Gene sequences encoding ribosome-inactivating proteins from soapwort (Saponaria officinalis L.)

Ribosome-inactivating proteins (RIPs) are found in a wide variety of plant species. They possess an RNA N-glycosidase activity whereby the removal of a specific adenine residue from 28 S RNA renders a eukaryotic ribosome inactive. Type II RIPS contain both an active polypeptide and a sugar-binding polypeptide. Type I RIPs are composed of a single polypeptide functionally homologous to the active type II polypeptide. This thesis describes studies of the gene sequences of RIPs representative of each class: Ricin, a type II RIP from the castor oil plant (Ricinus communis h.), and saporin, a type I RIP from soapwort (Saponaria officinalis L.). Two ricin gene sequences were isolated from a Ricinus genomic library and partially characterised. One gene was a badly damaged ricin-like pseudogene whilst the other was shown to encode an active polypeptide. A second ricin sequence encoding an active polypeptide was isolated using Polymerase Chain Reaction (PGR) DNA amplification. The specificity of PGR amplification was investigated using the ricin and related agglutinin gene sequences. Partial amino acid sequence data derived from protein sequencing of saporin-6 was used to synthesise degenerate inosine-containing oligonucleotides. These directed the PGR amplification of part of the saporin coding sequence from genomic DNA. The product was used as a saporin-specific hybridisation probe. Southern analysis of Saponaria genomic DNA indicated that saporin sequences comprised a small multigene family. Three independent saporin containing genomic clones were isolated from a Saponaria genomic library. Two clones were truncated whilst the third contained a complete saporin coding sequence. The saporin and ricin coding sequences were expressed in vitro and shown to inhibit protein synthesis. Aniline cleavage assays of ribosomal RNA extracted from ribosomes exposed to the products of the RIP coding sequences were carried out. These indicated that the polypeptides encoded by the RIP gene sequences had specific RNA N-glycosidase activity

The measurement errors in the Swift-UVOT and XMM-OM

The probability of photon measurement in some photon counting instrumentation, such as the Optical Monitor on the XMM-Newton satellite, and the UVOT on the Swift satellite, does not follow a Poisson distribution due to the detector characteristics, but a Binomial distribution. For a single-pixel approximation, an expression was derived for the incident countrate as a function of the measured count rate by Fordham, Moorhead and Galbraith (2000). We show that the measured countrate error is binomial, and extend their formalism to derive the error in the incident count rate. The error on the incident count rate at large count rates is larger than the Poisson-error of the incident count rate.Comment: 4 pages, 2 postscript figures, submitted to MNRA

Intrinsic myocardial recovery from the negative inotropic effects of acute hypercapnia

The inotropic effects of hypercapnia have been examined in the isometric papillary muscle preparation from the cat. The initial stage of depression which resulted from the acute induction of hypercapnia was followed by a significant degree of spontaneous recovery during the next hour. When the carbon dioxide concentration was returned to normal a temporary rebound in performance to well above control levels was observed. These findings are interpreted as being due to slow changes arising within heart muscle itself which partially compensate for the direct inotropic depressant effect of hypercapni

The Effects of Varying Composition and Build Direction on Direct Metal Deposition Fabricated Inconel 718

Inconel 718 (IN718) is a popular wrought superalloy, and is currently being investigated for additive manufacturing (AM) applications in the aerospace industry. However, overaging and the presence of microcracks have caused a significant reduction in properties. The purpose of this study is to meet or exceed the mechanical properties of wrought IN718 by varying the composition and build direction of the AM alloy. Alternative compositions were selected with Oerlilon Metco’s Rapid Alloy Development (RAD) software, and differ in niobium content, which increases the fraction of the primary strengthening phase (γʺ). Direct metal deposition (DMD) was used to fabricate the samples, which then underwent a heat treatment to precipitate γʺ. Tensile testing, metallography, and scanning electron microscopy (SEM) were performed on the samples. Tensile testing found that the AM samples could exceed wrought strength with the appropriate composition and build direction. The horizontal build containing the highest niobium percentage achieved an average yield strength of 1400 MPa, higher than the 1218 MPa for the wrought. Samples in the horizontal build direction were consistently stronger than vertical alternatives due to their anisotropic grain morphology. Despite comparable strength, AM samples of all compositions had significantly reduced ductility with an average range of 1-3% elongation compared to an average of 21% for the wrought samples. Microstructural analysis revealed dendritic structures and cracks between print layers in the AM samples, which contributed to this reduction in ductility

