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Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Lebanon has a need for innovative approaches to increase access to mental health care to meet the country's current high demand. E-mental health has been included in its national mental health strategy while in parallel the World Health Organization has produced an online intervention called ‘Step-by-Step’ to treat symptoms of depression that is being tested in Lebanon over the coming years.
The primary aim of this study is to conduct bottom-up, community-driven qualitative cognitive interviewing from a multi-stakeholder perspective to inform the cultural adaptation of an Internet-delivered mental health intervention based on behavioural activation in Lebanon.
National Mental Health Programme staff conducted a total of 11 key informant interviews with three mental health professionals, six front-line workers in primary health care centres (PHCCs) and two community members. Also, eight focus group discussions, one with seven front-line workers and seven others with a total of 66 community members (Lebanese, Syrians and Palestinians) were conducted in several PHCCs to inform the adaptation of Step-by-Step. Results were transcribed and analysed thematically by the project coordinator and two research assistants.
Feedback generated from the cognitive interviewing mainly revolved around amending the story, illustrations and the delivery methods to ensure relevance and sensitivity to the local context. The results obtained have informed major edits to the content of Step-by-Step and also to the model of provision. Notably, the intervention was made approximately 30% shorter; it includes additional videos of content alongside the originally proposed comic book-style delivery; there is less emphasis on total inactivity as a symptom of low mood and more focus on enjoyable activities to lift mood; the story and ways to contact participants to provide support were updated in line with local gender norms; and many of the suggested or featured activities have been revised in line with suggestions from community members.
These findings promote and advocate the use of community-driven adaptation of evidence-based psychological interventions. Some of the phenomena recorded mirror findings from other research about barriers to care seeking in the region and so changes made to the intervention should be useful in improving utility and uptake of ‘Step-by-Step’.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
The SkyMapper Transient survey (SMT) is exploring variability in the southern sky by performing (a) a rolling search to discover and study supernovæ, and (b) a Target of Opportunity programme that uses the robotic SkyMapper Telescope at Siding Spring Observatory. The supernova survey is obtaining a non-targeted sample of Type Ia supernovæ (SNe Ia) at low redshifts, z < 0.1, and studying other interesting transients found with the search strategy. We have a Target of Opportunity programme with an automatic response mechanism to search for optical counterparts to gravitational-wave and fast radio-burst events; it benefits from SkyMapper’s large field of view of 5.7 sq. deg. and a rapid data reduction pipeline.
We present first results of the SMT survey. The SMT pipeline can process and obtain potential candidates within 12 hours of observation. It disentangles real transients from processing artefacts using a machine-learning algorithm. To date, SMT has discovered over 60 spectroscopically confirmed supernovæ, several peculiar objects, and over 40 SNe Ia including one (SNIa 2016hhd) which was found within the first few days of explosion. We have also participated in searches for optical counterparts of gravitational waves, fast radio bursts and other transients, and have published observations of the optical counterpart of the gravitational-wave event GW170817. We also participate in coordinated observations with the Deeper Wider Faster programme, and the Kepler K2 cosmology project.
We present new far-IR and submillimeter broad-band and spectroscopic results on the dense and very luminous cores of massive star formation regions. The best-studied region, W51, contains one core around the source IRS2 and another around W51 MAIN. Our earlier submillimeter continuum mapping has shown that these two cores are very massive (2-4 × 104 M⊙) and have average densities of nH2 ∼ 105 over their inner parsec. New far-IR maps show that both cores are very luminous (L(MAIN) ∼2 × 106 L⊙; L(IRS2) ∼4x106 L⊙). Observations of the (1,1) and (2,1) transitions of NH3, indicate high kinetic temperatures (200-400 K) for the quiescent gas in the inner several arc seconds (0.1 pc) of both cores. Spectroscopy of the 370 μm J = 7 → 6 and 163 μm J = 16 → 15 transitions of CO toward the cores allows us to characterize the hot high velocity material seen previously on the H2O maser transitions and not readily visible in the low J transitions of CO. The high velocity flow in IRS2 is ∼ 60 times more massive than the very similar outflow in the ∼ 30 times less luminous Orion/KL core. The mass loss rate is ∼ 30 times greater than in Orion. Additional observations of W49 allow us to draw a few general conclusions about the most luminous star formation regions in our galaxy: (1) The luminous cores are 102-103 more massive than the Orion core with the same density. (2) Outflows and warm regions in these cores have physical conditions similar to those in their less luminous counterparts but far more mass is involved in the flows.
