1,651 research outputs found
The effect of density and feature size on mechanical properties of isostructural metaffic foams produced by additive manufacturing
Simple models describing the relationship between basic mechanical properties and the relative density of various types of porous metals (such as foams, sponges and lattice structures) are well established. Carefully evaluating these relationships experimentally is challenging, however, because of the stochastic structure of foams and the fact that it is difficult to systematically isolate density changes from variations in other factors, such as pore size and pore distribution. Here a new method for producing systematic sets of stochastic foams is employed based on electron beam melting (EBM) additive manufacturing (AM). To create idealised structures, structural blueprints were reverse-engineered by inverting X-ray computed tomographs of a randomly packed bed of glass beads. This three-dimensional structure was then modified by computer to create five foams of different relative density Ïr, but otherwise consistent structure. Yield strength and Youngâs modulus have been evaluated in compression tests and compared to existing models for foams. A power of 3 rather than a squared dependence of stiffness on relative density is found, which agrees with a recent model derived for replicated foams. A similar power of 3 relation was found for yield strength. Further analysis of the strength of nominally fully dense rods of different diameters built by EBM AM suggest that surface defects mean that the minimum size of features that can be created by EBM with similar strengths to machined samples is âŒ1 mm
Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)
Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis.
Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B.
Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype
The interview as narrative ethnography : seeking and shaping connections in qualitative research.
Acts of counter-subjectification in qualitative research are always present but are often submerged in accounts that seek to locate the power of subjectification entirely with the researcher. This is particularly so when talking to people about sensitive issues. Based on an interview-based study of infertility and reproductive disruption among British Pakistanis in Northeast England, we explore how we, as researchers, sought and were drawn into various kinds of connections with the study participants; connections that were actively and performatively constructed through time. The three of us that conducted interviews are all female academics with Ph.Ds in anthropology, but thereafter our backgrounds, life stories and experiences diverge in ways that intersected with those of our informants in complex and shifting ways. We describe how these processes shaped the production of narrative accounts and consider some of the associated analytical and ethical implications
Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis
The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction
Prevalence, incidence, and associated risk factors of tuberculosis in children with HIV living in the UK and Ireland (CHIPS): a cohort study
BACKGROUND: Tuberculosis is the most common serious co-infection in people living with HIV worldwide, but little is known about its incidence in HIV-infected children living in high-resource settings with low tuberculosis prevalence. We aimed to assess the incidence and prevalence of tuberculosis in children with HIV living in the UK and Ireland to understand rates, risk factors, and outcomes of the disease in this group. METHODS: We did an analysis of children enrolled in CHIPS, an observational multicentre cohort of children receiving HIV care in the UK and Ireland. We assessed characteristics and prevalence of tuberculosis at baseline, measured incidence of disease through the follow-up period using the CHIPS database, and calculated associated risk factors in these children with multivariable logistic and Cox regression models. FINDINGS: Between Jan 1, 1996, to Sept 18, 2014, data for 1848 children with 14â761 years of follow-up were reported to CHIPS. 57 (3%) children were diagnosed with tuberculosis: 29 children had tuberculosis at presentation (prevalent tuberculosis) and 29 had the disease diagnosed during follow-up (incident tuberculosis), including one child with recurrent tuberculosis events. Median age at diagnosis was 9 years (IQR 5-12). 