Anti-cancer Action of Metal Complexes: Electron Transfer and Oxidative Stress?

Evidence is presented in support of an electron transfer mechanism for various metal complexes possessing anti-neoplastic properties. Cyclic voltammetry was performed on several metallocenes, bis(acetato)bis(imidazole)Cu(II), and coordination compounds (Cu or Fe) of the anti-tumor agents, bipyridine, phenanthroline, hydroxyurea, diethyldithiocarbamate, and α, α1-bis(8-hydroxyquinolin-7-yl)-4-methoxytoluene. The favorable reduction potentials ranged from +0.5 to -0.5 V. Electrochemical behavior is correlated in some cases with structure and physiological activity. Relevant literature data are discussed

A Peptide Core Motif for Binding to Heterotrimeric G Protein α Subunits

Recently, in vitro selection using mRNA display was used to identify a novel peptide sequence that binds with high affinity to G{alpha}i1. The peptide was minimized to a 9-residue sequence (R6A-1) that retains high affinity and specificity for the GDP-bound state of G{alpha}i1 and acts as a guanine nucleotide dissociation inhibitor (GDI). Here we demonstrate that the R6A-1 peptide interacts with G{alpha} subunits representing all four G protein classes, acting as a core motif for G{alpha} interaction. This contrasts with the consensus G protein regulatory(GPR) sequence, a 28-mer peptide GDI derived from the GoLoco (G{alpha}i/0-Loco interaction)/GPR motif that shares no homology with R6A-1 and binds only to G{alpha}i1-3 in this assay. Binding of R6A-1 is generally specific to the GDP-bound state of the G{alpha} subunits and excludes association with G{beta}{gamma}. R6A-G{alpha}i1 complexes are resistant to trypsin digestion and exhibit distinct stability in the presence of Mg2+, suggesting that the R6A and GPR peptides exert their activities using different mechanisms. Studies using G{alpha}i1/G{alpha}s chimeras identify two regions of G{alpha}i1 (residues 1–35 and 57–88) as determinants for strong R6A-Gi{alpha}1 interaction. Residues flanking the R6A-1 peptide confer unique binding properties, indicating that the core motif could be used as a starting point for the development of peptides exhibiting novel activities and/or specificity for particular G protein subclasses or nucleotide-bound states

Calibration of Computational Models with Categorical Parameters and Correlated Outputs via Bayesian Smoothing Spline ANOVA

It has become commonplace to use complex computer models to predict outcomes in regions where data does not exist. Typically these models need to be calibrated and validated using some experimental data, which often consists of multiple correlated outcomes. In addition, some of the model parameters may be categorical in nature, such as a pointer variable to alternate models (or submodels) for some of the physics of the system. Here we present a general approach for calibration in such situations where an emulator of the computationally demanding models and a discrepancy term from the model to reality are represented within a Bayesian Smoothing Spline (BSS) ANOVA framework. The BSS-ANOVA framework has several advantages over the traditional Gaussian Process, including ease of handling categorical inputs and correlated outputs, and improved computational efficiency. Finally this framework is then applied to the problem that motivated its design; a calibration of a computational fluid dynamics model of a bubbling fluidized which is used as an absorber in a CO2 capture system

Galaxy pairs in the Sloan Digital Sky Survey - IX: Merger-induced AGN activity as traced by the Wide-field Infrared Survey Explorer

Interactions between galaxies are predicted to cause gas inflows that can potentially trigger nuclear activity. Since the inflowing material can obscure the central regions of interacting galaxies, a potential limitation of previous optical studies is that obscured Active Galactic Nuclei (AGNs) can be missed at various stages along the merger sequence. We present the first large mid-infrared study of AGNs in mergers and galaxy pairs, in order to quantify the incidence of obscured AGNs triggered by interactions. The sample consists of galaxy pairs and post-mergers drawn from the Sloan Digital Sky Survey that are matched to detections by the Wide Field Infrared Sky Explorer (WISE). We find that the fraction of AGN in the pairs, relative to a mass-, redshift- and environment-matched control sample, increases as a function of decreasing projected separation. This enhancement is most dramatic in the post-merger sample, where we find a factor of 10-20 excess in the AGN fraction compared with the control. Although this trend is in qualitative agreement with results based on optical AGN selection, the mid-infrared selected AGN excess increases much more dramatically in the post-mergers than is seen for optical AGN. Our results suggest that energetically dominant optically obscured AGNs become more prevalent in the most advanced mergers, consistent with theoretical predictions.Comment: 8 pages, 7 figures accepted to MNRAS (with minor revisions

Family Psychoeducation in Clinical High Risk and First- Episode Psychosis

Seventy percent of those who will have an episode of psychosis will have done so by age 25. Data from clinical trials of intervention during the clinical high risk period of psychosis have determined that the mean age is in mid-adolescence, 16-18 years of age. For those reasons, early intervention inherently involves adolescents, and by extension their parents and other family members and supports. Regarding the type of intervention, it is relevant that the current empirically-derived standard of treatment for schizophrenia, as concluded by the Agency for Health Care Policy and Research survey of the treatment outcome literature, includes family psychoeducation, supported employment, assertive community treatment and antipsychotic medication,; i.e., a combination of psychosocial and pharmacologic interventions. Combinations of all four of these treatments, as in Family-aided Assertive Community Treatment (FACT), achieve very low rates of relapse, substantial reductions of symptoms and remarkable functional outcomes, particularly in the domain of competitive employment. Furthermore, a large comparative study of outcomes in community settings found that psychoeducational multifamily groups were more effective than single-family psychoeducation specifically in the first episode and in high-risk-for relapse cases, suggesting that particular psychosocial treatments may be especially effective in early phases of illness

Tree-Independent Dual-Tree Algorithms

Dual-tree algorithms are a widely used class of branch-and-bound algorithms. Unfortunately, developing dual-tree algorithms for use with different trees and problems is often complex and burdensome. We introduce a four-part logical split: the tree, the traversal, the point-to-point base case, and the pruning rule. We provide a meta-algorithm which allows development of dual-tree algorithms in a tree-independent manner and easy extension to entirely new types of trees. Representations are provided for five common algorithms; for k-nearest neighbor search, this leads to a novel, tighter pruning bound. The meta-algorithm also allows straightforward extensions to massively parallel settings.Comment: accepted in ICML 201

Engineering Treatment of Hazardous Wastewaters Utilizing Dye-sensitized Photooxidation

Studies were conducted to determine the applicability of photooxidation for the degradation of selected hazardous and refractory organic compounds. These photochemical oxidation reactions occur through the transfer of energy from electronically excited sensitizer molecules which attain excited states by absorbing visible light energy. Optimum conditions for photooxidation were established based on sensitizer concentration and reaction pH for four polynuclear aromatic pollutants. The rate of photooxidation was found to be independent of the initial substrate concentration for methylene blue-sensitized reactions, and dependent on substrate concentration for solutions without a sensitizing dye. Photolysis of substrate mixtures established acridine and anthracene as photochemically active substrates. Photochemical reaction data suggest predictable trends in substrate reactivity based on pKa values of both sensitizer and substrate, initial substrate concentration and light absorbance characteristics. The photoproducts formed during the photolysis of acridine were found to be more toxic than the parent compound. These reaction products appear to be atable and warrant further study