The Winding Road to Relapse: Forging a New Understanding of Cue-Induced Reinstatement Models and Their Associated Neural Mechanisms

In drug addiction, cues previously associated with drug use can produce craving and frequently trigger the resumption of drug taking in individuals vulnerable to relapse. Environmental stimuli associated with drugs or natural reinforcers can become reliably conditioned to increase behavior that was previously reinforced. In preclinical models of addiction, these cues enhance both drug self-administration and reinstatement of drug seeking. In this review, we will dissociate the roles of conditioned stimuli as reinforcers from their modulatory or discriminative functions in producing drug-seeking behavior. As well, we will examine possible differences in neurobiological encoding underlying these functional differences. Specifically, we will discuss how models of drug addiction and relapse should more systematically evaluate these different types of stimuli to better understand the neurobiology underlying craving and relapse. In this way, behavioral and pharmacotherapeutic interventions may be better tailored to promote drug use cessation outcomes and long-term abstinence

Dr.Nod: computational framework for discovery of regulatory non-coding drivers in tissue-matched distal regulatory elements

The discovery of cancer driver mutations is a fundamental goal in cancer research. While many cancer driver mutations have been discovered in the protein-coding genome, research into potential cancer drivers in the non-coding regions showed limited success so far. Here, we present a novel comprehensive framework Dr.Nod for detection of non-coding cis-regulatory candidate driver mutations that are associated with dysregulated gene expression using tissue-matched enhancer-gene annotations. Applying the framework to data from over 1500 tumours across eight tissues revealed a 4.4-fold enrichment of candidate driver mutations in regulatory regions of known cancer driver genes. An overarching conclusion that emerges is that the non-coding driver mutations contribute to cancer by significantly altering transcription factor binding sites, leading to upregulation of tissue-matched oncogenes and down-regulation of tumour-suppressor genes. Interestingly, more than half of the detected cancer-promoting non-coding regulatory driver mutations are over 20 kb distant from the cancer-associated genes they regulate. Our results show the importance of tissue-matched enhancer-gene maps, functional impact of mutations, and complex background mutagenesis model for the prediction of non-coding regulatory drivers. In conclusion, our study demonstrates that non-coding mutations in enhancers play a previously underappreciated role in cancer and dysregulation of clinically relevant target genes

Empirical Evaluation of the Difficulty of Finding a Good Value of k for the Nearest Neighbor

As an analysis of the classification accuracy bound for the Nearest Neighbor technique, in this work we have studied if it is possible to find a good value of the parmeter k for each example according to their attribute values. Or at least, if there is a pattern for the parameter k in the original search space. We have carried out different approaches based onthe Nearest Neighbor technique and calculated the prediction accuracy for a group of databases from the UCI repository. Based on the experimental results of our study, we can state that, in general, it is not possible to know a priori a specific value of k to correctly classify an unseen example

Spin-orbit torques for current parallel and perpendicular to a domain wall

We report field- and current-induced domain wall (DW) depinning experiments in Ta/Co20Fe60B20/MgO nanowires through a Hall cross geometry. While purely field-induced depinning shows no angular dependence on in-plane fields, the effect of the current depends crucially on the internal DW structure, which we manipulate by an external magnetic in-plane field. We show for the first time depinning measurements for a current sent parallel to the DW and compare its depinning efficiency with the conventional case of current flowing perpendicularly to the DW. We find that the maximum efficiency is similar for both current directions within the error bars, which is in line with a dominating damping-like spin-orbit torque (SOT) and indicates that no large additional torques arise for currents parallel to the DW. Finally, we find a varying dependence of the maximum depinning efficiency angle for different DWs and pinning levels. This emphasizes the importance of our full angular scans compared to previously used measurements for just two field directions (parallel and perpendicular to the DW) and shows the sensitivity of the spin-orbit torque to the precise DW structure and pinning sites.Comment: 11 pages, 3 figure

