Search

Mammals have an evolutionary history spanning hundreds of millions of years. Today, mammals represent one of the most diverse groups of tetrapod vertebrates. In particular, they present a great postural diversity. The humerus adopts different positions: small mammals have a "crouched" posture with a quasi-horizontal humerus, while in the largest species, the humerus is more vertical. Some monotremes have more transversely oriented humeri similar to those of reptiles. The forelimb of moles is also modified in relation to their burrowing lifestyle. This postural diversity is accompanied by an important microanatomical disparity. Indeed, the bones of the appendicular skeleton support the weight of the body and are subjected to various forces that partly shape their external and internal morphology. We show here how geometric and microanatomical parameters measured in cross-section such as the polar section modulus or the position of the medullo-cortical transition can be related to posture. Using statistical methods that take phylogeny into account, we develop a postural model from a sample of humerus cross-sections belonging to 41 species of extant mammals. Our model can be used by palaeontologists to infer the posture of extinct synapsids. As an example, we infer the posture of two emblematic taxa: Dimetrodon natalis and Peratherium cuvieri. The results of the analysis indicate a sprawling posture for Dimetrodon and a crouched posture for Peratherium. This work contributes to unravel the complex interaction between phylogeny, humeral microanatomy and geometry, body mass, lifestyle and posture in mammals. [ABSTRACT FROM AUTHOR]

It is accepted that non-avian theropod dinosaurs, with their long muscular tails and small forelimbs, had a centre-of-mass close to the hip, while extant birds, with their reduced tails and enlarged wings have their mass centred more cranially. Transition between these states is considered crucial to two key innovations in the avian locomotor system: crouched bipedalism and powered flight. Here we use image-based models to challenge this dichotomy. Rather than a phylogenetic distinction between 'dinosaurian' and 'avian' conditions, we find terrestrial versus volant taxa occupy distinct regions of centre-of-mass morphospace consistent with the disparate demands of terrestrial bipedalism and flight. We track this decoupled evolution of body shape and mass distribution through bird evolution, including the origin of centre-of-mass positions more advantageous for flight and major reversions coincident with terrestriality. We recover modularity in the evolution of limb proportions and centre-of-mass that suggests fully crouched bipedalism evolved after powered flight. Here, the authors track the evolution of mass distribution through bird evolution challenging suggested coupling between body shape and centre-of-mass position, and instead showing that crouched bipedalism evolved after powered flight. [ABSTRACT FROM AUTHOR]

Drug-induced cytopenias are a prevalent and significant issue that worsens clinical outcomes and hinders the effective treatment of cancer. While reductions in blood cell numbers are classically associated with traditional cytotoxic chemotherapies, they also occur with newer targeted small molecules and the factors that determine the hematotoxicity profiles of oncologic drugs are not fully understood. Here, we explore why some Aurora kinase inhibitors cause preferential neutropenia. By studying drug responses of healthy human hematopoietic cells in vitro and analyzing existing gene expression datasets, we provide evidence that the enhanced vulnerability of neutrophil-lineage cells to Aurora kinase inhibition is caused by early developmental changes in ATP-binding cassette (ABC) transporter expression. These data show that hematopoietic cell-intrinsic expression of ABC transporters may be an important factor that determines how some Aurora kinase inhibitors affect the bone marrow. Patients treated with Aurora kinase inhibitors experience dose-limiting neutropenia while other cytopenias are rare. Here, Chou et al. show that this cell-type specific side effect is partly explained by loss of drug efflux pump expression during neutrophil differentiation. [ABSTRACT FROM AUTHOR]

Atelectasis is a frequent clinical condition, yet knowledge is limited and controversial on its biological contribution towards lung injury. We assessed the regional proteomics of atelectatic versus normally-aerated lung tissue to test the hypothesis that immune and alveolar-capillary barrier functions are compromised by purely atelectasis and dysregulated by additional systemic inflammation (lipopolysaccharide, LPS). Without LPS, 130 proteins were differentially abundant in atelectasis versus aerated lung, mostly (n = 126) with less abundance together with negatively enriched processes in immune, endothelial and epithelial function, and Hippo signaling pathway. Instead, LPS-exposed atelectasis produced 174 differentially abundant proteins, mostly (n = 108) increased including acute lung injury marker RAGE and chemokine CCL5. Functional analysis indicated enhanced leukocyte processes and negatively enriched cell–matrix adhesion and cell junction assembly with LPS. Additionally, extracellular matrix organization and TGF-β signaling were negatively enriched in atelectasis with decreased adhesive glycoprotein THBS1 regardless of LPS. Concordance of a subset of transcriptomics and proteomics revealed overlap of leukocyte-related gene-protein pairs and processes. Together, proteomics of exclusively atelectasis indicates decreased immune response, which converts into an increased response with LPS. Alveolar-capillary barrier function-related proteomics response is down-regulated in atelectasis irrespective of LPS. Specific proteomics signatures suggest biological mechanistic and therapeutic targets for atelectasis-associated lung injury. [ABSTRACT FROM AUTHOR]