A general description of ablation polygons is given and variations from widely distributed regions are examined. After discussion of the conditions in which they most frequently develop, possible explanations are considered, leading to the conclusion that the polygons result from ablation by turbulence in the surrounding air, and that the dirt fringes to the polygons may be explained by the “normal trajectory” theory.
Homotopy type theory is an extension of Martin-Löf type theory, based on a correspondence with homotopy theory and higher category theory. In homotopy type theory, the propositional equality type is proof-relevant, and corresponds to paths in a space. This allows for a new class of datatypes, called higher inductive types, which are specified by constructors not only for points but also for paths. In this paper, we consider a programming application of higher inductive types. Version control systems such as Darcs are based on the notion of patches—syntactic representations of edits to a repository. We show how patch theory can be developed in homotopy type theory. Our formulation separates formal theories of patches from their interpretation as edits to repositories. A patch theory is presented as a higher inductive type. Models of a patch theory are given by maps out of that type, which, being functors, automatically preserve the structure of patches. Several standard tools of homotopy theory come into play, demonstrating the use of these methods in a practical programming context.
The Center for Astrophysical Research in Antarctica conducts various educational outreach programs as part of its mission as a National Science Foundation Science and Technology Center. The method behind the outreach programs is one of forging partnerships between Center researchers and other educational organisations. The main program serves primary and secondary students in Chicago. The core of the program is called Space Explorers and is targeted at high school students. These students attend a summer residential institute at the University of Chicago’s Yerkes Observatory. The high school Space Explorers then extend the reach of the program during the academic year by teaching in primary schools using a portable planetarium. The Center also pursues many other outreach activities and is in the process of forming an Antarctic Education Alliance.
During the past three years the measurement of stellar radial velocities has formed an important part of the spectroscopic programme of most observatories possessing large telescopes. As observations are carried to fainter and fainter stars and the number of observable objects increases rapidly, a natural development has been the selection of special groups and types of stars, the radial velocities of which will aid in the solution of certain specific problems. Illustrations are the studies of the O, B and A type stars made at the Dominion Astrophysical, the Lick, and the Simeis Observatories, of the members of the galactic clusters at the Lick Observatory, and of the fainter Cepheid variables and early-type stars with strong interstellar lines at the Mount Wilson Observatory.
In November 1934 the President circulated a letter to the members of the Commission as follows:
Since the 1932 meeting the following projects have been completed, or are nearing completion:
(1)The publication of many lists of trigonometric parallaxes.
(2)The determination of the spectroscopic parallaxes of 4179 stars at Mt Wilson Observatory by Adams, Joy and Humason.
(3)A discussion of systematic errors of trigonometric parallaxes by van Maanen and a re-discussion in the Astrophysical Journal of the same material by Mitchell and by Sterne.
(4)The compilation of a second Yale Catalogue to include parallaxes completed before the end of 1934.
(5)Substantial progress on the proper motions of 32,000 stars by Boss and his associates at the Dudley Observatory.
(6)The publication at the Radcliffe Observatory of the proper motions of 32,000 stars from photographs on 115 Selected Areas.
(7)The completion of the dynamical parallaxes of 2000 stars.
(8)The completion of the proper motions of 18,000 stars derived from parallax plates at the Leander McCormick Observatory.
(9)The publication at the Yale Observatory of the proper motions of 40,000 stars with a probable error less than 0”.010 determined from photographs by re-observing in zones the Astronomische Gesellschaft stars.
(10)The determination of the proper motions of 50,000 stars in the Southern Hemisphere by Luyten from Harvard photographs.
In November 1931 the President circulated a letter to the members of the Commission which in part was as follows:
In view of the fact that it is now over a quarter of a century since Schlesinger by photography began to determine trigonometric parallaxes by a long focus telescope, and fifteen years since Adams and Kohlschütter derived the first spectroscopic parallaxes, it would seem appropriate to take stock of our present position and to make plans for future development.
Will you be good enough, therefore, to furnish such statements concerning the following topics as are appropriate to the work of your observatory?
The internet has altered how people engage with each other in myriad ways, including offering opportunities for people to act distrustfully. This fascinating set of essays explores the question of trust in computing from technical, socio-philosophical, and design perspectives. Why has the identity of the human user been taken for granted in the design of the internet? What difficulties ensue when it is understood that security systems can never be perfect? What role does trust have in society in general? How is trust to be understood when trying to describe activities as part of a user requirement program? What questions of trust arise in a time when data analytics are meant to offer new insights into user behavior and when users are confronted with different sorts of digital entities? These questions and their answers are of paramount interest to computer scientists, sociologists, philosophers and designers confronting the problem of trust.