An Intuitive Automated Modelling Interface for Systems Biology

We introduce a natural language interface for building stochastic pi calculus models of biological systems. In this language, complex constructs describing biochemical events are built from basic primitives of association, dissociation and transformation. This language thus allows us to model biochemical systems modularly by describing their dynamics in a narrative-style language, while making amendments, refinements and extensions on the models easy. We demonstrate the language on a model of Fc-gamma receptor phosphorylation during phagocytosis. We provide a tool implementation of the translation into a stochastic pi calculus language, Microsoft Research's SPiM

Moving walls accelerate mixing

Mixing in viscous fluids is challenging, but chaotic advection in principle allows efficient mixing. In the best possible scenario,the decay rate of the concentration profile of a passive scalar should be exponential in time. In practice, several authors have found that the no-slip boundary condition at the walls of a vessel can slow down mixing considerably, turning an exponential decay into a power law. This slowdown affects the whole mixing region, and not just the vicinity of the wall. The reason is that when the chaotic mixing region extends to the wall, a separatrix connects to it. The approach to the wall along that separatrix is polynomial in time and dominates the long-time decay. However, if the walls are moved or rotated, closed orbits appear, separated from the central mixing region by a hyperbolic fixed point with a homoclinic orbit. The long-time approach to the fixed point is exponential, so an overall exponential decay is recovered, albeit with a thin unmixed region near the wall.Comment: 17 pages, 13 figures. PDFLaTeX with RevTeX 4-1 styl

Suppression of the thermal hysteresis in magnetocaloric MnAs thin film by highly charged ion bombardment

We present the investigation on the modifications of structural and magnetic properties of MnAs thin film epitaxially grown on GaAs induced by slow highly charged ions bombardment under well-controlled conditions. The ion-induced defects facilitate the nucleation of one phase with respect to the other in the first-order magneto-structural MnAs transition with a consequent suppression of thermal hysteresis without any significant perturbation on the other structural and magnetic properties. In particular, the irradiated film keeps the giant magnetocaloric effect at room temperature opening new perspective on magnetic refrigeration technology for everyday use

Involvement of DnaE, the second replicative DNA polymerase from Bacillus subtilis, in DNA mutagenesis

In a large group of organisms including low G + C bacteria and eukaryotic cells, DNA synthesis at the replication fork strictly requires two distinct replicative DNA polymerases. These are designated pol C and DnaE in Bacillus subtilis. We recently proposed that DnaE might be preferentially involved in lagging strand synthesis, whereas pol C would mainly carry out leading strand synthesis. The biochemical analysis of DnaE reported here is consistent with its postulated function, as it is a highly potent enzyme, replicating as fast as 240 nucleotides/s, and stalling for more than 30 s when encountering annealed 5'-DNA end. DnaE is devoid of 3' --> 5'-proofreading exonuclease activity and has a low processivity (1-75 nucleotides), suggesting that it requires additional factors to fulfill its role in replication. Interestingly, we found that (i) DnaE is SOS-inducible; (ii) variation in DnaE or pol C concentration has no effect on spontaneous mutagenesis; (iii) depletion of pol C or DnaE prevents UV-induced mutagenesis; and (iv) purified DnaE has a rather relaxed active site as it can bypass lesions that generally block other replicative polymerases. These results suggest that DnaE and possibly pol C have a function in DNA repair/mutagenesis, in addition to their role in DNA replication

Postgraduate Year 1 Pharmacy Residency Accreditation Requirements and Challenges

The residency accreditation process can be a stress-inducing experience to many program directors. In 2014, the postgraduate year 1 (PGY1) pharmacy residency accreditation standards were updated from the previous 2005 version. The new standards were formulated to streamline program requirements with the intention of creating a more transparent accreditation process.1 The American Society of Health- System Pharmacists (ASHP) is the accrediting body for PGY1 residencies, PGY1 community pharmacy residencies, PGY1 residencies in managed care pharmacy, and PGY2 pharmacy residency programs in advanced practice areas. ASHP provides many resources to help programs to prepare for and navigate through the accreditation process [https://www.ashp.org/Professional-Development/Residency-Information/ Residency-Program-Directors]. Additionally, new Guidance Documents have been created for the PGY1 residency standards as well as the new competency areas, goals and objectives.2,3 The guidance documents aim to clarify the expectations of each standard and the manner in which it will be surveyed. However, during site visits and feedback from program directors, some common areas of the standards continue to be challenging for programs. Recently, ASHP released their bi-annual Communique’ newsletter for Spring 2016 [https://www.ashp.org/professional-development/residency-information/residencyprogram- directors/communique-newsletter].3 The Communique’ highlights common standards that are cited during accreditation visits. We will review some of these commonly cited standards as well as others that are often noted during site visits as being challenging to programs and provide some tips on how to navigate them

Elevated levels of protein phosphatase 1 and phosphatase 2A may contribute to cardiac dysfunction in diabetes

AbstractAlthough protein phosphorylation and dephosphorylation are known to regulate the activities of different enzymes, sufficient information on the role of dephosphorylation in cardiac function is not available. Since protein phosphatases mediate dephosphorylation, it is possible that cardiac dysfunction induced by diabetes may be due to alterations in the activities of these enzymes. We therefore determined cardiac protein phosphatase activity as well as protein contents of phosphatase 1 and phosphatase 2A in diabetic animals. For this purpose, rats were made diabetic by administering a single intravenous injection of streptozotocin (65 mg/kg body weight) and hearts were examined after 1, 2, 3, 4 and 8 weeks. Some of the 4-week diabetic animals received subcutaneous injections of insulin (3 U/day) for a further period of 4 weeks. Cardiac dysfunction was evident after 2 weeks of inducing diabetes and deteriorated further with time. A significant increase in protein phosphatase activity appeared after 1 week and persisted until 8 weeks. Increased protein phosphatase activity in the diabetic heart was associated with a corresponding increase in the protein contents of both phosphatase 1 and phosphatase 2A. Insulin treatment partly prevented the changes observed in diabetic animals. The results suggest that increased protein phosphatase activities and subsequent enhanced protein dephosphorylation may play a role in diabetes-induced cardiac dysfunction

A brief CBT intervention for depersonalisation-derealisation disorder in psychosis: Results from a feasibility randomised controlled trial

Background and objectives: Depersonalisation/derealisation symptoms are prevalent in psychosis patients, are associated with increased impairment, and may maintain psychosis symptoms. We aimed to establish the feasibility and acceptability of a brief, six session therapy protocol adapted from a Cognitive-Behavioural model of Depersonalisation-Derealisation Disorder (DDD) in participants with psychotic symptoms. // Methods: A single-blind, randomised controlled trial was conducted with a treatment-as-usual control condition. Feasibility and acceptability estimates included rates of referral, acceptance, eligibility, consent, satisfaction and improved skills/knowledge to manage depersonalisation. // Results: Twenty-one individuals were recruited to the trial. Results suggest that the intervention was feasible and acceptable to participants and there is some signal of effect on clinical outcomes. // Limitations: There were some challenges in recruitment. Recruitment feasibility estimates from the research register used may not be informative for future trials recruiting directly from teams. // Conclusions: Overall, the results suggest that further investigations would be of interest and recommendations for this are made