New 3-D gas density maps of NaI and CaII interstellar absorption within 300pc

We present new high resolution (R>50,000) absorption measurements of the NaI doublet (5889 - 5895A) along 482 nearby sight-lines, in addition to 807 new measurements of the CaII K (3933A) absorption line. We have combined these new data with previously reported measurements to produce a catalog of absorptions towards a total of 1857 early-type stars located within 800pc of the Sun. Using these data we have determined the approximate 3-dimensional spatial distribution of neutral and partly ionized interstellar gasdensity within a distance-cube of 300pc from the Sun. All newly recorded spectra were analyzed by means of a multi-component line profile-fitting program, in most cases using simultaneous fits to the line doublets. Normalized absorption profiles were fitted by varying the velocity, doppler width and column density for all intervening interstellar clouds. The resulting total column densities were then used in conjunction with the Hipparcos distances of the target stars to construct inversion maps of the 3-D spatial density distribution of the NaI and CaII bearing gas. A plot of the equivalent width of NaI versus distance reveals a wall of neutral gas at ~80pc that can be associated with the boundary wall to the central rarefied Local Cavity region. In contrast, a similar plot for the equivalent width of CaII shows no sharply increasing absorption at 80pc, but instead we observe a slowly increasing value of CaII equivalent width with increasing sight-line distance sampled.Comment: A&A accepte

Ontology-assisted database integration to support natural language processing and biomedical data-mining

Successful biomedical data mining and information extraction require a complete picture of biological phenomena such as genes, biological processes, and diseases; as these exist on different levels of granularity. To realize this goal, several freely available heterogeneous databases as well as proprietary structured datasets have to be integrated into a single global customizable scheme. We will present a tool to integrate different biological data sources by mapping them to a proprietary biomedical ontology that has been developed for the purposes of making computers understand medical natural language

Adaptable Imaging Package for Remote Vehicles

An easy-to-customize, low-cost solution for remote imagery is described. The system, denoted ImPROV (Imaging Package for Remote Vehicles), supports multiple cameras, live streaming, long-range encrypted communication using mobile networks, positioning and time-stamped imagery, etc. The adaptability of the system is demonstrated by its deployment on different remotely operated or autonomous vehicles, which include model aircraft, drones, balloon, kite and a submarine

Deficits of psychomotor and mnesic functions across aging in mouse lemur primates

International audienceOwing to a similar cerebral neuro-anatomy, non-human primates are viewed as the most valid models for understanding cognitive deficits. This study evaluated psychomotor and mnesic functions of 41 young to old mouse lemurs (Microcebus murinus). Psychomotor capacities and anxiety-related behaviors decreased abruptly from middle to late adulthood. However, mnesic functions were not affected in the same way with increasing age. While results of the spontaneous alternation task point to a progressive and widespread age-related decline of spatial working memory, both spatial reference and novel object recognition (NOR) memory tasks did not reveal any tendency due to large inter-individual variability in the middle-aged and old animals. Indeed, some of the aged animals performed as well as younger ones, whereas some others had bad performances in the Barnes maze and in the object recognition test. Hierarchical cluster analysis revealed that declarative-like memory was strongly impaired only in 7 out of 25 middle-aged/old animals. These results suggest that this analysis allows to distinguish elder populations of good and bad performers in this non-human primate model and to closely compare this to human aging

Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney.

BackgroundExcess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout.MethodssUA levels, fractional excretion of uric acid (FEUA), lesinurad plasma levels, and urinary excretion of lesinurad were measured in healthy volunteers treated with lesinurad. In addition, lesinurad, probenecid, and benzbromarone were compared in vitro for effects on urate transporters and the organic anion transporters (OAT)1 and OAT3, changes in mitochondrial membrane potential, and human peroxisome proliferator-activated receptor gamma (PPARγ) activity.ResultsAfter 6 hours, a single 200-mg dose of lesinurad elevated FEUA 3.6-fold (p < 0.001) and reduced sUA levels by 33 % (p < 0.001). At concentrations achieved in the clinic, lesinurad inhibited activity of URAT1 and OAT4 in vitro, did not inhibit GLUT9, and had no effect on ABCG2. Lesinurad also showed a low risk for mitochondrial toxicity and PPARγ induction compared to benzbromarone. Unlike probenecid, lesinurad did not inhibit OAT1 or OAT3 in the clinical setting.ConclusionThe pharmacodynamic effects and in vitro activity of lesinurad are consistent with inhibition of URAT1 and OAT4, major apical transporters for uric acid. Lesinurad also has a favorable selectivity and safety profile, consistent with an important role in sUA-lowering therapy for patients with gout

Clostridium perfringens Epsilon Toxin Targets Granule Cells in the Mouse Cerebellum and Stimulates Glutamate Release