Biomechanical models and simulations of musculoskeletal function rely on accurate muscle parameters, such as muscle masses and lines of action, to estimate force production potential and moment arms. These parameters are often obtained through destructive techniques (i.e., dissection) in living taxa, frequently hindering the measurement of other relevant parameters from a single individual, thus making it necessary to combine multiple specimens and/or sources. Estimating these parameters in extinct taxa is even more challenging as soft tissues are rarely preserved in fossil taxa and the skeletal remains contain relatively little information about the size or exact path of a muscle. Here we describe a new protocol that facilitates the estimation of missing muscle parameters (i.e., muscle volume and path) for extant and extinct taxa. We created three-dimensional volumetric reconstructions for the hindlimb muscles of the extant Nile crocodile and extinct stem-archosaur Euparkeria, and the shoulder muscles of an extant gorilla to demonstrate the broad applicability of this methodology across living and extinct animal clades. Additionally, our method can be combined with surface geometry data digitally captured during dissection, thus facilitating downstream analyses. We evaluated the estimated muscle masses against physical measurements to test their accuracy in estimating missing parameters. Our estimated muscle masses generally compare favourably with segmented iodine-stained muscles and almost all fall within or close to the range of observed muscle masses, thus indicating that our estimates are reliable and the resulting lines of action calculated sufficiently accurately. This method has potential for diverse applications in evolutionary morphology and biomechanics. [ABSTRACT FROM AUTHOR]

Purpose: Acute respiratory distress syndrome (ARDS) is accompanied by a dysfunctional immune-inflammatory response following lung injury, including during coronavirus disease 2019 (COVID-19). Limited causal biomarkers exist for ARDS development. We sought to identify novel genetic susceptibility targets for ARDS to focus further investigation on their biological mechanism and therapeutic potential. Methods: Meta-analyses of ARDS genome-wide association studies were performed with 1250 cases and 1583 controls in Europeans, and 387 cases and 387 controls in African Americans. The functionality of novel loci was determined in silico using multiple omics approaches. The causality of 114 factors potentially involved in ARDS development was assessed using Mendelian Randomization analysis. Results: There was distinct genetic heterogeneity in ARDS between Europeans and African Americans. rs7967111 at 12p13.2 was functionally associated with ARDS susceptibility in Europeans (odds ratio = 1.38; P = 2.15 × 10–8). Expression of two genes annotated at this locus, BORCS5 and DUSP16, was dynamic but ultimately decreased during ARDS development, as well as downregulated in immune cells alongside COVID-19 severity. Causal inference implied that comorbidity of inflammatory bowel disease and elevated levels of C-reactive protein and interleukin-10 causally increased ARDS risk, while vitamin D supplementation and vasodilator use ameliorated risk. Conclusion: Our findings suggest a novel susceptibility locus in ARDS pathophysiology that implicates BORCS5 and DUSP16 as potentially acting in immune-inflammatory processes. This locus warrants further investigation to inform the development of therapeutic targets and clinical care strategies for ARDS, including those induced by COVID-19. [ABSTRACT FROM AUTHOR]

Purpose: The naturally-occurring omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and inexpensive, making it an attractive anti-cancer intervention. However, EPA has only modest anti-colorectal cancer (CRC) activity, when used alone. Both cyclooxygenase (COX) isoforms metabolise EPA and are over-expressed in CRC cells. We investigated whether COX inhibition increases the sensitivity of CRC cells to growth inhibition by EPA. Methods: A panel of 18 human and mouse CRC cell lines was used to characterize the differential sensitivity of CRC cells to the growth inhibitory effects of EPA. The effect of CRISPR-Cas9 genetic deletion and pharmacological inhibition of COX-1 and COX-2 on the anti-cancer activity of EPA was determined using in vitro and in vivo models. Results: Genetic ablation of both COX isoforms increased sensitivity of CT26 mouse CRC cells to growth inhibition by EPA in vitro and in vivo. The non-selective COX inhibitor aspirin and the selective COX-2 inhibitor celecoxib increased sensitivity of several human and mouse CRC cell lines to EPA in vitro. However, in a MC38 mouse CRC cell tumour model, with dosing that mirrored low-dose aspirin use in humans, thereby producing significant platelet COX-1 inhibition, there was ineffective intra-tumoral COX-2 inhibition by aspirin and no effect on EPA sensitivity of MC38 cell tumours. Conclusion: Cyclooxygenase inhibition by non-steroidal anti-inflammatory drugs represents a therapeutic opportunity to augment the modest anti-CRC activity of EPA. However, intra-tumoral COX inhibition is likely to be critical for this drug-nutrient interaction and careful tissue pharmacodynamic profiling is required in subsequent pre-clinical and human studies. [ABSTRACT FROM AUTHOR]

The use of coupling agents to enhance the thermal conductivity of composites of epoxy and boron nitride (BN) has been investigated. Two types of BN particles, lightly aggregated platelets with an average size of 6 µm and agglomerates with an average size of 120 µm, have been used. Different proportions of these BN particles, up to a volume percentage of approximately 34%, were mixed with a stoichiometric epoxy–thiol system and cured either isothermally or non-isothermally. The cure kinetics was investigated by differential scanning calorimetry, and the thermal conductivity of isothermally fully cured samples was measured. The effect of surface treatment of the particles was extensively investigated, with respect to the characteristics of the particles themselves, the cure kinetics and the thermal conductivity of the cured composites. The BN particles were treated with a silane coupling agent, both with and without previously treating the BN with a sodium hydroxide solution. Infrared spectroscopy and thermogravimetric analysis were used to assess whether or not the silane had been attached to the BN particles, and the effect of the surface treatment on the cure kinetics was studied. Although the cure kinetics suggested that the surface treatment was more effective for the 6 µm particles than for the 120 µm agglomerates, it did not generally lead to an increase in the thermal conductivity, while scanning electron microscopy showed that the coupling agent was not attached to the BN particles. It is concluded that truly platelet-shaped particles are necessary for effective surface treatment. [ABSTRACT FROM AUTHOR]

The thymus is a primary lymphoid organ, essential for T cell maturation and selection. There has been long-standing interest in processes underpinning thymus generation and the potential to manipulate it clinically, because alterations of thymus development or function can result in severe immunodeficiency and autoimmunity. Here, we identify epithelial-mesenchymal hybrid cells, capable of long-term expansion in vitro, and able to reconstitute an anatomic phenocopy of the native thymus, when combined with thymic interstitial cells and a natural decellularised extracellular matrix (ECM) obtained by whole thymus perfusion. This anatomical human thymus reconstruction is functional, as judged by its capacity to support mature T cell development in vivo after transplantation into humanised immunodeficient mice. These findings establish a basis for dissecting the cellular and molecular crosstalk between stroma, ECM and thymocytes, and offer practical prospects for treating congenital and acquired immunological diseases. The thymus is essential for T cell maturation and selection, and thymic defects result in severe immune problems. Here the authors identify a thymus cell population that is expandable in vitro, and can repopulate natural thymic matrix to generate tissue that supports mature T cell development in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Thermally conducting and electrically insulating materials have been prepared by filling an epoxy–thiol system with boron nitride (BN) particles of different shapes (platelets and agglomerates) and sizes (from 2 to 180 μm), and hence with different specific surface areas. The cure kinetics has been studied by differential scanning calorimetry in both non-isothermal and isothermal modes, and it has been shown that there is a systematic dependence of the cure kinetics on the BN content, the cure reaction generally being retarded by the addition of the BN particles. For filler loadings greater than about 30 vol%, the retardation of the cure, in both isothermal and non-isothermal mode, appears also to decrease as the specific surface area decreases. For the smallest (2 μm) platelets, which have a significantly higher specific surface area (10 m2 g−1), the retardation is particularly pronounced, and this aspect is rationalized in terms of the activation energy and frequency factor of the reaction. The thermal conductivity of the cured epoxy–thiol–BN composites has been measured using the transient hot bridge method and is found to increase in the usual way with increasing BN content for all the particle types and sizes. For the platelets, the thermal conductivity increases with increasing particle size, mirroring the effect of BN content on the cure kinetics. The agglomerates, though, give the highest values of thermal conductivity, contrary to what might be expected in the light of their specific surface areas. Scanning electron microscopy of the fracture surfaces of the cured composites has been used to show that the interface between epoxy matrix and filler particles is better for the agglomerates. This, together with the reduced interfacial area, explains their higher thermal conductivity. [ABSTRACT FROM AUTHOR]

Extant Crocodylia are exceptional because they employ almost the full range of quadrupedal footfall patterns ("gaits") used by mammals; including asymmetrical gaits such as galloping and bounding. Perhaps this capacity evolved in stem Crocodylomorpha, during the Triassic when taxa were smaller, terrestrial, and long-legged. However, confusion about which Crocodylia use asymmetrical gaits and why persists, impeding reconstructions of locomotor evolution. Our experimental gait analysis of locomotor kinematics across 42 individuals from 15 species of Crocodylia obtained 184 data points for a wide velocity range (0.15–4.35 ms−1). Our results suggest either that asymmetrical gaits are ancestral for Crocodylia and lost in the alligator lineage, or that asymmetrical gaits evolved within Crocodylia at the base of the crocodile line. Regardless, we recorded usage of asymmetrical gaits in 7 species of Crocodyloidea (crocodiles); including novel documentation of these behaviours in 5 species (3 critically endangered). Larger Crocodylia use relatively less extreme gait kinematics consistent with steeply decreasing athletic ability with size. We found differences between asymmetrical and symmetrical gaits in Crocodylia: asymmetrical gaits involved greater size-normalized stride frequencies and smaller duty factors (relative ground contact times), consistent with increased mechanical demands. Remarkably, these gaits did not differ in maximal velocities obtained: whether in Alligatoroidea or Crocodyloidea, trotting or bounding achieved similar velocities, revealing that the alligator lineage is capable of hitherto unappreciated extreme locomotor performance despite a lack of asymmetrical gait usage. Hence asymmetrical gaits have benefits other than velocity capacity that explain their prevalence in Crocodyloidea and absence in Alligatoroidea—and their broader evolution. [ABSTRACT FROM AUTHOR]