25 (43%) children had pulmonary tuberculosis, 24 (41%) had extrapulmonary tuberculosis with or without pulmonary involvement, and the remainder (n=9; 16%) had unspecified-site tuberculosis. The overall incidence rate for the follow-up period was 196 cases per 100â000 person-years (95% CI 137-283). In our multivariable model, tuberculosis at presentation was associated with more severe WHO immunological stage at baseline (odds ratio 0·25, 95% CI 0·08-0·74; p=0·0331; for none vs severe) and being born abroad (odds ratio 0·28, 0·10-0·73; p=0·0036; for UK and Ireland vs abroad). Incident tuberculosis was associated with time-updated more severe WHO immunological stage (hazard ratio 0·15, 95% CI 0·06-0·41; p=0·0056; for none vs severe) and older age at baseline (1·11, 0·47-2·63; p=0·0027; for age >10 years vs 5-9 years). INTERPRETATION: Tuberculosis rates in HIV-infected children in the UK and Ireland were higher than those reported in the general paediatric population. Further study is warranted of tuberculosis screening and preventive treatment for children at high-risk of this disease to avoid morbidity and mortality in this population. FUNDING: NHS England, PENTA Foundation
X-ray Tomography Characterisation of Lattice Structures Processed by Selective Electron Beam Melting
Metallic lattice structures intentionally contain open porosity; however, they can also contain unwanted closed porosity within the structural members. The entrained porosity and defects within three different geometries of Ti-6Al-4V lattices, fabricated by Selective Electron Beam Melting (SEBM), is assessed from X-ray computed tomography (CT) scans. The results suggest that horizontal struts that are built upon loose powder show particularly high (~20 Ă 10â3 vol %) levels of pores, as do nodes at which many (in our case 24) struts meet. On the other hand, for struts more closely aligned (0° to 54°) to the build direction, the fraction of porosity appears to be much lower (~0.17 Ă 10â3%) arising mainly from pores contained within the original atomised powder particles
Understanding signaling cascades in melanoma
Understanding regulatory pathways involved in melanoma development and progression has advanced significantly in recent years. It is now appreciated that melanoma is the result of complex changes in multiple signaling pathways that affect growth control, metabolism, motility and the ability to escape cell death programs. Here we review the major signaling pathways currently known to be deregulated in melanoma with an implication to its development and progression. Among these pathways are Ras, B-Raf, MEK, PTEN, phosphatidylinositol-3 kinase (PI3Ks) and Akt which are constitutively activated in a significant number of melanoma tumors, in most cases due to genomic change. Other pathways discussed in this review include the [Janus kinase/signal transducer and activator of transcription (JAK/STAT), transforming growth factor-beta pathways which are also activated in melanoma, although the underlying mechanism is not yet clear. As a paradigm for remodeled signaling pathways, melanoma also offers a unique opportunity for targeted drug development.Fil: Lopez Bergami, Pablo Roberto. Sanford-burnham Medical Research Institute; Estados Unidos. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de BiologĂa y Medicina Experimental. FundaciĂłn de Instituto de BiologĂa y Medicina Experimental. Instituto de BiologĂa y Medicina Experimental; ArgentinaFil: Fitchmann, B. Sanford-burnham Medical Research Institute; Estados UnidosFil: Ronai, ZeÂŽev. Sanford-burnham Medical Research Institute; Estados Unido
Convergence and divergence in gesture repertoires as an adaptive mechanism for social bonding in primates
A key challenge for primates living in large, stable social groups is managing social relationships. Chimpanzee gestures may act as a time-efficient social bonding mechanism, and the presence (homogeneity) and absence (heterogeneity) of overlap in repertoires in particular may play an important role in social bonding. However, how homogeneity and heterogeneity in the gestural repertoire of primates relate to social interaction is poorly understood. We used social network analysis and generalized linear mixed modelling to examine this question in wild chimpanzees. The repertoire size of both homogeneous and heterogeneous visual, tactile and auditory gestures was associated with the duration of time spent in social bonding behaviour, centrality in the social bonding network and demography. The audience size of partners who displayed similar or different characteristics to the signaller (e.g. same or opposite age or sex category) also influenced the use of homogeneous and heterogeneous gestures. Homogeneous and heterogeneous gestures were differentially associated with the presence of emotional reactions in response to the gesture and the presence of a change in the recipientâs behaviour. Homogeneity and heterogeneity of gestural communication play a key role in maintaining a differentiated set of strong and weak social relationships in complex, multilevel societies
The European Photon Imaging Camera on XMM-Newton: The MOS Cameras
The EPIC focal plane imaging spectrometers on XMM-Newton use CCDs to record
