Investigation of Trypanothione Reductase as a Drug Target in Trypanosoma brucei

There is an urgent need for new drugs for the treatment of tropical parasitic diseases such as human African trypanosomiasis, which is caused by Trypanosoma brucei. The enzyme trypanothione reductase (TryR) is a potential drug target within these organisms. Herein we report the screening of a 62 000 compound library against T. brucei TryR. Further work was undertaken to optimise potency and selectivity of two novel‐compound series arising from the enzymatic and whole parasite screens and mammalian cell counterscreens. Both of these series, containing either a quinoline or pyrimidinopyrazine scaffold, yielded low micromolar inhibitors of the enzyme and growth of the parasite. The challenges of inhibiting TryR with druglike molecules is discussed.     

Silica Colloidal Membranes with Enantioselective Permeability

Robust mesoporous membranes composed of silica spheres were surface-modified with chiral selector moieties, including small molecules, macrocycles, and polymers. Diffusion rates of enantiomers of a chiral dye through the resulting asymmetrically modified colloidal membranes were measured and the corresponding permselectivities were calculated. The membranes showed enantioselectivities in the range of 1.2–1.8, which were not significantly affected by the structure of the surface-immobilized chiral electors. This selectivity is on par with most reported polymer-based solid membranes and bulk liquid membranes. The enantioselectivity results from the surface-facilitated mechanism of transport of enantiomers through the mesopores.     

High frequency response to the impedance complex properties of Nb-doped CaCu3Ti4O12 electroceramics

Impedance analyses was performed on undoped and Nb-doped CaCu₃Ti₄O₁₂ (CaCu₃Ti_4−xNb_xO_12+x/2; x = 0, 0.01, 0.03, 0.05, 0.1) to investigate their electrical properties. The pellet samples were prepared using the solid state reaction method. Silver electrode was deposited on both pellets’ surfaces for electrical measurement. The thermally etched samples showed tiny bumped domains within the grains. The existence of both domain and grain boundaries are believed to strongly influence the dielectric constant of CaCu₃Ti₄O₁₂ (CCTO). Undoped CCTO showed two arcs of impedance complex plane while Nb-doped samples have three arcs. Each arc represents the constituent elements of the CCTO. The highest frequency arc is evidence that CCTO consists of conductive domains which measure about 1 Ω and are insulated by two types of barriers, i.e. domain boundary and grain boundary.     

Is a sense of inequity an ancestral primate trait? Testing social inequity in cotton top tamarins (Saguinus oedipus).

To address a controversy in the literature concerning whether monkeys show an aversion to inequity, individuals of a New World monkey species, cotton top tamarins (Saguinus oedipus) were tested in an offering task and in a bartering task. At issue was whether the monkeys rejected rewards because of a violation of expectancy of the preferred reward, or whether they rejected rewards because of a sensitivity to socially mediated inequity. The data from both tasks indicated that the subjects were more likely to reject when preferred rewards were presented, either because of another animal eating the reward (the social condition) or because of rewards being presented but inaccessible. The bartering task led to the only behavioral indication of aversion due specifically to social inequity, which was demonstrated when tamarins' sensitivity to the difference in rewards increased with exposure to other tamarins working to receive the preferred rewards. The results suggest that social inequity aversion will be assessed by tamarins, and possibly by other primates, only under conditions of limited resources and a requirement of work, which may make the situation a bit more competitive and thus drives attention toward both social and reward evaluation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Invention from War: a circumstantial modernism for Australian architecture

Between 1942 and 1945, Australian architects and engineers within the Allied Works Council and the US Army Corps of Engineers undertook a vast programme of building works to assist the campaign to drive Japanese forces northward through the Southwest Pacific and avoid invasion.¹ Huge distances, lack of time and the need to wage a campaign from the air lay behind US General Douglas Macarthur’s phrase that it would be an ‘engineer’s war’. By necessity, buildings such as airfields, hospitals, camps, warehouses, and other structures had to be light weight, constructed quickly, and inevitably dropped in by air as easily handled pre-cut packages. With the lack of American and European softwoods in the Australasian region, an unlikely local material was pressed into war service – unseasoned or ‘green’ Australian hardwood. It was a material choice that would have profound implications for two reasons. First, in the years of conflict, circumstances dictated the unprecedented innovation and experiment in light-weight timber structures. Second, in an echo of Lewis Mumford’s poignant maxim that ‘war is the health of the machine’², the systematisation and ruthless economy inherent in wartime timber buildings would influence the development and practice of a particular form of modern architecture in Australia in the late 1940s and the 1950s.     

