HaploShare: identification of extended haplotypes shared by cases and evaluation against controls

Recent founder mutations may play important roles in complex diseases and Mendelian disorders. Detecting shared haplotypes that are identical by descent (IBD) could facilitate discovery of these mutations. Several programs address this, but are usually limited to detecting pair-wise shared haplotypes and not providing a comparison of cases and controls. We present a novel algorithm and software package, HaploShare, which detects extended haplotypes that are shared by multiple individuals, and allows comparisons between cases and controls. Testing on simulated and real cases demonstrated significant improvements in detection power and reduction of false positive rate by HaploShare relative to other programs.published_or_final_versio

Detection of ipsilateral and contralateral activation components in unilateral fingers-tapping using spinal BOLD fMR

Ipsilateral activation component has been reported in brain fMRI studies using unilateral finger motion. However, the ipsilateral component is usually taskdependent and sparsely distributed. In this study, spinal BOLD fMRI has been performed on 4 healthy right-handed volunteers performing unilateral fingerstapping to investigate the ipsilateral and contralateral activation inside the cervical spinal cord. Our results showed that more activation were found at the spinal level C5-C6/C7. Bilateral activation was observed in all subjects both in left/right hand fingers-tapping. Spinal fMRI was sensitive to detect bilateral firing in fingers-tapping using dominant or non-dominant hands.published_or_final_versio

Disruption of Parasite hmgb2 Gene Attenuates Plasmodium berghei ANKA Pathogenicity

Eukaryotic high-mobility-group-box (HMGB) proteins are nuclear factors involved in chromatin remodeling and transcription regulation. When released into the extracellular milieu, HMGB1 acts as a proinflammatory cytokine that plays a central role in the pathogenesis of several immune-mediated inflammatory diseases. We found that the Plasmodium genome encodes two genuine HMGB factors, Plasmodium HMGB1 and HMGB2, that encompass, like their human counterparts, a proinflammatory domain. Given that these proteins are released from parasitized red blood cells, we then hypothesized that Plasmodium HMGB might contribute to the pathogenesis of experimental cerebral malaria (ECM), a lethal neuroinflammatory syndrome that develops in C57BL/6 (susceptible) mice infected with Plasmodium berghei ANKA and that in many aspects resembles human cerebral malaria elicited by P. falciparum infection. The pathogenesis of experimental cerebral malaria was suppressed in C57BL/6 mice infected with P. berghei ANKA lacking the hmgb2 gene (Δhmgb2 ANKA), an effect associated with a reduction of histological brain lesions and with lower expression levels of several proinflammatory genes. The incidence of ECM in pbhmgb2-deficient mice was restored by the administration of recombinant PbHMGB2. Protection from experimental cerebral malaria in Δhmgb2 ANKA-infected mice was associated with reduced sequestration in the brain of CD4(+) and CD8(+) T cells, including CD8(+) granzyme B(+) and CD8(+) IFN-γ(+) cells, and, to some extent, neutrophils. This was consistent with a reduced parasite sequestration in the brain, lungs, and spleen, though to a lesser extent than in wild-type P. berghei ANKA-infected mice. In summary, Plasmodium HMGB2 acts as an alarmin that contributes to the pathogenesis of cerebral malaria.Pitié-Salpêtrière, Institut Pasteur (Paris)

Increasing negotiation performance at the edge of the network

Automated negotiation has been used in a variety of distributed settings, such as privacy in the Internet of Things (IoT) devices and power distribution in Smart Grids. The most common protocol under which these agents negotiate is the Alternating Offers Protocol (AOP). Under this protocol, agents cannot express any additional information to each other besides a counter offer. This can lead to unnecessarily long negotiations when, for example, negotiations are impossible, risking to waste bandwidth that is a precious resource at the edge of the network. While alternative protocols exist which alleviate this problem, these solutions are too complex for low power devices, such as IoT sensors operating at the edge of the network. To improve this bottleneck, we introduce an extension to AOP called Alternating Constrained Offers Protocol (ACOP), in which agents can also express constraints to each other. This allows agents to both search the possibility space more efficiently and recognise impossible situations sooner. We empirically show that agents using ACOP can significantly reduce the number of messages a negotiation takes, independently of the strategy agents choose. In particular, we show our method significantly reduces the number of messages when an agreement is not possible. Furthermore, when an agreement is possible it reaches this agreement sooner with no negative effect on the utility.Comment: Accepted for presentation at The 7th International Conference on Agreement Technologies (AT 2020

Arabidopsis thaliana VDAC2 involvement in salt stress response pathway

Soil salinity seriously affects plants distribution and yield, while salt stress induces SOS genes, and voltage-dependent anion channels (VDAC) and a mitochondrial porin, are induced too. In this paper, phenotypes of AtVDAC2 transgenic lines and wild type (RLD) were analyzed. It was found that AtVDAC2 over-expressing transgenic plants were more sensitive to NaCl, and produced more H2O2 in the NaCl treatment. Also, to find the inner reason, the salt overly sensitive gene 3 (SOS3) expression level was changed with the expression of AtVDAC2. So, it was conjectured that the signal of salt stress response was first sent to AtVDAC2, then AtVDAC2 expression improved, leading to the down-stream signals changes, such as accumulation of H2O2 and improved expression of SOS3. So, it was found that in the over-expression of transgenic lines with AtVDAC2 up-regulation, SOS3 expression increased significantly, and in the inhibited-expressing lines, it was vice versa. In summary, AtVDAC2 was involved in salt stress signaling pathway, and it regulated SOS3 gene expression.Key words: Arabidopsis thaliana, voltage-dependent anion channels (VDAC), salt stress, signaling pathway