16 Multiple Linear Regression Viewpoints

This paper analyzes two methods for testing moderation effects in regression models that contain a continuous dependent variable, a continuous independent variable, and a dichotomized grouped moderator; a test of the interaction term in the full regression model and a test of the difference between the simple slopes. Typically, researchers test the significance of the interaction term. Based on mathematical equations and empirical examples, we argue that the test for the difference between the simple slopes should be utilized when researchers are interested in testing for moderation effects. By decomposing the test statistics for these two methods, we demonstrate that the test for the difference between the simple slopes has increased power and less Type II error, while retaining equivalent Type I error rates. oderated relationships in social science research exist when the relationship between two variables, X and Y, varies depending on the value of a third variable Z. This study examines a specific type of moderated relationship with a continuous dependent variable (Y), a continuous independent variable (X), and an independent dichotomous categorical variable (Z). Given these variables, a moderated relationship exists if the relationship between X and Y is different for both levels of Z. This can be estimated with an interaction term using the following regression equatio

Preceding rule induction with instance reduction methods

A new prepruning technique for rule induction is presented which applies instance reduction before rule induction. An empirical evaluation records the predictive accuracy and size of rule-sets generated from 24 datasets from the UCI Machine Learning Repository. Three instance reduction algorithms (Edited Nearest Neighbour, AllKnn and DROP5) are compared. Each one is used to reduce the size of the training set, prior to inducing a set of rules using Clark and Boswell's modification of CN2. A hybrid instance reduction algorithm (comprised of AllKnn and DROP5) is also tested. For most of the datasets, pruning the training set using ENN, AllKnn or the hybrid significantly reduces the number of rules generated by CN2, without adversely affecting the predictive performance. The hybrid achieves the highest average predictive accuracy

Inversion asymmetry effects in modulation-doped Cd1-xMnxTe quantum wells

We report a striking in-plane anisotropy of the spin-flip Raman signals observed for dilute magnetic Cd1−xMnxTe quantum wells containing a two-dimensional electron gas. The effect depends upon electron concentration, which can be varied within a single sample via secondary above-barrier illumination. The experimental results are described in a simple, single-electron picture by a model of the conduction band Hamiltonian that includes contributions from Dresselhaus, Rashba, and Zeeman terms

The Effect of Fish Oil Supplementation on Resistance Training-induced Adaptations

Background: Resistance exercise training (RET) is a common and well-established method to induce hypertrophy and improvement in strength. Interestingly, fish oil supplementation (FOS) may aug-ment RET-induced adaptations. However, few studies have been conducted on young, healthy adults. Methods: A randomized, placebo-controlled design was used to determine the effect of FOS, a concentrated source of eicosapen-taenoic acid (EPA) and docosahexaenoic acid (DHA), compared to placebo (PL) on RET-induced adaptations following a 10-week RET program (3 days·week−1). Body composition was measured by dual- energy x-ray absorptiometry (LBM, fat mass [FM], percent body fat [%BF]) and strength was measured by 1-repetition maximum bar-bell back squat (1RMSQT) and bench press (1RMBP) at PRE (week 0) and POST (10 weeks). Supplement compliance was assessed via self-report and bottle collection every two weeks and via fatty acid dried blood spot collection at PRE and POST. An a priori α- level of 0.05 was used to determine statistical significance and Cohen’s d was used to quantify effect sizes (ES). Results: Twenty-one of 28 male and female participants (FOS, n = 10 [4 withdrawals]; PL, n = 11 [3 withdrawals]) completed the 10- week progressive RET program and PRE/POST measurements. After 10-weeks, blood EPA+DHA substantially increased in the FOS group (+109.7%, p\u3c .001) and did not change in the PL group (+1.3%, p = .938). Similar between-group changes in LBM (FOS: +3.4%, PL: +2.4%, p = .457), FM (FOS: −5.2%, PL: 0.0%, p = .092), and %BF (FOS: −5.9%, PL: −2.5%, p = .136) were observed, although, the between- group ES was considered large for FM (d = 0.84). Absolute and relative (kg·kg [body mass]−1) 1RMBP was significantly higher in the FOS group compared to PL (FOS: +17.7% vs. PL: +9.7%, p = .047; FOS: +17.6% vs. PL: +7.3%, p = .011; respectively), whereas absolute 1RMSQT was similar between conditions (FOS: +28.8% vs. PL: +20.5%, p = .191). Relative 1RMSQT was higher in the FOS group (FOS: +29.3% vs. PL: +17.9%, p = .045). Conclusions: When combined with RET, FOS improves absolute and relative 1RM upper-body and relative 1RM lower-body strength to a greater extent than that observed in the PL group of young, recreationally trained adults