2,591 research outputs found

    A5_1 Did Superman really save Lois Lane?

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    This article investigates an implication of being caught after falling from great height. This is seen in the film Superman (1978). A scene depicts Lois Lane falling from the top of a skyscraper, only to be caught safely by Superman. It was found that the impact of landing on Supermans arms would not have caused damage to Lois Lane.

    3α-Dimethyl­amino-20-(N-methyl­acetamido)­pregn-5-ene

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    The title compond, C26H44N2O, is an steroidal alkaloid isolated from the medicinally important plant Sarcococca saligna. The mol­ecule consists of four fused rings (A–D), having chair, half-chair, chair and envelope conformations, respectively. The dimethyl­amino group is axially oriented on ring A, whereas the (N-methyl­acetamido)­ethyl group is attached equatorially on ring D. The crystal structure is stabilized only by van der Waals forces

    Causal Effects of the Timing of Life-course Events Age at Retirement and Subsequent Health

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    In this article, we combine the extensive literature on the analysis of life-course trajectories as sequences with the literature on causal inference and propose a new matching approach to investigate the causal effect of the timing of life-course events on subsequent outcomes. Our matching approach takes into account pre-event confounders that are both time-independent and time-dependent as well as life-course trajectories. After matching, treated and control individuals can be compared using standard statistical tests or regression models. We apply our approach to the study of the consequences of the age at retirement on subsequent health outcomes, using a unique data set from Swedish administrative registers. Once selectivity in the timing of retirement is taken into account, effects on hospitalization are small, while early retirement has negative effects on survival. Our approach also allows for heterogeneous treatment effects. We show that the effects of early retirement differ according to preretirement income, with higher income individuals tending to benefit from early retirement, while the opposite is true for individuals with lower income

    Bioreactor analyses of tissue ingrowth, ongrowth and remodelling around implants: an alternative to live animal testing

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    Introduction: Preclinical assessment of bone remodelling onto, into or around novel implant technologies is underpinned by a large live animal testing burden. The aim of this study was to explore whether a lab-based bioreactor model could provide similar insight. Method: Twelve ex vivo trabecular bone cylinders were extracted from porcine femora and were implanted with additively manufactured stochastic porous titanium implants. Half were cultured dynamically, in a bioreactor with continuous fluid flow and daily cyclic loading, and half in static well plates. Tissue ongrowth, ingrowth and remodelling around the implants were evaluated with imaging and mechanical testing. Results: For both culture conditions, scanning electron microscopy (SEM) revealed bone ongrowth; widefield, backscatter SEM, micro computed tomography scanning, and histology revealed mineralisation inside the implant pores; and histology revealed woven bone formation and bone resorption around the implant. The imaging evidence of this tissue ongrowth, ingrowth and remodelling around the implant was greater for the dynamically cultured samples, and the mechanical testing revealed that the dynamically cultured samples had approximately three times greater push-through fixation strength (p < 0.05). Discussion: Ex vivo bone models enable the analysis of tissue remodelling onto, into and around porous implants in the lab. While static culture conditions exhibited some characteristics of bony adaptation to implantation, simulating physiological conditions with a bioreactor led to an accelerated response

    Interactions between the quality control ubiquitin ligase CHIP and ubiquitin conjugating enzymes

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    <p>Abstract</p> <p>Background</p> <p>Ubiquitin (E3) ligases interact with specific ubiquitin conjugating (E2) enzymes to ubiquitinate particular substrate proteins. As the combination of E2 and E3 dictates the type and biological consequence of ubiquitination, it is important to understand the basis of specificity in E2:E3 interactions. The E3 ligase CHIP interacts with Hsp70 and Hsp90 and ubiquitinates client proteins that are chaperoned by these heat shock proteins. CHIP interacts with two types of E2 enzymes, UbcH5 and Ubc13-Uev1a. It is unclear, however, why CHIP binds these E2 enzymes rather than others, and whether CHIP interacts preferentially with UbcH5 or Ubc13-Uev1a, which form different types of polyubiquitin chains.</p> <p>Results</p> <p>The 2.9 Å crystal structure of the CHIP U-box domain complexed with UbcH5a shows that CHIP binds to UbcH5 and Ubc13 through similar specificity determinants, including a key S-P-A motif on the E2 enzymes. The determinants make different relative contributions to the overall interactions between CHIP and the two E2 enzymes. CHIP undergoes auto-ubiquitination by UbcH5 but not by Ubc13-Uev1a. Instead, CHIP drives the formation of unanchored polyubiquitin by Ubc13-Uev1a. CHIP also interacts productively with the class III E2 enzyme Ube2e2, in which the UbcH5- and Ubc13-binding specificity determinants are highly conserved.</p> <p>Conclusion</p> <p>The CHIP:UbcH5a structure emphasizes the importance of specificity determinants located on the long loops and central helix of the CHIP U-box, and on the N-terminal helix and loops L4 and L7 of its cognate E2 enzymes. The S-P-A motif and other specificity determinants define the set of cognate E2 enzymes for CHIP, which likely includes several Class III E2 enzymes. CHIP's interactions with UbcH5, Ube2e2 and Ubc13-Uev1a are consistent with the notion that Ubc13-Uev1a may work sequentially with other E2 enzymes to carry out K63-linked polyubiquitination of CHIP substrates.</p

