Identification of tubulin drug binding sites and prediction of relative differences in binding affinities to tubulin isotypes using digital signal processing

Microtubules are involved in numerous cellular processes including chromosome segregation during mitosis and, as a result, their constituent protein, tubulin, has become a successful target of several chemotherapeutic drugs. In general, these drugs bind indiscriminately to tubulin within both cancerous and healthy cells, resulting in unwanted side effects. However, differences between beta-tubulin isotypes expressed in a wide range of cell types may aid in the development of anti-tubulin drugs having increased specificity for only certain types of cells. Here, we describe a digital signal processing (DSP) method that is capable of predicting hot spots for the tubulin family of proteins as well as determining relative differences in binding affinities to these hot spots based only on the primary sequence of 10 human tubulin isotypes. Due to the fact that several drug binding sites have already been characterized within beta-tubulin, we are able to correlate hot spots with the binding sites for known chemotherapy drugs. We have also verified the accuracy of this method using the correlation between the binding affinities of characterized drugs and the tubulin isotypes. Additionally, the DSP method enables the rapid estimation of relative differences in binding affinities within the binding sites of tubulin isotypes that are yet to be experimentally determined.     

Peirce algebras

We present a two-sorted algebra, called aPeirce algebra, of relations and sets interacting with each other. In a Peirce algebra, sets can combine with each other as in a Boolean algebra, relations can combine with each other as in a relation algebra, and in addition we have both a set-forming operator on relations (the Peirce product of Boolean modules) and a relation-forming operator on sets (a cylindrification operation). Two applications of Peirce algebras are given. The first points out that Peirce algebras provide a natural algebraic framework for modelling certain programming constructs. The second shows that the so-calledterminological logics arising in knowledge representation have evolved a semantics best described as a calculus of relations interacting with sets.     

A detection system for energetic light heavy ions

A light heavy ion detection system which consists of a gas-filled ionization chamber (IC) connected to a scattering chamber via a time-of-flight (TOF) system has been constructed. The entrance window of the IC has an area of 14 × 40 cm², the active depth is 115 cm. Filled with CF₄ at a pressure of 350 Torr, the energy range for ¹²C and ⁴⁰Ar is 5–20 MeV/A and 6–30 MeV/A, respectively. The TOF system consists of two parallel plate avalanche counters with a flightpath of 70 cm in between. The IC has been tested with ¹²C ions at an energy of 39 MeV. The energy resolution of the IC (1.1%) is mainly determined by the energy straggling in the foils of the TOF system and the ionization chamber. The energy-loss resolution is 3.5%, the horizontal position resolution varies between 6 and 20 mm and the vertical position resolution is 2 mm. The time resolution of the TOF system ranges from 800 ps for ⁴He at 5.0 MeV, to 280 ps for ²⁸Si at 55 MeV.     

Macrozoobenthos of floodplain waters of the rivers rhine and meuse in the Netherlands: A structural and functional analysis in relation to hydrology

The river systems of the Rhine and Meuse include a large number of floodplain waters showing differences in hydrology and geomorphology. A classification of 100 water bodies based on their macroinvertebrate communities has been worked out as a tool for ecological management. Analyses were performed on structural (species composition) and functional (trophic relations) aspects of macrozoobenthos in relation to hydrological, vegetational, and physicochemical parameters. Based on the classification of macroinvertebrate communities, three major groups of water bodies can be distinguished, which are related to the frequency of inundation. The flood frequency constitutes the major environmental gradient which structures the zoobenthos communities in the Dutch floodplain waters. Faunal composition is mediated by substrate availability, water chemistry, and the availability of nutritional resources. This typology serves as a basis for the prediction of the impact of hydrology changes on the macrozoobenthic communities of floodplain waters of highly eutrophic and polluted rivers.     

Procedures: Do we really want to know them? An examination of the effects of procedural justice on self-esteem.

This study examined the effects of procedural justice on state-dependent self-esteem using the group-value model and attribution theory to present competing theoretical perspectives. The group-value model predicts a positive relationship between self-esteem and fair procedures. In contrast, attribution theory suggests procedural fairness interacts with outcome favorability to influence self-esteem. Thus, fair procedures will result in higher self-esteem ratings than unfair procedures when the outcome is positive but will result in lower self-esteem ratings than unfair procedures when the outcome is negative. The results of a laboratory and field study provide converging evidence to support the attribution theory predictions. The results of a 2nd laboratory study suggest that self-esteem is influenced by outcome expectancies, not actual outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Proton Spin–Spin Relaxation Study of the Effect of Temperature on White Cement Hydration

The chemical and microstructural changes within a white cement paste were characterized in situ using proton nuclear magnetic resonance spin–spin relaxation at 30 MHz, and X-ray diffraction. Paste samples with a water-to-cement ratio of 0.42 were cured at constant temperatures of 2°, 20°, 60°, and 100°C. Proton nuclear magnetic resonance spin–spin relaxation allows tracking the evolution of the mixing water into the solid fractions of calcium silicate hydrate, calcium hydroxide, and monosulfate, and the liquid phases: the calcium silicate hydrate interlayer water, gel pore water, and capillary pore water. It is shown that the hydration process is markedly accelerated with increasing hydration temperature, and that proton nuclear magnetic resonance relaxation measurements can quantitatively determine the proportions of water phases, their magnetic resonance characteristics, as well as the setting times of the cement during the hydration process.     

A standard protocol for the quality control of microbiological media.

A protocol, comprising standardized analysis and data forms, has been drawn up for the quality control of microbiological media. It was developed in order to standardize the testing procedures in our laboratory and to test media with minimal investment in time and resources. The forms encourage proper recording of the trials, which facilitates internal and external consideration of the results. The protocol was validated in a comparative investigation of the quality of media obtained from different suppliers and were shown to work satisfactorily. Based on the overall results, preferred suppliers for each medium were chosen. The standardized forms can be used in conjunction with the documents drafted by the International Committee for Food Microbiology and Hygiene (ICFMH) Working Party for Culture Media, bringing standardization of testing procedures one step nearer.     

A comparison of administration procedures for the Rey-Osterrieth Complex Figure: Flowcharts versus pen switching.

The Rey-Osterrieth Complex Figure (ROCF) is commonly used to assess visuospatial skills, visuoconstruction, visual memory, and executive functioning. Two different methods are traditionally used to record the order in which the figure is drawn: the flowchart method and the pen-switching method. Although it has been suggested that pen switching may interfere with performance, to date no research has been conducted to assess whether ROCF performance significantly differs due to administration method. As part of routine neuropsychological evaluation, 100 inpatients and outpatients were randomly assigned to either method. Using the Boston Qualitative Scoring System and the traditional 36-point scoring method, the authors unexpectedly found that the pen-switching group generally performed better than the flowchart group, and productions drawn with pen switching were also significantly faster to score. (PsycINFO Database Record (c) 2010 APA, all rights reserved)