Epsilon toxin (ET) produced by C. perfringens types B and D is a highly potent pore-forming toxin. ET-intoxicated animals express severe neurological disorders that are thought to result from the formation of vasogenic brain edemas and indirect neuronal excitotoxicity. The cerebellum is a predilection site for ET damage. ET has been proposed to bind to glial cells such as astrocytes and oligodendrocytes. However, the possibility that ET binds and attacks the neurons remains an open question. Using specific anti-ET mouse polyclonal antibodies and mouse brain slices preincubated with ET, we found that several brain structures were labeled, the cerebellum being a prominent one. In cerebellar slices, we analyzed the co-staining of ET with specific cell markers, and found that ET binds to the cell body of granule cells, oligodendrocytes, but not astrocytes or nerve endings. Identification of granule cells as neuronal ET targets was confirmed by the observation that ET induced intracellular Ca2+ rises and glutamate release in primary cultures of granule cells. In cultured cerebellar slices, whole cell patch-clamp recordings of synaptic currents in Purkinje cells revealed that ET greatly stimulates both spontaneous excitatory and inhibitory activities. However, pharmacological dissection of these effects indicated that they were only a result of an increased granule cell firing activity and did not involve a direct action of the toxin on glutamatergic nerve terminals or inhibitory interneurons. Patch-clamp recordings of granule cell somata showed that ET causes a decrease in neuronal membrane resistance associated with pore-opening and depolarization of the neuronal membrane, which subsequently lead to the firing of the neuronal network and stimulation of glutamate release. This work demonstrates that a subset of neurons can be directly targeted by ET, suggesting that part of ET-induced neuronal damage observed in neuronal tissue is due to a direct effect of ET on neurons

Lake Imaging and Monitoring Aerial Drone

We describe the development of a BVLOS (Beyond Visual Line-Of-Sight) model aircraft (UAV). The broad design requirements included (i) fuselage capable of accommodating an imaging package or other instrumentation, (ii) suitability for over-lake BVLOS authorization in Switzerland, (iii) capability of land or water take-offs/landing, (iv) at least 90-min flight autonomy, (v) modularity of the imaging package and (vi) real-time IR/RGB imagery. Requirement (i) was to ensure an aircraft amenable to future developments. Requirements (ii)-(iv) were driven by the goal of improving estimates of lake surface energy fluxes, since such fluxes have a major impact on long-term lake temperatures and hence ecological status. Requirement (v), in conjunction with (i), allows the UAV to be adapted to other imaging applications. The real-time imagery requirement (vi) permits modifications of on-going missions to map areas of specific interest as they are detected. The prototype UAV produced to satisfy these characteristics was built on the twin-motor My Twin Dream (MTD) aircraft, which has a 1.8-m wing span airframe and a spacious fuselage. The legal authorization necessitated, where feasible, hardware redundancy as well as installation of a parachute system. Continuous communication between the ground station and UAV is provided by the LTE cellular telephone network. The UAV communication is handled by an on-board Linux computer, which is also responsible for control of the imagery package. The avionics involved modifications of the open-source APM autopilot software and the associated ground control station. A key modification was to support a custom-built emergency recovery system, which is triggered by loss of a heartbeat signal from the autopilot. The MTD airframe was modified to accommodate the system electronics and imaging hardware. Results from test flights over Lake Geneva demonstrate the ability of the aircraft to produce imagery data

Effect of closed and permanent stoma on disease course, psychological well-being and working capacity in Swiss IBD cohort study patients

BACKGROUND Little is known about the impact of ostomy formation in inflammatory bowel disease patients on course of disease, psychological well-being, quality of life and working capacity. METHODS We analyzed patients over a follow-up of up to 16 years in the Swiss inflammatory bowel disease cohort study (SIBDCS) with prospective data collection. We compared Ulcerative colitis and Crohn's disease patients with and without ostomy as well as permanent and closed stoma formation before and after surgery, investigating disease activity, psychological wellbeing and working capacity in a case-control design. RESULTS Of 3825 SIBDCS patients, 176 with ostomy were included in the study and matched with 176 patients without ostomy using propensity score, equaling 352 patients for the analysis. As expected, we observed a lower mean and maximal disease activity in patients after stoma surgery compared with control patients without stoma. Overall, psychological wellbeing in patients with stomas vs. controls as well as patients with permanent vs. closed stoma was similar in terms of disease-specific quality of life (total score of the Inflammatory Bowel Disease Quality of Life questionnaire), psychological distress (total score of the Hospital Anxiety and Depression Scale), and stress at work (effort-reward-imbalance ratio), with the exception of a higher Posttraumatic Diagnostic Scale total score in patient with vs. without stoma. Compared to IBD patients without stoma, the adverse impact on working capacity in overall stoma IBD patients appeared to be modest. However we observe a significantly higher reduction in working capacity in permanent vs. closed stoma in CD but not UC patients. CONCLUSION As to be expected, IBD patients may benefit from closed and permanent stoma application. Stoma surgery appears to only modestly impact working capacity. Importantly, stoma surgery was not associated with adverse psychological outcomes, with comparable psychological well-being regardless of presence and type of stoma