the images and spectra of celestial X-ray sources focused by the three X-ray
mirrors. There is one camera at the focus of each mirror; two of the cameras
contain seven MOS CCDs, while the third uses twelve PN CCDs, defining a
circular field of view of 30 arcmin diameter in each case. The CCDs were
specially developed for EPIC, and combine high quality imaging with spectral
resolution close to the Fano limit. A filter wheel carrying three kinds of
X-ray transparent light blocking filter, a fully closed, and a fully open
position, is fitted to each EPIC instrument. The CCDs are cooled passively and
are under full closed loop thermal control. A radio-active source is fitted for
internal calibration. Data are processed on-board to save telemetry by removing
cosmic ray tracks, and generating X-ray event files; a variety of different
instrument modes are available to increase the dynamic range of the instrument
and to enable fast timing. The instruments were calibrated using laboratory
X-ray beams, and synchrotron generated monochromatic X-ray beams before launch;
in-orbit calibration makes use of a variety of celestial X-ray targets. The
current calibration is better than 10% over the entire energy range of 0.2 to
10 keV. All three instruments survived launch and are performing nominally in
orbit. In particular full field-of-view coverage is available, all electronic
modes work, and the energy resolution is close to pre-launch values. Radiation
damage is well within pre-launch predictions and does not yet impact on the
energy resolution. The scientific results from EPIC amply fulfil pre-launch
expectations.Comment: 9 pages, 11 figures, accepted for publication in the A&A Special
Issue on XMM-Newto
Effects of mountain gorilla foraging activities on the productivity of their food plant species
Mountain gorillas subsist principally on foliage from the dense herbaceous understorey that is found throughout most of their habitat in the Virunga Volcanoes region. Their foraging activities cause considerable structural damage to this vegetation. Those plant species that are quantitatively most important in the gorillas' diet respond to this damage by increasing primary productivity. At a sample of spots at which gorillas had fed, these species showed significantly higher growth rates over a 6-month interval than they did at nearby spots that had not been touched by the gorillas. Stem densities of herbaceous food species at feeding spots increased markedly both in comparison to their original values and to values for the same species at untouched spots. As a result, spots at which gorillas have fed are likely to become very attractive as future feeding spots. It is unlikely that gorillas âmanageâ their habitat in any specific fashion, largely because they do not have exclusive use of their home ranges. Their activities appear to maintain habitat productivity over the short term, on a time scale relevant to patterns of area revisits by social groups, and may contribute to long term beneficial alterations of regularly used areas, however. Effects of the type reported here may have been an important aspect of the adaptation by gorillas to terrestrial folivory. RĂSUMEĂ Les gorilles de montagne s'alimentent principalement de feuillages dans le sous-bois herbacĂ dense prĂsent presque partout dans leur habitat de la rĂgion des volcans Virunga. Leurs activitĂs alimentaires causent des dommages structurels considĂrables Ă cette vĂgĂtation. Les plantes des espĂces qui sont quantitativement les plus importants dans le rĂgime du gorille rĂagissent Ă ces dĂgats en augmentant leur productivitĂ primaire. Aux postes Ăchantillons oĂ les gorilles se sont nourris, ces espĂces prĂsentent des taux de croissance significantivement supĂrieurs sur un intervalle de six mois, par rapport aux postes voisins qui n'ont pas ĂtĂ touchĂs par les gorilles. Les densitĂs de tiges des espĂces herbacĂes appĂtĂes aux postes de nourrissage augmentent nettement aussi bien en comparaison avec leurs valeurs antĂrieures qu'avec celles de ces mÄmes espĂces dans des stations non touchĂes. En consĂquence, les postes oĂ les gorilles se sont nourris ont plus de chance de devenir des futurs postes de nourrissage trĂs attractifs. Il est peu probable que les gorilles âgĂrentâ leur habitat d'une quelconque faĂon, surtout parce qu'ils n'ont pas l'utilisation exclusive de leur domaine vital. Leurs activitĂs semblent maintenir Ă court terme la productivitĂ de leur habitat, sur une Ăchelle de temps comprenant les visites successives de groupes sociaux, et peuvent contribuer Ă long terme Ă des altĂrations bĂnĂfiques pour ces zones rĂguliĂrement frĂquentĂes. Des effets du type rapportĂ ici peuvent avoir ĂtĂ un ĂlĂment important de l'adaptation des gorilles Ă la folivorie terrestre.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75171/1/j.1365-2028.1987.tb01102.x.pd
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