Corticotropin releasing hormone antagonist does not prevent adrenalectomy-induced apoptosis in the dentate gyrus of the rat hippocampus.

Adrenalectomy in the mature rat leads to death of granule cells in the dentate gyrus of the hippocampal formation. The mechanisms underlying this cell death have not been fully clarified: It has been considered that the granule cells require adrenal steroids for their survival, since corticosterone replacement prevents their death. However, adrenalectomy-induced loss of negative feedback also increases levels of corticotropin releasing hormone (CRH) in several limbic brain regions. CRH is known to induce neuronal death in hippocampal regions rich in CRH receptors. This study tested the hypothesis that adrenalectomy-induced granule cell death is mediated via the enhanced activation of CRH receptors. The extent of granule cell degeneration was compared among 4 groups of young adult male rats: Sham-adrenalectomy controls, adrenalectomized rats, adrenalectomized rats infused with a CRH antagonist from the onset of steroid deprivation to the time of sacrifice, and adrenalectomized rats infused with vehicle only. (9-41)-alpha-helical CRH was administered using an osmotic pump into the cerebral ventricles. Adrenalectomy led to robust granule cell degeneration, which was maximal in the suprapyramidal blade of the dentate gyrus. Infusion of the CRH antagonist in doses shown to block CRH actions on limbic neurons did not decrease the number of degenerating granule cells compared with the untreated or vehicle-infused adrenalectomized groups. Therefore, blocking the actions of CRH does not prevent adrenalectomy-induced granule cell death, consistent with a direct effect of corticoids on the survival of these neurons

Enzyme evolution: innovation is easy, optimization is complicated

Enzymes have been evolving to catalyze new chemical reactions for billions of years, and will continue to do so for billions more. Here, we review examples in which evolutionary biochemists have used big data and high-throughput experimental tools to shed new light on the enormous functional diversity of extant enzymes, and the evolutionary processes that gave rise to it. We discuss the role that gene loss has played in enzyme evolution, as well as the more familiar processes of gene duplication and divergence. We also review insightful studies that relate not only catalytic activity, but also a host of other biophysical and cellular parameters, to organismal fitness. Finally, we provide an updated perspective on protein engineering, based on our new-found appreciation that most enzymes are sloppy and mediocre

Compositional semantics for real-time distributed computing

We give a compositional denotational semantics for a real-time distributed language, based on the linear history semantics for CSP of Francez et al. Concurrent execution is not modelled by interleaving but by an extension of the maximal parallelism model of Salwicki, that allows the modelling of transmission time for communications. The importance of constructing a semantics (and in general a proof theory) for real-time is stressed by such different sources as the problem of formalizing the real-time aspects of Ada and the elimination of errors in real-time flight control software ([Sunday Times 7-22-84])

Electron beam profile imaging in the presence of coherent optical radiation effects

High-brightness electron beams with low energy spread at existing and future x-ray free-electron lasers are affected by various collective beam self-interactions and microbunching instabilities. The corresponding coherent optical radiation effects, e.g., coherent optical transition radiation, render electron beam profile imaging impossible and become a serious issue for all kinds of electron beam diagnostics using imaging screens. Furthermore, coherent optical radiation effects can also be related to intrinsically ultrashort electron bunches or the existence of ultrashort spikes inside the electron bunches. In this paper, we discuss methods to suppress coherent optical radiation effects both by electron beam profile imaging in dispersive beamlines and by using scintillation imaging screens in combination with separation techniques. The suppression of coherent optical emission in dispersive beamlines is shown by analytical calculations, numerical simulations, and measurements. Transverse and longitudinal electron beam profile measurements in the presence of coherent optical radiation effects in non-dispersive beamlines are demonstrated by applying a temporal separation technique.Comment: 12 pages, 11 figures, submitted to Phys. Rev. ST Accel. Beam

The relationships between nasal hyperreactivity, quality of life, and nasal symptoms in patients with perennial allergic rhinitis

