Insights into DNA platination within unusual structural settings

2D [1H, 15N] HSQC NMR spectroscopy has been used to monitor reaction and product formation between [Pt(15NH3)2I2] and nucleic acids possessing irregular topologies and containing site specific phosphorothioate substitution in the phosphodiester backbone. Comparison of the reaction profiles of dimer nucleic acids with and without phosphorothioate substitution is made with their short nucleic acid counterparts containing the key dimer components. Whereas d(GpA) is relatively unreactive towards [Pt(15NH3)2I2], NMR evidence suggests that the tandem sheared mismatch duplex d(GCG3pAGC)2 reacts to form the head-to-tail inter-strand G3-N7-Pt-G3-N7 cross-link. The equivalent phosphorothioate R,S-d(GsA) reacts to form a mono-iodo, mono-sulphur adduct, whereas the tandem sheared mismatch phosphorothioate duplex d(GCGsAG5C)2 (VIs) reacts to form the unusual intra-strand macrochelate [Pt(15NH3)2{d(VIs-G5-N7)},S]2+ in which platinum is attached at both sulphur and G5-N7. Experimental evidence supports the formation of a stabilized mismatch duplex in which platinum is attached to two nitrogen centres in the sequence d(CGCGpTGCG) in contrast to R,S-d(CGCGsT5GCG) for which NMR evidence supports macrochelate-stabilized hairpin loop formation cross-linked at both phosphorothioate sulphur and T5-N

Raman gain and lasing from cold potassium atoms in a ring cavity

This thesis describes an experiment with a cloud of magneto-optically trapped Potassium-39 spatially overlapped with the modes of a high-finesse ring cavity. Optical gain was observed with the system in steady state, without any beams additional to the normal cooling and repump beams in a potassium-39 magneto-optical trap. This was found to operate on a Raman gain mechanism between atomic hyperfine ground states, which has not been seen under similar conditions with other atomic species. Lasing into the cavity modes was then studied, with a particular focus on aspects specific to the ring cavity geometry. This showed a directional bistability and non-reciprocity. The bistability can be described by existing theory, but the mechanism of the non-reciprocity is unknown, despite a detailed investigation. The second order coherence time of the system was explored below threshold, and demonstrates a strong dependence on gain, which may have applications in the detection of extremely small gains

Peer-Led Team Learning Strategies in Engineering Pathways

Train Peer-Leaders on difference between mentor/tutor and Peer Leader. Focuses on leadership skills. Provides technology resources tutorial. Provided suggested teaching and learning strategies for PLTL activities

Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis:results from a longitudinal, matched-cohort data linkage study

We wish to thank Information Division Services Scotland for assisting with data linkage and data access in the National Safe Haven. Information presented in this article was previously presented as a poster at the American College of Rheumatology Annual Conference 2018, Chicago, IL, USA. The study was conceived by S.H.S., A.M., C.B. and N.B. All authors contributed to the study design and data collection. Data analysis and interpretation and drafting of the manuscript were conducted by all authors. C.B. and N.B. were joint senior authors. All authors critically reviewed the manuscript and approved the final version. Funding: S.H.S. and the study were funded by the Aberdeen Development Trust and the Farr Institute of Health Informatics Research. The Farr Institute is supported by a 10-funder consortium: Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates) and the Wellcome Trust (Scotland MR/K007017/1). Disclosure statement: L.E. is a GlaxoSmithKline employee. The other authors have declared no conflicts of interest.Peer reviewedPublisher PD

OLIA: An open-source digital lock-in amplifier

The Open Lock-In Amplifier (OLIA) is a microcontroller-based digital lock-in amplifier built from a small number of inexpensive and easily sourced electronic components. Despite its small credit card-sized form-factor and low build-cost of around US$35, OLIA is a capable instrument that offers many features associated with far costlier commercial devices. Key features include dual-phase lock-in detection at multiple harmonic frequencies up to 50 kHz, internal and external reference modes, adjustable levels of input gain, a choice between low-pass filtering and synchronous filtering, noise estimation, and a comprehensive programming interface for remote software control. OLIA comes with an optional optical breakout board that allows noise-tolerant optical detection down to the 40-pW level. OLIA and its breakout board are released here as open hardware, with technical diagrams, full parts-lists, and source-code for the firmware

Utility of Self-Rated Adherence for Monitoring Dietary and Physical Activity Compliance and Assessment of Participant Feedback of the Healthy Diet and Lifestyle Study pilot.

We examined the utility of self-rated adherence to dietary and physical activity (PA) prescriptions as a method to monitor intervention compliance and facilitate goal setting during the Healthy Diet and Lifestyle Study (HDLS). In addition, we assessed participants’ feedback of HDLS. HDLS is a randomized pilot intervention that compared the effect of intermittent energy restriction combined with a Mediterranean diet (IER + MED) to a Dietary Approaches to Stop Hypertension (DASH) diet, with matching PA regimens, for reducing visceral adipose tissue area (VAT)

Breast Cancer Risk in Young Women in the National Breast Screening Programme: Implications for Applying NICE Guidelines for Additional Screening and Chemoprevention

In the United Kingdom, women at moderate and high risk of breast cancer between the ages of 40 and 49 years are eligible for annual mammographic screening and preventive therapy with tamoxifen. Here, we estimate the numbers of women in a population eligible for this service and the proportion of breast cancers detected in this group compared with the whole population. Wome

The Scottish Early Rheumatoid Arthritis (SERA) Study:an inception cohort and biobank

Background: The Scottish Early Rheumatoid Arthritis (SERA) study is an inception cohort of rheumatoid (RA) and undifferentiated arthritis (UA) patients that aims to provide a contemporary description of phenotype and outcome and facilitate discovery of phenotypic and prognostic biomarkers Methods: Demographic and clinical outcome data are collected from newly diagnosed RA/UA patients every 6 months from around Scotland. Health service utilization data is acquired from Information Services Division, NHS National Services Scotland. Plain radiographs of hands and feet are collected at baseline and 12 months. Additional samples of whole blood, plasma, serum and filtered urine are collected at baseline, 6 and 12 months Results: Results are available for 1073 patients; at baseline, 76 % were classified as RA and 24 % as UA. Median time from onset to first review was 163 days (IQR97-323). Methotrexate was first-line DMARD for 75 % patients. Disease activity, functional ability and health-related quality of life improved significantly between baseline and 24 months, however the proportion in any employment fell (51 to 38 %, p = 0.0005). 24 % patients reported symptoms of anxiety and/or depression at baseline. 35/391 (9 %) patients exhibited rapid radiographic progression after 12 months. The SERA Biobank has accrued 60,612 samples Conclusions: In routine care, newly diagnosed RA/UA patients experience significant improvements in disease activity, functional ability and health-related quality of life but have high rates of psychiatric symptoms and declining employment rates. The co-existence of a multi-domain description of phenotype and a comprehensive biobank will facilitate multi-platform translational research to identify predictive markers of phenotype and prognosis

Co-ordinated Gene Expression in the Liver and Spleen during Schistosoma japonicum Infection Regulates Cell Migration

Determining the molecular events induced in the spleen during schistosome infection is an essential step in better understanding the immunopathogenesis of schistosomiasis and the mechanisms by which schistosomes modulate the host immune response. The present study defines the transcriptional and cellular events occurring in the murine spleen during the progression of Schistosoma japonicum infection. Additionally, we compared and contrasted these results with those we have previously reported for the liver. Microarray analysis combined with flow cytometry and histochemistry demonstrated that transcriptional changes occurring in the spleen were closely related to changes in cellular composition. Additionally, the presence of alternatively activated macrophages, as indicated by up-regulation of Chi3l3 and Chi3l4 and expansion of F4/80+ macrophages, together with enhanced expression of the immunoregulatory genes ANXA1 and CAMP suggests the spleen may be an important site for the control of S. japonicum-induced immune responses. The most striking difference between the transcriptional profiles of the infected liver and spleen was the contrasting expression of chemokines and cell adhesion molecules. Lymphocyte chemokines, including the homeostatic chemokines CXCL13, CCL19 and CCL21, were significantly down-regulated in the spleen but up-regulated in the liver. Eosinophil (CCL11, CCL24), neutrophil (CXCL1) and monocyte (CXCL14, CCL12) chemokines and the cell adhesion molecules VCAM1, NCAM1, PECAM1 were up-regulated in the liver but unchanged in the spleen. Chemokines up-regulated in both organs were expressed at significantly higher levels in the liver. Co-ordinated expression of these genes probably contributes to the development of a chemotactic signalling gradient that promotes recruitment of effector cells to the liver, thereby facilitating the development of hepatic granulomas and fibrosis. Together these data provide, for the first time, a comprehensive overview of the molecular events occurring in the spleen during schistosomiasis and will substantially further our understanding of the local and systemic mechanisms driving the immunopathogenesis of this disease