Model selection and prediction of outcomes in recent onset schizophrenia patients who undergo cognitive training.

Predicting treatment outcomes in psychiatric populations remains a challenge, but is increasingly important in the pursuit of personalized medicine. Patients with schizophrenia have deficits in cognition, and targeted cognitive training (TCT) of auditory processing and working memory has been shown to improve some of these impairments; but little is known about the baseline patient characteristics predictive of cognitive improvement. Here we use a model selection and regression approach called least absolute shrinkage and selection operator (LASSO) to examine predictors of cognitive improvement in response to TCT for patients with recent onset schizophrenia. Forty-three individuals with recent onset schizophrenia randomized to undergo TCT were assessed at baseline on measures of cognition, symptoms, functioning, illness duration, and demographic variables. We carried out 10-fold cross-validation of LASSO for model selection and regression. We followed up on these results using linear models for statistical inference. No individual variable was found to correlate with improvement in global cognition using a Pearson correlation approach, and a linear model including all variables was also found not to be significant. However, the LASSO model identified baseline global cognition, education, and gender in a model predictive of improvement on global cognition following TCT. These findings offer guidelines for personalized approaches to cognitive training for patients with schizophrenia

Cosmology and Astrophysical Constraints of Gauss-Bonnet Dark Energy

Cosmological consequences of a string-motivated dark energy scenario featuring a scalar field coupled to the Gauss-Bonnet invariant are investigated. We study the evolution of the universe in such a model, identifying its key properties. The evolution of the homogeneous background and cosmological perturbations, both at large and small scales, are calculated. The impact of the coupling on galaxy distributions and the cosmic microwave background is examined. We find the coupling provides a mechanism to viably onset the late acceleration, to alleviate the coincidence problem, and furthermore to effectively cross the phantom divide at the present while avoiding a Big Rip in the future. We show the model could explain the present cosmological observations, and discuss how various astrophysical and cosmological data, from the Solar system, supernovae Ia, cosmic microwave background radiation and large scale structure constrain it.Comment: 6 pages, 3 figures. References added. Accepted for publication in Phys. Lett.

On the gravitational, dilatonic and axionic radiative damping of cosmic strings

We study the radiation reaction on cosmic strings due to the emission of dilatonic, gravitational and axionic waves. After verifying the (on average) conservative nature of the time-symmetric self-interactions, we concentrate on the finite radiation damping force associated with the half-retarded minus half-advanced ``reactive'' fields. We revisit a recent proposal of using a ``local back reaction approximation'' for the reactive fields. Using dimensional continuation as convenient technical tool, we find, contrary to previous claims, that this proposal leads to antidamping in the case of the axionic field, and to zero (integrated) damping in the case of the gravitational field. One gets normal positive damping only in the case of the dilatonic field. We propose to use a suitably modified version of the local dilatonic radiation reaction as a substitute for the exact (non-local) gravitational radiation reaction. The incorporation of such a local approximation to gravitational radiation reaction should allow one to complete, in a computationally non-intensive way, string network simulations and to give better estimates of the amount and spectrum of gravitational radiation emitted by a cosmologically evolving network of massive strings.Comment: 48 pages, RevTex, epsfig, 1 figure; clarification of the domain of validity of the perturbative derivation of the string equations of motion, and of their renormalizabilit

Mechanical control of the directional stepping dynamics of the kinesin motor

Among the multiple steps constituting the kinesin's mechanochemical cycle, one of the most interesting events is observed when kinesins move an 8-nm step from one microtubule (MT)-binding site to another. The stepping motion that occurs within a relatively short time scale (~100 microsec) is, however, beyond the resolution of current experiments, therefore a basic understanding to the real-time dynamics within the 8-nm step is still lacking. For instance, the rate of power stroke (or conformational change), that leads to the undocked-to-docked transition of neck-linker, is not known, and the existence of a substep during the 8-nm step still remains a controversial issue in the kinesin community. By using explicit structures of the kinesin dimer and the MT consisting of 13 protofilaments (PFs), we study the stepping dynamics with varying rates of power stroke (kp). We estimate that 1/kp <~ 20 microsec to avoid a substep in an averaged time trace. For a slow power stroke with 1/kp>20 microsec, the averaged time trace shows a substep that implies the existence of a transient intermediate, which is reminiscent of a recent single molecule experiment at high resolution. We identify the intermediate as a conformation in which the tethered head is trapped in the sideway binding site of the neighboring PF. We also find a partial unfolding (cracking) of the binding motifs occurring at the transition state ensemble along the pathways prior to binding between the kinesin and MT.Comment: 26 pages, 10 figure

