Optimum design of an artificial wrist implant

This paper describes the anatomy and biomechanics of the normal wrist, proposes the requirements for ideal wrist prosthesis and suggests an optimum design solution with the aid of FEA techniques

Inference by belief propagation in composite systems

We devise a message passing algorithm for probabilistic inference in composite systems, consisting of a large number of variables, that exhibit weak random interactions among all variables and strong interactions with a small subset of randomly chosen variables; the relative strength of the two interactions is controlled by a free parameter. We examine the performance of the algorithm numerically on a number of systems of this type for varying mixing parameter values

A Selenium-Dependent Xanthine Dehydrogenase Triggers Biofilm Proliferation in Enterococcus faecalis through Oxidant Production

Selenium has been shown to be present as a labile cofactor in a small class of molybdenum hydroxylase enzymes in several species of clostridia that specialize in the fermentation of purines and pyrimidines. This labile cofactor is poorly understood, yet recent bioinformatic studies have suggested that Enterococcus faecalis could serve as a model system to better understand the way in which this enzyme cofactor is built and the role of these metalloenzymes in the physiology of the organism. An mRNA that encodes a predicted selenium-dependent molybdenum hydroxylase (SDMH) has also been shown to be specifically increased during the transition from planktonic growth to biofilm growth. Based on these studies, we examined whether this organism produces an SDMH and probed whether selenoproteins may play a role in biofilm physiology. We observed a substantial increase in biofilm density upon the addition of uric acid to cells grown in a defined culture medium, but only when molybdate (Mo) and selenite (Se) were also added. We also observed a significant increase in biofilm density in cells cultured in tryptic soy broth with 1% glucose (TSBG) when selenite was added. In-frame deletion of selD, which encodes selenophosphate synthetase, also blocked biofilm formation that occurred upon addition of selenium. Moreover, mutation in the gene encoding the molybdoenzyme (xdh) prevented the induction of biofilm proliferation upon supplementation with selenium. Tungstate or auranofin addition also blocked this enhanced biofilm density, likely through inhibition of molybdenum or selenium cofactor synthesis. A large protein complex labeled with Se-75 is present in higher concentrations in biofilms than in planktonic cells, and the same complex is formed in TSBG. Xanthine dehydrogenase activity correlates with the presence of this labile selenoprotein complex and is absent in a selD or an xdh mutant. Enhanced biofilm density correlates strongly with higher levels of extracellular peroxide, which is produced upon the addition of selenite to TSBG. Peroxide levels are not increased in either the selD or the xdh mutant upon addition of selenite. Extracellular superoxide production, a phenomenon well established to be linked to clinical isolates, is abolished in both mutant strains. Taken together, these data provide evidence that an SDMH is involved in biofilm formation in Enterococcus faecalis, contributing to oxidant production either directly or alternatively through its involvement in redox-dependent processes linked to oxidant production

Current and Nascent SETI Instruments in the Radio and Optical

Here we describe our ongoing efforts to develop high-performance and sensitive instrumentation for use in the search for extra-terrestrial intelligence (SETI). These efforts include our recently deployed Search for Extraterrestrial Emissions from Nearby Developed Intelligent Populations Spectrometer (SERENDIP V.v) and two instruments currently under development; the Heterogeneous Radio SETI Spectrometer (HRSS) for SETI observations in the radio spectrum and the Optical SETI Fast Photometer (OSFP) for SETI observations in the optical band. We will discuss the basic SERENDIP V.v instrument design and initial analysis methodology, along with instrument architectures and observation strategies for OSFP and HRSS. In addition, we will demonstrate how these instruments may be built using low-cost, modular components and programmed and operated by students using common languages, e.g. ANSI C

First Report of Root and Collar Rot Caused by Fusarium tricinctum and Fusarium avenaceum on Carrot in France

