Comparative molecular field analysis of the antitumor activity of 9H-thioxanthen-9-one derivatives against pancreatic ductal carcinoma 03

The present study establishes correlations of in vivo growth inhibition of a solid tumor, pancreatic ductal adenocarcinoma (Panc03), of mice with the steric and electrostatic fields and the hydrophobic parameter log P of a series (32) of 1-[[2-(dialkylamino)alkyl]amino]- 9H-thioxanthen-9-ones by the 3D-QSAR method comparative molecular field analysis (CoMFA). The template molecular model was hycanthone methanesulfonate (19), the structure of which had been established previously by X-ray crystallography. The hycanthone base is protonated at the terminal nitrogen N(2), and an intramolecular hydrogen bond is present between the proximal nitrogen N(1) and carbonyl oxygen O(1) atoms. Crystallographic data also indicate a planar arrangement of bonds around N(1). However, the molecular geometry of 19, optimized by semiempirical molecular orbital methods (PM3, MNDO, AM1), showed the expected trigonal-pyramidal configuration for N(1). A comparison of MO and ab initio methods applied to a model compound, 1-amino-9H-thioxanthen-9-one, led to the selection of PM3 as the method for full geometry optimization of first the cationic and then the neutral forms of 1-32, whereas AM1 provided atomic charges for these same structures save those incorporating a sulfonamide moiety (5, 7, 20, 25, 26, 29, 31, and 32). Acceptable values for the latter were obtained from ab initio calculations. Structures were aligned by minimizing root-mean-square (rms) differences in the fitting of structures to 19 using the FIT option of SYBYL. An alternative strategy of alignment, steric and electrostatic alignment (SEAL), was invoked to provide a comparison of statistical data generated with the rms alignment. The rms-fit alignment of structures produced slightly better cross-validated and conventional r2 values than those generated with the SEAL method. In addition, the rms-fit data indicate that a shift in the lattice of one-half of its spacing has a much smaller effect on the CoMFA data for a lattice of 1 A than one of 2 A. Inclusion of log P in a CoMFA of the neutral structures effected a small (ca. 8-10%) but significant improvement in cross-validated r2 values. The relative contributions of the hydrophobic effects and the steric and electrostatic fields to the conventional r2 values were 16%, 42%, and 42%, respectively. By contrast, incorporation of frontier molecular orbital (HOMO and LUMO) energies or their gaps in the PLS analyses failed to enhance correlation coefficients derived for either the charged or uncharged compounds.(ABSTRACT TRUNCATED AT 400 WORDS)     

A Sketch-Based Interface for Clothing Virtual Characters

This interactive system for garment creation determines a garment's shape and how the character wears it based on a user-drawn sketch. The system then uses distances between the 2D garment silhouette and the character model to infer remaining distance variations in 3D     

Double-diffusive convection in a circular cylinder

Summary A theoretical study is made of the onset of steady double-diffusive convection in a circular cylinder of small to moderate aspect ratio. An eigenfunction expansion method is used to derive systems of amplitude equations for weakly nonlinear evolution of critical disturbances. It is shown that the nature of the convective solution near criticality depends strongly on the cylinder's aspect ratio; this is particularly the case at or near aspect ratios where two modes become unstable at the same Rayleigh number. There is also a strong dependence on Prandtl number, which is discussed.With 7 Figure     

Time series analysis of wind speed using VAR and the generalized impulse response technique

This research examines the interdependence in time series wind speed data measured in the same location at four different heights. A multiple-equation system known as a vector autoregression is proposed for characterizing the time series dynamics of wind. Additionally, the recently developed method of generalized impulse response analysis provides insight into the cross-effects of the wind series and their responses to shocks. Findings are based on analysis of contemporaneous wind speed time histories taken at 13, 33, 70 and 160 ft above ground level with a sampling rate of 10 Hz. The results indicate that wind speeds measured at 70 ft was the most variable. Further, the turbulence persisted longer at the 70-ft measurement than at the other heights. The greatest interdependence is observed at 13 ft. Gusts at 160 ft led to the greatest persistence to an “own” shock and led to greatest persistence in the responses of the other wind series.     

Analysis of Distance Collaboration Modalities: Alternatives to Meeting Face-to-Face

Physical and temporal boundaries are rapidly diminishing in an age of swiftly advancing information communication technologies. Today’s technologically sophisticated business and organizational environments offer a number of distance collaboration modalities (DSMs) that can facilitate efficient and cost-effective meetings that have traditionally required face-to-face meeting venues. Selection of the DCMs that maximize meeting effectiveness is significantly challenging given the wide diversity of available options. Theory and empirical data can be useful as a guide in the selection of the most appropriate DCMs to maximize organizational productivity and success. This article reviews the literature on the behavioral and technical affordances and limitations of the various DCMs. It also provides a theoretical model based on media synchronicity theory to help guide selection of effective DCMs. This theoretical framework emphasizes the primacy of media alignment with core communication processes as well as social and interpersonal factors that influence meeting effectiveness.     

Adherence rates to ferric citrate as compared to active control in patients with end stage kidney disease on dialysis

Introduction: Oral phosphate binders are the main stay of treatment of hyperphosphatemia. Adherence rates to ferric citrate, a recently approved phosphate binder, are unknown. Methods: We conducted a post‐hoc analysis to evaluate whether adherence rates were different for ferric citrate vs. active control in 412 subjects with end stage kidney disease (ESKD) who were randomized to ferric citrate vs. active control (sevelamer carbonate and/or calcium acetate). Adherence was defined as percent of actual number of pills taken to total number of pills prescribed. Findings: There were no significant differences in baseline characteristics including gender, race/ethnicity, and age between the ferric citrate and active control groups. Baseline phosphorus, calcium, and parathyroid hormone levels were similar. Mean (SD) adherence was 81.4% (17.4) and 81.7% (15.9) in the ferric citrate and active control groups, respectively (P = 0.88). Adherence remained similar between both groups after adjusting for gender, race/ethnicity, age, cardiovascular disease (CVD), and diabetic nephropathy (mean [95% CI]: 81.4% [78.2, 84.6] and 81.5% [77.7, 85.2] for ferric citrate and active control, respectively). Gender, race/ethnicity, age, and diagnosis of diabetic nephropathy did not influence adherence to the prescribed phosphate binder. Subjects with CVD had lower adherence rates to phosphate binder; this was significant only in the active control group. Discussion: Adherence rates to the phosphate binder, ferric citrate, were similar to adherence rates to active control. Similar adherence rates to ferric citrate are notable since tolerance to active control was an entry criteria and the study was open label. Gender, race/ethnicity, nor age influenced adherence.