Competing risk models of stillbirth inform populations but not individuals.

This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/1471-0528.1394

Low-temperature reactions: Tunnelling in space.

International audienceChemical reactions with activation barriers generally slow to a halt in the extreme cold of dense interstellar clouds. Low-temperature experiments on the reaction of OH with methanol have now shown that below 200 K there is a major acceleration in the rate that can only be explained by enhanced quantum mechanical tunnelling through the barrier

Acute anti-allodynic action of gabapentin in dorsal horn and primary somatosensory cortex: Correlation of behavioural and physiological data

Neuropathic pain is a debilitating consequence of neuronal injury or disease. Although first line treatments include the alpha-2-delta (a2d)-ligands, pregabalin and gabapentin (GBP), the mechanism of their anti-allodynic action is poorly understood. One specific paradox is that GBP relieves signs of neuropathic pain in animal models within 30min of an intraperitoneal (IP) injection yet its actions in vitro on spinal dorsal horn or primary afferent neurons take hours to develop. We found, using confocal Ca2þ imaging, that substantia gelatinosa neurons obtained ex vivo from rats subjected to sciatic chronic constriction injury (CCI) were more excitable than controls. We confirmed that GBP (100 mg/kg) attenuated mechanical allodynia in animals subject to CCI within 30min of IP injection.Substantia gelatinosa neurons obtained ex vivo from these animals no longer displayed CCI-induced increased excitability. Electrophysiological analysis of substantia gelatinosa neurons ex vivo suggest that rapidly developing in vivo anti-allodynic effects of GBP i) are mediated intracellularly, ii) involve actions on the neurotransmitter release machinery and iii) depend on decreased excitatory synaptic drive to excitatory neurons without major actions on inhibitory neurons or on intrinsic neuronal excitability. Experiments using in vivo Ca2þ imaging showed that 100 mg/kg GBP also suppressed the response of the S1 somatosensory cortex of CCI rats, but not that of control rats, to vibrotactile stimulation. Since the level of a2d1 protein is increased in primary afferent fibres after sciatic CCI, we suggest this dictates the rate of GBP action; rapidly developing actions can only be seen when a2d1 levels are elevated

A Cervid Vocal Fold Model Suggests Greater Glottal Efficiency in Calling at High Frequencies

Male Rocky Mountain elk (Cervus elaphus nelsoni) produce loud and high fundamental frequency bugles during the mating season, in contrast to the male European Red Deer (Cervus elaphus scoticus) who produces loud and low fundamental frequency roaring calls. A critical step in understanding vocal communication is to relate sound complexity to anatomy and physiology in a causal manner. Experimentation at the sound source, often difficult in vivo in mammals, is simulated here by a finite element model of the larynx and a wave propagation model of the vocal tract, both based on the morphology and biomechanics of the elk. The model can produce a wide range of fundamental frequencies. Low fundamental frequencies require low vocal fold strain, but large lung pressure and large glottal flow if sound intensity level is to exceed 70 dB at 10 m distance. A high-frequency bugle requires both large muscular effort (to strain the vocal ligament) and high lung pressure (to overcome phonation threshold pressure), but at least 10 dB more intensity level can be achieved. Glottal efficiency, the ration of radiated sound power to aerodynamic power at the glottis, is higher in elk, suggesting an advantage of high-pitched signaling. This advantage is based on two aspects; first, the lower airflow required for aerodynamic power and, second, an acoustic radiation advantage at higher frequencies. Both signal types are used by the respective males during the mating season and probably serve as honest signals. The two signal types relate differently to physical qualities of the sender. The low-frequency sound (Red Deer call) relates to overall body size via a strong relationship between acoustic parameters and the size of vocal organs and body size. The high-frequency bugle may signal muscular strength and endurance, via a ‘vocalizing at the edge’ mechanism, for which efficiency is critical

M5 spikes and operators in the HVZ membrane theory

In this note we study some aspects of the so-called dual ABJM theory introduced by Hanany, Vegh & Zaffaroni. We analyze the spectrum of chiral operators, and compare it with the spectrum of functions on the mesonic moduli space M=C^2\times C^2/Z_k, finding expected agreement for the coherent branch. A somewhat mysterious extra branch of dimension N^2 opens up at the orbifold fixed point. We also study BPS solutions which represent M2/M5 intersections. The mesonic moduli space suggests that there should be two versions of this spike: one where the M5 lives in the orbifolded C^2 and another where it lives in the unorbifolded one. While expectedly the first class turns out to be like the ABJM spike, the latter class looks like a collection of stacks of M5 branes with fuzzy S^3 profiles. This shows hints of the appearance of the global SO(4) at the non-abelian level which is otherwise not present in the bosonic potential. We also study the matching of SUGRA modes with operators in the coherent branch of the moduli space. As a byproduct, we present some formulae for the laplacian in conical CY_4 of the form C^n\times CY_{4-n}.Comment: 22 pages, 1 figure. Published version with corrected typos

Radiation tolerance of GaAs1-xSbx solar cells

High radiation tolerance of GaAs1-xSbx based solar cells is demonstrated for the low-intensity-low-temperature (LILT) conditions of the target planets Saturn, Jupiter, and Mars. The GaAs1-xSbx-based cells are irradiated with high energy electrons to assess the effect of harsh radiation environment on the solar cell and the response of the cell is then investigated in terms of its photovoltaic operation. This system shows significant radiation resistance to the high energy electron environment for the conditions of the planets of interest. An unusual increase of the short circuit current after irradiation is observed at low temperature, which is supported by a simultaneous increase in the external quantum efficiency of the cell under the same conditions. The open circuit voltage and fill factor of the cell are especially tolerant to irradiation, which is also reflected in unchanged dark current-voltage characteristics of the solar cell upon irradiation particularly at LILT

Radiation tolerance of GaAs1-xSbx solar cells: A candidate III-V system for space applications

The high radiation tolerance of GaAs0.86Sb0.14 based solar cells with a band gap suitable for PV is demonstrated at the low intensity low temperature (LILT) conditions. This system shows remarkable radiation hardness at AM0, and more prominently, at the conditions of several outer planetary targets. This is attributed to an irradiation induced change in the absorber band gap due to local heating and strain relaxation, and the generation of less prohibitive shallow Sb-based defects in the GaAs 1-x Sb x absorber

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

Rabies screen reveals GPe control of cocaine-triggered plasticity.

Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations