Computer Simulation and the Design of New Biological Molecules

Molecular dynamics simulations have been carried out for the enzyme bovine trypsin, for the small inhibitor benzamidine, and for the complex formed by these two molecules, all in the presence of enough water to approximate dilute solution conditions. The simulations have been analyzed to characterize the structure and dynamics of the enzyme and its solvent surroundings. Using the recently developed thermodynamic cycle-perturbation method, the simulations have also been analyzed to determine how changes in the structure of the enzyme and the inhibitor alter the free energy of complex formation. The results suggest that such simulations may be useful in the design of new enzymes and enzyme inhibitors.     

Benzofuran-terminated infrared dyes and their electro-optic properties in guest-host polymers

Molecular first hyperpolarizabilities and dipole moments of new benzo-fused dyes were calculated using quantum-mechanical density functional theory (DFT). Two new infrared dyes were synthesized: each one was terminated with 6-diethylaminobenzo[b]furan on one end, and with CF₃-tricyanodihydrofuran on the other end. The midsection of the π-electron framework for one dye contained a morpholino-substituted cyclohexenylene unit, and the other dye contained an ethoxysiloxane-substituted cyclohexenylene unit. Guest-host films were deposited on ITO-glass and contact poled. Electro-optic coefficients (r₃₃) were measured at a wavelength of 1550 nm by the attenuated total reflection method and by a modified simple Teng-Man reflection method. The measured values of r₃₃ were compared with values estimated from a well-known model that employs the molecular properties of the dyes and the film poling parameters. Thermal stability and electronic absorption spectra of the dyes were measured.     

Functional recovery of respiratory behavior during axonal regeneration in snails (Lymnaea stagnalis) is experience dependent.

This study investigated the role of experience in recovery of pulmonary respiration during axonal regeneration in Lymnaea stagnalis. Pulmonary respiration occurs when snails break the water surface and open the lung orifice, the pneumostome. It was shown that axotomy of all the axons innervating the pneumostome and surrounding area prevents the occurrence of lung respiration in 69% of snails. In the remaining 31%, lung respiration persisted, indicating that peripheral components alone are capable of initiating pneumostome openings and closures. Five weeks postsurgery, all snails with previous nerve crushes showed opening of the pneumostome with normal latency after breaking the water surface. However, prevention of pulmonary respiration during the recovery period dramatically changed the recovered behavior. Thus, experience in pulmonary respiration during axonal regeneration plays a role in the recovery of this behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social learning of an artificial fruit task in capuchin monkeys (Cebus apella).

Social learning in 11 human-raised capuchin monkeys (Cebus apella) was investigated using an artificial fruit that was designed as an analogue of natural foraging problems faced by primates. Each subject observed a human model open each of 3 principal components on the fruit in 1 of 2 alternative ways ("morphs"). The capuchin monkeys reproduced, to differing extents, the alternative techniques used for opening 1 component of the task (poking vs. pulling while twisting out a pair of smooth plastic bolts) but not the other 2. From the subjects' actions on the bolt latch, independent coders could recognize which morph they had witnessed, and they observed a degree of matching to the demonstrator's act consistent with simple imitation or object movement reenactment (A learns from watching B how an object, or parts of an object, move). Thus, these capuchins were capable of more complex social learning than has been recently ascribed to monkeys. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bioproduction of cis‐(1S,2R)‐indandiol,a chiral pharmaceutical intermediate,using a solid–liquid two‐phase partitioning bioreactor for enhanced removal of inhibitors

BACKGROUND: A solid‐liquid two‐phase partitioning bioreactor (TPPB) was used in the biotransformation of indene to cis‐(1S,2R)‐indandiol by Pseudomonas putida 421‐5 (ATCC 55687). Metered substrate feeding in single‐phase operation, or delivery from an immiscible liquid, have previously been employed to regulate the exposure of the biocatalyst to inhibitory concentrations of the substrate. In contrast, the solid‐liquid platform provided in situ substrate addition (ISSA) as well as simultaneous it in situ product removal (ISPR) as a means of overcoming substrate and product toxicity. Three different modes of operation were compared for their effects on the performance of this biotransformation: single‐phase, fed‐batch operation was carried out as a benchmark in 2.75 L aqueous medium, and subsequently with the inclusion of either 700 g liquid silicone oil or 700 g solid polymer beads. RESULTS: Biphasic modes achieved a 3‐fold productivity improvement with respect to single‐phase (30 to 90 mg L^?1 h^?1), and solid‐liquid productivity was similar to liquid‐liquid operation while achieving more extensive removal of inhibitory compounds resulting in a slightly higher product titer (1.29 vs 1.16 g L^?1). The operability of the reactor was improved by the phase stability of the solid polymer beads relative to immiscible organic solvents, preventing emulsion formation and facilitating analytics. CONCLUSION: Solid polymer beads replaced the immiscible liquid auxiliary phase for substrate delivery while performing simultaneous inhibitory molecule sequestration. Copyright © 2011 Society of Chemical Industry     

Exercising your brain: A review of human brain plasticity and training-induced learning.

