Biogenesis of the mitochondrial phosphate carrier

The mitochondrial phosphate carrier (PiC) is a member of the family of inner-membrane carrier proteins which are generally synthesized without a cleavable presequence. Surprisingly, the cDNA sequences of bovine and rat PiC suggested the existence of an amino-terminal extension sequence in the precursor of PiC. By expressing PiC in vitro, we found that PiC is indeed synthesized as a larger precursor. This precursor was imported and proteolytically processed by mitochondria, whereby the correct amino-terminus of the mature protein was generated. Import of PiC showed the characteristics of mitochondrial protein uptake, such as dependence on ATP and a membrane potential and involvement of contact sites between mitochondrial outer and inner membranes. The precursor imported in vitro was correctly assembled into the functional form, demonstrating that the authentic import and assembly pathway of PiC was reconstituted when starting with the presequence-carrying precursor. These results are discussed in connection with the recently postulated role of PiC as an import receptor located in the outer membrane

Wide-Field InfraRed Survey Telescope (WFIRST) Final Report

In December 2010, NASA created a Science Definition Team (SDT) for WFIRST, the Wide Field Infra-Red Survey Telescope, recommended by the Astro 2010 Decadal Survey as the highest priority for a large space mission. The SDT was chartered to work with the WFIRST Project Office at GSFC and the Program Office at JPL to produce a Design Reference Mission (DRM) for WFIRST. Part of the original charge was to produce an interim design reference mission by mid-2011. That document was delivered to NASA and widely circulated within the astronomical community. In late 2011 the Astrophysics Division augmented its original charge, asking for two design reference missions. The first of these, DRM1, was to be a finalized version of the interim DRM, reducing overall mission costs where possible. The second of these, DRM2, was to identify and eliminate capabilities that overlapped with those of NASA's James Webb Space Telescope (henceforth JWST), ESA's Euclid mission, and the NSF's ground-based Large Synoptic Survey Telescope (henceforth LSST), and again to reduce overall mission cost, while staying faithful to NWNH. This report presents both DRM1 and DRM2.Comment: 102 pages, 57 figures, 17 table

Tissue-specific expression of high-voltage-activated dihydropyridine-sensitive L-type calcium channels

The cloning of the cDNA for the α1 subunit of L-type calcium channels revealed that at least two genes (CaCh1 and CaCh2) exist which give rise to several splice variants. The expression of mRNA for these α1 subunits and the skeletal muscle α2/δ, β and γ subunits was studied in rabbit tissues and BC3H1 cells. Nucleic-acid-hybridization studies showed that the mRNA of all subunits are expressed in skeletal muscle, brain, heart and aorta. However, the α1-, β- and γ-specific transcripts had different sizes in these tissues. Smooth muscle and heart contain different splice variants of the CaCh2 gene. The α1, β and γ mRNA are expressed together in differentiated but not in proliferating BC3H1 cells. A probe specific for the skeletal muscle α2/δ subunit did not hybridize to poly(A)-rich RNA from BC3H1 cells. These results suggest that different splice variants of the genes for the α1, β and γ subunits exist in tissues containing L-type calcium channels, and that their expression is regulated in a coordinate manner

Wide-Field Infrared Survey Telescope (WFIRST) Interim Report

The New Worlds, New Horizons (NWNH) in Astronomy and Astrophysics 2010 Decadal Survey prioritized the community consensus for ground-based and space-based observatories. Recognizing that many of the community s key questions could be answered with a wide-field infrared survey telescope in space, and that the decade would be one of budget austerity, WFIRST was top ranked in the large space mission category. In addition to the powerful new science that could be accomplished with a wide-field infrared telescope, the WFIRST mission was determined to be both technologically ready and only a small fraction of the cost of previous flagship missions, such as HST or JWST. In response to the top ranking by the community, NASA formed the WFIRST Science Definition Team (SDT) and Project Office. The SDT was charged with fleshing out the NWNH scientific requirements to a greater level of detail. NWNH evaluated the risk and cost of the JDEM-Omega mission design, as submitted by NASA, and stated that it should serve as the basis for the WFIRST mission. The SDT and Project Office were charged with developing a mission optimized for achieving the science goals laid out by the NWNH re-port. The SDT and Project Office opted to use the JDEM-Omega hardware configuration as an initial start-ing point for the hardware implementation. JDEM-Omega and WFIRST both have an infrared imager with a filter wheel, as well as counter-dispersed moderate resolution spectrometers. The primary advantage of space observations is being above the Earth's atmosphere, which absorbs, scatters, warps and emits light. Observing from above the atmosphere enables WFIRST to obtain precision infrared measurements of the shapes of galaxies for weak lensing, infrared light-curves of supernovae and exoplanet microlensing events with low systematic errors, and infrared measurements of the H hydrogen line to be cleanly detected in the 1<z<2 redshift range important for baryon acoustic oscillation (BAO) dark energy measurements. The Infrared Astronomical Satellite (IRAS), the Cosmic Background Explorer (COBE), Herschel, Spitzer, and Wide-field Infrared Sur-vey Explorer (WISE) are all space missions that have produced stunning new scientific advances by going to space to observe in the infrared. This interim report describes progress as of June 2011 on developing a requirements flowdown and an evaluation of scientific performance. An Interim Design Reference Mission (IDRM) configuration is presented that is based on the specifications of NWNH with some refinements to optimize the design in accordance with the new scientific requirements. Analysis of this WFIRST IDRM concept is in progress to ensure the capability of the observatory is compatible with the science requirements. The SDT and Project will continue to refine the mission concept over the coming year as design, analysis and simulation work are completed, resulting in the SDT s WFIRST Design Reference Mission (DRM) by the end of 2012

