral burdens as compared to wild type controls. We further observed that the phenotype of Ifitm3-specific knockout mice was indistinguishable from that of mice lacking the entire Ifitm locus. Ifitm3 was expressed by IAV target cells including alveolar type II pneumocytes and tracheal/bronchial respiratory epithelial cells. Robust Ifitm3 expression was also observed in several tissues in the absence of infection. Among murine Ifitm promoters, only that of Ifitm3 could be induced by type I and II interferons. Ifitm3 could also be upregulated by the gp130 cytokines IL-6 and oncostatin M on cells expressing appropriate receptors, suggesting that multiple cytokine signals could contribute to Ifitm3 expression in a cell or tissue-specific manner. Collectively, these findings establish a central role for Ifitm3 in limiting acute influenza in vivo, and provide further insight into Ifitm3 expression and regulation

Rational design of aptazyme riboswitches for efficient control of gene expression in mammalian cells

Efforts to control mammalian gene expression with ligand-responsive riboswitches have been hindered by lack of a general method for generating efficient switches in mammalian systems. Here we describe a rational-design approach that enables rapid development of efficient cis-acting aptazyme riboswitches. We identified communication-module characteristics associated with aptazyme functionality through analysis of a 32-aptazyme test panel. We then developed a scoring system that predicts an aptazymes\u27s activity by integrating three characteristics of communication-module bases: hydrogen bonding, base stacking, and distance to the enzymatic core. We validated the power and generality of this approach by designing aptazymes responsive to three distinct ligands, each with markedly wider dynamic ranges than any previously reported. These aptayzmes efficiently regulated adeno-associated virus (AAV)-vectored transgene expression in cultured mammalian cells and mice, highlighting one application of these broadly usable regulatory switches. Our approach enables efficient, protein-independent control of gene expression by a range of small molecules

Luciferase expression and bioluminescence does not affect tumor cell growth in vitro or in vivo

Live animal imaging is becoming an increasingly common technique for accurate and quantitative assessment of tumor burden over time. Bioluminescence imaging systems rely on a bioluminescent signal from tumor cells, typically generated from expression of the firefly luciferase gene. However, previous reports have suggested that either a high level of luciferase or the resultant light reaction produced upon addition of D-luciferin substrate can have a negative influence on tumor cell growth. To address this issue, we designed an expression vector that allows simultaneous fluorescence and luminescence imaging. Using fluorescence activated cell sorting (FACS), we generated clonal cell populations from a human breast cancer (MCF-7) and a mouse melanoma (B16-F10) cell line that stably expressed different levels of luciferase. We then compared the growth capabilities of these clones in vitro by MTT proliferation assay and in vivo by bioluminescence imaging of tumor growth in live mice. Surprisingly, we found that neither the amount of luciferase nor biophotonic activity was sufficient to inhibit tumor cell growth, in vitro or in vivo. These results suggest that luciferase toxicity is not a necessary consideration when designing bioluminescence experiments, and therefore our approach can be used to rapidly generate high levels of luciferase expression for sensitive imaging experiments

Better the donor you know?:A qualitative study of renal patients' views on ‘altruistic’ live-donor kidney transplantation

AbstractBackgroundIn the UK there is a short-fall between individuals requiring a renal transplant and kidneys available for transplantation. Non-directed ‘altruistic’ living kidney donation has emerged as a strategy for bridging this gap between supply and demand, with the number increasing each year.ObjectiveThis study aimed to explore the views of potential recipients towards non-directed ‘altruistic’ live-donor kidney transplantation.MethodsSemi-structured interviews with 32 UK deceased-donor kidney transplant recipients were performed. Interviews explored willingness to consider directed and non-directed live-donor kidney transplants (LDKTs). Interviews were recorded, transcribed verbatim and transcripts were analysed using the constant comparison method described in Grounded Theory.ResultsFor those not willing to accept a non-directed ‘altruistic’ LDKT, the following themes were identified: i) Prioritising other recipients above self; ii) Fear of acquiring an unknown donor's characteristics, and iii) Concern for the donor – unnecessary risk. For those willing to accept a non-directed ‘altruistic’ LDKT the following themes were identified: iv) Prioritising known above unknown persons, v) Belief that they are as deserving as other potential recipients, and vi) Advantages of a LDKT.ConclusionsDrawing on ‘gift exchange theory’, this study contributes to our understanding of the experience of the intended recipient of a gift. The anonymity of the donor-recipient appears to be seen as a benefit of non-directed ‘altruistic’ live-donor transplants, freeing recipients from the obligations of the gift. However, those who feel unworthy of the ‘gifted transplant’ are concerned about the donor and by the lack of opportunity for direct reciprocity. Highlighting the ‘reciprocal benefits’ reported by donors may allow individuals whose preference is a live-donor transplant to accept one if offered. These insights provide the transplant community with targets for intervention, through which the concerns of potential recipients might be addressed

