The arithmetic of hyperelliptic curves

We summarise recent advances in techniques for solving Diophantine problems on hyperelliptic curves; in particular, those for finding the rank of the Jacobian, and the set of rational points on the curve

A New Method for Obtaining Binary Pulsar Distances and its Implications for Tests of General Relativity

We demonstrate how measuring orbital period derivatives can lead to more accurate distance estimates and transverse velocities for some nearby binary pulsars. In many cases this method will estimate distances more accurately than is possible by annual parallax, as the relative error decreases as t^-5/2. Unfortunately, distance uncertainties limit the degree to which nearby relativistic binary pulsars can be used for testing the general relativistic prediction of orbital period decay to a few percent. Nevertheless, the measured orbital period derivative of PSR B1534+12 agrees within the observational uncertainties with that predicted by general relativity if the proper-motion contribution is accounted for.Comment: 4 pages, latex, uuencoded compressed postscript + source, no figures, uses aaspptwo.sty and dec.sty, accepted for publication in ApJL, omitted reference now include

Harnessing the purinergic receptor pathway to develop functional engineered cartilage constructs

Objective: Mechanical stimulation is a widely used method to enhance the formation and properties of tissue-engineered cartilage. While this approach can be highly successful, it may be more efficient and effective to harness the known underlying mechanotransduction pathways responsible. With this aim, the purpose of this study was to assess the effect of directly stimulating the purinergic receptor pathway through exogenous adenosine 5\u27-triphosphate (ATP) in absence of externally applied forces. Methods: Isolated bovine articular chondrocytes were seeded in high density, 3D culture and supplemented with varying doses of ATP for up to 4 weeks. The effects on biosynthesis, extracellular matrix accumulation and mechanical properties were then evaluated. Experiments were also conducted to assess whether exogenous ATP elicited any undesirable effects, such as: inflammatory mediator release, matrix turn-over and mineralization. Results: Supplementation with ATP had a profound effect on the growth and maturation of the developed tissue. Exogenous ATP (62.5-250. μM) increased biosynthesis by 80-120%, and when stimulated for a period of 4 weeks resulted in increased matrix accumulation (80% increase in collagen and 60% increase in proteoglycans) and improved mechanical properties (6.5-fold increase in indentation modulus). While exogenous ATP did not stimulate the release of inflammatory mediators or induce mineralization, high doses of ATP (250μM) elicited a 2-fold increase in matrix metalloproteinase-13 expression suggesting the emergence of a catabolic response. Conclusions: Harnessing the ATP-purinergic receptor pathway is a highly effective approach to improve tissue formation and impart functional mechanical properties. However, the dose of ATP needs to be controlled as not to elicit a catabolic response. © 2010 Osteoarthritis Research Society International

Identifying the active ingredients of training interventions for healthcare professionals to promote and support increased levels of physical activity in adults with heart failure: a systematic review

Heart failure (HF) is characterised by breathlessness and fatigue that impacts negatively on patients’ intentions to prioritise physical activity (PA). Healthcare professionals (HCPs) experience challenges when motivating patients to increase PA. It is essential to develop an understanding of how to support HCPs to deliver PA interventions. We aimed to identify active ingredients of HCP training interventions to enable delivery of PA interventions to HF patients. Nine databases were searched. Data were extracted on study characteristics, active ingredients, outcomes, and fidelity measures. Data were synthesised narratively, and a promise analysis was conducted on intervention features. Ten RCTs, which reported a training intervention for HCPs were included (N = 22 HCPs: N = 1,414 HF patients). Two studies reported the use of theory to develop HCP training. Seven behaviour change techniques (BCTs) were identified across the 10 training interventions. The most ‘promising’ BCTs were ‘instruction on how to perform the behaviour’ and ‘problem solving’. Two studies reported that HCP training interventions had been formally evaluated. Fidelity domains including study design, monitoring and improving the delivery of treatment, intervention delivery, and provider training were infrequently reported. Future research should prioritise theory-informed development and robust evaluation of training interventions for HCPs to enable faithful and quality delivery of patient interventions

Chemical genetic identification of CDKL5 substrates reveals its role in neuronal microtubule dynamics.

Loss-of-function mutations in CDKL5 kinase cause severe neurodevelopmental delay and early-onset seizures. Identification of CDKL5 substrates is key to understanding its function. Using chemical genetics, we found that CDKL5 phosphorylates three microtubule-associated proteins: MAP1S, EB2 and ARHGEF2, and determined the phosphorylation sites. Substrate phosphorylations are greatly reduced in CDKL5 knockout mice, verifying these as physiological substrates. In CDKL5 knockout mouse neurons, dendritic microtubules have longer EB3-labelled plus-end growth duration and these altered dynamics are rescued by reduction of MAP1S levels through shRNA expression, indicating that CDKL5 regulates microtubule dynamics via phosphorylation of MAP1S. We show that phosphorylation by CDKL5 is required for MAP1S dissociation from microtubules. Additionally, anterograde cargo trafficking is compromised in CDKL5 knockout mouse dendrites. Finally, EB2 phosphorylation is reduced in patient-derived human neurons. Our results reveal a novel activity-dependent molecular pathway in dendritic microtubule regulation and suggest a pathological mechanism which may contribute to CDKL5 deficiency disorder

Optimal seismic upgrade timing in seaports with increasing throughput demand via real options

A real options (RO) formulation is proposed for decision-making on the timing to upgrade the seismic performance of existing seaports with increasing throughput demand in earthquake prone areas. The pay-off of the seismic upgrade investment option is estimated based on projected net earnings, repair cost, and downtime for a damaging reference seismic event having a pre-specified annual probability of occurrence. These projections inform a discrete-time RO binomial tree, following the American option valuation framework, which propagates the probability of the reference seismic event assuming Poisson temporal distribution of earthquake occurrence. The net present value of the expected annual payoff of the considered investment is used as an index supporting risk-informed decision-making discounted by the weighted average cost of capital (WACC). Numerical examples pertaining to decision makers with different capital cost, namely port authorities and terminal operators, operating in different economic environments typical of developed and developing countries are furnished to illustrate the applicability of the proposed RO formulation. It is found that high WACC and/or low throughput growth bring the optimal seismic upgrade timing forward, while earthquake consequences and upgrade cost have almost no influence on this timing