Novel Bayesian Networks for Genomic Prediction of Developmental Traits in Biomass Sorghum.

The ability to connect genetic information between traits over time allow Bayesian networks to offer a powerful probabilistic framework to construct genomic prediction models. In this study, we phenotyped a diversity panel of 869 biomass sorghum (Sorghum bicolor (L.) Moench) lines, which had been genotyped with 100,435 SNP markers, for plant height (PH) with biweekly measurements from 30 to 120 days after planting (DAP) and for end-of-season dry biomass yield (DBY) in four environments. We evaluated five genomic prediction models: Bayesian network (BN), Pleiotropic Bayesian network (PBN), Dynamic Bayesian network (DBN), multi-trait GBLUP (MTr-GBLUP), and multi-time GBLUP (MTi-GBLUP) models. In fivefold cross-validation, prediction accuracies ranged from 0.46 (PBN) to 0.49 (MTr-GBLUP) for DBY and from 0.47 (DBN, DAP120) to 0.75 (MTi-GBLUP, DAP60) for PH. Forward-chaining cross-validation further improved prediction accuracies of the DBN, MTi-GBLUP and MTr-GBLUP models for PH (training slice: 30-45 DAP) by 36.4-52.4% relative to the BN and PBN models. Coincidence indices (target: biomass, secondary: PH) and a coincidence index based on lines (PH time series) showed that the ranking of lines by PH changed minimally after 45 DAP. These results suggest a two-level indirect selection method for PH at harvest (first-level target trait) and DBY (second-level target trait) could be conducted earlier in the season based on ranking of lines by PH at 45 DAP (secondary trait). With the advance of high-throughput phenotyping technologies, our proposed two-level indirect selection framework could be valuable for enhancing genetic gain per unit of time when selecting on developmental traits

Impacts of elevated atmospheric CO₂ on nutrient content of important food crops.

One of the many ways that climate change may affect human health is by altering the nutrient content of food crops. However, previous attempts to study the effects of increased atmospheric CO2 on crop nutrition have been limited by small sample sizes and/or artificial growing conditions. Here we present data from a meta-analysis of the nutritional contents of the edible portions of 41 cultivars of six major crop species grown using free-air CO2 enrichment (FACE) technology to expose crops to ambient and elevated CO2 concentrations in otherwise normal field cultivation conditions. This data, collected across three continents, represents over ten times more data on the nutrient content of crops grown in FACE experiments than was previously available. We expect it to be deeply useful to future studies, such as efforts to understand the impacts of elevated atmospheric CO2 on crop macro- and micronutrient concentrations, or attempts to alleviate harmful effects of these changes for the billions of people who depend on these crops for essential nutrients

Low specificity of determine HIV1/2 RDT using whole blood in south west Tanzania

Objective: To evaluate the diagnostic performance of two rapid detection tests (RDTs) for HIV 1/2 in plasma and in whole blood samples. Methods: More than 15,000 study subjects above the age of two years participated in two rounds of a cohort study to determine the prevalence of HIV. HIV testing was performed using the Determine HIV 1/2 test (Abbott) in the first (2006/2007) and the HIV 1/2 STAT-PAK Dipstick Assay (Chembio) in the second round (2007/2008) of the survey. Positive results were classified into faint and strong bands depending on the visual appearance of the test strip and confirmed by ELISA and Western blot. Results: The sensitivity and specificity of the Determine RDT were 100% (95% confidence interval = 86.8 to 100%) and 96.8% (95.9 to 97.6%) in whole blood and 100% (99.7 to 100%) and 97.9% (97.6 to 98.1%) in plasma respectively. Specificity was highly dependent on the tested sample type: when using whole blood, 67.1% of positive results were false positive, as opposed to 17.4% in plasma. Test strips with only faint positive bands were more often false positive than strips showing strong bands and were more common in whole blood than in plasma. Evaluation of the STAT-PAK RDT in plasma during the second year resulted in a sensitivity of 99.7% (99.1 to 99.9%) and a specificity of 99.3% (99.1 to 99.4%) with 6.9% of the positive results being false. Conclusions: Our study shows that the Determine HIV 1/2 strip test with its high sensitivity is an excellent tool to screen for HIV infection, but that – at least in our setting – it can not be recommended as a confirmatory test in VCT campaigns where whole blood is used

