501 research outputs found

    Physical and dynamical characterisation of low Delta-V NEA (190491) 2000 FJ10

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    We investigated the physical properties and dynamical evolution of Near Earth Asteroid (NEA) (190491) 2000 FJ10 in order to assess the suitability of this accessible NEA as a space mission target. Photometry and colour determination were carried out with the 1.54 m Kuiper Telescope and the 10 m Southern African Large Telescope during the object's recent favourable apparition in 2011-12. During the earlier 2008 apparition, a spectrum of the object in the 6000-9000 Angstrom region was obtained with the 4.2 m William Herschel Telescope. Interpretation of the observational results was aided by numerical simulations of 1000 dynamical clones of 2000 FJ10 up to 10^6 yr in the past and in the future. The asteroid's spectrum and colours determined by our observations suggest a taxonomic classification within the S-complex although other classifications (V, D, E, M, P) cannot be ruled out. On this evidence, it is unlikely to be a primitive, relatively unaltered remnant from the early history of the solar system and thus a low priority target for robotic sample return. Our photometry placed a lower bound of 2 hrs to the asteroid's rotation period. Its absolute magnitude was estimated to be 21.54+-0.1 which, for a typical S-complex albedo, translates into a diameter of 130+-20 m. Our dynamical simulations show that it has likely been an Amor for the past 10^5 yr. Although currently not Earth-crossing, it will likely become so during the period 50 - 100 kyr in the future. It may have arrived from the inner or central Main Belt > 1 Myr ago as a former member of a low-inclination S-class asteroid family. Its relatively slow rotation and large size make it a suitable destination for a human mission. We show that ballistic Earth-190491-Earth transfer trajectories with Delta-V < 2 km s^-1 at the asteroid exist between 2052 and 2061.Comment: 2 Tables, 11 Figures, accepted for publication in Astronomy & Astrophysic

    Pharmacological and Toxicological Properties of the Potent Oral γ-Secretase Modulator BPN-15606.

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    Alzheimer's disease (AD) is characterized neuropathologically by an abundance of 1) neuritic plaques, which are primarily composed of a fibrillar 42-amino-acid amyloid-β peptide (Aβ), as well as 2) neurofibrillary tangles composed of aggregates of hyperphosporylated tau. Elevations in the concentrations of the Aβ42 peptide in the brain, as a result of either increased production or decreased clearance, are postulated to initiate and drive the AD pathologic process. We initially introduced a novel class of bridged aromatics referred tγ-secretase modulatoro as γ-secretase modulators that inhibited the production of the Aβ42 peptide and to a lesser degree the Aβ40 peptide while concomitantly increasing the production of the carboxyl-truncated Aβ38 and Aβ37 peptides. These modulators potently lower Aβ42 levels without inhibiting the γ-secretase-mediated proteolysis of Notch or causing accumulation of carboxyl-terminal fragments of APP. In this study, we report a large number of pharmacological studies and early assessment of toxicology characterizing a highly potent γ-secretase modulator (GSM), (S)-N-(1-(4-fluorophenyl)ethyl)-6-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methylpyridazin-3-amine (BPN-15606). BPN-15606 displayed the ability to significantly lower Aβ42 levels in the central nervous system of rats and mice at doses as low as 5-10 mg/kg, significantly reduce Aβ neuritic plaque load in an AD transgenic mouse model, and significantly reduce levels of insoluble Aβ42 and pThr181 tau in a three-dimensional human neural cell culture model. Results from repeat-dose toxicity studies in rats and dose escalation/repeat-dose toxicity studies in nonhuman primates have designated this GSM for 28-day Investigational New Drug-enabling good laboratory practice studies and positioned it as a candidate for human clinical trials

    Prospective, multicentre study of external ventricular drainage-related infections in the UK and Ireland.

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    OBJECTIVES: External ventricular drain (EVD) insertion is a common neurosurgical procedure. EVD-related infection (ERI) is a major complication that can lead to morbidity and mortality. In this study, we aimed to establish a national ERI rate in the UK and Ireland and determine key factors influencing the infection risk. METHODS: A prospective multicentre cohort study of EVD insertions in 21 neurosurgical units was performed over 6 months. The primary outcome measure was 30-day ERI. A Cox regression model was used for multivariate analysis to calculate HR. RESULTS: A total of 495 EVD catheters were inserted into 452 patients with EVDs remaining in situ for 4700 days (median 8 days; IQR 4-13). Of the catheters inserted, 188 (38%) were antibiotic-impregnated, 161 (32.5%) were plain and 146 (29.5%) were silver-bearing. A total of 46 ERIs occurred giving an infection risk of 9.3%. Cox regression analysis demonstrated that factors independently associated with increased infection risk included duration of EVD placement for ≥8 days (HR=2.47 (1.12-5.45); p=0.03), regular sampling (daily sampling (HR=4.73 (1.28-17.42), p=0.02) and alternate day sampling (HR=5.28 (2.25-12.38); p<0.01). There was no association between catheter type or tunnelling distance and ERI. CONCLUSIONS: In the UK and Ireland, the ERI rate was 9.3% during the study period. The study demonstrated that EVDs left in situ for ≥8 days and those sampled more frequently were associated with a higher risk of infection. Importantly, the study showed no significant difference in ERI risk between different catheter types