Effectiveness of preoperative planning in the restoration of balance and view in ankylosing spondylitis

Object. The object of this study was to assess the effectiveness of preoperative planning in the restoration of balance and view angle in patients treated with lumbar osteotomy in ankylosing spondylitis (AS). Methods. The authors prospectively analyzed 8 patients with a thoracolumbar kyphotic deformity due to AS that was treated using a closing wedge osteotomy (CWO) of the lumbar spine to correct sagittal imbalance and horizontal view. Preoperative planning to predict postoperative balance, defined by the sagittal vertical axis (SVA) and the sacral endplate angle (SEA), and the view angle, defined by the chin-brow to vertical angle (CBVA), was performed using the ASKyphoptan computational program. Results. All patients were treated with a CWO at level L-4 and improved in balance and view angle. The mean correction angle was 35° (range 24-47°). The postoperative SEA improved from 21 to 36° for a mean correction of 15°. In addition, the SVA and CBVA improved significantly. Note, however, that the postoperative results did not exactly reflect the predicted values of the analyzed parameters. Conclusions. Preoperative planning for the restoration of balance and view angle in AS improves understanding of the biomechanical and clinical effects of a correction osteotomy of the lumbar spine. The adaptation of basic clinical and biomechanical principles to restore balance is advised in such a way that the individual SEA is corrected by 15° (maximum 40°) in relation to the horizon and C-7 is balanced exactly above the posterosuperior corner of the sacrum

Inter-layer free cobalt-doped silica membranes for pervaporation of ammonia solutions

This study demonstrated the application of a new type of interlayer-free cobalt-doped silica membrane in treating ammonia solutions by pervaporation applied towards wastewater treatment. For enhanced hydrothermal stability, cobalt-doped silica (CoSi) membranes with increasing cobalt concentrations from 1 to 35 mol% were prepared and evaluated, namely CoSi-1, 5, 20 and 35. These membranes exhibited high water fluxes of 66 L m h for CoSi-1 and 15.5 L m h for CoSi-35 at 45 °C. The fluxes of the membranes decreased with increasing cobalt concentration; while the rejection to total nitrogen (TN, ammonia nitrogen) increased and hence allowed selective passage of water molecules. Enhanced thermostability was observed for the membranes, particularly CoSi-35 that exhibited TN rejection up to 99% at high temperature of 65 °C and highly alkaline environment (pH > 10). Also, the CoSi-35 membrane showed stable performance in treating ammonia present in industry wastewater by achieving stable TN and mineral rejections of 97% and 99%, respectively. Fouling was observed and confirmed by SEM morphological analysis and EDX elemental inspection. The results indicated the deposition of low solubility salts such as CaSO

Hot Streaks in Artistic, Cultural, and Scientific Careers

The hot streak, loosely defined as winning begets more winnings, highlights a specific period during which an individual's performance is substantially higher than her typical performance. While widely debated in sports, gambling, and financial markets over the past several decades, little is known if hot streaks apply to individual careers. Here, building on rich literature on lifecycle of creativity, we collected large-scale career histories of individual artists, movie directors and scientists, tracing the artworks, movies, and scientific publications they produced. We find that, across all three domains, hit works within a career show a high degree of temporal regularity, each career being characterized by bursts of high-impact works occurring in sequence. We demonstrate that these observations can be explained by a simple hot-streak model we developed, allowing us to probe quantitatively the hot streak phenomenon governing individual careers, which we find to be remarkably universal across diverse domains we analyzed: The hot streaks are ubiquitous yet unique across different careers. While the vast majority of individuals have at least one hot streak, hot streaks are most likely to occur only once. The hot streak emerges randomly within an individual's sequence of works, is temporally localized, and is unassociated with any detectable change in productivity. We show that, since works produced during hot streaks garner significantly more impact, the uncovered hot streaks fundamentally drives the collective impact of an individual, ignoring which leads us to systematically over- or under-estimate the future impact of a career. These results not only deepen our quantitative understanding of patterns governing individual ingenuity and success, they may also have implications for decisions and policies involving predicting and nurturing individuals with lasting impact

New arylated benzo[h]quinolines induce anti-cancer activity by oxidative stress-mediated DNA damage

© 2016 The Author(s).The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound. In addition, molecular docking revealed that benzo[h]quinolines can correctly dock into the hydrophobic pocket of the targets receptor protein aromatase and CDK2, while their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. These findings reveal that benzo[h]quinolines act as anti-cancer agents by inducing oxidative stress-mediated DNA damage

Changes in BMI before and during economic development and subsequent risk of cardiovascular disease and total mortality: A 35-year follow-up study in China

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