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ABSTRACT We present a new approach to calculate the particle distribution function about relativistic shocks including synchrotron losses using the method of lines with an explicit finite-difference scheme. A steady, continuous, one-dimensional plasma flow is considered to model thick (modified) shocks, leading to a calculation in three dimensions plus time, the former three being momentum, pitch angle and position. The method accurately reproduces the expected power-law behaviour in momentum at the shock for upstream flow speeds ranging from 0.1 c to 0.995 c (Γ∈ (1, 10]). It also reproduces approximate analytical results for the synchrotron cutoff shape for a non-relativistic shock, demonstrating that the loss process is accurately represented. The algorithm has been implemented as a hybrid OpenMP-MPI parallel algorithm to make efficient use of SMP cluster architectures and scales well up to many hundreds of CPUs. [ABSTRACT FROM AUTHOR]

Objective: To examine venous partial pressure of oxygen (Pvo2), transcutaneous oxygen tension (tcPo2), and VO2MM in a normobaric environment after a single hyperbaric oxygen (HBo2) treatment. Methods: This was a prospective study of conditions after the intervention compared with baseline. The participants were 10 moderately trained (Vo2MAS = 57.6 mI/kg/min) men. Two HBo2 treatments consisting of breathing 95% oxygen at 2.5 atmospheres absolute (ATA) for 90 minutes were administered on non-consecutive days. Baseline testing included measures of Vo2MAX, tcPo2, and anthropometry. At 6.0 (1 .0) minutes after the first HBo2 treatment, a Vo2MAX test was performed. After the second HBo2 treatment, leg and chest tcPo2 and Pvo2 were monitored for 60 minutes. Results: Vo2MAX, running time, and peak blood lactate were not altered after the HBo2 treatment. Leg tcPo2 was lower (p = 0.003) and chest tcPo2 was unchanged after the HBo2 treatment compared with baseline values. Pvo2 was significantly (p<0.001) lower in the first three minutes after treatment than subsequent values, but no other differences were found. Conclusions: A single HBo2 treatment at 2.5 ATA for 90 minutes does not raise Pvo2, tcPo2, or Vo2MAX in a normoboric, normoxic environment. [ABSTRACT FROM AUTHOR]

Child labour is the most common form of child abuse in the world today, with almost half of child workers employed in hazardous industries. The large-scale employment of children during the rapid industrialisation of the late 18th and early 19th centuries in England is well documented. During this period, the removal of pauper children from workhouses in cities to work as apprentices in rural mills in the North of England was commonplace. Whilst the experiences of some of these children have been recorded historically, this study provides the first direct evidence of their lives through bioarchaeological analysis. The excavation of a rural churchyard cemetery in the village of Fewston, North Yorkshire, yielded the skeletal remains of 154 individuals, including an unusually large proportion of children aged between 8 to 20 years. A multi-method approach was undertaken, including osteological and palaeopathological examination, stable isotope and amelogenin peptide analysis. The bioarchaeological results were integrated with historical data regarding a local textile mill in operation during the 18th-19th centuries. The results for the children were compared to those obtained from contemporaneous individuals of known identity (from coffin plates) of comparable date. Most of the children exhibited distinctive 'non-local' isotope signatures and a diet low in animal protein when compared to the named local individuals. These children also showed severe growth delays and pathological lesions indicative of early life adversity, as well as respiratory disease, which is a known occupational hazard of mill work. This study has provided unique insights into the harrowing lives of these children; born into poverty and forced to work long hours in dangerous conditions. This analysis provides a stark testimony of the impacts of industrial labour on the health, growth and mortality risk of children, with implications for the present as well as our understanding of the past. [ABSTRACT FROM AUTHOR]

Background:Cyclin-dependent kinases (CDKs) control cell cycle progression, RNA transcription and apoptosis, making them attractive targets for anticancer drug development. Unfortunately, CDK inhibitors developed to date have demonstrated variable efficacy.Methods:We generated drug-resistant cells by continuous low-dose exposure to a model pyrazolo[1,5-a]pyrimidine CDK inhibitor and investigated potential structural alterations for optimal efficacy.Results:We identified induction of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2, in resistant cells. Assessment of features involved in the ABC transporter substrate specificity from a compound library revealed high polar surface area (>100 Å2) as a key determinant of transporter interaction. We developed ICEC-0782 that preferentially inhibited CDK2, CDK7 and CDK9 in the nanomolar range. The compound inhibited phosphorylation of CDK substrates and downregulated the short-lived proteins, Mcl-1 and cyclin D1. ICEC-0782 induced G2/M arrest and apoptosis. The permeability and cytotoxicity of ICEC-0782 were unaffected by ABC transporter expression. Following daily oral dosing, the compound inhibited growth of human colon HCT-116 and human breast MCF7 tumour xenografts in vivo by 84% and 94%, respectively.Conclusion:We identified a promising pyrazolo[1,5-a]pyrimidine compound devoid of ABC transporter interaction, highly suitable for further preclinical and clinical evaluation for the treatment of cancer. [ABSTRACT FROM AUTHOR]