The extinct, giant giraffid Sivatherium giganteum: skeletal reconstruction and body mass estimation

Sivatherium giganteum is an extinct giraffid from the Plio–Pleistocene boundary of the Himalayan foothills. To date, there has been no rigorous skeletal reconstruction of this unusual mammal. Historical and contemporary accounts anecdotally state that Sivatherium rivalled the African elephant in terms of its body mass, but this statement has never been tested. Here, we present a three-dimensional composite skeletal reconstruction and calculate a representative body mass estimate for this species using a volumetric method. We find that the estimated adult body mass of 1246 kg (857—1812 kg range) does not approach that of an African elephant, but confirms that Sivatherium was certainly a large giraffid, and may have been the largest ruminant mammal that has ever existed. We contrast this volumetric estimate with a bivariate scaling estimate derived from Sivatherium's humeral circumference and find that there is a discrepancy between the two. The difference implies that the humeral circumference of Sivatherium is greater than expected for an animal of this size, and we speculate this may be linked to a cranial shift in centre of mass

Simulations of Ductile Fracture in an Idealized Ship Grounding Scenario Using Phenomenological Damage and Cohesive Zone Models

Two complementary simulation methodologies for ductile fracture in large sheet metal components are presented and evaluated in this paper. The first approach is based on the phenomenological dilatational plasticity-damage model developed by Woelke and Abboud [68], which accounts for pressure-dependent volumetric damage growth through a scalar damage variable. The damage function represents phenomenologically micromechanical changes the material undergoes during the process of necking. Secondly, the cohesive zone model with an opening mode traction-separation law is employed to simulate the same ductile fracture problems accounting for significant variation of the multiaxial stress state along the crack path. Both methods are examined as to their capabilities to reproduce and predict the outcome of large scale experimental fracture tests of welded and unwelded ductile plates subjected to large-scale penetration, simulating an idealized ship grounding (Alsos and Amdahl, [1, 2]). The results of the current study indicate that, with appropriate calibration, both approaches can be successfully employed to simulate ductile fracture in structural components under multiaxial stress. The advantages and shortcomings of each approach is discussed from the point of view of post-test numerical investigation as well as its predictive capabilities as an engineering tool.Engineering and Applied Science

Academic Resilience: A Retrospective Study of Adults With Learning Difficulties

This article reports qualitative analyses of two sets of retrospective interviews with adults with learning difficulties. The purpose of the study was to examine the high school experiences of these adults from a holistic perspective to understand possible factors that contributed to one group staying in school and the other group leaving school early. One set of interviews was conducted with adults who had returned to complete high school at an adult learning center (the late successful group). The second set of interviews was conducted with the early successful group, adults who had completed high school during adolescence. Interview questions focused on interests, friends, and general aspects of the high school experience. Analyses yielded three themes: intrapersonal support, interpersonal support, and institutional support. These data suggest that schools might act in a number of ways to counter the high rate of early leaving by adolescents with learning disabilities, including building strong teacher-student relationships, using students' interests to develop curricula and structured activities, and fostering a sense of purpose.Cet article expose deux analyses qualitatives de deux séries d'entrevues rétrospectives auprès d'adultes présentant des difficultés d'apprentissage. Le but de l'étude consistait à examiner, dans une perspective holistique, les expériences qu'avaient vécues ces adultes quand ils étaient au secondaire, pour ensuite déterminer si des facteurs avaient influencé le fait que certaines personnes étaient restées à l'école alors que d'autres avaient décroché. Une série d'entrevues a été effectuée auprès d'adultes qui avaient repris leurs études secondaires dans un institut d'apprentissage pour adultes (le groupe de diplômés tardifs). La deuxième série d'entrevues a eu lieu auprès d'adultes ayant terminé l'école secondaire alors qu'ils étaient adolescents dégroupe de diplômés précoces). Les questions d'entrevues portaient sur les intérêts, les amis et les aspects généraux de leur expérience à l'école secondaire. Trois thèmes sont ressortis des analyses: l'appui intrapersonnel, l'appui interpersonnel et l'appui institutionnel. Ces données donnent à penser que les écoles pourraient intervenir de diverses façons pour contrer le taux élevé de décrochage chez les adolescents ayant des difficultés d'apprentissage. Parmi ces stratégies notons la création de rapports solides entre les enseignants et les élèves, le développement de programmes d'études et d'activités structurées basés sur les intérêts des élèves et le fait de favoriser des buts bien précis