In 2017, carrot (Daucus carota L.) seed production represented around 22% of the area devoted to the production of vegetable fine seeds. Since 2015, symptoms of root and collar rot have been observed in carrot seed parcels located in the Central Region, one of the most important production zone in France. Diseased plants became dried prematurely, compromising seed development. Depending on the year and the climatic conditions, the disease in a same field can be considered as epidemic (rate losses between 30 to 100% of plants in 2016) or can impact plants more sporadically (less than 10% in 2017 and 2018). Sixteen diseased carrot samples (Nantaise type) were collected from five fields of seed production in the Central Region: two fields in 2016 and 2017, one field in 2018. Seven fungal isolates, obtained from lesions, were grown on Potato Dextrose Agar (PDA) medium and incubated for one week at 20°C in darkness. From the colony top, fluffy mycelium pigmented in pink, red, purple or orange was observed, with a red color at the reverse. To induce sporulation, isolates were grown on Synthetischer Nährstoffarmer Agar (SNA) medium during three weeks at 24°C in near-UV radiations under a 12h-photoperiod. Four isolates (FT001, FT003, FT007, FT017) developed orange sporodochia with lunar or crescent-shaped macroconidia (40.3 ± 0.8 × 5.9 ± 0.1 µm; n=90) and lime or pear-shaped microconidia (10.7 ± 0.2 × 7.7 ± 0.2 µm; n=60), as described in Fusarium tricinctum (Leslie and Summerell 2006). Three isolates (FA001, FA002, FA006) developed orange sporodochia with sickle-shaped macroconidia (50.5 ± 1.1 × 5.0 ± 0.1 µm; n= 60), but no microconidia, as observed in Fusarium avenaceum (Leslie and Summerell 2006). To confirm the identification, DNA was extracted from the mycelium of the seven isolates and molecular markers (ATP citrate lyase, ACL1; RNA polymerase II, RPB2) were used for PCR amplification (Gräfenhan et al. 2011; O’Donnell et al. 2013). The ACL1 sequences from the seven field isolates (GenBank Accession numbers MK183788-MK183791; MK181528-MK181530) were 99-100% identical with the ACL1 sequence of a reference F. tricinctum isolate (query coverages 99-100%; E-values of 0.0) and a reference F. avenaceum isolate (query coverages 98-99%; E-values of 0.0) [respectively DAOM 235630 isolate, GenBank Acc. No. JX397813 and BBA64135 isolate, GenBank Acc. No. JX397768, Niessen et al. 2012]. Using RPB2, sequences from field isolates (GenBank Acc. No. MK183109-MK183115) were 98.5-99.9% identical with the RPB2 sequence of a reference F. tricinctum isolate (query coverages 96-100%; E-values of 0.0) and a reference F. avenaceum isolate (query coverages 95-100%; E-values of 0.0) [respectively MRC 1895 isolate, GenBank Acc. No. MH582113 and MRC 1413 isolate, GenBank Acc. No. MH582082, O’Donnell et al. 2018]. To confirm pathogenicity, FT001 and FA002 were inoculated on collars of 10-weeks old carrot plants in the greenhouse. Forty plants per isolate and 40 control plants were used. Ten microliters of a conidial suspension (105 conidia.mL-1) - or sterile water for the controls - were deposited at the collar, previously wounded using a scalpel blade. Necrotic lesions developed at 20 dpi (FT001) and at 30 dpi (FA002). Fusarium tricinctum and F. avenaceum were re-isolated from the lesions and identified by sequencing using ACL1 and RPB2 markers. No isolation of Fusarium was obtained from the controls. To our knowledge, this is the first report of F. tricinctum and F. avenaceum in carrot in France

Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction

Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5 million people, our approach is statistically more powerful than single-trait analyses and identifies more than 500 genetic loci. The loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results predicts a range of behavioral and medical outcomes that were not part of genome-wide analyses, including traits that until now lacked well-performing polygenic scores, such as opioid use disorder, suicide, HIV infections, criminal convictions and unemployment. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental trait with complex and far-reaching social and health correlates

The potential effects of climate change on air quality across the conterminous US at 2030 under three Representative Concentration Pathways