Human beings have an amazing capacity to learn new skills and adapt to new environments. However, several obstacles remain to be overcome in designing paradigms to broadly improve quality of life. Arguably, the most notable impediment to this goal is that learning tends to be quite specific to the trained regimen and does not transfer to even qualitatively similar tasks. This severely limits the potential benefits of learning to daily life. This review discusses training regimens that lead to the acquisition of new knowledge and strategies that can be used flexibly across a range of tasks and contexts. Possible characteristics of training regimens are proposed that may be responsible for augmented learning, including the manner in which task difficulty is progressed, the motivational state of the learner, and the type of feedback the training provides. When maximally implemented in rehabilitative paradigms, these characteristics may greatly increase the efficacy of training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

New Technology for Preventing Residential Electrical Fires: Arc-Fault Circuit Interrupters (AFCIs)

A new generation of residential electrical branch circuit breakers that incorporates technology to detect and mitigate the effects of arcing faults is described. Fire loss estimates attributed to electrical wiring and the development of the arc-fault circuit interrupter for the prevention of residential electrical fires are discussed. The industry voluntary standard for arc-fault circuit interrupters as well as the 1999 National Electrical Code requirement are reviewed.     

Geomembrane Strain Observed in Large-Scale Testing of Protection Layers

A method for estimating the local strain in a geomembrane due to the indentation of gravel particles is presented. The accuracy of various strain calculation methods is evaluated by a series of tests, and it is shown that the traditional arch elongation method provides only an approximate estimate of the magnitude of strain induced in the geomembrane due to indentation and does not adequately define the distribution of strain. Consideration of the combined membrane and bending strains as proposed here is shown to provide a better representation of the distribution of strains and enhances the evaluation of the peak strains in the geomembrane caused by local indentations. Large-scale tests are conducted using different protection layers, and the strains are reported based on both the arch elongation method and the combined bending and membrane theory. The results indicate that the best protection for the underlying geomembrane was provided by a sand-filled geocushion or a special rubber geomat, which limited strains induced by coarse (40–50 mm) angular gravel to 0.9% at 900 kPa and 1.2% at 600 kPa. The poorest performance was achieved using nonwoven geotextiles with a maximum strain of 8% being obtained with a 435 g∕m2 geotextile at 250 kPa and 13% with two layers of 600 g∕m2 geotextile at 900 kPa.     

Tissue-level segmentation and tracking of cells in growing plant roots

With the spread of systems approaches to biological research, there is increasing demand for methods and tools capable of extracting quantitative measurements of biological samples from individual and time-based sequences of microscope images. To this end, we have developed a software tool for tissue level segmentation and automatic tracking of a network of cells in confocal images of the roots of the model plant Arabidopsis thaliana. The tool implements a novel hybrid technique, which is a combination of the recently developed Network Snakes technique and MCMC-based particle filters and incorporates automatic initialisation of the network snakes. A novel method of evaluation of network-structured multi-target tracking is also presented, and is used to evaluate the developed tracking framework for accuracy and robustness against several timelapse sequences of Arabidopsis roots. Evaluation results are presented, along with a comparison between the results of the component techniques and the hybrid approach. The results show that the hybrid approach performed consistently well at all levels of complexity and better than the component methods alone.     

Intracerebral hemorrhage after carotid endarterectomy: incidence, contribution to neurologic morbidity, and predictive factors

PURPOSE: With a diminishing rate of cardiac and neurologic events after carotid endarterectomy, intracerebral hemorrhage is gaining increasing importance as a cause of perioperative morbidity and mortality. To date, information has been largely anecdotal, and there has been no comparison with a control group of patients. METHODS: The records of all patients experiencing symptomatic intracerebral hemorrhage after carotid endarterectomy were reviewed and compared with data from 50 randomly selected patients who did not experience intracranial bleeding. Univariate analyses were performed, using the Fisher exact test for dichotomous data and the Student t test for continuous data. RESULTS: During a 6-year period, symptomatic intracranial hemorrhage developed in 11 (0.75%) of 1471 patients undergoing carotid endarterectomy, accounting for 35% of the 31 total perioperative neurologic events. Hemorrhage occurred a median of 3 days postoperatively (range, 0 to 18 days). Signs and symptoms included hypertension in all 11 patients, headache in 7 conscious patients (64%), and bradycardia in 6 patients (55%). Massive hemorrhage with herniation and death occurred in 4 patients (36%). Moderate hemorrhage developed in 5 patients (45%); 3 of these patients had partial recovery, and 2 had complete recovery. Petechial hemorrhage occurred in the remaining 2 patients (18%), 1 with partial and 1 with complete recovery. In comparison with the control group, there were no differences in respect to sex, indication for operation, smoking or diabetic history, and antiplatelet therapy or perioperative heparin management. Patients with intracranial hemorrhage were, however, younger, more frequently hypertensive, had a higher degree of ipsilateral and contralateral carotid stenosis, and had a higher rate of contralateral carotid occlusion. CONCLUSION: Intracranial hemorrhage occurs with notable frequency after carotid endarterectomy and accounts for a significant proportion of neurologic morbidity and mortality. Younger patients, hypertensive patients, and patients with severe cerebrovascular occlusive disease appear to be at greatest risk for the complication.