Untranslated regions of diverse plant viral RNAs vary greatly in translation enhancement efficiency

Background: Whole plants or plant cell cultures can serve as low cost bioreactors to produce massive amounts of a specific protein for pharmacological or industrial use. To maximize protein expression, translation of mRNA must be optimized. Many plant viral RNAs harbor extremely efficient translation enhancers. However, few of these different translation elements have been compared side-by-side. Thus, it is unclear which are the most efficient translation enhancers. Here, we compare the effects of untranslated regions (UTRs) containing translation elements from six plant viruses on translation in wheat germ extract and in monocotyledenous and dicotyledenous plant cells.Results: The highest expressing uncapped mRNAs contained viral UTRs harboring Barley yellow dwarf virus (BYDV)-like cap-independent translation elements (BTEs). The BYDV BTE conferred the most efficient translation of a luciferase reporter in wheat germ extract and oat protoplasts, while uncapped mRNA containing the BTE from Tobacco necrosis virus-D translated most efficiently in tobacco cells. Capped mRNA containing the Tobacco mosaic virus omega sequence was the most efficient mRNA in tobacco cells. UTRs from Satellite tobacco necrosis virus, Tomato bushy stunt virus, and Crucifer-infecting tobamovirus (crTMV) did not stimulate translation efficiently. mRNA with the crTMV 5′ UTR was unstable in tobacco protoplasts.Conclusions: BTEs confer the highest levels of translation of uncapped mRNAs in vitro and in vivo, while the capped omega sequence is most efficient in tobacco cells. These results provide a basis for understanding mechanisms of translation enhancement, and for maximizing protein synthesis in cell-free systems, transgenic plants, or in viral expression vectors

Cation-dependent folding of 30 cap-independent translation elements facilitates interaction of a 17-nucleotide conserved sequence with eIF4G

The 3\u27-untranslated regions of many plant viral RNAs contain cap-independent translation elements (CITEs) that drive translation initiation at the 5\u27-end of the mRNA. The barley yellow dwarf virus-like CITE (BTE) stimulates translation by binding the eIF4G subunit of translation initiation factor eIF4F with high affinity. To understand this interaction, we characterized the dynamic structural properties of the BTE, mapped the eIF4G-binding sites on the BTE and identified a region of eIF4G that is crucial for BTE binding. BTE folding involves cooperative uptake of magnesium ions and is driven primarily by charge neutralization. Footprinting experiments revealed that functional eIF4G fragments protect the highly conserved stem-loop I and a downstream bulge. The BTE forms a functional structure in the absence of protein, and the loop that base pairs the 5\u27-untranslated region (5\u27-UTR) remains solventaccessible at high eIF4G concentrations. The region in eIF4G between the eIF4E-binding site and the MIF4G region is required for BTE binding and translation. The data support the model in which the eIF4F complex binds directly to the BTE which base pairs simultaneously to the 5\u27-UTR, allowing eIF4F to recruit the 40S ribosomal subunit to the 5\u27-end

On a class of invariant coframe operators with application to gravity

Let a differential 4D-manifold with a smooth coframe field be given. Consider the operators on it that are linear in the second order derivatives or quadratic in the first order derivatives of the coframe, both with coefficients that depend on the coframe variables. The paper exhibits the class of operators that are invariant under a general change of coordinates, and, also, invariant under the global SO(1,3)-transformation of the coframe. A general class of field equations is constructed. We display two subclasses in it. The subclass of field equations that are derivable from action principles by free variations and the subclass of field equations for which spherical-symmetric solutions, Minkowskian at infinity exist. Then, for the spherical-symmetric solutions, the resulting metric is computed. Invoking the Geodesic Postulate, we find all the equations that are experimentally (by the 3 classical tests) indistinguishable from Einstein field equations. This family includes, of course, also Einstein equations. Moreover, it is shown, explicitly, how to exhibit it. The basic tool employed in the paper is an invariant formulation reminiscent of Cartan's structural equations. The article sheds light on the possibilities and limitations of the coframe gravity. It may also serve as a general procedure to derive covariant field equations

Problematic internet use (PIU): Associations with the impulsive-compulsive spectrum. An application of machine learning in psychiatry.

