Development of an inducible transposon system for efficient random mutagenesis in Clostridium acetobutylicum

Clostridium acetobutylicum is an industrially important Gram-positive organism which is capable of producing economically important chemicals in the ABE (Acetone, Butanol and Ethanol) fermentation process. Renewed interests in the ABE process necessitate the availability of additional genetics tools to facilitate the derivation of a greater understanding of the underlying metabolic and regulatory control processes in operation through forward genetic strategies. In this study, a xylose inducible, mariner-based, transposon system was developed and shown to allow high-efficient random mutagenesis in the model strain ATCC 824. Of the thiamphenicol resistant colonies obtained, 91.9% were shown to be due to successful transposition of the catP-based mini-transposon element. Phenotypic screening of 200 transposon clones revealed a sporulation-defective clone with an insertion in spo0A, thereby demonstrating that this inducible transposon system can be used for forward genetic studies in C. acetobutylicum

Genomic analysis of the domestication and post-Spanish conquest evolution of the llama and alpaca

Background Despite their regional economic importance and being increasingly reared globally, the origins and evolution of the llama and alpaca remain poorly understood. Here we report reference genomes for the llama, and for the guanaco and vicuña (their putative wild progenitors), compare these with the published alpaca genome, and resequence seven individuals of all four species to better understand domestication and introgression between the llama and alpaca. Results Phylogenomic analysis confirms that the llama was domesticated from the guanaco and the alpaca from the vicuña. Introgression was much higher in the alpaca genome (36%) than the llama (5%) and could be dated close to the time of the Spanish conquest, approximately 500 years ago. Introgression patterns are at their most variable on the X-chromosome of the alpaca, featuring 53 genes known to have deleterious X-linked phenotypes in humans. Strong genome-wide introgression signatures include olfactory receptor complexes into both species, hypertension resistance into alpaca, and fleece/fiber traits into llama. Genomic signatures of domestication in the llama include male reproductive traits, while in alpaca feature fleece characteristics, olfaction-related and hypoxia adaptation traits. Expression analysis of the introgressed region that is syntenic to human HSA4q21, a gene cluster previously associated with hypertension in humans under hypoxic conditions, shows a previously undocumented role for PRDM8 downregulation as a potential transcriptional regulation mechanism, analogous to that previously reported at high altitude for hypoxia-inducible factor 1α. Conclusions The unprecedented introgression signatures within both domestic camelid genomes may reflect post-conquest changes in agriculture and the breakdown of traditional management practices

Insight-HXMT observations of Swift J0243.6+6124 during its 2017-2018 outburst

The recently discovered neutron star transient Swift J0243.6+6124 has been monitored by {\it the Hard X-ray Modulation Telescope} ({\it Insight-\rm HXMT). Based on the obtained data, we investigate the broadband spectrum of the source throughout the outburst. We estimate the broadband flux of the source and search for possible cyclotron line in the broadband spectrum. No evidence of line-like features is, however, found up to $\rm 150~keV$. In the absence of any cyclotron line in its energy spectrum, we estimate the magnetic field of the source based on the observed spin evolution of the neutron star by applying two accretion torque models. In both cases, we get consistent results with $B\rm \sim 10^{13}~G$, $D\rm \sim 6~kpc$ and peak luminosity of $\rm >10^{39}~erg~s^{-1}$ which makes the source the first Galactic ultraluminous X-ray source hosting a neutron star.Comment: publishe

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Multilateral Teleoperation With New Cooperative Structure Based on Reconfigurable Robots and Type-2 Fuzzy Logic

This paper develops an innovative multilateral teleoperation system with two haptic devices in the master side and a newly-designed reconfigurable multi-fingered robot hand in the slave side. A novel non-singular fast terminal sliding mode (NFTSM) algorithm together with varying dominance factors for cooperation is proposed to offer this system fast position and force tracking, as well as an integrate perception for the operator on the robot hand. Type-2 fuzzy model is used to describe the overall system dynamics, and accordingly a new fuzzy-model-based state observer is proposed to compensate for the system uncertainties. A sliding mode adaptive controller is designed to deal with the varying zero drift of the force sensors and force observers. The stability of the closed-loop system under time-varying delays is proved using Lyapunov-Krasovskii functions. Finally, experiments to grasp different objects are performed to verify the effectiveness of this multilateral teleoperation system.Funding Agencies:Office of Naval Research Global ONRG-NICOP-N62909-15-1-2029  NUSRI China Jiangsu Provincial  BK20150386  BE2016077 Singapore NMRC Bedside and Bench Grant  R-397-000-245-511 </p

Compliant and Flexible Robotic System with Parallel Continuum Mechanism for Transoral Surgery: A Pilot Cadaveric Study

As one of the minimally invasive surgeries (MIS), transoral robotic surgery (TORS) contributes to excellent oncological and functional outcomes. This paper introduces a compliant and flexible robotic system for transoral surgery, consisting of an execution part with flexible parallel mechanisms and a positioning part with a continuum structure. A pilot cadaveric study that mimics the procedure of the TORS using an intact cadaveric human head was conducted to evaluate the feasibility and efficiency of this robotic system. Both the initial setup time and the time cost by the robot to safely access the deep surgical area in the upper aerodigestive tract are shortened due to the enlarged workspace, compact structure, and increased flexibility. The proposed surgical robotic system is preliminarily demonstrated to be feasible for TORS, especially for the in-depth surgical sites in the upper aerodigestive tract

Three-Dimensional Electro-Thermal Analysis of a New Type Current Transformer Design for Power Distribution Networks

In recent years, the new type design of current transformer with bushing structure has been widely used in the distribution network system due to its advantages of miniaturization, high mechanical strength, maintenance-free, safety and environmental protection. The internal temperature field distribution is an important characteristic parameter to characterize the thermal insulation and aging performance of the transformer, and the internal temperature field distribution is mainly derived from the joule heat generated by the primary side guide rod after flowing through the current. Since the electric environment is a transient field and the thermal environment changes slowly with time as a steady field under the actual conditions, it is more complex and necessary to study the electrothermal coupling field of current transformer (CT). In this paper, a 3D simulation model of a new type design of current transformer for distribution network based on electric-thermal coupling is established by using finite element method (FEM) software. Considering that the actual thermal conduction process of CT is mainly by conduction, convection and radiation, three different kinds of boundary conditions such as solid heat transfer boundary condition, heat convection boundary condition and surface radiation boundary condition are applied to the CT. Through the model created above, the temperature rise process and the distribution characteristics of temperature gradient of the inner conductor under different current, different ambient temperatures and different core diameters conditions are studied. Meanwhile, the hottest temperature and the maximum temperature gradient difference are calculated. According to this, the position of weak insulation of the transformer is determined. The research results can provide a reference for the factory production of new type design of current transformer