The potential impacts of climate change on regional ozone (O3) and fine particulate (PM2.5) air quality in the United States (US) are investigated by linking global climate simulations with regional-scale meteorological and chemical transport models. Regional climate at 2000 and at 2030 under three Representative Concentration Pathways (RCPs) is simulated by using the Weather Research and Forecasting (WRF) model to downscale 11-year time slices from the Community Earth System Model (CESM). The downscaled meteorology is then used with the Community Multiscale Air Quality (CMAQ) model to simulate air quality during each of these 11-year periods. The analysis isolates the future air quality differences arising from climate-driven changes in meteorological parameters and specific natural emissions sources that are strongly influenced by meteorology. Other factors that will affect future air quality, such as anthropogenic air pollutant emissions and chemical boundary conditions, are unchanged across the simulations. The regional climate fields represent historical daily maximum and daily minimum temperatures well, with mean biases of less than 2&thinsp;K for most regions of the US and most seasons of the year and good representation of variability. Precipitation in the central and eastern US is well simulated for the historical period, with seasonal and annual biases generally less than 25&thinsp;%, with positive biases exceeding 25&thinsp;% in the western US throughout the year and in part of the eastern US during summer. Maximum daily 8&thinsp;h ozone (MDA8 O3) is projected to increase during summer and autumn in the central and eastern US. The increase in summer mean MDA8 O3 is largest under RCP8.5, exceeding 4&thinsp;ppb in some locations, with smaller seasonal mean increases of up to 2&thinsp;ppb simulated during autumn and changes during spring generally less than 1&thinsp;ppb. Increases are magnified at the upper end of the O3 distribution, particularly where projected increases in temperature are greater. Annual average PM2.5 concentration changes range from −1.0 to 1.0&thinsp;µg&thinsp;m−3. Organic PM2.5 concentrations increase during summer and autumn due to increased biogenic emissions. Aerosol nitrate decreases during winter, accompanied by lesser decreases in ammonium and sulfate, due to warmer temperatures causing increased partitioning to the gas phase. Among meteorological factors examined to account for modeled changes in pollution, temperature and isoprene emissions are found to have the largest changes and the greatest impact on O3 concentrations.</p

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

Systemic Stimulation of TLR2 Impairs Neonatal Mouse Brain Development

Background: Inflammation is associated with perinatal brain injury but the underlying mechanisms are not completely characterized. Stimulation of Toll-like receptors (TLRs) through specific agonists induces inflammatory responses that trigger both innate and adaptive immune responses. The impact of engagement of TLR2 signaling pathways on the neonatal brain is still unclear. The aim of this study was to investigate the potential effect of a TLR2 agonist on neonatal brain development. Methodology/Principal Findings: Mice were injected intraperitoneally (i.p.) once a day from postnatal day (PND) 3 to PND11 with endotoxin-free saline, a TLR2 agonist Pam$_{3}$CSK$_{4}$ (5 mg/kg) or Lipopolysaccharide (LPS, 0.3 mg/kg). Pups were sacrificed at PND12 or PND53 and brain, spleen and liver were collected and weighed. Brain sections were stained for brain injury markers. Long-term effects on memory function were assessed using the Trace Fear Conditioning test at PND50. After 9 days of Pam$_{3}$CSK$_{4}$ administration, we found a decreased volume of cerebral gray matter, white matter in the forebrain and cerebellar molecular layer that was accompanied by an increase in spleen and liver weight at PND12. Such effects were not observed in Pam$_{3}$CSK$_{4}$-treated TLR 2-deficient mice. Pam$_{3}$CSK$_{4}$-treated mice also displayed decreased hippocampus neuronal density, and increased cerebral microglia density, while there was no effect on caspase-3 or general cell proliferation at PND12. Significantly elevated levels of IL-1β, IL-6, KC, and MCP-1 were detected after the first Pam$_{3}$CSK$_{4}$ injection in brain homogenates of PND3 mice. Pam$_{3}$CSK$_{4}$administration did not affect long-term memory function nor the volume of gray or white matter. Conclusions/Significance: Repeated systemic exposure to the TLR2 agonist Pam$_{3}$CSK$_{4}$ can have a short-term negative impact on the neonatal mouse brain