Colon contradictions: NF-κB signaling in intestinal tumorigenesis

No abstract available

A feminist vision for transformative change to disaster risk reduction policies and practices

Gender has received increased attention in disaster risk reduction (DRR) policies and practices over the past three decades. However, a critical analysis raises a number of questions: has the attention to gender brought transformative change to the lives of people, especially women and sexual minorities in all their diversity? To what extent has the inclusion of a gender perspective in DRR challenged the root causes of vulnerability and marginalization? Do the current gender sensitive DRR policies and practices have transformative potential? In this paper, we explore some of these questions with particular reference to the recent Disaster Risk Reduction and Management (DRRM) Act 2017 and current DRR practices in Nepal in which gender has been included. We present findings from three research projects, undertaken between 2016 and 2019 in six locations in Nepal. These comprised 105 individual interviews, 11 group interviews and 3 focus group discussions (FGDs) with internally displaced women; pregnant and newly delivered women; health and community workers; policy makers, political leaders and organisations working on DRR. We argue that, despite increased attention to gender, current DRR policies and practices do little to challenge existing, unequal social and institutional structures; instead, they accommodate the gender status quo. We suggest that in order for transformative social change to occur, we require a transformative vision; one that allows us to see the biases and problems within the current DRR policies and practices and allows us to imagine our future differently. A feminist vision offers that possibility

Epidemiology of injuries in adventure racing athletes

OBJECTIVES: To assess the demographics and training characteristics of adventure racing athletes in the United Kingdom, the prevalence and anatomical distribution of hazardous encounter, and overuse injury in this population, and the effects these injuries have on training. METHODS: A retrospective training and injury questionnaire for the previous 18 months was distributed to 300 adventure racing athletes at two national race meetings. The definition of an injury was "any musculoskeletal problem causing a stop in training for at least one day, reduction in training mileage, taking of medicine, or seeking of medical aid." RESULTS: The data were derived from the responses of 223 athletes. Advanced level athletes did 11 (4) sessions and 17 (8) hours of training a week (mean (SD)). An injury was reported in the previous 18 months by 73% of the respondents. The most common site of acute injury was the ankle (23%) and of chronic/overuse injury, the knee (30%), followed by the lower back, shin, and Achilles tendon (12% each). There were significant correlations (p<0.01) between the hours spent cycling per week and number of acute injuries, and between the number of days off per week and number of chronic/overuse injuries. Injuries resulted in an average of 23 days training cessation or reduction. CONCLUSIONS: Acute injuries were sustained mainly as a result of the nature of the terrain over which athletes train and compete. In overuse injuries lack of adequate rest days was a significant contributing factor. Only a small proportion of training time was spent developing flexibility and core stability

Integrating cogeneration and intermittent waste-heat recovery in food processing: Microturbines vs. ORC systems in the coffee roasting industry

Coffee roasting is a highly energy intensive process wherein a large quantity of heat is discharged from the stack at medium-to-high temperatures. Much of the heat is released from the afterburner, which is required to remove volatile organic compounds and other pollutants from the flue gases. In this work, intermittent waste-heat recovery via thermal energy storage (TES) and organic Rankine cycles (ORCs) is compared to combined heat and power (CHP) based on micro gas-turbines (MGTs) for a coffee roasting plant. With regard to the former, a promising solution is proposed that involves recovering waste heat from the flue gas stream by partial hot-gas recycling at the rotating drum coffee roaster, and coupling this to a thermal store and an ORC engine for power generation. The two solutions (CHP + MGT prime mover vs. waste-heat recovery + ORC engine) are investigated based on mass and energy balances, and a cost assessment methodology is adopted to compare the profitability of three system configurations integrated into the selected roasting process. The case study involves a major Italian roasting plant with a 3,000 kg per hour coffee production capacity. Three options are investigated: (i) intermittent waste-heat recovery from the hot flue-gases with an ORC engine coupled to a TES system; (ii) regenerative topping MGT coupled to the existing modulating gas burner to generate hot air for the roasting process; and (iii) non-regenerative topping MGT with direct recovery of the turbine outlet air for the roasting process. The results show that the profitability of these investments is highly influenced by the natural gas and electricity prices and by the coffee roasting production capacity. The CHP solution via an MGT appears as a more profitable option than waste-heat recovery via an ORC engine primarily due to the intermittency of the heat-source availability and the high electricity cost relative to the cost of natural gas