Reconstructing the locomotion of extinct vertebrates offers insights into their palaeobiology and helps to conceptualize major transitions in vertebrate evolution1-4. However, estimating the locomotor behaviour of a fossil species remains a challenge because of the limited information preserved and the lack of a direct correspondence between form and function5,6. The evolution of advanced locomotion on land—that is, locomotion that is more erect, balanced and mechanically power-saving than is assumed of anamniote early tetrapods—has previously been linked to the terrestrialization and diversification of amniote lineages7. To our knowledge, no reconstructions of the locomotor characteristics of stem amniotes based on multiple quantitative methods have previously been attempted: previous methods have relied on anatomical features alone, ambiguous locomotor information preserved in ichnofossils or unspecific modelling of locomotor dynamics. Here we quantitatively examine plausible gaits of the stem amniote Orobates pabsti, a species that is known from a complete body fossil preserved in association with trackways8. We reconstruct likely gaits that match the footprints, and investigate whether Orobates exhibited locomotor characteristics that have previously been linked to the diversification of crown amniotes. Our integrative methodology uses constraints derived from biomechanically relevant metrics, which also apply to extant tetrapods. The framework uses in vivo assessment of locomotor mechanics in four extant species to guide an anatomically informed kinematic simulation of Orobates, as well as dynamic simulations and robotics to filter the parameter space for plausible gaits. The approach was validated using two extant species that have different morphologies, gaits and footprints. Our metrics indicate that Orobates exhibited more advanced locomotion than has previously been assumed for earlier tetrapods7,9, which suggests that advanced terrestrial locomotion preceded the diversification of crown amniotes. We provide an accompanying website for the exploration of the filters that constrain our simulations, which will allow revision of our approach using new data, assumptions or methods. Quantitative explorations using biomechanics and robotics of the gait of Orobates, a stem amniote, indicate that the development of relatively erect, power-saving and balanced locomotion preceded the diversification of crown amniotes [ABSTRACT FROM AUTHOR]

Objectives: Diffusion-weighted MRI provides information regarding body water movement following death, which may be an imaging marker of post-mortem interval (time since death; PMI) or maceration (degree of tissue degradation during intra-uterine retention) in perinatal deaths. Our aim was to evaluate the relationship between maceration, PMI and body organ apparent diffusion coefficient (ADC) values in a cohort of subjects across a wide gestational range.Materials: Whole body post-mortem MRI with diffusion-weighted imaging (DWI) sequences were performed at 1.5 T, with b values of 0, 500 and 1000 mm2/s. Mean ADC values were calculated from regions of interest (ROIs) placed in the lungs, myocardium, spleen, renal cortex, liver and psoas muscle by two independent readers. Multivariable regression analysis was performed against PMI, gestational age, post-mortem weight, maceration score and gender.Results: Eighty perinatal deaths were imaged with mean gestational age of 32 weeks (18-41 weeks), of which 49 (61.3%) were male. The mean PMI was 8 days (1-18 days). Maceration scores were statistically significant predictive factors for ADC values in all included body organs except the lungs, but PMI was not a predictor for ADC values in any body organ. In the absence of maceration (n = 14), PMI was not statistically associated with ADC values in any of the body areas. The ratio of agreement in the majority of body areas was close to 1 (range between 0.95 and 1.10).Conclusion: Maceration, not PMI, is significantly associated with ADC values in perinatal deaths. Further research is needed to understand organ-specific changes in the post-mortem period. [ABSTRACT FROM AUTHOR]

Although poor tool support is often blamed for the low uptake of model-driven engineering (MDE), recent studies have shown that adoption problems are as likely to be down to social and organizational factors as with tooling issues. This article discusses the impact of tools on MDE adoption and practice and does so while placing tooling within a broader organizational context. The article revisits previous data on MDE use in industry (19 in-depth interviews with MDE practitioners) and reanalyzes that data through the specific lens of MDE tools in an attempt to identify and categorize the issues that users had with the tools they adopted. In addition, the article presents new data: 20 new interviews in two specific companies-and analyzes it through the same lens. A key contribution of the paper is a loose taxonomy of tool-related considerations, based on empirical industry data, which can be used to reflect on the tooling landscape as well as inform future research on MDE tools. [ABSTRACT FROM AUTHOR]

Mechanical integrity of the interfacial region between ceramic coatings and substrates is critical to high performance coated mechanical components and manufacturing tools. Mechanical failure of the coating/substrate interfacial region often leads to catastrophic failure of the coated system as a whole. Despite extensive research over the past two decades, quantitative assessment of the mechanical response of coating/substrate interfacial regions remains a challenge. The lack of reliable protocols for measuring the mechanical response of coating/substrate interfacial regions quantitatively hampers the understanding of key factors controlling the mechanical integrity of coating/substrate interfaces. In this paper, we describe a new micro-pillar testing protocol for quantitative measurement of critical stresses for inducing shear failure of interfacial regions in ceramic-coating/metal-adhesion-layer/substrate systems. We observe significant differences in the critical stress for shear failure of interfacial regions in CrN/Cu/Si, CrN/Cr/Si, and CrN/Ti/Si systems. The present testing protocol has general applicability to a wide range of coating/interlayer/substrate systems. [ABSTRACT FROM AUTHOR]

