1,243 research outputs found

    PMD34: COMPARISON OF SF-36 SUMMARY AND PREFERENCE-BASED UTILITY SCORES ACROSS GROUPS DIFFERING IN DISEASE SEVERITY: RESULTS FROM THE MEDICARE HEALTH OUTCOMES SURVEY

    Get PDF

    Capturing Marangoni flow via synchrotron imaging of selective laser melting

    Get PDF
    Marangoni flow has a substantial influence on the quality of components fabricated via laser powder bed fusion (LPBF). However, Marangoni flow in melt pools is rarely quantified due to the opacity of liquid metals and the necessity for in situ evaluation. Here we report the findings of high-temporal-resolution synchrotron x-ray radiography experiments tracking the flow in the melt-pool. Dense, highly attenuating tungsten carbide particles are seeded within an elemental powder blend of aluminium and copper of varying composition. Due to the extremely high temporal resolution of greater than 50 kfps at the 31-ID-B beamline at the Advanced Photon Source, USA, we can track the position of tracer particles from frame to frame. This data provides valuable process guidance for optimising mixing and informs the development and validation of multiphysics models

    Methylated DNA recognition during the reversal of epigenetic silencing is regulated by cysteine and cerine residues in the Epstein-Barr Virus lytic switch protein

    Get PDF
    Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with various malignancies, including Burkitt's lymphoma and nasopharyngeal carcinoma. Like all herpesviruses, the EBV life cycle alternates between latency and lytic replication. During latency, the viral genome is largely silenced by host-driven methylation of CpG motifs and, in the switch to the lytic cycle, this epigenetic silencing is overturned. A key event is the activation of the viral BRLF1 gene by the immediate-early protein Zta. Zta is a bZIP transcription factor that preferentially binds to specific response elements (ZREs) in the BRLF1 promoter (Rp) when these elements are methylated. Zta's ability to trigger lytic cycle activation is severely compromised when a cysteine residue in its bZIP domain is mutated to serine (C189S), but the molecular basis for this effect is unknown. Here we show that the C189S mutant is defective for activating Rp in a Burkitt's lymphoma cell line. The mutant is compromised both in vitro and in vivo for binding two methylated ZREs in Rp (ZRE2 and ZRE3), although the effect is striking only for ZRE3. Molecular modeling of Zta bound to methylated ZRE3, together with biochemical data, indicate that C189 directly contacts one of the two methyl cytosines within a specific CpG motif. The motif's second methyl cytosine (on the complementary DNA strand) is predicted to contact S186, a residue known to regulate methyl-ZRE recognition. Our results suggest that C189 regulates the enhanced interaction of Zta with methylated DNA in overturning the epigenetic control of viral latency. As C189 is conserved in many bZIP proteins, the selectivity of Zta for methylated DNA may be a paradigm for a more general phenomenon

    A multi-exon deletion within WWOX is associated with a 46,XY disorder of sex development

    Get PDF
    Disorders of sex development (DSD) are congenital conditions where chromosomal, gonad or genital development is atypical. In a significant proportion of 46,XY DSD cases it is not possible to identify a causative mutation, making genetic counseling difficult and potentially hindering optimal treatment. Here, we describe the analysis of a 46,XY DSD patient that presented at birth with ambiguous genitalia. Histological analysis of the surgically removed gonads showed bilateral undifferentiated gonadal tissue and immature testis, both containing malignant germ cells. We screened genomic DNA from this patient for deletions and duplications using an Illumina whole-genome SNP microarray. This analysis revealed a heterozygous deletion within the WWOX gene on chromosome 16, removing exons 6-8. Analysis of parental DNA showed that the deletion was inherited from the mother. cDNA analysis confirmed that the deletion maintained the reading frame, with exon 5 being spliced directly onto exon 9. This deletion is the first description of a germline rearrangement affecting the coding sequence of WWOX in humans. Previously described Wwox knockout mouse models showed gonadal abnormalities, supporting a role for WWOX in human gonad development

    The effects of sprint vs. resisted sled-based training; an 8-week in-season randomized control intervention in elite rugby league players