    Regulation of D-galacturonate metabolism in Caulobacter crescentus by HumR, a LacI-family transcriptional repressor

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    The oligotrophic freshwater bacterium Caulobacter crescentus encodes a cluster of genes (CC_1487 to CC_1495) shown here to be necessary for metabolism of D-galacturonate, the primary constituent of pectin, a major plant polymer. Sequence analysis suggests that these genes encode a version of the bacterial hexuronate isomerase pathway. A conserved 14 bp sequence motif is associated with promoter regions of three operons within this cluster, and is conserved in homologous gene clusters in related alpha-Proteobacteria. Embedded in the hexuronate gene cluster is a gene (CC_1489) encoding a member of the LacI family of bacterial transcription factors. This gene product, designated here as HumR (hexuronate metabolism regulator), represses expression of the uxaA and uxaC operon promoters by binding to the conserved operator sequence. Repression is relieved in the presence of galacturonate or, to a lesser extent, by glucuronate. Other genes potentially involved in pectin degradation and hexuronate transport are also under the control of HumR. Adoption of a LacI-type repressor to control hexuronate metabolism parallels the regulation of xylose, glucose, and maltose utilization in C. crescentus, but is distinct from the use of GntR-type repressors to control pectin and hexuronate utilization in gamma-Proteobacteria such as Escherichia coli

    Elastic constants of nematic liquid crystals of uniaxial symmetry

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    We study in detail the influence of molecular interactions on the Frank elastic constants of uniaxial nematic liquid crystals composed of molecules of cylindrical symmetry. A brief summary of the status of theoretical development for the elastic constants of nematics is presented. Considering a pair potential having both repulsive and attractive parts numerical calculations are reported for three systems MBBA, PAA and 8OCB. For these systems the length-to-width ratio x0{x_0} is estimated from the experimentally proposed structure of the molecules. The repulsive interaction is represented by a repulsion between hard ellipsoids of revolution (HER) and the attractive potential is represented by the quadrupole and dispersion interactions. From the numerical results we observe that in the density range of nematics the contribution of the quadrupole and dispersion interactions are small as compared to the repulsive HER interaction. The inclusion of attractive interaction reduces the values of elastic constants ratios. The temperature variation of elastic constants ratios are reported and compared with the experimental values. A reasonably good agreement between theory and experiment is observed

    Economic growth in India during 1950-2015:Nehruvian socialism to market capitalism

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    Comparisons of pre and postreform economic growth in India are widely researched in the literature. This paper adds to this literature, but with a sectoral growth accounting perspective. We compare the proximate sources of economic growth in India during the 1950-1980 periods, the so-called Nehruvian socialist regime, with that of the post-1980 period, which includes the pro-business reforms in the 1980s and more aggressive pro-market reforms in the 1990s. We document two important features of India's growth dynamics. First, the overriding importance of the services sector in India's growth is not new, but it has always been the case in independent India. However, there has been a major shift in the composition of service sector growth. While the socialist regime fostered more nonmarket services, including the government sector, the market services sector flourished in the market regime, in terms of labour productivity, TFP and economic growth. Second, the economic growth in the socialist period was substantially driven by capital accumulation, except in the nonmarket services, whereas the market regime sees a combination of both productivity and capital accumulation

    The temporal event-based model: Learning event timelines in progressive diseases

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    Timelines of events, such as symptom appearance or a change in biomarker value, provide powerful signatures that characterise progressive diseases. Understanding and predicting the timing of events is important for clinical trials targeting individuals early in the disease course when putative treatments are likely to have the strongest effect. However, previous models of disease progression cannot estimate the time between events and provide only an ordering in which they change. Here, we introduce the temporal event-based model (TEBM), a new probabilistic model for inferring timelines of biomarker events from sparse and irregularly sampled datasets. We demonstrate the power of the TEBM in two neurodegenerative conditions: Alzheimer's disease (AD) and Huntington's disease (HD). In both diseases, the TEBM not only recapitulates current understanding of event orderings but also provides unique new ranges of timescales between consecutive events. We reproduce and validate these findings using external datasets in both diseases. We also demonstrate that the TEBM improves over current models; provides unique stratification capabilities; and enriches simulated clinical trials to achieve a power of 80% with less than half the cohort size compared with random selection. The application of the TEBM naturally extends to a wide range of progressive conditions
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