Relationship between muscular extensibility, strength and stability and the transmission of impacts during fatigued running.

The aim was to analyse the relationship between isokinetic strength, dynamic stability, muscular extensibility and impacts transmission during fatigued running. Low- and high-frequency impacts related to body movements and the severity of impacts, respectively were assessed in 17 male recreational runners, before and after a treadmill running fatigue protocol, using a triaxial accelerometry system. High-frequency impacts in the tibia were negatively correlated to the knee angle at which the quadriceps peak torque was reached (p = 0.014), and also to the extensibility of the hamstrings and soleus (p = 0.001 and p = 0.023, respectively). The increases of high-frequency impacts in tibia caused by fatigue were positively related to the knee angle at which the hamstrings peak torque was reached (p = 0.001) and to stability after landing (p = 0.007). The attenuation of high-frequency impacts was positively related to hamstrings/quadriceps ratio of strength (p = 0.010) and to stability (p = 0.006). Limiting possible deficits in hamstring and soleus range of motion, improving stability after landing, developing hamstring and quadriceps strength in elongated muscle range, and maintaining a balanced ratio of hamstring/quadriceps strength could help to reduce the injury risk in running

Cryogenic Insulation Systems

The results of a comparative study of cryogenic insulation systems performed are presented. The key aspects of thermal insulation relative to cryogenic system design, testing, manufacturing, and maintenance are discussed. An overview of insulation development from an energy conservation perspective is given. Conventional insulation materials for cryogenic applications provide three levels of thermal conductivity. Actual thermal performance of standard multilayer insulation (MLI) is several times less than laboratory performance and often 10 times worse than ideal performance. The cost-effectiveness of the insulation system depends on thermal performance; flexibility and durability; ease of use in handling, installation, and maintenance; and overall cost including operations, maintenance, and life cycle. Results of comprehensive testing of both conventional and novel materials such as aerogel composites using cryostat boil-off methods are given. The development of efficient, robust cryogenic insulation systems that operate at a soft vacuum level is the primary focus of this paper

The effects of aetiology on outcome in patients treated with cardiac resynchronization therapy in the CARE-HF trial

Aims: Cardiac dyssynchrony is common in patients with heart failure, whether or not they have ischaemic heart disease (IHD). The effect of the underlying cause of cardiac dysfunction on the response to cardiac resynchronization therapy (CRT) is unknown. This issue was addressed using data from the CARE-HF trial.Methods and resultsPatients (n = 813) were grouped by heart failure aetiology (IHD n = 339 vs. non-IHD n = 473), and the primary composite (all-cause mortality or unplanned hospitalization for a major cardiovascular event) and principal secondary (all-cause mortality) endpoints analysed. Heart failure severity and the degree of dyssynchrony were compared between the groups by analysing baseline clinical and echocardiographic variables. Patients with IHD were more likely to be in NYHA class IV (7.5 vs. 4.0; P = 0.03) and to have higher NT-proBNP levels (2182 vs. 1725 pg/L), indicating more advanced heart failure. The degree of dyssynchrony was more pronounced in patients without IHD (assessed using mean QRS duration, interventricular mechanical delay, and aorta-pulmonary pre-ejection time). Left ventricular ejection fraction and left ventricular end-systolic volume improved to a lesser extent in the IHD group (4.53 vs. 8.50 and -35.68 vs. -58.52 cm 3). Despite these differences, CRT improved all-cause mortality, NYHA class, and hospitalization rates to a similar extent in patients with or without IHD.ConclusionThe benefits of CRT in patients with or without IHD were similar in relative terms in the CARE-HF study but as patients with IHD had a worse prognosis, the benefit in absolute terms may be greater

Mitochondrial precursor proteins are imported through a hydrophilic membrane environment

We have analyzed how translocation intermediates of imported mitochondrial precursor proteins, which span contact sites, interact with the mitochondrial membranes. F1-ATPase subunit β(F1β) was trapped at contact sites by importing it into Neurospora mitochondria in the presence of low levels of nucleoside triphosphates. This F1β translocation intermediate could be extracted from the membranes by treatment with protein denaturants such as alkaline pH or urea. By performing import at low temperatures, the ADP/ATP carrier was accumulated in contact sites of Neurospora mitochondria and cytochrome b2 in contact sites of yeast mitochondria. These translocation intermediates were also extractable from the membranes at alkaline pH. Thus, translocation of precursor proteins across mitochondrial membranes seems to occur through an environment which is accessible to aqueous perturbants. We propose that proteinaceous structures are essential components of a translocation apparatus present in contact sites

Starting to Stop: Young Offenders' Desistance from Crime

This paper explores the complexities of the interplay between structural and agentic changes in 21 young offenders' lives as they start to stop offending. The young people's ability to desist from crime was dependent upon their engagement with a 'hook for change', their development of prosocial relationships and 'knifing off' of elements of their offending past, the extent of their identity change, and their confidence about desistance. Desistance was less likely in the absence of a 'hook' and where offenders were running a 'condemnation script'. The study challenges previous research that argues that desistance from crime in adolescence is unlikely

Annihilation vs. Decay: Constraining dark matter properties from a gamma-ray detection

