A new family of synthetic diterpenes that regulates cytokine synthesis by inhibiting IkappaBalpha phosphorylation

The synthesis and the biological evaluation of a new family diterpenes are presented. The synthetic studies were inspired by the structural framework of acanthoic acid (1) and yielded a family of compounds that were evaluated as anti-inflammatory agents. Among them, compounds 2, 10, 12, and 16 exhibited a very low nonspecific cytotoxicity and inhibited the synthesis of TNF-alpha with greater than 65 % efficacy at low micromolar concentrations. Cytokine-specificity studies revealed that these compounds also inhibited the synthesis of the proinflammatory cytokines IL-1beta and IL-6, while inhibition of IL-1ra and IL-8 synthesis was marginal and only occurred at high concentrations. Further studies, through EMSA and Western blot analyses, indicated that these compounds decreased the extent of phosphorylation of IkappaBalpha; this suggests that they exert their anti-inflammatory profile by inhibiting NF-kappaB-mediated cytokine synthesis. These findings imply that these diterpenes represent promising leads for the development of novel anti-inflammatory agents.     

Self Organising Maps for variable selection: Application to human saliva analysed by nuclear magnetic resonance spectroscopy to investigate the effect of an oral healthcare product

SOMs (Self Organising Maps) are derived from the machine learning literature and serve as a valuable method for representing data. In this paper, the use of SOMs as a technique for determining the most significant variables (or markers) in a dataset is described. The method is applied to the NMR spectra of 96 human saliva samples, half of which have been treated with an oral rinse formulation and half of which are controls, and 49 variables consisting of bucketed intensities. In addition, three simulations, two of which consist of the same number of samples and variables as the experimental dataset and a third that contains a much larger number of variables, are described. Two of the simulations contain known discriminatory variables, and the remaining is treated as a null dataset without any specific discriminatory variables added. The described SOM method is contrasted to Partial Least Squares Discriminant Analysis, and a list of the markers determined to be most significant using both approaches was obtained and the differences arising are discussed. A SOM Discrimination Index (SOMDI) is defined, whose magnitude relates to how strongly a variable is considered to be a discriminator. In order to ensure that the model is stable and not dependent on the random starting point of the SOM, one hundred iterations were performed and variables that were consistently of high rank were selected. A variety of approaches for data representation are illustrated, and the main theoretical principles of employing SOMs for determining which variables are most significant are outlined. Software used in this paper was written in-house, allowing greater flexibility over existing packages, and tailored for the specific application in hand.     

High hydrogen production from glycerol or glucose by electrohydrogenesis using microbial electrolysis cells

The use of glycerol for hydrogen gas production was examined via electrohydrogenesis using microbial electrolysis cells (MECs). A hydrogen yield of 3.9 mol-H₂/mol was obtained using glycerol, which is higher than that possible by fermentation, at relatively high rates of 2.0 ± 0.4 m³/m³ d (E_ap = 0.9 V). Under the same conditions, hydrogen was produced from glucose at a yield of 7.2 mol-H₂/mol and a rate of 1.9 ± 0.3 m³/m³ d. Glycerol was completely removed within 6 h, with 56% of the electrons in intermediates (primarily 1,3-propanediol), with the balance converted to current, intracellular storage products or biomass. Glucose was removed within 5 h, but intermediates (mainly propionate) accounted for only 19% of the electrons. Hydrogen was also produced using the glycerol byproduct of biodiesel fuel production at a rate of 0.41 ± 0.1 m³/m³ d. These results demonstrate that electrohydrogenesis is an effective method for producing hydrogen from either pure glycerol or glycerol byproducts of biodiesel fuel production.     

The perceived utility of human and automated aids in a visual detection task

Although increases in the use of automation have occurred across society, research has found that human operators often underutilize (disuse) and overly rely on (misuse) automated aids (R. Parasuraman & V. Riley, 1997). Nearly 275 Cameron University students participated in 1 of 3 experiments performed to examine the effects of perceived utility (M. T. Dzindolet, H. P. Beck, L. G. Pierce, & L. A. Dawe, 2001) on automation use in a visual detection task and to compare reliance on automated aids with reliance on humans. Results revealed a bias for human operators to rely on themselves. Although self-report data indicate a bias toward automated aids over human aids, performance data revealed that participants were more likely to disuse automated aids than to disuse human aids. This discrepancy was accounted for by assuming human operators have a "perfect automation" schema. Actual or potential applications of this research include the design of future automateddecision aids and training procedures for operators relying on such aids.     