Constraint methods for determining pathways and free energy of activated processes

Activated processes from chemical reactions up to conformational transitions of large biomolecules are hampered by barriers which are overcome only by the input of some free energy of activation. Hence, the characteristic and rate-determining barrier regions are not sufficiently sampled by usual simulation techniques. Constraints on a reaction coordinate r have turned out to be a suitable means to explore difficult pathways without changing potential function, energy or temperature. For a dense sequence of values of r, the corresponding sequence of simulations provides a pathway for the process. As only one coordinate among thousands is fixed during each simulation, the pathway essentially reflects the system's internal dynamics. From mean forces the free energy profile can be calculated to obtain reaction rates and insight in the reaction mechanism. In the last decade, theoretical tools and computing capacity have been developed to a degree where simulations give impressive qualitative insight in the processes at quantitative agreement with experiments. Here, we give an introduction to reaction pathways and coordinates, and develop the theory of free energy as the potential of mean force. We clarify the connection between mean force and constraint force which is the central quantity evaluated, and discuss the mass metric tensor correction. Well-behaved coordinates without tensor correction are considered. We discuss the theoretical background and practical implementation on the example of the reaction coordinate of targeted molecular dynamics simulation. Finally, we compare applications of constraint methods and other techniques developed for the same purpose, and discuss the limits of the approach

Novel scaling behavior of the Ising model on curved surfaces

We demonstrate the nontrivial scaling behavior of Ising models defined on (i) a donut-shaped surface and (ii) a curved surface with a constant negative curvature. By performing Monte Carlo simulations, we find that the former model has two distinct critical temperatures at which both the specific heat $C(T)$ and magnetic susceptibility $\chi(T)$ show sharp peaks.The critical exponents associated with the two critical temperatures are evaluated by the finite-size scaling analysis; the result reveals that the values of these exponents vary depending on the temperature range under consideration. In the case of the latter model, it is found that static and dynamic critical exponents deviate from those of the Ising model on a flat plane; this is a direct consequence of the constant negative curvature of the underlying surface.Comment: 11 pages 5 figure

A proteomic and phosphoproteomic analysis of Oryza sativa plasma membrane and vacuolar membrane

Proteomic and phosphoproteomic analyses of rice shoot and root tonoplast-enriched and plasma membrane-enriched membrane fractions were carried out to look at tissue-specific expression, and to identify putative regulatory sites of membrane transport proteins. Around 90 unique membrane proteins were identified, which included primary and secondary transporters, ion channels and aquaporins. Primary H+ pumps from the AHA family showed little isoform specificity in their tissue expression pattern, whereas specific isoforms of the Ca2+ pump ECA/ACA family were expressed in root and shoot tissues. Several ABC transporters were detected, particularly from the MDR and PDR subfamilies, which often showed expression in either roots or shoots. Ammonium transporters were expressed in root, but not shoot, tissue. Large numbers of sugar transporters were expressed, particularly in green tissue. The occurrence of phosphorylation sites in rice transporters such as AMT1;1 and PIP2;6 agrees with those previously described in other species, pointing to conserved regulatory mechanisms. New phosphosites were found in many transporters, including H+ pumps and H+:cation antiporters, often at residues that are well conserved across gene families. Comparison of root and shoot tissue showed that phosphorylation of AMT1;1 and several further transporters may be tissue dependent

Tau Signals of R-parity breaking at LEP 200

The detectability at LEP 200 of explicit $R$-parity breaking by tau-number $(L_\tau)$ violating operators is considered. The assumption of $L_\tau$-violation is motivated by the relative lack of constraints on such couplings but similar considerations apply to explicit $L_e$- or $L_\mu$-violation. The $LSP$, now unstable, and not necessarily neutral, decays via $L_\tau$-violating modes. Only signals from the production and decays of $LSP$ pairs are considered, thereby avoiding any dependence on the sparticle mass spectrum. Rather spectacular signals are predicted: spherical events with $m$ leptons (usually containing at least one $\tau$) and $n$ jets $(m,n \leq 4)$, the most characteristic of which are like-sign $\tau\tau$ events. These signals are enumerated for each $LSP$ candidate and quantitative estimates are provided for the favoured case when the $LSP$ is a neutralino. Other new physics signals, which can mimic these signatures, are also briefly discussed.Comment: 27 pages in PHYZZX, six figures (not included, available on request). TIFR/TH/92-29,UH-511-751-92,CERN-TH.6613/9