Background: A clinical test that could inform the clinician about the severity of a patient's nasal symptoms and health-related quality of life (QOL) would be very useful. Objective: We attempted to determine whether, in patients with perennial allergic rhinitis, nasal challenge with histamine could be used to estimate daily symptoms and QOL. Methods: Forty-eight patients with perennial allergic rhinitis were challenged with histamine to determine nasal hyperreactivity. Nasal response was monitored by the number of sneezes, the amount of secretion, and a symptom score. Daily nasal symptoms were recorded during the 2 preceding weeks. Patients also completed a rhinitis QOL questionnaire. Results: Responsiveness to histamine and total daily nasal symptoms were moderately correlated (r = 0.51, p = 0.001). Comparison of total daily nasal symptoms with the overall QOL score showed a moderate correlation (r = 0.59, p &lt; 0.001). Nasal response to histamine and overall QOL score were also correlated (r = 0.43, p = 0.0052). However, overall QOL and daily nasal symptoms could be predicted by wide 95% confidence intervals only for each decade of nasal responsiveness to histamine (expressed as a composite symptom score). Conclusion: In patients with perennial allergic rhinitis nasal hyperreactivity as determined by histamine challenge, QOL, and daily nasal symptoms are moderately correlated. Therefore nasal histamine challenge can be used as a tool for estimating the severity of daily nasal symptoms and QOL, although it cannot predict nasal symptoms and QOL very accurately.</p

SAT-based Explicit LTL Reasoning

We present here a new explicit reasoning framework for linear temporal logic (LTL), which is built on top of propositional satisfiability (SAT) solving. As a proof-of-concept of this framework, we describe a new LTL satisfiability tool, Aalta\_v2.0, which is built on top of the MiniSAT SAT solver. We test the effectiveness of this approach by demonnstrating that Aalta\_v2.0 significantly outperforms all existing LTL satisfiability solvers. Furthermore, we show that the framework can be extended from propositional LTL to assertional LTL (where we allow theory atoms), by replacing MiniSAT with the Z3 SMT solver, and demonstrating that this can yield an exponential improvement in performance

Geometric representations for minimalist grammars

We reformulate minimalist grammars as partial functions on term algebras for strings and trees. Using filler/role bindings and tensor product representations, we construct homomorphisms for these data structures into geometric vector spaces. We prove that the structure-building functions as well as simple processors for minimalist languages can be realized by piecewise linear operators in representation space. We also propose harmony, i.e. the distance of an intermediate processing step from the final well-formed state in representation space, as a measure of processing complexity. Finally, we illustrate our findings by means of two particular arithmetic and fractal representations.Comment: 43 pages, 4 figure

Do people who load their feet differently need insoles that have different stiffness?

Background: Plantar pressure reduction is an important aspect of diabetic foot management. However little information exists about the optimum cushioning properties of materials used in diabetic footwear as insoles/foot-beds. Numerical analyses have indicated that optimizing the material properties of footwear materials can improve their ability to reduce pressure. Aim: To investigate if the optimal insole stiffness would vary based on patients’ body mass (BM) in people with diabetic neuropathy. Method: Custom PU foams were produced using different ratios of chemical components to achieve a range of different stiffness. Uniform thickness (400 mm × 400 mm × 10 mm) foam sheets were produced with shore-A hardness between 3 and 45 and average(±stdev) increments of 5(±3). Standardized compression tests were performed for all 10 custom materials as well as for 3 commercially available foam materials used in diabetic footwear. Plantar pressure was measured during balanced standing on all custom material sheets for 4 diabetic neuropathic volunteers: 2 with BM of 49 kg ± 1 kg and 2 with BM of 73 kg ± 2 kg. Results: The maximum compressive force for 50% compression of the commercially available foams was similar to custom foams with 11–28 shore-A hardness. Peak plantar pressure was minimised for materials with shore-A hardness 6 and 11 in subjects with BM of 49 kg ± 1 kg and 73 kg ± 2 kg respectively. In all cases using softer or stiffer material (by 1 shore hardness increment) increased pressure by 24% ± 26% and 32% ± 34% respectively. Conclusions: Careful selection of insole/foot-bed stiffness can improve the pressure reduction capacity of diabetic footwear. Optimum material stiffness increased with the BM of the volunteers

Choreography, controversy and child sex abuse: Theoretical reflections on a cultural criminological analysis of dance in a pop music video

This article was inspired by the controversy over claims of ‘pedophilia!!!!’ undertones and the ‘triggering’ of memories of childhood sexual abuse in some viewers by the dance performance featured in the music video for Sia’s ‘Elastic Heart’ (2015). The case is presented for acknowledging the hidden and/or overlooked presence of dance in social scientific theory and cultural studies and how these can enhance and advance cultural criminological research. Examples of how these insights have been used within other disciplinary frameworks to analyse and address child sex crime and sexual trauma are provided, and the argument is made that popular cultural texts such as dance in pop music videos should be regarded as significant in analysing and tracing public perceptions and epistemologies of crimes such as child sex abuse