Physician decision making and cardiac risk: Effects of knowledge, risk perception, risk tolerance, and fuzzy processing.

Despite training, professionals sometimes make serious errors in risky decision making. The authors investigated judgments and decisions for 9 hypothetical patients at 3 levels of cardiac risk, comparing student and physician groups varying in domain-specific knowledge. Decisions were examined regarding whether they deviated from guidelines, how risk perceptions and risk tolerances determined decisions, and how the latter differed for knowledge groups. More knowledgeable professionals were better at discriminating levels of risk according to external correspondence criteria but committed similar errors in disjunctive probability judgments, violating internal coherence criteria. Also, higher knowledge groups relied on fewer dimensions of information than did lower knowledge groups. Consistent with fuzzy-trace theory, experts achieved better discrimination by processing less information and made sharper all-or-none distinctions among decision categories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

THE BREAKING OF TERNARY ACETATE-ALCOHOL-WATER AZEOTROPES BY EXTRACTIVE DISTILLATION

The breaking of seven ternary acetate-alcohol-water azeotropes by extractive distillation was accomplished. They are n-propyl acetate-n-propanol-water, isopropyl acetate-isopropanol-water, n-butyl acetate-n-butanol-water, 2-butyl acetate-2-butanol-water, isobutyl acetate-isobutanol-water, n-amyl acetate-n-amyl alcohol-water and n-hexyl acetate-n-hexanol-water. The acetates, usually the highest boiling constituents, are obtained as overhead product as a two-phase mixture with water. The most effective agents are glycols and dimethylsulfoxide. Solubility parameters were found to be a qualitative indication for selecting extractive distillation agents. When the formation of a chemical complex is dominant, solubility parameter does not explain solution behavior satisfactorily.     

v-raf suppresses apoptosis and promotes growth of interleukin-3-dependent myeloid cells

Interleukin-3 (IL-3) is required for the proliferation, survival and differentiation of myeloid progenitors. In the absence of IL-3, murine myeloid 32D.3 cells accumulate in the G1 phase of the cell cycle and subsequently undergo programmed cell death, or apoptosis. Here we demonstrate that enforced expression of the v-raf oncogene suppresses apoptosis of myeloid 32D.3 cells following the withdrawal of IL-3. Surprisingly, steady state levels of Bcl-2, an oncogene known to suppress apoptosis, were not dependent upon IL-3 in 32D.3 cells and its levels were not augmented in v-raf clones. This suggests that ability of v-raf to suppress apoptosis in the absence of ligand is either Bcl-2 independent or that v-raf kinase promotes Bcl-2 function. v-raf also promoted growth of these cells in the presence of IL-3. v-raf clones proliferated at an increased rate due to a shortened G1 phase and had decreased requirements for IL-3 for growth. Therefore, transformation of myeloid cells by v-raf involves signaling pathways which promote both cell cycle progression and cell survival.     

Comparative effectiveness of guided mastery and exposure treatments for intractable phobias.

Compared the exposure model and the self-efficacy model by randomly assigning 32 18–76 yr old individuals with driving or height phobias to 1 of the treatment conditions or to a control condition. Results show that treatments were equivalent in duration of exposure and in degree of inducement to confront threats rapidly, but the self-efficacy (mastery) model was significantly more effective than exposure in restoring Ss' behavioral functioning and diminishing their anticipated anxiety and performance-related anxiety. Both treatments were more effective than the control condition. It is suggested that self-efficacy predicted therapeutic behavior change significantly better than did anxiety, exposure duration, or performance level achieved during treatment. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Binocular stereo algorithm based on the disparity-gradient limit and using optimization theory

A new algorithm for stereo matching is presented, based on the idea of imposing a limit on disparity gradients allowed in the matched image. The matching problem will be expressed as one of maximizing a certain function, subject to constraints. Standard methods from optimization theory may then be used to find a solution.