KELT-18b: Puffy Planet, Hot Host, Probably Perturbed

We report the discovery of KELT-18b, a transiting hot Jupiter in a 2.87-day orbit around the bright ( V = 10.1), hot, F4V star BD+60 1538 (TYC 3865-1173-1). We present follow-up photometry, spectroscopy, and adaptive optics imaging that allow a detailed characterization of the system. Our preferred model fits yield a host stellar temperature of K and a mass of , situating it as one of only a handful of known transiting planets with hosts that are as hot, massive, and bright. The planet has a mass of , a radius of , and a density of , making it one of the most inflated planets known around a hot star. We argue that KELT-18b’s high temperature and low surface gravity, which yield an estimated ∼600 km atmospheric scale height, combined with its hot, bright host, make it an excellent candidate for observations aimed at atmospheric characterization. We also present evidence for a bound stellar companion at a projected separation of ∼1100 au, and speculate that it may have contributed to the strong misalignment we suspect between KELT-18\u27s spin axis and its planet’s orbital axis. The inferior conjunction time is 2457542.524998 ± 0.000416 (BJD TDB ) and the orbital period is 2.8717510 ± 0.0000029 days. We encourage Rossiter–McLaughlin measurements in the near future to confirm the suspected spin–orbit misalignment of this system

The Secret to Successful User Communities: An Analysis of Computer Associates’ User Groups

This paper provides the first large scale study that examines the impact of both individual- and group-specific factors on the benefits users obtain from their user communities. By empirically analysing 924 survey responses from individuals in 161 Computer Associates' user groups, this paper aims to identify the determinants of successful user communities. To measure success, the amount of time individual members save through having access to their user networks is used. As firms can significantly profit from successful user communities, this study proposes four key implications of the empirical results for the management of user communities

Periferne osteoporotske frakture osim kuka - epidemiologija i značenje

Fractures are the most serious consequence of osteoporosis. Non-vertebral and non-hip fractures are seldom recognised as important, even though they account for the majority of all fractures. The most prevalent localisations are distal radius, proximal humerus, ribs, clavicle, and the pelvis. According to the results from large phase III clinical trials for placebo groups, their incidence ranges from 4.9 % to 12.0 %. Hospital morbidity data in Croatia in 2006 show that peripheral non-hip fractures ranked among the leading fifteen injuries, accounting for 23.7 % of all injuries in patients aged 60 years and above. Risk factors for non-hip and non-vertebral fractures are similar to other osteoporotic fractures, and the main are low bone mineral density and earlier fractures. Quality of life is considerably affected by these fractures, and medical costs are very high, soaring as high as 36.9 % of all national medical costs in the USA. Nonvertebral non-hip fractures need more attention, which was also recognised by the European regulatory bodies that approve use of anti-osteoporotic drugs.Prijelomi su najozbiljnija posljedica osteoporoze. Iako čine većinu svih fraktura, nevertebralne frakture osim kuka rijetko se prepoznaju kao značajne. Najčešće lokalizacije tih prijeloma su: distalni dio radijusa, proksimalni dio humerusa, rebra, klavikula i zdjelica. Prema rezultatima iz placebo-grupa III. faze velikih kliničkih ispitivanja raspon njihove incidencije iznosi između 4,9 % i 12,0 %. Prema podacima bolničkog pobolijevanja za 2006. g. u Hrvatskoj, među 15 vodećih ozljeda u dobnoj grupi 60 i više godina 23,7 % bile su periferne frakture osim kuka. Čimbenici rizika za nevertebralne frakture osim onih kuka slični su kao i za druge osteoporotske frakture gdje središnje mjesto imaju niska mineralna gustoća kosti i prethodne frakture. Ove frakture imaju velik utjecaj na kvalitetu `ivota, a njihovi su troškovi vrlo visoki, tako da u SAD-u iznose čak 36.9 % svih nacionalnih medicinskih troškova. Nevertebralne frakture osim kuka zahtijevaju veću pozornost, što su i prepoznala europska regulatorna tijela koja odobravaju upotrebu antiosteoporotskih lijekova

Applying human factors principles to alert design increases efficiency and reduces prescribing errors in a scenario-based simulation

OBJECTIVE: To apply human factors engineering principles to improve alert interface design. We hypothesized that incorporating human factors principles into alerts would improve usability, reduce workload for prescribers, and reduce prescribing errors. MATERIALS AND METHODS: We performed a scenario-based simulation study using a counterbalanced, crossover design with 20 Veterans Affairs prescribers to compare original versus redesigned alerts. We redesigned drug-allergy, drug-drug interaction, and drug-disease alerts based upon human factors principles. We assessed usability (learnability of redesign, efficiency, satisfaction, and usability errors), perceived workload, and prescribing errors. RESULTS: Although prescribers received no training on the design changes, prescribers were able to resolve redesigned alerts more efficiently (median (IQR): 56 (47) s) compared to the original alerts (85 (71) s; p=0.015). In addition, prescribers rated redesigned alerts significantly higher than original alerts across several dimensions of satisfaction. Redesigned alerts led to a modest but significant reduction in workload (p=0.042) and significantly reduced the number of prescribing errors per prescriber (median (range): 2 (1-5) compared to original alerts: 4 (1-7); p=0.024). DISCUSSION: Aspects of the redesigned alerts that likely contributed to better prescribing include design modifications that reduced usability-related errors, providing clinical data closer to the point of decision, and displaying alert text in a tabular format. Displaying alert text in a tabular format may help prescribers extract information quickly and thereby increase responsiveness to alerts. CONCLUSIONS: This simulation study provides evidence that applying human factors design principles to medication alerts can improve usability and prescribing outcomes