    PELATIHAN PEMASARAN DIGITAL BAGI SANTRI PONDOK PASANTREN ABU DZAR DESA SUKAWANGI KABUPATEN BOGOR PAOPINSI JAWA BARAT

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    The PKM activity was carried out aiming to see the self-ability of the students of the Abu Dzar Islamic Boarding School through their self-concept, interest in particular in the entrepreneurship they pioneered. Therefore, it is necessary to make efforts to cultivate and develop skills in supporting these entrepreneurial activities. The problems raised were that they had never received briefing on how to market their products, especially online, and also the anxiety of the students to start a business. The method of implementing this service is carried out in several activities, namely (a). Preparation phase includes: (1). Initial survey (2) Consolidation and determination of target locations, (3). Preparation of training materials/materials. The results of this activity are very useful for the Abu Dzar Islamic Boarding School Santri in adding insight and knowledge about digital marketing. . Keywords: digital marketing, MSM

    Protocol for a multicentre randomiSed controlled TRial of IntraVEnous immunoglobulin versus standard therapy for the treatment of transverse myelitis in adults and children (STRIVE)

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    Introduction Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord which causes motor and sensory disturbance and limited recovery in 50% of patients. Standard treatment is steroids, and patients with more severe disease appear to respond to plasma exchange (PLEX). Intravenous immunoglobulin (IVIG) has also been used as an adjunct to steroids, but evidence is lacking. We propose the first randomised control trial in adults and children, to determine the benefit of additional treatment with IVIG. Methods and analysis 170 adults and children aged over 1 year with acute first episode TM or neuromyelitis optica (with myelitis) will be recruited over a 2.5-year period and followed up for 12 months. Participants randomised to the control arm will receive standard therapy of intravenous methylprednisolone (IVMP). The intervention arm will receive the above standard therapy, plus additional IVIG. Primary outcome will be a 2-point improvement on the American Spinal Injury Association (ASIA) Impairment scale at 6 months postrandomisation by blinded assessors. Additional secondary and tertiary outcome measures will be collected: ASIA motor and sensory scales, Kurtzke expanded disability status scale, International Spinal Cord Injury (SCI) Bladder/Bowel Data Set, Client Services Receipt Index, Pediatric Quality of Life Inventory, EQ-5D, SCI Pain and SCI Quality of Life Data Sets. Biological samples will be biobanked for future studies. After 6-months' follow-up of the first 52 recruited patients futility analysis will be carried out. Health economics analysis will be performed to calculate cost-effectiveness. After 6 months’ recruitment futility analysis will be performed

    B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells

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    B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6–secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell–specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6–sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6–producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell–driven pathogenesis in T cell–mediated autoimmune disease such as EAE and MS

    PENGELOALAAN SDM UNTUK PENGEMBANGAN WISATA GOA GUDAWANG

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    Pengabdian Kepada Masyarakat ini bertujuan untuk membantu mengembangkan wisata Goa Gudawang dari segi manajemen kususnya pengelolaan SDM. Permasalahan yang diangkat mengenai pengelolaan SDM wisata Goa Gudawang adalah kurangnya SDM yang professional sehingga tujuan organisasi sulit dicapai. Metode pelaksanaan pengabdian ini dilakukan dalam beberapa kegiatan yaitu (a). Tahap Persiapan meliputi : (1). Survey awal (2) Pemantapan dan penentuan lokasi sasaran, (3). Penyusunan bahan/materi pelatihan. Hasil kegiatan ini sangat bermanfaat bagi pengelola wisata Goa Gudawang dalam menambah wawasan serta pengetahuan mengenai manajemen strategi.Kata Kunci: Manajemen SDM, Pengelol

    Spatial distribution of micrometre‐scale porosity and permeability across the damage zone of a reverse‐reactivated normal fault in a tight sandstone : Insights from the Otway Basin, SE Australia

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    This research forms part of a PhD project supported by the Australian Research Council [Discovery Project DP160101158] and through an Australian Government Research Training Program Scholarship. Dave Healy acknowledges the support of the Natural Environment Research Council (NERC, UK) through the award NE/N003063/1 ‘Quantifying the Anisotropy of Permeability in Stressed Rock’. This study was also funded by scholarships from the Petroleum Exploration Society of Australia and the Australian Petroleum Production and Exploration Association. We thank Gordon Holm for preparing thin sections and Colin Taylor for carrying out particle size measurements and mercury injection capillary pressure analyses. Aoife McFadden and David Kelsey from Adelaide Microscopy, Braden Morgan, and Sophie Harland are acknowledged for their assistance with laboratory work. Field assistants James Hall, Rowan Hansberry, and Lachlan Furness are also gratefully acknowledged for their assistance with sample collection. Discussions with Ian Duddy on the mineralogy of the Eumeralla Formation are also greatly appreciated. This forms TRaX record 416.Peer reviewedPublisher PD

    The Effect Of Competency On Employee Performance at PT. Steelforce Indonesia In Jakarta

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    This research aims to determine the effect of competence on employee performance at PT. Steelforce Indonesia in Jakarta. The method used is explanatory research with a sample of 54 respondents. The analysis technique uses statistical analysis with regression testing, correlation, determination and hypothesis testing. The results of this research of the competency variable obtained an average score of 3,761 with good criteria. Employee performance variables obtained an average score of 3.783 with good criteria. Competence has a positive and significant effect on employee performance with a regression equation value of Y = 10.976 + 0.714X, and a correlation coefficient value of 0.787 or has a strong level of relationship with a determination value of 61.9%. Hypothesis testing obtained a significance of 0.000 &lt;0.05. Keywords: Competence; Competency; Employee Performanc
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