Problematic internet use is common, functionally impairing, and in need of further study. Its relationship with obsessive-compulsive and impulsive disorders is unclear. Our objective was to evaluate whether problematic internet use can be predicted from recognised forms of impulsive and compulsive traits and symptomatology. We recruited volunteers aged 18 and older using media advertisements at two sites (Chicago USA, and Stellenbosch, South Africa) to complete an extensive online survey. State-of-the-art out-of-sample evaluation of machine learning predictive models was used, which included Logistic Regression, Random Forests and Naïve Bayes. Problematic internet use was identified using the Internet Addiction Test (IAT). 2006 complete cases were analysed, of whom 181 (9.0%) had moderate/severe problematic internet use. Using Logistic Regression and Naïve Bayes we produced a classification prediction with a receiver operating characteristic area under the curve (ROC-AUC) of 0.83 (SD 0.03) whereas using a Random Forests algorithm the prediction ROC-AUC was 0.84 (SD 0.03) [all three models superior to baseline models p < 0.0001]. The models showed robust transfer between the study sites in all validation sets [p < 0.0001]. Prediction of problematic internet use was possible using specific measures of impulsivity and compulsivity in a population of volunteers. Moreover, this study offers proof-of-concept in support of using machine learning in psychiatry to demonstrate replicability of results across geographically and culturally distinct settings.This research received internal departmental funds of the Department of Psychiatry at the University of Chicago.This is the final version of the article. It first appeared from Elsevier at http://dx.doi.org/10.1016/j.jpsychires.2016.08.010

A fully relativistic radial fall

Radial fall has historically played a momentous role. It is one of the most classical problems, the solutions of which represent the level of understanding of gravitation in a given epoch. A {\it gedankenexperiment} in a modern frame is given by a small body, like a compact star or a solar mass black hole, captured by a supermassive black hole. The mass of the small body itself and the emission of gravitational radiation cause the departure from the geodesic path due to the back-action, that is the self-force. For radial fall, as any other non-adiabatic motion, the instantaneous identity of the radiated energy and the loss of orbital energy cannot be imposed and provide the perturbed trajectory. In the first part of this letter, we present the effects due to the self-force computed on the geodesic trajectory in the background field. Compared to the latter trajectory, in the Regge-Wheeler, harmonic and all others smoothly related gauges, a far observer concludes that the self-force pushes inward (not outward) the falling body, with a strength proportional to the mass of the small body for a given large mass; further, the same observer notes an higher value of the maximal coordinate velocity, this value being reached earlier on during infall. In the second part of this letter, we implement a self-consistent approach for which the trajectory is iteratively corrected by the self-force, this time computed on osculating geodesics. Finally, we compare the motion driven by the self-force without and with self-consistent orbital evolution. Subtle differences are noticeable, even if self-force effects have hardly the time to accumulate in such a short orbit.Comment: To appear in Int. J. Geom. Meth. Mod. Phy

The Relativistic Electrodynamics Least Action Principles Revisited: New Charged Point Particle and Hadronic String Models Analysis

The classical relativistic least action principle is revisited from the vacuum field theory approach. New physically motivated versions of relativistic Lorentz type forces are derived, a new relativistic hadronic string model is proposed and analyzed in detail.Comment: n/

Invariance and variability in interaction error-related potentials and their consequences for classification

© 2017 IOP Publishing Ltd. Objective. This paper discusses the invariance and variability in interaction error-related potentials (ErrPs), where a special focus is laid upon the factors of (1) the human mental processing required to assess interface actions (2) time (3) subjects. Approach. Three different experiments were designed as to vary primarily with respect to the mental processes that are necessary to assess whether an interface error has occurred or not. The three experiments were carried out with 11 subjects in a repeated-measures experimental design. To study the effect of time, a subset of the recruited subjects additionally performed the same experiments on different days. Main results. The ErrP variability across the different experiments for the same subjects was found largely attributable to the different mental processing required to assess interface actions. Nonetheless, we found that interaction ErrPs are empirically invariant over time (for the same subject and same interface) and to a lesser extent across subjects (for the same interface). Significance. The obtained results may be used to explain across-study variability of ErrPs, as well as to define guidelines for approaches to the ErrP classifier transferability problem

Fourth order gravity: equations, history, and applications to cosmology

The field equations following from a Lagrangian L(R) will be deduced and solved for special cases. If L is a non-linear function of the curvature scalar, then these equations are of fourth order in the metric. In the introduction we present the history of these equations beginning with the paper of H. Weyl from 1918, who first discussed them as alternative to Einstein's theory. In the third part, we give details about the cosmic no hair theorem, i.e., the details how within fourth order gravity with L= R + R^2 the inflationary phase of cosmic evolution turns out to be a transient attractor. Finally, the Bicknell theorem, i.e. the conformal relation from fourth order gravity to scalar-tensor theory, will be shortly presented.Comment: 51 pages, LaTeX, no figure, lecture for 42nd Karpacz Winter School 6.-11.2.06, references 99-109 and related comments are adde