Recruitment efforts to reduce adverse impact: Targeted recruiting for personality, cognitive ability, and diversity.

Noting the presumed tradeoff between diversity and performance goals in contemporary selection practice, the authors elaborate on recruiting-based methods for avoiding adverse impact while maintaining aggregate individual productivity. To extend earlier work on the primacy of applicant pool characteristics for resolving adverse impact, they illustrate the advantages of simultaneous cognitive ability– and personality-based recruiting. Results of an algebraic recruiting model support general recruiting for cognitive ability, combined with recruiting for conscientiousness within the underrepresented group. For realistic recruiting effect sizes, this type of recruiting strategy greatly increases average performance of hires and percentage of hires from the underrepresented group. Further results from a policy-capturing study provide initial guidance on how features of organizational image can attract applicants with particular job-related personalities and abilities, in addition to attracting applicants on the basis of demographic background. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of Viscoelasticity and HIV Transport as a Function of pH in a Reversibly Crosslinked Hydrogel

Materials that respond to physiological stimuli are important in developing advanced biomaterials for modern therapies. The reversibility of covalent crosslinks formed by phenylboronate (PBA) and salicylhydroxamate (SHA) has been exploited to provide a pH‐responsive gel for application to the vaginal tract. Dynamic rheology reveals that the gel frequency‐dependent viscoelastic properties are modulated by pH. At pH 4.8 the viscous component dominates throughout most of the frequency range. As the pH increases, the characteristic relaxation time continues to increase while the G′_Plateau levels off above pH 6. At pH 7.5, the elastic component dominates throughout the frequency sweep and is predominately independent of frequency. Particle tracking assesses the transport of both fluorescently labeled HIV‐1 and 100‐nm latex particles in the PBA–SHA crosslinked gel as a function of pH. At pH 4.8 the ensemble‐averaged mean squared displacement at lag times greater than three seconds reveals that transport of the HIV‐1 and 100‐nm particles becomes significantly impeded by the matrix, exhibiting diffusion coefficients less than 0.0002 µm² s^?1. This pH‐responsive gel thus displays properties that have the potential to significantly reduce the transport of HIV‐1 to susceptible tissues and thus prevent the first stage of male‐to‐female transmission of HIV‐1.     

USGS Streamflow Data and Modeling Sand-Bed Rivers

United States Geological Survey streamflow data are commonly used for hydraulic model calibration and boundary conditions. The transitory nature of sand-bed rivers’ bathymetry is problematic for the traditional automated stream gauging methods used by the USGS. This note seeks to assess the limitations of streamflow measurements for use in hydraulic models. An overview of USGS rating-curve development and use is presented with a focus on the specific challenges of sand-bed rivers. Measurements from three consecutive USGS gauges for a storm event on the Rio Grande in Albuquerque, New Mexico, illustrate the outlined problems with rating curves. These gauges are utilized to study the impact of uncertainty in rating-curve discharges on hydraulic model results. A one dimensional hydraulic model of the study reach indicates up to 25% reduction in the calculated flow depth if questionable rating-curve discharges are used as model input. Recommendations for using USGS streamflow data in hydraulic models are outlined.     

Similarity and assumed similarity in personality reports of well-acquainted persons.

The authors obtained self- and observer reports of personality from pairs of well-acquainted college students. Consistent with previous findings, results of Study 1 showed strong cross-source agreement for all 6 HEXACO personality factors (rs ≈ .55). In addition, the authors found modest levels of similarity (r ≈ .25) between dyad members' self-reports on each of 2 dimensions, Honesty-Humility and Openness to Experience. For these same 2 factors, dyad members' self-reports were correlated with their observer reports of the other dyad member (r ≈ .40), thus indicating moderately high assumed similarity. In Study 2, Honesty-Humility and Openness to Experience were the 2 personality factors most strongly associated with the 2 major dimensions of personal values, which also showed substantial assumed similarity. In Study 3, assumed similarity was considerably stronger for close friends than for nonfriend acquaintances. Results suggest that assumed similarity for Honesty-Humility and Openness to Experience reflects a tendency to overestimate one's similarity to persons with whom one has a close relationship, but only on those personality characteristics whose relevance to values gives them central importance to one's identity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)