Supersymmetric QCD: Exact Results and Strong Coupling

We revisit two longstanding puzzles in supersymmetric gauge theories. The first concerns the question of the holomorphy of the coupling, and related to this the possible definition of an exact (NSVZ) beta function. The second concerns instantons in pure gluodynamics, which appear to give sensible, exact results for certain correlation functions, which nonetheless differ from those obtained using systematic weak coupling expansions. For the first question, we extend an earlier proposal of Arkani-Hamed and Murayama, showing that if their regulated action is written suitably, the holomorphy of the couplings is manifest, and it is easy to determine the renormalization scheme for which the NSVZ formula holds. This scheme, however, is seen to be one of an infinite class of schemes, each leading to an exact beta function; the NSVZ scheme, while simple, is not selected by any compelling physical consideration. For the second question, we explain why the instanton computation in the pure supersymmetric gauge theory is not reliable, even at short distances. The semiclassical expansion about the instanton is purely formal; if infrared divergences appear, they spoil arguments based on holomorphy. We demonstrate that infrared divergences do not occur in the perturbation expansion about the instanton, but explain that there is no reason to think this captures all contributions from the sector with unit topological charge. That one expects additional contributions is illustrated by dilute gas corrections. These are infrared divergent, and so difficult to define, but if non-zero give order one, holomorphic, corrections to the leading result. Exploiting an earlier analysis of Davies et al, we demonstrate that in the theory compactified on a circle of radius beta, due to infrared effects, finite contributions indeed arise which are not visible in the formal limit that beta goes to infinity.Comment: 28 pages, two references added, one typo correcte

Index Theorem and Overlap Formalism with Naive and Minimally Doubled Fermions

We present a theoretical foundation for the Index theorem in naive and minimally doubled lattice fermions by studying the spectral flow of a Hermitean version of Dirac operators. We utilize the point splitting method to implement flavored mass terms, which play an important role in constructing proper Hermitean operators. We show the spectral flow correctly detects the index of the would-be zero modes which is determined by gauge field topology. Using the flavored mass terms, we present new types of overlap fermions from the naive fermion kernels, with a number of flavors that depends on the choice of the mass terms. We succeed to obtain a single-flavor naive overlap fermion which maintains hypercubic symmetry.Comment: 27 pages, 17 figures; references added, version accepted in JHE

Incentivizing research into the effectiveness of medical devices

Introduction Medical devices (MDs) often obtain market authorization with much less clinical evidence than other health technologies, especially pharmaceuticals. This is due to a number of reasons. First, in contrast to pharmaceuticals, there is no legal requirement to conduct adequately controlled clinical studies, other than for ‘high-risk’ devices in some jurisdictions. In the US for example, high-risk devices and innovative lower-risk devices are required to demonstrate ‘reasonable assurance of safety and effectiveness’, which may imply clinical evidence based on randomized studies in many instances. In contrast, in the EU the requirement is to demonstrate adequate performance and safety, which can often be achieved by conducting observational studies such as registries [1, 2]. Secondly, the devices industry comprises many small and medium-size enterprises (SMEs), which would find the cost of conducting clinical studies, especially randomized controlled trials, prohibitive. However, although some larger manufacturers do undertake clinical studies of some of their products, manufacturers with similar products (called ‘fast-followers’) can often claim ‘substantial equivalence’ to a product that already has market authorization, thus avoiding the need to conduct costly and timeconsuming clinical studies. Since regulatory agencies often accept these claims of equivalence, for example under the 510(k) process in the US [3], this further reduces the incentives for manufacturers to conduct expensive clinical studies. Therefore, although device manufacturers have patent protection, they are often not granted data exclusivity in the same way as pharmaceutical manufacturers. Finally, unlike pharmaceuticals, devices are often modified once on the market, meaning that even if clinical evidence was available for the original version of the product, it may not necessarily be available for the version currently being marketed. For example in the US, one analysis showed that for 77 original market authorization applications for cardiac implantable electronic devices (e.g., pacemakers, implantable cardioverter-defibrillators) since 1979, the FDA approved 5829 ‘supplements’ reflecting product modifications in the period up until 2012. Of course, many of these product modifications were minor and unlikely to affect the performance of the device, but 37 % involved a change to the device’s design. In the vast majority of these cases the FDA deemed that new clinical data were not necessary for approval [4]. The lack of clinical evidence prior to product launch, especially evidence of comparative effectiveness, limits the possibilities for health technology assessment [2]. However, it should be remembered that clinical evidence can be gathered both pre-market (i.e., through conducting controlled clinical trials in an experimental setting), and postmarket, through clinical studies undertaken in regular clinical practice. Post-market effectiveness research may be more important for MDs than pharmaceuticals, as the performance of the device often depends on the interaction with the user (the so-called learning curve) [5]. This suggests that solutions to the problem of inadequate clinical evidence should address the issue of conducting clinical research in both the pre- and post-market phase. In this editorial we consider ways in which MD manufacturers could be incentivized to produce more clinical evidence to facilitate health technology assessments, including economic evaluations

Haloalkane-utilizing Rhodococcus strains isolated from geographically distinct locations possess a highly conserved gene cluster encoding haloalkane catabolism