The Risk of Exposure to Diagnostic Ultrasound in Postnatal Subjects

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135382/1/jum2008274565.pd

Post exercise hot water immersion and hot water immersion in isolation enhance vascular, blood marker, and perceptual responses when compared to exercise alone

Exercise and passive heating induce some similar vascular hemodynamic, circulating blood marker, and perceptual responses. However, it remains unknown whether post exercise hot water immersion can synergise exercise derived responses and if they differ from hot water immersion alone. This study investigated the acute responses to post moderate-intensity exercise hot water immersion (EX+HWI) when compared to exercise (EX+REST) and hot water immersion (HWI+HWI) alone. Sixteen physically inactive middle-aged adults (nine males and seven females) completed a randomized cross-over counterbalanced design. Each condition consisted of two 30-min bouts separated by 10 min of rest. Cycling was set at a power output equivalent to 50% V̇o2 peak. Water temperature was controlled at 40°C up to the mid sternum with arms not submerged. Venous blood samples and artery ultrasound scans were assessed at 0 (baseline), 30 (immediately post stressor one), 70 (immediately post stressor two), and 100 min (recovery). Additional physiological and perceptual measures were assessed at 10-min intervals. Brachial and superficial femoral artery shear rates were higher after EX+HWI and HWI+HWI when compared with EX+REST (p < 0.001). Plasma nitrite was higher immediately following EX+HWI and HWI+HWI than EX+REST (p < 0.01). Serum interleukin-6 was higher immediately after EX+HWI compared to EX+REST (p = 0.046). Serum cortisol was lower at 30 min in the HWI+HWI condition in contrast to EX+REST (p = 0.026). EX+HWI and HWI+HWI were more enjoyable than EX+REST (p < 0.05). Irrespective of whether hot water immersion proceeded exercise or heating, hot water immersion enhanced vascular and blood marker responses, while also being more enjoyable than exercise alone

Tumour-infiltrating lymphocyte scores effectively stratify outcomes over and above p16 post chemo-radiotherapy in anal cancer

Background: The majority (90%) of anal cancers are human papillomavirus (HPV)-driven, identified using immunochemistry for p16. Compared with HPV? patients, those with HPV+ disease generally show improved survival, although relapse rates around 25% indicate a need for further stratification of this group.Methods: Using two cohorts of anal cancer, previously characterised for p16, we assessed the prognostic value of tumour-infiltrating lymphocytes (TILs).Results: Tumour-infiltrating lymphocyte scores were used to stratify p16+ cases, where tumours with absent/low levels of TIL had a relapse-free rate of 63%, as opposed to 92% with high levels of TIL (log rank P=0.006).Conclusions: Assessment of TIL adds to p16 status in the prognosis of anal cancer following chemo-radiotherapy and provides evidence of the clinical importance of the immune response

Model development of the Aquistore CO2 storage project

AbstractThe Plains CO2 Reduction (PCOR) Partnership, through the Energy & Environmental Research Center, is collaborating with Petroleum Technology Research Centre in site characterization; risk assessment; public outreach; and monitoring, verification, and accounting activities at the Aquistore project. The PCOR Partnership constructed a static geological model to assess the potential volumetric storage capacity of the Aquistore site and provide the foundation for dynamic simulation for the dynamic CO2 storage capacity. Results of the predictive simulations will be used in the risk assessment process to define an overall monitoring plan and assure stakeholders that the injected CO2 will remain safely stored