Perinatal autopsy practice is undergoing a state of change with the introduction of evidence-based cross-sectional imaging, driven primarily by parental choice. In particular, the introduction of post mortem magnetic resonance imaging (PMMR) has helped to advance less-invasive perinatal autopsy in the United Kingdom (UK) and Europe. However, there are limitations to PMMR and other imaging techniques which need to be overcome, particularly with regard to imaging very small fetuses. Imaging is also now increasingly used to investigate particular deaths in childhood, such as suspected non-accidental injury (NAI) and sudden unexpected death in infancy (SUDI). Here we focus on current topical developments the field, with particular emphasis on the application of imaging to perinatal autopsy, and pediatric forensic deaths. Different imaging modalities and their relative advantages and disadvantages are discussed, together with other benefits of more advanced cross-sectional imaging which currently lie in the research domain. Whilst variations in local imaging service provision and need may determine different practice patterns, and access to machines and professionals with appropriate expertise and experience to correctly interpret the findings may limit current practices, we propose that gold standard perinatal and pediatric autopsy services would include complete PMMR imaging prior to autopsy, with PMCT in suspicious childhood deaths. This approach would provide maximal diagnostic yield to the pathologist, forensic investigator and most importantly, the parents. [ABSTRACT FROM AUTHOR]

Recent advances in geometric morphometrics provide improved techniques for extraction of biological information from shape and have greatly contributed to the study of ecomorphology and morphological evolution. However, the vertebral column remains an under-studied structure due in part to a concentration on skull and limb research, but most importantly because of the difficulties in analysing the shape of a structure composed of multiple articulating discrete units (i.e. vertebrae). Here, we have applied a variety of geometric morphometric analyses to three-dimensional landmarks collected on 19 presacral vertebrae to investigate the influence of potential ecological and functional drivers, such as size, locomotion and prey size specialisation, on regional morphology of the vertebral column in the mammalian family Felidae. In particular, we have here provided a novel application of a method-phenotypic trajectory analysis (PTA)-that allows for shape analysis of a contiguous sequence of vertebrae as functionally linked osteological structures. Our results showed that ecological factors influence the shape of the vertebral column heterogeneously and that distinct vertebral sections may be under different selection pressures. While anterior presacral vertebrae may either have evolved under stronger phylogenetic constraints or are ecologically conservative, posterior presacral vertebrae, specifically in the post-T10 region, show significant differentiation among ecomorphs. Additionally, our PTA results demonstrated that functional vertebral regions differ among felid ecomorphs mainly in the relative covariation of vertebral shape variables (i.e. direction of trajectories, rather than in trajectory size) and, therefore, that ecological divergence among felid species is reflected by morphological changes in vertebral column shape. [ABSTRACT FROM AUTHOR]

The development of polymer layered silicate (PLS) nanocomposites goes back over 20 years now, and yet they still have not achieved their full potential. A principal reason for this is the difficulty of obtaining a truly exfoliated nanostructure. The fabrication procedure for such PLS nanocomposites based upon epoxy resin includes several stages, including dispersion of the clay in the resin, intercalation of the resin into the clay galleries, and finally curing of the nanocomposite system. Many attempts have been made to improve the degree of exfoliation in the final nanostructure by modifying the procedures involved in these fabrication stages, and the usual approach is to examine the nanostructure, by techniques such as small-angle X-ray scattering (SAXS) and transmission electron microscopy (TEM), as a function of the fabrication procedure. We show here, however, that thermal analytical techniques, and in particular differential scanning calorimetry, can complement the techniques of SAXS and TEM in the search for ways in which to achieve improved degrees of exfoliation in PLS nanocomposites based upon epoxy resin. [ABSTRACT FROM AUTHOR]

In the original publication of the article [ABSTRACT FROM AUTHOR]

It has been shown, for three different polymer layered silicate (PLS) nanocomposite systems, how differential scanning calorimetry (DSC) can identify the different reactions of homopolymerisation and of crosslinking that occur in the intra- and extra-gallery regions of these nanocomposites, respectively, and hence how DSC can be used to assess the cure conditions for optimising their nanostructure. The PLS nanocomposites are based upon: (i) diglycidyl ether of bisphenol-A (DGEBA) cured with a polyoxypropylene diamine; (ii) DGEBA cured with an -NH terminated hyperbranched polymer (HBP); and (iii) tri-glycidyl p-amino phenol (TGAP) cured with a diamine. In each case, the existence of both intra- and extra-gallery reactions in the DSC cure curves, and whether they occur simultaneously or sequentially, and in what order, are identified and correlated with the nanostructure as observed by small angle X-ray scattering and transmission electron microscopy. In particular, it is shown that the intra-gallery reaction must precede the extra-gallery for significant exfoliation to occur. In accordance with this scenario, the TGAP/diamine system displays the greatest degree of exfoliation, the DGEBA/diamine system the least, with the DGEBA/HBP system intermediate. For those systems in which significant exfoliation occurs, the DSC cure curves also allow the optimum cure conditions, such as the isothermal cure temperature, to be determined. [ABSTRACT FROM AUTHOR]