    Get PDF
    The aim of the current study was to examine the efficacy of resisted sled-based training compared to traditional unresisted sprint training in terms of mediating improvements in speed, agility, and power during an eight-week period of in-season training in elite rugby league players. Participants were randomly separated into either resisted sled or traditional sprint-based training groups and they completed an eight-week in-season training block with training prescribed based on the group to which they were assigned. Measures of 5 m, 10 m, and 20 m sprint times in addition to countermovement jump height and 505-agility test time were measured at baseline, four-weeks and eight-weeks. For sprint-based outcomes, although both groups improved significantly, there were no statistical differences between the two training methods. However, at the eight-week time point there were significant improvements in 505-agility test (sprint group: baseline = 2.45 and eight-weeks = 2.42 s/sled group: baseline = 2.43 and eight-weeks = 2.37 s) and countermovement jump (sprint group: baseline = 39.18 and eight-weeks = 39.49 cm/sled group: baseline = 40.43 and eight-weeks = 43.07 cm) performance in the sled training group. Therefore, the findings from this investigation may be important to strength and conditioning coaches working in an elite rugby league in that resisted sled training may represent a more effective method of sprint training prescription

    Sinter formation during directed energy deposition of titanium alloy powders

    Get PDF
    During directed energy deposition (DED) additive manufacturing, powder agglomeration and sintering can occur outside of the melt pool when using titanium alloy powders. Using in situ synchrotron radiography we investigate the mechanisms by which sintering of Ti6242 powder occurs around the pool, performing a parametric study to determine the influence of laser power and stage traverse speed on sinter build-up. The results reveal that detrimental sinter can be reduced using a high laser power or increased stage traverse speed, although the latter also reduces deposition layer thickness. The mechanism of sinter formation during DED was determined to be in-flight heating of the powder particles in the laser beam. Calculations of particle heating under the processing conditions explored in this study confirm that powder particles can reasonably exceed 700 °C, the threshold for Ti surface oxide dissolution, and thus the powder is prone to sintering if not incorporated into the melt pool. The build-up of sinter powder layer on deposit surfaces led to lack of fusion pores. To mitigate sinter formation and its detrimental effects on DED component quality, it is essential that the powder delivery spot area is smaller than the melt pool, ensuring most powder lands in the melt pool

    Differential modulation of corticospinal excitability during haptic sensing of 2-D patterns vs. textures

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Recently, we showed a selective enhancement in corticospinal excitability when participants actively discriminated raised 2-D symbols with the index finger. This extra-facilitation likely reflected activation in the premotor and dorsal prefrontal cortices modulating motor cortical activity during attention to haptic sensing. However, this parieto-frontal network appears to be finely modulated depending upon whether haptic sensing is directed towards material or geometric properties. To examine this issue, we contrasted changes in corticospinal excitability when young adults (n = 18) were engaged in either a roughness discrimination on two gratings with different spatial periods, or a 2-D pattern discrimination of the relative offset in the alignment of a row of small circles in the upward or downward direction.</p> <p>Results</p> <p>A significant effect of task conditions was detected on motor evoked potential amplitudes, reflecting the observation that corticospinal facilitation was, on average, ~18% greater in the pattern discrimination than in the roughness discrimination.</p> <p>Conclusions</p> <p>This differential modulation of corticospinal excitability during haptic sensing of 2-D patterns vs. roughness is consistent with the existence of preferred activation of a visuo-haptic cortical dorsal stream network including frontal motor areas during spatial vs. intensive processing of surface properties in the haptic system.</p

    The decline of the Serengeti Thomson's gazelle population

    Full text link
    The population of Thomson's gazelles in the Serengeti National Park, Tanzania has declined by almost two thirds over a 13 year period. In the early 1970s, numbers stood at 0.66 million animals but had decreased to less than 0.25 million animals in 1985 as estimated by 5 different censuses using two different counting techniques. Predation, interspecific competition and disease are all factors that could have contributed to this decline, and at least one of these factors, predation, could now prevent the Thomson's gazelle population from increasing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47770/1/442_2004_Article_BF00376974.pd
    corecore