Response of Metallic Pyramidal Lattice Core Sandwich Panels to High Intensity Impulsive Loading in Air

Small scale explosive loading of sandwich panels with low relative density pyramidal lattice cores has been used to study the large scale bending and fracture response of a model sandwich panel system in which the core has little stretch resistance. The panels were made from a ductile stainless steel and the practical consequence of reducing the sandwich panel face sheet thickness to induce a recently predicted beneficial fluid–structure interaction (FSI) effect was investigated. The panel responses are compared to those of monolithic solid plates of equivalent areal density. The impulse imparted to the panels was varied from 1.5 to 7.6 kPa s by changing the standoff distance between the center of a spherical explosive charge and the front face of the panels. A decoupled finite element model has been used to computationally investigate the dynamic response of the panels. It predicts panel deformations well and is used to identify the deformation time sequence and the face sheet and core failure mechanisms. The study shows that efforts to use thin face sheets to exploit FSI benefits are constrained by dynamic fracture of the front face and that this failure mode is in part a consequence of the high strength of the inertially stabilized trusses. Even though the pyramidal lattice core offers little in-plane stretch resistance, and the FSI effect is negligible during loading by air, the sandwich panels are found to suffer slightly smaller back face deflections and transmit smaller vertical component forces to the supports compared to equivalent monolithic plates.Engineering and Applied Science

A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains

BACKGROUND: Noncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller RNA species, larger noncoding transcripts are also thought to be highly abundant in mammalian cells. To search for large noncoding RNAs that might control gene expression or mRNA metabolism, we used Affymetrix expression arrays to identify polyadenylated RNA transcripts displaying nuclear enrichment. RESULTS: This screen identified no more than three transcripts; XIST, and two unique noncoding nuclear enriched abundant transcripts (NEAT) RNAs strikingly located less than 70 kb apart on human chromosome 11: NEAT1, a noncoding RNA from the locus encoding for TncRNA, and NEAT2 (also known as MALAT-1). While the two NEAT transcripts share no significant homology with each other, each is conserved within the mammalian lineage, suggesting significant function for these noncoding RNAs. NEAT2 is extraordinarily well conserved for a noncoding RNA, more so than even XIST. Bioinformatic analyses of publicly available mouse transcriptome data support our findings from human cells as they confirm that the murine homologs of these noncoding RNAs are also nuclear enriched. RNA FISH analyses suggest that these noncoding RNAs function in mRNA metabolism as they demonstrate an intimate association of these RNA species with SC35 nuclear speckles in both human and mouse cells. These studies show that one of these transcripts, NEAT1 localizes to the periphery of such domains, whereas the neighboring transcript, NEAT2, is part of the long-sought polyadenylated component of nuclear speckles. CONCLUSION: Our genome-wide screens in two mammalian species reveal no more than three abundant large non-coding polyadenylated RNAs in the nucleus; the canonical large noncoding RNA XIST and NEAT1 and NEAT2. The function of these noncoding RNAs in mRNA metabolism is suggested by their high levels of conservation and their intimate association with SC35 splicing domains in multiple mammalian species

Allele-Specific Methylation Occurs at Genetic Variants Associated with Complex Disease

We hypothesize that the phenomenon of allele-specific methylation (ASM) may underlie the phenotypic effects of multiple variants identified by Genome-Wide Association studies (GWAS). We evaluate ASM in a human population and document its genome-wide patterns in an initial screen at up to 380,678 sites within the genome, or up to 5% of the total genomic CpGs. We show that while substantial inter-individual variation exists, 5% of assessed sites show evidence of ASM in at least six samples; the majority of these events (81%) are under genetic influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with variants linked to complex disease. Finally, focusing on autoimmune phenotypes, we extend this initial screen to confirm the association of cis-regulated ASM with multiple complex disease-associated variants in an independent population using next-generation bisulfite sequencing. These four variants are implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434), Celiac disease (rs2762051), Crohn's disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875) and height (rs6569648). Our results suggest cis-regulated ASM may provide a mechanistic link between the non-coding genetic changes and phenotypic variation observed in these diseases and further suggests a route to integrating DNA methylation status with GWAS results

Glycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-(13)C2 glucose.