In this paper, we review recent results on hybrid silicon mode-locked lasers with a focus on low phase noise optical pulse generation. Taking a high level design approach to lowering phase noise, we show the need for long on-chip optical delay lines for mode-locked lasers to reach and overcome material limits. Key results include demonstration of the longest (cavity length 9 cm) integrated on-chip mode locked laser, 14 dB reduction of Lorentzian noise on a 20 GHz radio-frequency (RF) signal, and greater than 55 dB optical supermode noise suppression using harmonically mode locked long cavity laser, 10 GHz passively mode locked laser with 15 kHz linewidth using on-chip all optical feedback stabilization. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop and validate a novel method of identifying scoliosis on total-body dual energy X-ray absorptiometric (DXA) scans. Scoliosis was identified on total-body DXA scans by triaging to distinguish true curves from positioning errors, followed by a modified Ferguson method to measure angles. Precision was assessed on 174 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), who underwent repeat DXA scans at age 15, 2-6 weeks apart. In addition, precision of angle estimation was evaluated on 20 scans measured five times. To evaluate accuracy, angle size was compared to spinal radiographs in 13 individuals with known scoliosis. Subsequently, this method was applied to estimate scoliosis prevalence rates and curve patterns from DXA scans previously obtained in 7,298 ALSPAC participants at age 9 and 5,122 at age 15. There was substantial agreement in identifying those with scoliosis on repeat DXA scans taken 2-6 weeks apart (kappa 0.74, 95 % CI 0.59-0.89). Of repeat angle measures, 95 % were within 5°. Angle size was underestimated by approximately 40 %. Prevalence of scoliosis ≥10° in the ALSPAC was 0.3 % at age 9 and 3.5 % at age 15 and was higher in girls at both time points. The mean ± SD curve size was 12 ± 4° at age 9 years and 15 ± 7° at age 15. We have developed and validated a novel method for identifying scoliosis from DXA scans. Comparison with prevalence data using more established techniques suggests our method provides valid estimates of scoliosis prevalence in population-based cohorts. [ABSTRACT FROM AUTHOR]

Locomotion in living birds (Neornithes) has two remarkable features: feather-assisted flight, and the use of unusually crouched hindlimbs for bipedal support and movement. When and how these defining functional traits evolved remains controversial. However, the advent of computer modelling approaches and the discoveries of exceptionally preserved key specimens now make it possible to use quantitative data on whole-body morphology to address the biomechanics underlying this issue. Here we use digital body reconstructions to quantify evolutionary trends in locomotor biomechanics (whole-body proportions and centre-of-mass position) across the clade Archosauria. We use three-dimensional digital reconstruction to estimate body shape from skeletal dimensions for 17 archosaurs along the ancestral bird line, including the exceptionally preserved, feathered taxa Microraptor, Archaeopteryx, Pengornis and Yixianornis, which represent key stages in the evolution of the avian body plan. Rather than a discrete transition from more-upright postures in the basal-most birds (Avialae) and their immediate outgroup deinonychosauria, our results support hypotheses of a gradual, stepwise acquisition of more-crouched limb postures across much of theropod evolution, although we find evidence of an accelerated change within the clade Maniraptora (birds and their closest relatives, such as deinonychosaurs). In addition, whereas reduction of the tail is widely accepted to be the primary morphological factor correlated with centre-of-mass position and, hence, evolution of hindlimb posture, we instead find that enlargement of the pectoral limb and several associated trends have a much stronger influence. Intriguingly, our support for the onset of accelerated morpho-functional trends within Maniraptora is closely correlated with the evolution of flight. Because we find that the evolution of enlarged forelimbs is strongly linked, via whole-body centre of mass, to hindlimb function during terrestrial locomotion, we suggest that the evolution of avian flight is linked to anatomical novelties in the pelvic limb as well as the pectoral. [ABSTRACT FROM AUTHOR]

The construction of the vertebral column has been used as a key anatomical character in defining and diagnosing early tetrapod groups. Rhachitomous vertebrae-in which there is a dorsally placed neural arch and spine, an anteroventrally placed intercentrum and paired, posterodorsally placed pleurocentra-have long been considered the ancestral morphology for tetrapods. Nonetheless, very little is known about vertebral anatomy in the earliest stem tetrapods, because most specimens remain trapped in surrounding matrix, obscuring important anatomical features. Here we describe the three-dimensional vertebral architecture of the Late Devonian stem tetrapod Ichthyostega using propagation phase-contrast X-ray synchrotron microtomography. Our scans reveal a diverse array of new morphological, and associated developmental and functional, characteristics, including a possible posterior-to-anterior vertebral ossification sequence and the first evolutionary appearance of ossified sternal elements. One of the most intriguing features relates to the positional relationships between the vertebral elements, with the pleurocentra being unexpectedly sutured or fused to the intercentra that directly succeed them, indicating a 'reverse' rhachitomous design. Comparison of Ichthyostega with two other stem tetrapods, Acanthostega and Pederpes, shows that reverse rhachitomous vertebrae may be the ancestral condition for limbed vertebrates. This study fundamentally revises our current understanding of vertebral column evolution in the earliest tetrapods and raises questions about the presumed vertebral architecture of tetrapodomorph fish and later, more crownward, tetrapods. [ABSTRACT FROM AUTHOR]

Molten deposits based on calcium-magnesium alumino-silicates (CMAS), originating from siliceous debris ingested with the intake air, represent a fundamental threat to progress in gas turbine technology by limiting the operating surface temperature of coated components. The thermomechanical and thermochemical aspects of the CMAS interactions with thermal-barrier coatings, as well as the current status of mitigating strategies, are discussed in this article. Key challenges and research needs for developing adequate solutions are highlighted. [ABSTRACT FROM PUBLISHER]

