Fiber-Flux Diffusion Density for White Matter Tracts Analysis: Application to Mild Anomalies Localization in Contact Sports Players

We present the concept of fiber-flux density for locally quantifying white matter (WM) fiber bundles. By combining scalar diffusivity measures (e.g., fractional anisotropy) with fiber-flux measurements, we define new local descriptors called Fiber-Flux Diffusion Density (FFDD) vectors. Applying each descriptor throughout fiber bundles allows along-tract coupling of a specific diffusion measure with geometrical properties, such as fiber orientation and coherence. A key step in the proposed framework is the construction of an FFDD dissimilarity measure for sub-voxel alignment of fiber bundles, based on the fast marching method (FMM). The obtained aligned WM tract-profiles enable meaningful inter-subject comparisons and group-wise statistical analysis. We demonstrate our method using two different datasets of contact sports players. Along-tract pairwise comparison as well as group-wise analysis, with respect to non-player healthy controls, reveal significant and spatially-consistent FFDD anomalies. Comparing our method with along-tract FA analysis shows improved sensitivity to subtle structural anomalies in football players over standard FA measurements

Preparation and Use of a General Solid-Phase Intermediate to Biomimetic Scaffolds and Peptide Condensations

The Distributed Drug Discovery (D3) program develops simple, powerful, and reproducible procedures to enable the distributed synthesis of large numbers of potential drugs for neglected diseases. The synthetic protocols are solid-phase based and inspired by published work. One promising article reported that many biomimetic molecules based on diverse scaffolds with three or more sites of variable substitution can be synthesized in one or two steps from a common key aldehyde intermediate. This intermediate was prepared by the ozonolysis of a precursor functionalized at two variable sites, restricting their presence in the subsequently formed scaffolds to ozone compatible functional groups. To broaden the scope of the groups available at one of these variable sites, we developed a synthetic route to an alternative, orthogonally protected key intermediate that allows the incorporation of ozone sensitive groups after the ozonolysis step. The utility of this orthogonally protected intermediate is demonstrated in the synthesis of several representative biomimetic scaffolds containing ozonolytically labile functional groups. It is compatible with traditional Fmoc peptide chemistry, permitting it to incorporate peptide fragments for use in fragment condensations with peptides containing cysteine at the N-terminus. Overall yields for its synthesis and utilization (as many as 13 steps) indicate good conversions at each step

Acquired resistance to anti-PD1 therapy: checkmate to checkpoint blockade?

Editorial summary Anti-programmed cell death 1 (PD1) immunotherapies are among the most effective anti-cancer immunotherapies available; however, a large number of patients present with or develop resistance to them. Unfortunately, very little is known regarding the mechanisms of resistance to such therapies. A recent study sought to identify mutations associated with resistance to anti-PD1 therapy. Results from this study demonstrated that mutations which affected the sensitivity of tumor cells to T-cell-derived interferons, and mutations limiting tumor-cell antigen presentation, could cause acquired resistance. These findings have significant implications for understanding the mechanisms by which anti-PD1 therapies exert their efficacy, comprehending why and how some patients acquire resistance over time, and ultimately guiding the development of combination therapies designed to overcome, or potentially prevent, the development of acquired immunotherapeutic resistance

Neutrinoless Double Beta Decay and CP Violation

We study the relation between the Majorana neutrino mass matrices and the neutrinoless double beta decay when CP is not conserved. We give an explicit form of the decay rate in terms of a rephasing invariant quantity and demonstrate that in the presence of CP violation it is impossible to have vanishing neutrinoless double beta decay in the case of two neutrino generations (or when the third generation leptons do not mix with other leptons and hence decouple).Comment: 9 pages, UTPT-93-1

Charm and Bottom Semileptonic Decays

We review the present status of theoretical attempts to calculate the semileptonic charm and bottom decays and then present a calculation of these decays in the light--front frame at the kinematic point $q^2=0$. This allows us to evaluate the form factors at the same value of $q^2$, even though the allowed kinematic ranges for charm and bottom decays are very different. Also, at this kinematic point the decay is given in terms of only one form factor $A_{0}(0)$. For the ratio of the decay rates given by the E653 collaboration we show that the determination of the ratio of the Cabibbo--Kobayashi--Maskawa (CKM) matrix elements is consistent with that obtained from the unitarity constraint. At present, though, the unitarity method still has greater accuracy. Since comparisons of the semileptonic decays into $\rho$ and either electrons or muons will be available soon from the E791 Fermilab experiment, we also look at the massive muon case. We show that for a range of $q^2$ the $SU(3)_F$ symmetry breaking is small even though the contributions of the various helicity amplitudes becomes more complicated. For $B$ decays, the decay $B \rightarrow K^{*} \ell \bar{\ell}$ at $q^2=0$ involves an extra form factor coming from the photon contribution and so is not amenable to the same kind of analysis, leaving only the decay $B \rightarrow K^{*}\nu \bar{\nu}$ as a possibility. As the mass of the decaying particle increases we note that the $SU(3)$ symmetry becomes badly broken at $q^2=0$.Comment: Latex, 19 pages, two figures are attached, a minor change in the manuscript related to thi

When and how video games can be good: a review of the positive effects of video games on well-being

peer-reviewedVideo games are a source of entertainment for a wide population and have varied effects on well-being. The purpose of this article is to comprehensively examine game-play research to identify the factors that contribute to these disparate well-being outcomes and to highlight the potential positive effects. On the basis of existing literature, we argue that the effects of gaming on well-being are moderated by other variables, such as motivations for gaming and video-game characteristics. Specifically, the inclusion of social activity can benefit prosocial behaviors and affect the relationship between violent video games and aggression that some studies have demonstrated. Moreover, the research on the relationship between violent video games and aggression depends greatly on individual and sociocontextual variables outside of game play. The inclusion of physical activity in games can provide an improvement in physical health with high levels of enjoyment, potentially increasing adherence rates. Overall, following our review, we determined that the effects of gaming on well-being are moderated by and depend on the motivation for gaming, outside variables, the presence of violence, social interaction, and physical activity. Thus, we argue that there is potential for an 'optimal gaming profile' that can be used in the future for both academic- and industry-related research.peer-reviewe

Thermodynamic metrics and optimal paths

A fundamental problem in modern thermodynamics is how a molecular-scale machine performs useful work, while operating away from thermal equilibrium without excessive dissipation. To this end, we derive a friction tensor that induces a Riemannian manifold on the space of thermodynamic states. Within the linear-response regime, this metric structure controls the dissipation of finite-time transformations, and bestows optimal protocols with many useful properties. We discuss the connection to the existing thermodynamic length formalism, and demonstrate the utility of this metric by solving for optimal control parameter protocols in a simple nonequilibrium model.Comment: 5 page