Interplay of water and a supramolecular capsule for catalysis of reductive elimination reaction from gold.

Supramolecular assemblies have gained tremendous attention due to their ability to catalyze reactions with the efficiencies of natural enzymes. Using ab initio molecular dynamics, we identify the origin of the catalysis by the supramolecular capsule Ga4L612- on the reductive elimination reaction from gold complexes and assess their similarity to natural enzymes. By comparing the free energies of the reactants and transition states for the catalyzed and uncatalyzed reactions, we determine that an encapsulated water molecule generates electric fields that contributes the most to the reduction in the activation free energy. Although this is unlike the biomimetic scenario of catalysis through direct host-guest interactions, the electric fields from the nanocage also supports the transition state to complete the reductive elimination reaction with greater catalytic efficiency. However it is also shown that the nanocage poorly organizes the interfacial water, which in turn creates electric fields that misalign with the breaking bonds of the substrate, thus identifying new opportunities for catalytic design improvements in nanocage assemblies

Chinese Papermaking: A Multicultural and Environmental Education Strategy for Pre-K Teachers

Many scholars see the urgency of implementing multicultural education (ME) and environmental education (EE) in the primary level (Abdullah, 2009; Bower, 1998; Cohen & Horm-Wingerd, 1993; Trubowitz, 1995). The scholars also share how hands-on and art approaches fit well in both Multicultural Education and Environmental Education fields (Adams & Chisholm, 1999; Bower, 1998; Damm, 2006; Seltzer-Kelly, Westwood, & Peña-Guzman, 2010). Chinese papermaking, an interactive and hands-on exercise in the creation of handmade paper, can be a means of integrating concepts of multiculturalism and sustainability into a young child‘s education. To address this issue, this study aimed at (a) introducing multicultural education, sustainability, and Chinese papermaking; (b) creating a new model MATCH to synthesize multicultural education and environmental education; (c) showing how papermaking is a culturally enriching activity; and, (d) demonstrating child-centered papermaking activities

What Do NCI Data Tell Us About the Characteristics and Outcomes of Older Adults with IDD?

The number of older adults with intellectual and developmental disabilities (IDD) is growing and will continue to expand as the baby boom generation moves into older adulthood. This descriptive analysis provides information on the characteristics and outcomes of a subsample of individuals with IDD aged 55 and over in the 2018-2019 National Core Indicators In Person Survey. Selected findings are compared to characteristics of the general population as measured by the National Health Interview Survey (NHIS). Findings suggest the older adults with IDD are more isolated, have smaller social networks than their younger peers, and have less access to transportation to get where they want to go. Further, the NCI data show that those over 55 are more likely to have vision and hearing challenges than the general public, have a greater need for mobility supports, and are more likely than the general population to have a mood and/or anxiety disorder. The analysis concludes with recommendations for policy and practice that anticipate the supports necessary as people with IDD enter their later years including targeted assessments, accessible housing, and the use of “smart” technology

Twice-Daily Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex Reduces Methamphetamine Craving: A Pilot Study.

Transcranial magnetic stimulation (TMS) holds potential promise as a therapeutic modality for disorders of addiction. Our previous findings indicate that high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsal-lateral prefrontal cortex (DLPFC) and low-frequency rTMS over the right DLPFC can reduce drug craving for methamphetamine. One major issue with rTMS is the duration of treatment and hence potential dropout rate. Theta burst stimulation (TBS) has been recently shown to be non-inferior relative to repetitive transcranial magnetic stimulation for major depression. Here, we aim to compare the clinical efficacy and tolerability of intermittent and continuous theta burst stimulation protocols targeting left or right dorsolateral prefrontal cortex on methamphetamine craving in abstinent-dependent subjects. In this randomized single-blind pilot study, 83 abstinent methamphetamine-dependent subjects from a long-term residential treatment program were randomly allocated into three groups: intermittent theta burst stimulation (iTBS) over the left DLPFC (active group), continuous theta burst stimulation (cTBS) over the left DLPFC (active control group), or cTBS over the right DLPFC (active group) was administered twice daily over 5 days for a total of 10 sessions. We measured the primary outcome of cue-induced craving and secondarily sleep quality, depression, anxiety, impulsivity scores, and adverse effects. We show a pre- vs. postintervention effect on craving, which, on paired t tests, showed that the effect was driven by iTBS of the left DLPFC and cTBS of the right DLPFC, reducing cue-induced craving but not cTBS of the left DLPFC. We did not show the critical group-by-time interaction. The secondary outcomes of depression, anxiety, and sleep were unrelated to the improvement in craving in the left iTBS and right cTBS group. In the first two sessions, self-reported adverse effects were higher with left iTBS when compared to right cTBS. The distribution of craving change suggested greater clinical response (50% improvement) with right cTBS and a bimodal pattern of effect with left iTBS, suggesting high interindividual variable response in the latter. Accelerated twice-daily TBS appears feasible and tolerable at modulating craving and mood changes in abstinent methamphetamine dependence critically while reducing session length. We emphasize the need for a larger randomized controlled trial study with a sham control to confirm these findings and longer duration of clinically relevant follow-up. Chinese Clinical Trial Registry number, 17013610

Learning ‘‘graph-mer’’ Motifs that Predict Gene Expression Trajectories in Development

A key problem in understanding transcriptional regulatory networks is deciphering what cis regulatory logic is encoded in gene promoter sequences and how this sequence information maps to expression. A typical computational approach to this problem involves clustering genes by their expression profiles and then searching for overrepresented motifs in the promoter sequences of genes in a cluster. However, genes with similar expression profiles may be controlled by distinct regulatory programs. Moreover, if many gene expression profiles in a data set are highly correlated, as in the case of whole organism developmental time series, it may be difficult to resolve fine-grained clusters in the first place. We present a predictive framework for modeling the natural flow of information, from promoter sequence to expression, to learn cis regulatory motifs and characterize gene expression patterns in developmental time courses. We introduce a cluster-free algorithm based on a graph-regularized version of partial least squares (PLS) regression to learn sequence patterns—represented by graphs of k-mers, or “graph-mers”—that predict gene expression trajectories. Applying the approach to wildtype germline development in Caenorhabditis elegans, we found that the first and second latent PLS factors mapped to expression profiles for oocyte and sperm genes, respectively. We extracted both known and novel motifs from the graph-mers associated to these germline-specific patterns, including novel CG-rich motifs specific to oocyte genes. We found evidence supporting the functional relevance of these putative regulatory elements through analysis of positional bias, motif conservation and in situ gene expression. This study demonstrates that our regression model can learn biologically meaningful latent structure and identify potentially functional motifs from subtle developmental time course expression data

Happiness

Everyone wants to be happy. Happiness is obviously a good thing and if we can get it without sacrificing other important things, we would. Most people wish not just for their own happiness but also the happiness of people they love; some compassionate souls may even wish for the happiness of all sentient creatures. What exactly is it that we all want? Is it to be pleased or satisfied? To feel tranquil or joyous? To attain certain objective goods? And what role does happiness play in morality? Is the production of happiness the goal of morally right action? Is it the organizing principle of moral theory? Or is it just one contingent value among many? This entry reviews answers to these questions from the perspectives of ancient, modern, and contemporary philosophy