Most proposed dark matter candidates are stable and are produced thermally in the early Universe. However, there is also the possibility of unstable (but long-lived) dark matter, produced thermally or otherwise. We propose a strategy to distinguish between dark matter annihilation and/or decay in the case that a clear signal is detected in gamma-ray observations of Milky Way dwarf spheroidal galaxies with gamma-ray experiments. The sole measurement of the energy spectrum of an indirect signal would render the discrimination between these cases impossible. We show that by examining the dependence of the intensity and energy spectrum on the angular distribution of the emission, the origin could be identified as decay, annihilation, or both. In addition, once the type of signal is established, we show how these measurements could help to extract information about the dark matter properties, including mass, annihilation cross section, lifetime, dominant annihilation and decay channels, and the presence of substructure. Although an application of the approach presented here would likely be feasible with current experiments only for very optimistic dark matter scenarios, the improved sensitivity of upcoming experiments could enable this technique to be used to study a wider range of dark matter models.Comment: 29 pp, 8 figs; replaced to match published version (minor changes and some new references

The politics of the digital single market:Culture vs. competition vs. copyright

This paper examines the implications for European music culture of the European Union’s Digital Single Market strategy. It focuses on the regulatory framework being created for the management of copyright policy, and in particular the role played by Collective Management Organisations (or Collecting Societies). One of the many new opportunities created by digitalization has been the music streaming services. These depend on consumers being able to access music wherever they are, but such a system runs counter to the management of rights on a national basis and through collecting organisations who act as monopolies within their own territories. The result has been ‘geo-blocking’. The EU has attempted to resolve this problem in a variety of ways, most recently in a Directive designed to reform the CMOs. In this paper, we document these various efforts, showing them to be motivated by a deep-seated and persisting belief in the capacity of ‘competition’ to resolve problems that, we argue, actually lie elsewhere - in copyright policy itself. The result is that the EU’s intervention fails to address its core concern and threatens the diversity of European music culture by rewarding those who are already commercially successful

A Novel High-Throughput Assay for Islet Respiration Reveals Uncoupling of Rodent and Human Islets

The pancreatic beta cell is unique in its response to nutrient by increased fuel oxidation. Recent studies have demonstrated that oxygen consumption rate (OCR) may be a valuable predictor of islet quality and long term nutrient responsiveness. To date, high-throughput and user-friendly assays for islet respiration are lacking. The aim of this study was to develop such an assay and to examine bioenergetic efficiency of rodent and human islets.The XF24 respirometer platform was adapted to islets by the development of a 24-well plate specifically designed to confine islets. The islet plate generated data with low inter-well variability and enabled stable measurement of oxygen consumption for hours. The F1F0 ATP synthase blocker oligomycin was used to assess uncoupling while rotenone together with myxothiazol/antimycin was used to measure the level of non-mitochondrial respiration. The use of oligomycin in islets was validated by reversing its effect in the presence of the uncoupler FCCP. Respiratory leak averaged to 59% and 49% of basal OCR in islets from C57Bl6/J and FVB/N mice, respectively. In comparison, respiratory leak of INS-1 cells and C2C12 myotubes was measured to 38% and 23% respectively. Islets from a cohort of human donors showed a respiratory leak of 38%, significantly lower than mouse islets.The assay for islet respiration presented here provides a novel tool that can be used to study islet mitochondrial function in a relatively high-throughput manner. The data obtained in this study shows that rodent islets are less bioenergetically efficient than human islets as well as INS1 cells

Young people, crime and school exclusion: a case of some surprises

During the 1990s the number of young people being permanently excluded from schools in England and Wales increased dramatically from 2,910 (1990/91) to a peak of 12,700 (1996/97). Coinciding with this rise was a resurgence of the debate centring on lawless and delinquent youth. With the publication of Young People and Crime (Graham and Bowling 1995) and Misspent Youth (Audit Commission 1996) the 'common sense assumption' that exclusion from school inexorably promoted crime received wide support, with the school excludee portrayed as another latter day 'folk devil'. This article explores the link between school exclusion and juvenile crime, and offers some key findings from a research study undertaken with 56 young people who had experience of being excluded from school. Self-report interview questions reveal that whilst 40 of the young people had offended, 90% (36) reported that the onset of their offending commenced prior to their first exclusion. Moreover, 50 (89.2% of the total number of young people in the sample), stated that they were no more likely to offend subsequent to being excluded and 31 (55.4%) stated that they were less likely to offend during their exclusion period. Often, this was because on being excluded, they were 'grounded' by their parents

A Natural Genetic Variant of Granzyme B Confers Lethality to a Common Viral Infection

Many immune response genes are highly polymorphic, consistent with the selective pressure imposed by pathogens over evolutionary time, and the need to balance infection control with the risk of auto-immunity. Epidemiological and genomic studies have identified many genetic variants that confer susceptibility or resistance to pathogenic micro-organisms. While extensive polymorphism has been reported for the granzyme B (GzmB) gene, its relevance to pathogen immunity is unexplored. Here, we describe the biochemical and cytotoxic functions of a common allele of GzmB (GzmBW) common in wild mouse. While retaining ‘Asp-ase ’ activity, GzmBW has substrate preferences that differ considerably from GzmBP, which is common to all inbred strains. In vitro, GzmBW preferentially cleaves recombinant Bid, whereas GzmBP activates pro-caspases directly. Recombinant GzmBW and GzmBP induced equivalent apoptosis of uninfected targets cells when delivered with perforin in vitro. Nonetheless, mice homozygous for GzmBW were unable to control murine cytomegalovirus (MCMV) infection, and succumbed as a result of excessive liver damage. Although similar numbers of anti-viral CD8 T cells were generated in both mouse strains, GzmBW-expressing CD8 T cells isolated from infected mice were unable to kill MCMV