Reasoning about goal-directed real-time teleo-reactive programs

The teleo-reactive programming model is a high-level approach to developing real-time systems that supports hierarchical composition and durative actions. The model is different from frameworks such as action systems, timed automata and TLA+, and allows programs to be more compact and descriptive of their intended behaviour. Teleo-reactive programs are particularly useful for implementing controllers for autonomous agents that must react robustly to their dynamically changing environments. In this paper, we develop a real-time logic that is based on Duration Calculus and use this logic to formalise the semantics of teleo-reactive programs. We develop rely/guarantee rules that facilitate reasoning about a program and its environment in a compositional manner. We present several theorems for simplifying proofs of teleo-reactive programs and present a partially mechanised method for proving progress properties of goal-directed agents. © 2013 British Computer Society

Targeted deletions of complement lectin pathway genes improve outcome in traumatic brain injury, with MASP-2 playing a major role.

The lectin pathway (LP) of complement activation is believed to contribute to brain inflammation. The study aims to identify the key components of the LP contributing to TBI outcome as possible novel pharmacological targets. We compared the long-term neurological deficits and neuropathology of wild-type mice (WT) to that of mice carrying gene deletions of key LP components after experimental TBI. WT or MASP-2 (Masp2-/-), ficolin-A (Fcna-/-), CL-11 (Colec11-/-), MASP-1/3 (Masp1-/-), MBL-C (Mbl2-/-), MBL-A (Mbl1-/-) or MBL-/- (Mbl1-/-/Mbl2-/-) deficient male C57BL/6J mice were used. Mice underwent sham surgery or TBI by controlled cortical impact. The sensorimotor response was evaluated by neuroscore and beam walk tests weekly for 4 weeks. To obtain a comparative analysis of the functional outcome each transgenic line was rated according to a health score calculated on sensorimotor performance. For selected genotypes, brains were harvested 6 weeks after injury for histopathological analysis. MASP-2-/-, MBL-/- and FCN-A-/- mice had better outcome scores compared to WT. Of these, MASP-2-/- mice had the best recovery after TBI, showing reduced sensorimotor deficits (by 33% at 3 weeks and by 36% at 4 weeks). They also showed higher neuronal density in the lesioned cortex with a 31.5% increase compared to WT. Measurement of LP functional activity in plasma from MASP-2-/- mice revealed the absence of LP functional activity using a C4b deposition assay. The LP critically contributes to the post-traumatic inflammatory pathology following TBI with the highest degree of protection achieved through the absence of the LP key enzyme MASP-2, underlining a therapeutic utility of MASP-2 targeting in TBI

Transient early preeclampsia in twin pregnancy with a triploid fetus: a case report

INTRODUCTION: Triploid pregnancies have an increased risk of early preeclampsia. Twin pregnancies consisting of one healthy fetus and one complete or partial molar, with or without a triploid fetus, are rare and management is complex. CASE PRESENTATION: A 33-year-old Caucasian woman presented with a dichorionic diamniotic twin pregnancy. One fetus showed early growth restriction resulting in fetal death at 20 weeks. The placenta was enlarged with some cysts. Chorionic villus biopsy confirmed triploidy. At 21 weeks, the patient developed preeclampsia with a blood pressure of 154/98 mmHg and proteinuria (24 hour protein excretion of 2.5 g/L), for which she was hospitalized. Without pharmacological interventions, the blood pressure normalized and proteinuria disappeared. At 35 weeks, she again developed preeclampsia. A cesarean section was performed at 38 weeks and a healthy child was born. CONCLUSIONS: Survival of the healthy fetus is possible in a twin pregnancy with a triploid fetus complicated by early preeclampsia. The pregnancy should not be terminated if the triploid twin has died and as long as conservative management is safe

Edible crabs “Go West”: migrations and incubation cycle of Cancer pagurus revealed by electronic tags

Crustaceans are key components of marine ecosystems which, like other exploited marine taxa, show seasonable patterns of distribution and activity, with consequences for their availability to capture by targeted fisheries. Despite concerns over the sustainability of crab fisheries worldwide, difficulties in observing crabs’ behaviour over their annual cycles, and the timings and durations of reproduction, remain poorly understood. From the release of 128 mature female edible crabs tagged with electronic data storage tags (DSTs), we demonstrate predominantly westward migration in the English Channel. Eastern Channel crabs migrated further than western Channel crabs, while crabs released outside the Channel showed little or no migration. Individual migrations were punctuated by a 7-month hiatus, when crabs remained stationary, coincident with the main period of crab spawning and egg incubation. Incubation commenced earlier in the west, from late October onwards, and brooding locations, determined using tidal geolocation, occurred throughout the species range. With an overall return rate of 34%, our results demonstrate that previous reluctance to tag crabs with relatively high-cost DSTs for fear of loss following moulting is unfounded, and that DSTs can generate precise information with regards life-history metrics that would be unachievable using other conventional means

Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle

The development of skeletal muscle insulin resistance is an early physiological defect, yet the intracellular mechanisms accounting for this metabolic defect remained unresolved. Here, we have examined the role of glucose-6-phosphate dehydrogenase (G6PDH) activity in the pathogenesis of insulin resistance in skeletal muscle. Methods Multiple mouse disease states exhibiting insulin resistance and glucose intolerance, as well as obese humans defined as insulin-sensitive, insulin-resistant, or pre-diabetic, were examined. Results We identified increased glucose-6-phosphate dehydrogenase (G6PDH) activity as a common intracellular adaptation that occurs in parallel with the induction of insulin resistance in skeletal muscle and is present across animal and human disease states with an underlying pathology of insulin resistance and glucose intolerance. We observed an inverse association between G6PDH activity and nitric oxide synthase (NOS) activity and show that increasing NOS activity via the skeletal muscle specific neuronal (n)NOS&mu; partially suppresses G6PDH activity in skeletal muscle cells. Furthermore, attenuation of G6PDH activity in skeletal muscle cells via (a) increased nNOS&mu;/NOS activity, (b) pharmacological G6PDH inhibition, or (c) genetic G6PDH inhibition increases insulin-independent glucose uptake. Conclusions We have identified a novel, previously unrecognized role for G6PDH in the regulation of skeletal muscle glucose metabolism. <br /

Radio Emission from Ultra-Cool Dwarfs

The 2001 discovery of radio emission from ultra-cool dwarfs (UCDs), the very low-mass stars and brown dwarfs with spectral types of ~M7 and later, revealed that these objects can generate and dissipate powerful magnetic fields. Radio observations provide unparalleled insight into UCD magnetism: detections extend to brown dwarfs with temperatures <1000 K, where no other observational probes are effective. The data reveal that UCDs can generate strong (kG) fields, sometimes with a stable dipolar structure; that they can produce and retain nonthermal plasmas with electron acceleration extending to MeV energies; and that they can drive auroral current systems resulting in significant atmospheric energy deposition and powerful, coherent radio bursts. Still to be understood are the underlying dynamo processes, the precise means by which particles are accelerated around these objects, the observed diversity of magnetic phenomenologies, and how all of these factors change as the mass of the central object approaches that of Jupiter. The answers to these questions are doubly important because UCDs are both potential exoplanet hosts, as in the TRAPPIST-1 system, and analogues of extrasolar giant planets themselves.Comment: 19 pages; submitted chapter to the Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag

FaIRv2.0.0: a generalized impulse response model for climate uncertainty and future scenario exploration

Here we present an update to the FaIR model for use in probabilistic future climate and scenario exploration, integrated assessment, policy analysis, and education. In this update we have focussed on identifying a minimum level of structural complexity in the model. The result is a set of six equations, five of which correspond to the standard impulse response model used for greenhouse gas (GHG) metric calculations in the IPCC's Fifth Assessment Report, plus one additional physically motivated equation to represent state-dependent feedbacks on the response timescales of each greenhouse gas cycle. This additional equation is necessary to reproduce non-linearities in the carbon cycle apparent in both Earth system models and observations. These six equations are transparent and sufficiently simple that the model is able to be ported into standard tabular data analysis packages, such as Excel, increasing the potential user base considerably. However, we demonstrate that the equations are flexible enough to be tuned to emulate the behaviour of several key processes within more complex models from CMIP6. The model is exceptionally quick to run, making it ideal for integrating large probabilistic ensembles. We apply a constraint based on the current estimates of the global warming trend to a million-member ensemble, using the constrained ensemble to make scenario-dependent projections and infer ranges for properties of the climate system. Through these analyses, we reaffirm that simple climate models (unlike more complex models) are not themselves intrinsically biased “hot” or “cold”: it is the choice of parameters and how those are selected that determines the model response, something that appears to have been misunderstood in the past. This updated FaIR model is able to reproduce the global climate system response to GHG and aerosol emissions with sufficient accuracy to be useful in a wide range of applications and therefore could be used as a lowest-common-denominator model to provide consistency in different contexts. The fact that FaIR can be written down in just six equations greatly aids transparency in such contexts

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?

Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination

The Transit Phase of Migration: Circulation of Malaria and Its Multidrug-Resistant Forms in Africa

In the third article in a six-part <I>PLoS Medicine</I> series on Migration & Health, Cally Roper and Caroline Lynch use a case study of migration and anti-malarial drug resistance in Uganda to discuss the specific health risks and policy needs associated with the transit phase of migration