Measured electron contribution to Shuttle plasma environment: Abbreviated update

The differential energy spectra of electrons between 1 and 100 eV were measured by an electron spectrometer flown on an early shuttle. This energy range was scanned in 64 incremental steps with a resolution of 7%. The most striking feature that was observed throughout these spectra was a relatively flat distribution of the higher energy electrons out to 100 eV. This is in contrast to normal ambient spectra which consistently show a rapid decline in quantitative flux beyond 50 to 55 eV. The lower energy (1 to 2 eV) end of these spectra showed steep thermal trails comparable to normal ambient spectral structure. In general, daytime fluxes were significantly higher than those obtained during nighttime measurements. Quantitative flux excursions which may possibly be associated with thruster firing were frequently observed. Spectral structure suggestive of the N2 vibrational excitation energy loss mechanism was also seen in the data from some measurement periods. Examples of these spectra are shown and possible correlations are discussed

Metamorphic Domain-Specific Languages: A Journey Into the Shapes of a Language

External or internal domain-specific languages (DSLs) or (fluent) APIs? Whoever you are -- a developer or a user of a DSL -- you usually have to choose your side; you should not! What about metamorphic DSLs that change their shape according to your needs? We report on our 4-years journey of providing the "right" support (in the domain of feature modeling), leading us to develop an external DSL, different shapes of an internal API, and maintain all these languages. A key insight is that there is no one-size-fits-all solution or no clear superiority of a solution compared to another. On the contrary, we found that it does make sense to continue the maintenance of an external and internal DSL. The vision that we foresee for the future of software languages is their ability to be self-adaptable to the most appropriate shape (including the corresponding integrated development environment) according to a particular usage or task. We call metamorphic DSL such a language, able to change from one shape to another shape

Stepwise-edited, human melanoma models reveal mutations' effect on tumor and microenvironment.

Establishing causal relationships between genetic alterations of human cancers and specific phenotypes of malignancy remains a challenge. We sequentially introduced mutations into healthy human melanocytes in up to five genes spanning six commonly disrupted melanoma pathways, forming nine genetically distinct cellular models of melanoma. We connected mutant melanocyte genotypes to malignant cell expression programs in vitro and in vivo, replicative immortality, malignancy, rapid tumor growth, pigmentation, metastasis, and histopathology. Mutations in malignant cells also affected tumor microenvironment composition and cell states. Our melanoma models shared genotype-associated expression programs with patient melanomas, and a deep learning model showed that these models partially recapitulated genotype-associated histopathological features as well. Thus, a progressive series of genome-edited human cancer models can causally connect genotypes carrying multiple mutations to phenotype

A Trouble Shared Is a Trouble Halved: Social Context and Status Affect Pain in Mouse Dyads

In mice behavioral response to pain is modulated by social status. Recently, social context also has been shown to affect pain sensitivity. In our study, we aimed to investigate the effects of interaction between status and social context in dyads of outbred CD-1 male mice in which the dominance/submission relationship was stable. Mice were assessed for pain response in a formalin (1% concentration) test either alone (individually tested-IT), or in pairs of dominant and subordinate mice. In the latter condition, they could be either both injected (BI) or only one injected (OI) with formalin. We observed a remarkable influence of social context on behavioral response to painful stimuli regardless of the social status of the mice. In the absence of differences between OI and IT conditions, BI mice exhibited half as much Paw-licking behavior than OI group. As expected, subordinates were hypoalgesic in response to the early phase of the formalin effects compared to dominants. Clear cut-differences in coping strategies of dominants and subordinates appeared. The former were more active, whereas the latter were more passive. Finally, analysis of behavior of the non-injected subjects (the observers) in the OI dyads revealed that dominant observers were more often involved in Self-grooming behavior upon observation of their subordinate partner in pain. This was not the case for subordinate mice observing the pain response of their dominant partner. In contrast, subordinate observers Stared at the dominant significantly more frequently compared to observer dominants in other dyads. The observation of a cagemate in pain significantly affected the observer's behavior. Additionally, the quality of observer's response was also modulated by the dominance/submission relationship

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Effect of obesity on constant workrate exercise in hyperinflated men with COPD

