Utility and Efficiency of Homologous Recombination for Introducing Targeted Modifications to the Pig Genome

The production and utilization of genetically modified animals greatly improves their utility in agriculture, as biomedical research models of human disease, for the production of recombinant pharmaceutical proteins, and for production of organs with greater potential for xenotransplantation. While numerous strategies have been utilized in the production of transgenic large animals, cell-based transgenesis followed by somatic cell nuclear transfer (SCNT) is currently the most widely applied method. We constructed a targeting vector with 2774 and 1890 bp arms of homology flanking a neomycin resistant gene. Following delivery of the DNA targeting vector into the porcine fetal fibroblasts by electroporation and selection with G418, PCR and sequencing confirmed one of 547 transgenic clonal colonies contained the targeted introduction of the neomycin resistance gene. Genetically modified fibroblast donor cells can be utilized for SCNT for the development of genetically modified pigs to study biological mechanisms important for animal agriculture and to create biomedical models

Effects of Sample Disturbance and Consolidation Procedures on Cyclic Strengths of Intermediate Soils

Sampling and testing of soils to measure engineering properties, such as monotonic and cyclic undrained shear strengths, requires an understanding of the potential effects of sampling disturbance and the selection of appropriate laboratory testing procedures. For clays, past research has provided insights on how sampling methods and laboratory testing procedures can be used in practice to assess and minimize sample disturbance effects. For sands, past research has shown that conventional tube sampling techniques cause excessive disturbance to the soil fabric, such that subsequent measurement of monotonic or cyclic strengths can be greatly in error and misleading. For intermediate soils, the effects of disturbance and consolidation procedures on monotonic and cyclic strengths are not well understood. In the present study, a test protocol was developed to assess the effects that disturbance during sample extrusion, trimming, and mounting have on subsequent measurements of compressibility, monotonic undrained strength, and cyclic undrained strength. Detailed laboratory tests were performed on tube samples from deposits of low-plasticity silty clay, for which conventional sampling and testing were expected to work reasonably well, and low-plasticity clayey sand, for which the effects of sample disturbance were of primary concern. Test results using this protocol for these two soils are presented and discussed

The role of the systemic inflammatory response in predicting outcomes in patients with operable cancer: Systematic review and meta-analysis

Cancer remains a leading causes of death worldwide and an elevated systemic inflammatory response (SIR) is associated with reduced survival in patients with operable cancer. This review aims to examine the evidence for the role of systemic inflammation based prognostic scores in patients with operable cancers. A wide-ranging literature review using targeted medical subject headings for human studies in English was carried out in the MEDLINE, EMBASE, and CDSR databases until the end of 2016. The SIR has independent prognostic value, across tumour types and geographical locations. In particular neutrophil lymphocyte ratio (NLR) (n = 158), platelet lymphocyte ratio (PLR) (n = 68), lymphocyte monocyte ratio (LMR) (n = 21) and Glasgow Prognostic Score/ modified Glasgow Prognostic Score (GPS/mGPS) (n = 60) were consistently validated. On meta-analysis there was a significant relationship between elevated NLR and overall survival (OS) (p < 0.00001)/ cancer specific survival (CSS) (p < 0.00001), between elevated LMR and OS (p < 0.00001)/CSS (p < 0.00001), and elevated PLR and OS (p < 0.00001)/CSS (p = 0.005). There was also a significant relationship between elevated GPS/mGPS and OS (p < 0.00001)/CSS (p < 0.00001). These results consolidate the prognostic value of the NLR, PLR, LMR and GPS/mGPS in patients with resectable cancers. This is particularly true for the NLR/GPS/mGPS which should form part of the routine preoperative and postoperative workup

The global distribution of Bacillus anthracis and associated anthrax risk to humans, livestock and wildlife.