Increased 'anaerobic' glucose metabolism is observed after traumatic brain injury (TBI) attributed to increased glycolysis. An alternative route is the pentose phosphate pathway (PPP), which generates putatively protective and reparative molecules. To compare pathways we employed microdialysis to perfuse 1,2-(13)C2 glucose into the brains of 15 TBI patients and macroscopically normal brain in six patients undergoing surgery for benign tumors, and to simultaneously collect products for nuclear magnetic resonance (NMR) analysis. (13)C enrichment for glycolytic 2,3-(13)C2 lactate was the median 5.4% (interquartile range (IQR) 4.6-7.5%) in TBI brain and 4.2% (2.4-4.4%) in 'normal' brain (P<0.01). The ratio of PPP-derived 3-(13)C lactate to glycolytic 2,3-(13)C2 lactate was median 4.9% (3.6-8.2%) in TBI brain and 6.7% (6.3-8.9%) in 'normal' brain. An inverse relationship was seen for PPP-glycolytic lactate ratio versus PbtO2 (r=-0.5, P=0.04) in TBI brain. Thus, glycolytic lactate production was significantly greater in TBI than 'normal' brain. Several TBI patients exhibited PPP-lactate elevation above the 'normal' range. There was proportionally greater PPP-derived lactate production with decreasing PbtO2. The study raises questions about the roles of the PPP and glycolysis after TBI, and whether they can be manipulated to achieve a better outcome. This study is the first direct comparison of glycolysis and PPP in human brain.We gratefully acknowledge financial support as follows. Study support: Medical Research Council (Grant Nos. G0600986 ID79068 and G1002277 ID98489) and National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme). Authors’ support: I.J. – Medical Research Council (Grant no. G1002277 ID 98489) and National Institute for Health Research Biomedical Research Centre, Cambridge; K.L.H.C. – National Institute for Health Research Biomedical Research Centre, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme); C.G. – the Canadian Institute of Health Research; A.H. – Medical Research Council/ Royal College of Surgeons of England Clinical Research Training Fellowship (Grant no. G0802251) and Raymond and Beverly Sackler Fellowship; D.K.M. and J.D.P. - National Institute for Health Research Senior Investigator Awards; P.J.H. – National Institute for Health Research Professorship, Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship.This is the accepted manuscript version. The final version is available from the Nature Publishing Group http://www.nature.com/jcbfm/journal/v35/n1/full/jcbfm2014177a.html

Cord compression defined by MRI is the driving factor behind the decision to operate in Degenerative Cervical Myelopathy despite poor correlation with disease severity.

OBJECTIVES:The mainstay treatment for Degenerative Cervical Myelopathy (DCM) is surgical decompression. Not all cases, however, are suitable for surgery. Recent international guidelines advise surgery for moderate to severe disease as well as progressive mild disease. The goal of this study was to examine the factors in current practice that drive the decision to operate in DCM. STUDY DESIGN:Retrospective cohort study. METHODS:1 year of cervical spine MRI scans (N = 1123) were reviewed to identify patients with DCM with sufficient clinical documentation (N = 39). Variables at surgical assessment were recorded: age, sex, clinical signs and symptoms of DCM, disease severity, and quantitative MRI measures of cord compression. Bivariate correlations were used to compare each variable with the decision to offer the patient an operation. Subsequent multivariable analysis incorporated all significant bivariate correlations. RESULTS:Of the 39 patients identified, 25 (64%) were offered an operation. The decision to operate was significantly associated with narrower non-pathological canal and cord diameters as well as cord compression ratio, explaining 50% of the variance. In a multivariable model, only cord compression ratio was significant (p = 0.017). Examination findings, symptoms, functional disability, disease severity, disease progression, and demographic factors were all non-significant. CONCLUSIONS:Cord compression emerged as the main factor in surgical decision-making prior to the publication of recent guidelines. Newly identified predictors of post-operative outcome were not significantly associated with decision to operate