It has not been a simple matter to obtain a sound extension of the classical J flow theory of plasticity that incorporates a dependence on plastic strain gradients and that is capable of capturing size-dependent behaviour of metals at the micron scale. Two classes of basic extensions of classical J theory have been proposed: one with increments in higher order stresses related to increments of strain gradients and the other characterized by the higher order stresses themselves expressed in terms of increments of strain gradients. The theories proposed by Muhlhaus and Aifantis in 1991 and Fleck and Hutchinson in 2001 are in the first class, and, as formulated, these do not always satisfy thermodynamic requirements on plastic dissipation. On the other hand, theories of the second class proposed by Gudmundson in 2004 and Gurtin and Anand in 2009 have the physical deficiency that the higher order stress quantities can change discontinuously for bodies subject to arbitrarily small load changes. The present paper lays out this background to the quest for a sound phenomenological extension of the rateindependent J flow theory of plasticity to include a dependence on gradients of plastic strain. A modification of the Fleck-Hutchinson formulation that ensures its thermodynamic integrity is presented and contrasted with a comparable formulation of the second class where in the higher order stresses are expressed in terms of the plastic strain rate. Both versions are constructed to reduce to the classical J flow theory of plasticity when the gradients can be neglected and to coincide with the simpler and more readily formulated J deformation theory of gradient plasticity for deformation histories characterized by proportional straining. [ABSTRACT FROM AUTHOR]

The origin of tetrapods and the transition from swimming to walking was a pivotal step in the evolution and diversification of terrestrial vertebrates. During this time, modifications of the limbs-particularly the specialization of joints and the structures that guide their motions-fundamentally changed the ways in which early tetrapods could move. Nonetheless, little is known about the functional consequences of limb anatomy in early tetrapods and how that anatomy influenced locomotion capabilities at this very critical stage in vertebrate evolution. Here we present a three-dimensional reconstruction of the iconic Devonian tetrapod Ichthyostega and a quantitative and comparative analysis of limb mobility in this early tetrapod. We show that Ichthyostega could not have employed typical tetrapod locomotory behaviours, such as lateral sequence walking. In particular, it lacked the necessary rotary motions in its limbs to push the body off the ground and move the limbs in an alternating sequence. Given that long-axis rotation was present in the fins of tetrapodomorph fishes, it seems that either early tetrapods evolved through an initial stage of restricted shoulder and hip joint mobility or that Ichthyostega was unique in this respect. We conclude that early tetrapods with the skeletal morphology and limb mobility of Ichthyostega were unlikely to have made some of the recently described Middle Devonian trackways. [ABSTRACT FROM AUTHOR]

Over the last two decades the share of national income which accrues to labour has followed a marked downward trend across a host of industrialised countries. This paper reassesses the relative importance of several potential causes of this phenomenon. Overall, the findings suggest that lower trade costs and factors often associated with economic integration such as international low-wage competition and industry concentration have contributed to the decline in the labour share. However, their effects have been limited when compared to the effects of skill-based technological change and cyclical price changes of intermediary goods. [ABSTRACT FROM AUTHOR]

We show that the stylized facts of the Firm Size Distribution (FSD) by age cohorts, as shown in Cabral and Mata (2003), bind within 4-digit manufacturing industries in the UK and Belgium. This paper investigates whether the time to build a portfolio of products from inter-industry diversification is a mechanism that helps explain the stylized facts of the FSD by age cohorts. We find that the degree of inter-industry diversification has a separate impact on firm size when controlling for age, amongst other factors. Using the techniques of Cabral and Mata, we find that inter-industry diversification does shift the FSD to the right, and more so in older age groups. [ABSTRACT FROM AUTHOR]

In this article, the author discusses the development of drug for bioactive lipid targets. The author states that the earliest pharmaceutically aimed bioactive lipid pathway was the arachidonic acid-deduced prostaglandin pathway. The author says that new drugs had to be able to bring pathological procedures back into physiological balance without themselves harming the body.

The definition of the glass transition temperature, Tg, is recalled and its experimental determination by various techniques is reviewed. The diversity of values of Tg obtained by the different methods is discussed, with particular attention being paid to Differential Scanning Calorimetry (DSC) and to dynamic techniques such as Dynamic Mechanical Thermal Analysis (DMTA) and Temperature Modulated DSC (TMDSC). This last technique, TMDSC, in particular, is considered in respect of ways in which the heterogeneity of the glass transformation process can be quantified. [ABSTRACT FROM AUTHOR]

In this paper we compare the role of internal finance on the growth of firms between a leading transition country, Slovenia and an established market economy, Belgium. We find that firms in Slovenia are more sensitive to internal financing constraints than their Belgian counterparts. Furthermore, we find that de novo firms and firms with long term debt are most constrained and that micro and SMES can face great difficulties in accessing external sources of finance. Foreign firms, however, are able to raise external finance and consequently their growth is less reliant on the availability of internal finance. Our findings appear to indicate that although Slovenian firms are no longer recipients of soft budget constraints, the financial environment is not yet fully functional. [ABSTRACT FROM AUTHOR]

The paper is concerned with the higher regularity properties of the minimizers of the Mumford–Shah functional. It is shown that, near to singular points where the scaled Dirichlet integral tends to 0, the discontinuity set is close to an Almgren area minimizing set. As a byproduct, the set of singular points of this type has Hausdorff dimension at most N-2, N being the dimension of the ambient space. Assuming higher integrability of the gradient this leads to an optimal estimate of the Hausdorff dimension of the full singular set. [ABSTRACT FROM AUTHOR]

Examines the skeletal muscle of tyrannosaurus in relation to the running speed of the species. Controversy on the gait and speed of the species; Demonstration of method for gauging the running ability of tyrannosaurus; Data on the anatomy of the species.