The sequences of the 16S rRNA and haloalkane dehalogenase (dhaA) genes of five gram-positive haloalkane-utilizing bacteria isolated from contaminated sites in Europe, Japan, and the United States and of the archetypal haloalkane-degrading bacterium Rhodococcus sp. strain NCIMB13064 were compared. The 16S rRNA gene sequences showed less than 1% sequence divergence, and all haloalkane degraders clearly belonged to the genus Rhodococcus. All strains shared a completely conserved dhaA gene, suggesting that the dhaA genes were recently derived from a common ancestor. The genetic organization of the dhaA gene region in each of the haloalkane degraders was examined by hybridization analysis and DNA sequencing. Three different groups could be defined on the basis of the extent of the conserved dhaA segment. The minimal structure present in all strains consisted of a conserved region of 12.5 kb, which included the haloalkane-degradative gene cluster that was previously found in strain NCIMB13064. Plasmids of different sizes were found in all strains. Southern hybridization analysis with a dhaA gene probe suggested that all haloalkane degraders carry the dhaA gene region both on the chromosome and on a plasmid (70 to 100 kb). This suggests that an ancestral plasmid was transferred between these Rhodococcus strains and subsequently has undergone insertions or deletions. In addition, transposition events and/or plasmid integration may be responsible for positioning the dhaA gene region on the chromosome. The data suggest that the haloalkane dehalogenase gene regions of these gram-positive haloalkane-utilizing bacteria are composed of a single catabolic gene cluster that was recently distributed world-wide

In Vivo Time- Resolved Microtomography Reveals the Mechanics of the Blowfly Flight Motor

Dipteran flies are amongst the smallest and most agile of flying animals. Their wings are driven indirectly by large power muscles, which cause cyclical deformations of the thorax that are amplified through the intricate wing hinge. Asymmetric flight manoeuvres are controlled by 13 pairs of steering muscles acting directly on the wing articulations. Collectively the steering muscles account for <3% of total flight muscle mass, raising the question of how they can modulate the vastly greater output of the power muscles during manoeuvres. Here we present the results of a synchrotron-based study performing micrometre-resolution, time-resolved microtomography on the 145 Hz wingbeat of blowflies. These data represent the first four-dimensional visualizations of an organism's internal movements on sub-millisecond and micrometre scales. This technique allows us to visualize and measure the three-dimensional movements of five of the largest steering muscles, and to place these in the context of the deforming thoracic mechanism that the muscles actuate. Our visualizations show that the steering muscles operate through a diverse range of nonlinear mechanisms, revealing several unexpected features that could not have been identified using any other technique. The tendons of some steering muscles buckle on every wingbeat to accommodate high amplitude movements of the wing hinge. Other steering muscles absorb kinetic energy from an oscillating control linkage, which rotates at low wingbeat amplitude but translates at high wingbeat amplitude. Kinetic energy is distributed differently in these two modes of oscillation, which may play a role in asymmetric power management during flight control. Structural flexibility is known to be important to the aerodynamic efficiency of insect wings, and to the function of their indirect power muscles. We show that it is integral also to the operation of the steering muscles, and so to the functional flexibility of the insect flight motor

Attosecond control of electrons emitted from a nanoscale metal tip

Attosecond science is based on steering of electrons with the electric field of well-controlled femtosecond laser pulses. It has led to, for example, the generation of XUV light pulses with a duration in the sub-100-attosecond regime, to the measurement of intra-molecular dynamics by diffraction of an electron taken from the molecule under scrutiny, and to novel ultrafast electron holography. All these effects have been observed with atoms or molecules in the gas phase. Although predicted to occur, a strong light-phase sensitivity of electrons liberated by few-cycle laser pulses from solids has hitherto been elusive. Here we show a carrier-envelope (C-E) phase-dependent current modulation of up to 100% recorded in spectra of electrons laser-emitted from a nanometric tungsten tip. Controlled by the C-E phase, electrons originate from either one or two sub-500as long instances within the 6-fs laser pulse, leading to the presence or absence of spectral interference. We also show that coherent elastic re-scattering of liberated electrons takes place at the metal surface. Due to field enhancement at the tip, a simple laser oscillator suffices to reach the required peak electric field strengths, allowing attosecond science experiments to be performed at the 100-Megahertz repetition rate level and rendering complex amplified laser systems dispensable. Practically, this work represents a simple, exquisitely sensitive C-E phase sensor device, which can be shrunk in volume down to ~ 1cm3. The results indicate that the above-mentioned novel attosecond science techniques developed with and for atoms and molecules can also be employed with solids. In particular, we foresee sub-femtosecond (sub-) nanometre probing of (collective) electron dynamics, such as plasmon polaritons, in solid-state systems ranging in size from mesoscopic solids via clusters to single protruding atoms.Comment: Final manuscript version submitted to Natur