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) and a high body mass index (BMI) can both affect pulmonary volumes as well as exercise tolerance, but their combined effect on these outcomes is not well known. The aim of this study was to investigate the effects of increased BMI during constant workrate cycle ergometry in patients with COPD.</p> <p>Methods</p> <p>Men with COPD and hyperinflation were divided according to World Health Organization BMI classification: 84 normal BMI (NBMI), 130 overweight (OW) and 64 obese (OB). Patients underwent spirometric and lung volumes assessment and an incremental cycling exercise test. This was followed by a constant workrate exercise test (CET) at 75% of peak capacity. Inspiratory capacity and Borg dyspnea scores were measured at baseline, during and at the end of CET.</p> <p>Results and discussion</p> <p>FEV₁% predicted was not different across BMI classes. Total lung capacity and functional residual capacity were significantly lower in OB and OW compared to NBMI patients. Peak VO₂in L·min^-1was significantly higher in OB and OW patients than in NBMI patients. CET time was not different across BMI classes (p = 0.11). Changes in lung volumes and dyspnea during CET were not different between BMI categories.</p> <p>Conclusions</p> <p>OB and OW patients with COPD had a higher peak VO₂than their lean counterparts. Endurance time, dyspnea and changes in lung volumes during CET were similar between BMI categories.</p

Mechanisms of Action of Currently Prescribed and Newly Developed Antiepileptic Drugs

Clinically available antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed before 1980 appear to act on sodium (Na) channels, -y-aminobutyric acid A (GABA A ) receptors, or calcium (Ca) channels. Benzodiazepines and barbiturates enhance GABA A -receptor-mediated inhibition. Phenytoin, car-bamazepine and, possibly, valproate (VPA) decrease high-frequency repetitive firing of action potentials by enhancing Na channel inactivation. Ethosuximide and VPA reduce a low threshold (T-type) Ca-channel current. The mechanisms of action of recently developed AEDs are less clear. Lamotrigine may decrease sustained high-frequency repetitive firing of voltage-dependent Na action potentials, and gabapentin (GBP) appears to bind to a specific binding site in the CNS with a restricted regional distribution. However, the identity of the binding site and the mechanism of action of GBP remain uncertain. The antiepileptic effect of felbamate may involve interaction at the strychnine-insensitive glycine site of the Af-methyl-D-aspartate receptor, but the mechanism of action is not yet proven.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65554/1/j.1528-1157.1994.tb05955.x.pd

Multiple expressions of plume-ridge interaction in the Galapagos : volcanic lineaments and ridge jumps

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 13 (2012): Q05018, doi:10.1029/2012GC004093.Anomalous volcanism and tectonics between near-ridge mantle plumes and mid-ocean ridges provide important insights into the mechanics of plume-lithosphere interaction. We present new observations and analysis of multibeam, side scan sonar, sub-bottom chirp, and total magnetic field data collected during the R/V Melville FLAMINGO cruise (MV1007; May–June, 2010) to the Northern Galápagos Volcanic Province (NGVP), the region between the Galápagos Archipelago and the Galápagos Spreading Center (GSC) on the Nazca Plate, and to the region east of the Galápagos Transform Fault (GTF) on the Cocos Plate. The NGVP exhibits pervasive off-axis volcanism related to the nearby Galápagos hot spot, which has dominated the tectonic evolution of the region. Observations indicate that ~94% of the excess volcanism in our survey area occurs on the Nazca Plate in three volcanic lineaments. Identified faults in the NGVP are consistent with normal ridge spreading except for those within a ~60 km wide swath of transform-oblique faults centered on the GTF. These transform-oblique faults are sub-parallel to the elongation direction of larger lineament volcanoes, suggesting that lineament formation is influenced by the lithospheric stress field. We evaluate current models for lineament formation using existing and new observations as well as numerical models of mantle upwelling and melting. The data support a model where the lithospheric stress field controls the location of volcanism along the lineaments while several processes likely supply melt to these eruptions. Synthetic magnetic models and an inversion for crustal magnetization are used to determine the tectonic history of the study area. Results are consistent with creation of the GTF by two southward ridge jumps, part of a series of jumps that have maintained a plume-ridge separation distance of 145 km to 215 km since ~5 Ma.This work was supported by NSF grant OCE-0926637 and OCE-1030904 to DF and KH. DG’s work was supported by NSF grants EAR- 0838461 and EAR-1145271. Additional support was provided to E.M. by the Deep Ocean Exploration Institute at the Woods Hole Oceanographic Institution.2012-11-3