The pathogenesis of human breast cancer is thought to involve multiple genetic events, the majority of which fall into two categories, gain of function mutations in proto-oncogenes such as c-myc, cyclin D1, ErbB-2 and various growth factors which are involved in supporting cell growth, division and survival, and loss of function mutations in so called ‘tumor suppressor’ genes, such as p53, which are involved in preventing unrestrained cellular growth. A number of mouse systems exist to address the significance of these mutations in the pathogenesis of breast cancer including transgenic mice expressing high levels of a specific gene in target tissues and knockout mice in which specific genes have been ablated via homologous recombination. More recently, the combination of these techniques to create bigenics as well as the use of ‘knockin’ and conditional tissue specific gene targeting strategies have allowed the models more reflective of the human disease to be devised. Studies with these models have not only implicated particular genetic events in the progression of the disease but have emphasized the complex, multi-step nature of breast cancer progression. These models also provide the opportunity to study various aspects of the pathogenesis of this disease, from hormonal effects to responses to chemotherapeutic drugs. It is hoped that through the combined use of these models, and the further development of more relevant models, that a deeper understanding of this disease and the generation of new therapeutic agents will result. Oncogene (2000) 19, 6130–6137. [ABSTRACT FROM AUTHOR]

We study the general asymptotic behavior of critical points, including those of non-minimal energy type, of the functional for the van der Waals-Cahn-Hilliard theory of phase transitions. We prove that the interface is close to a hypersurface with mean curvature zero when no Lagrange multiplier is present, and with locally constant mean curvature in general. The energy density of the limiting measure has integer multiplicity almost everywhere modulo division by a surface energy constant. [ABSTRACT FROM AUTHOR]

Lower semicontinuity for polyconvex functionals of the form ∫ g(det Du) dx with respect to sequences of functions from W (Ω;ℝ) which converge in L (Ωℝ) and are uniformly bounded in W (Ω;ℝ), is proved. This was first established in [5] using results from [1] on Cartesian Currents. We give a simple direct proof which does not involve currents. We also show how the method extends to prove natural, essentially optimal, generalizations of these results. [ABSTRACT FROM AUTHOR]

We prove C almost everywhere regularity for minimisers of functionals of the form ∫F(x,u,Du), where F is uniformly strictly quasiconvex. This extends a recent result of Evans in which F is allowed only to depend on Du. [ABSTRACT FROM AUTHOR]

We prove optimal convergence results for discrete approximations to (possibly unstable) minimal surfaces. This appears to be the first class of results of this type for geometric objects solving a highly non-linear geometric variational problem. We introduce a number of new techniques which we expect will be of use in other geometric problems. The theoretical approximation results are confirmed by numerical test computations. [ABSTRACT FROM AUTHOR]

Let R be a ring, and let (ℐ, ℱ) be an hereditary torsion theory of left R-modules. An epimorphism ψ: M→X is called a torsion-free cover of X if (1) M∈ ℱ, (2) every homomorphism from a torsion-free module into X can be factored through M, and (3) ker ψ contains no nonzero ℐ -closed submodules of M. Conditions on M and N are studied to determine when the natural maps M→M/N and Q(M)→Q(M)/N are torsion-free covers, when Q(M) is the localization of M with respect to (ℐ, ℱ). If M→M/N is a torsion-free cover and M is projective, then N⊆rad M. Consequently, the concepts of projective cover and torsion-free cover coincide in some interesting cases. [ABSTRACT FROM AUTHOR]

We develop a technique for applying models of set theory to obtain results in the model theory of infinitary languages. Some results on Δ-logics are also discussed. [ABSTRACT FROM AUTHOR]

The complexes [PPh][MoO{S(CH)S}], n=2 ( 1) n=3 ( 3), were synthesised from the Mo dioxoprecursor complex [MoO(butane-2,3-diolato)] and the appropriate thiol in the presence of base. Complex ( 3) exhibits a square pyramidal geometry. Crystal Data: P2, Z=4, a=9.612(2), b=21.202(4), c=15.462(3) Å, β=103.06(1)°, V=3043.3Å, F(000)=1364.0, 3687 reflections collected, and 1957 used in solution with R=0.058. [MoO(SCHCHCHS)] reacts with hydrazoic acid in methanol to produce [MoO(μ-N)-(SCHCHCHS)] ( 5), crystal data: $$P_{2_{1} 2_{1} 2_{1} } $$ a=9.398(3), b=14.650(2), c=27.42(2) (Å), α=β=γ=90°, Z=4 V=3775.8Å, F(000)=1872.0, 2563 reflections collected and 1244 were used in the solution with R=0.058. The complex is an asymmetric dimer with a triple bridge comprising two dithiolate sulphurs and a nitrogen of the azide ligand. Convolution analysis of the cyclic voltammetric response of complex ( 1) confirmed a diffusion controlled one electron reversible reduction process. [ABSTRACT FROM AUTHOR]