The cost of treating diabetic ketoacidosis in an adolescent population in the UK: a national survey of hospital resource use

Aims: Adolescents with Type 1 diabetes commonly experience episodes of ketoacidosis. In 2014, we conducted a nationwide survey on the management of diabetic ketoacidosis in young people. The survey reported how individual adolescents with diabetes were managed. However, the costs of treating diabetic ketoacidosis were not reported. Methods: Using this mixed population sample of adolescents, we took a ‘bottom-up’ approach to cost analysis aiming to determine the total expense associated with treating diabetic ketoacidosis. The data were derived using the information from the national UK survey of 71 individuals, collected via questionnaires sent to specialist paediatric diabetes services in England and Wales. Results: Several assumptions had to be made when analysing the data because the initial survey collection tool was not designed with a health economic model in mind. The mean time to resolution of diabetic ketoacidosis was 15.0 h [95% confidence interval (CI) 13.2, 16.8] and the mean total length of stay was 2.4 days (95% CI 1.9, 3.0). Based on data for individuals and using the British Society of Paediatric Endocrinology and Diabetes (BSPED) guidelines, the cost analysis shows that for this cohort, the average cost for an episode of diabetic ketoacidosis was £1387 (95% CI 1120, 1653). Regression analysis showed a significant cost saving of £762 (95% CI 140, 1574; P = 0.04) among those treated using BSPED guidelines. Conclusion: We have used a bottom-up approach to calculate the costs of an episode of diabetic ketoacidosis in adolescents. These data suggest that following treatment guidelines can significantly lower the costs for managing episodes of diabetic ketoacidosis

Feasibility study of a randomised controlled trial to investigate the treatment of sarcoidosis-associated fatigue with methylphenidate (FaST-MP): a study protocol

Introduction: Fatigue is a frequent and troublesome manifestation of chronic sarcoidosis. This symptom can be debilitating and difficult to treat, with poor response to the treatment. Symptomatic management with neurostimulants, such as methylphenidate, is a possible treatment option. The use of such treatment strategies is not without precedent and has been trialled in cancer-related fatigue. Their use in sarcoidosis requires further evaluation before it can be recommended for clinical practice. Methods and analysis: The Fatigue and Sarcoidosis—Treatment with Methylphenidate study is a randomised, controlled, parallel-arm and feasibility trial of methylphenidate for the treatment of sarcoidosis-associated fatigue. Patients are eligible if they have a diagnosis of sarcoidosis, significant fatigue (measured using the Fatigue Assessment Scale) and have stable disease. Up to 30 participants will be randomly assigned to either methylphenidate (20 mg two times per day) or identical placebo in a 3:2 ratio for 24 weeks. The primary objective is to collect data determining the feasibility of a future study powered to determine the clinical efficacy of methylphenidate for sarcoidosis-associated fatigue. The trial is presently open and will continue until July 2018. Ethics and dissemination: Ethical approval for the study was granted by the Cambridge Central Research Ethics Committee on 21 June 2016 (reference 16/EE/0087) and was approved and sponsored by the Norfolk and Norwich University Hospital (reference 190280). Clinical Trial Authorisation (EudraCT number 2016-000342-60) from the Medicines and Healthcare products Regulatory Agency (MHRA) was granted on 19 April 2016. Results will be presented at relevant conferences and submitted to appropriate journals following trial closure and analysis