Bacillus anthracis is a spore-forming, Gram-positive bacterium responsible for anthrax, an acute infection that most significantly affects grazing livestock and wild ungulates, but also poses a threat to human health. The geographic extent of B. anthracis is poorly understood, despite multi-decade research on anthrax epizootic and epidemic dynamics; many countries have limited or inadequate surveillance systems, even within known endemic regions. Here, we compile a global occurrence dataset of human, livestock and wildlife anthrax outbreaks. With these records, we use boosted regression trees to produce a map of the global distribution of B. anthracis as a proxy for anthrax risk. We estimate that 1.83 billion people (95% credible interval (CI): 0.59-4.16 billion) live within regions of anthrax risk, but most of that population faces little occupational exposure. More informatively, a global total of 63.8 million poor livestock keepers (95% CI: 17.5-168.6 million) and 1.1 billion livestock (95% CI: 0.4-2.3 billion) live within vulnerable regions. Human and livestock vulnerability are both concentrated in rural rainfed systems throughout arid and temperate land across Eurasia, Africa and North America. We conclude by mapping where anthrax risk could disrupt sensitive conservation efforts for wild ungulates that coincide with anthrax-prone landscapes

Neuromotor Changes in Participants with a Concussion History can be Detected with a Custom Smartphone App

Neuromotor dysfunction after a concussion is common, but balance tests used to assess neuromotor dysfunction are typically subjective. Current objective balance tests are either cost- or space-prohibitive, or utilize a static balance protocol, which may mask neuromotor dysfunction due to the simplicity of the task. To address this gap, our team developed an Android-based smartphone app (portable and cost-effective) that uses the sensors in the device (objective) to record movement profiles during a stepping-in-place task (dynamic movement). The purpose of this study was to examine the extent to which our custom smartphone app and protocol could discriminate neuromotor behavior between concussed and non-concussed participants. Data were collected at two university laboratories and two military sites. Participants included civilians and Service Members (N = 216) with and without a clinically diagnosed concussion. Kinematic and variability metrics were derived from a thigh angle time series while the participants completed a series of stepping-in-place tasks in three conditions: eyes open, eyes closed, and head shake. We observed that the standard deviation of the mean maximum angular velocity of the thigh was higher in the participants with a concussion history in the eyes closed and head shake conditions of the stepping-in-place task. Consistent with the optimal movement variability hypothesis, we showed that increased movement variability occurs in participants with a concussion history, for which our smartphone app and protocol were sensitive enough to capture

Mechanically Stabilized Tetrathiafulvalene Radical Dimers

Two donor−acceptor [3]catenanes—composed of a tetracationic molecular square, cyclobis(paraquat-4,4′-biphenylene), as the π-electron deficient ring and either two tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP) containing macrocycles or two TTF-butadiyne-containing macrocycles as the π-electron rich components—have been investigated in order to study their ability to form TTF radical dimers. It has been proven that the mechanically interlocked nature of the [3]catenanes facilitates the formation of the TTF radical dimers under redox control, allowing an investigation to be performed on these intermolecular interactions in a so-called “molecular flask” under ambient conditions in considerable detail. In addition, it has also been shown that the stability of the TTF radical-cation dimers can be tuned by varying the secondary binding motifs in the [3]catenanes. By replacing the DNP station with a butadiyne group, the distribution of the TTF radical-cation dimer can be changed from 60% to 100%. These findings have been established by several techniques including cyclic voltammetry, spectroelectrochemistry and UV−vis−NIR and EPR spectroscopies, as well as with X-ray diffraction analysis which has provided a range of solid-state crystal structures. The experimental data are also supported by high-level DFT calculations. The results contribute significantly to our fundamental understanding of the interactions within the TTF radical dimers

Electron multiplication CCD detector technology advancement for the WFIRST-AFTA coronagraph

The WFIRST-AFTA (Wide Field InfraRed Survey Telescope-Astrophysics Focused Telescope Asset) is a NASA space observatory. It will host two major astronomical instruments: a wide-field imager (WFI) to search for dark energy and carry out wide field near infrared (NIR) surveys, and a coronagraph instrument (CGI) to image and spectrally characterize extrasolar planets. In this paper, we discuss the work that has been carried out at JPL in advancing Electron Multiplying CCD (EMCCD) technology to higher flight maturity, with the goal of reaching a NASA technology readiness level of 6 (TRL-6) by early-to-mid 2016. The EMCCD has been baselined for both the coronagraph's imager and integral field spectrograph (IFS) based on its sub-electron noise performance at extremely low flux levels - the regime where the AFTA CGI will operate. We present results from a study that fully characterizes the beginning of life performance of the EMCCD. We also discuss, and present initial results from, a recent radiation test campaign that was designed and carried out to mimic the conditions of the WFIRST-AFTA space environment in an L2 orbit, where we sought to assess the sensor's end of life performance, particularly degradation of its charge transfer efficiency, in addition to other parameters such as dark current, electron multiplication gain, clock induced charge and read noise