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It has been suggested recently that data on mutations in human haemoglobin is consistent with the hypothesis that evolution takes place in the direction of increasing informational entropy of DNA. We argue that the mutation data sheds no light on the above hypothesis and show how the data can be understood in terms of random mutation of the bases in DNA.
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The conformational statistics of atactic polystyrene have been investigated by solid-state NMR, on a sample labeled with 25% 13CH2 groups. Double-quantum pulse sequences are used to select statistically formed 13C-13C spin pairs. An experiment correlating the 13C-13C internuclear vector with the 13C chemical-shift anisotropy determines the conformational statistics of a single backbone torsion angle. Double-quantum experiments correlating the 13CH2 chemical-shift anisotropies of two adjacent segments provide information on two consecutive torsion angles. The analysis of the spectra yields a trans content of 68% (+/-10%). This represents the first direct experimental estimate of the trans/gauche ratio in atactic polystyrene. The trans content found here agrees well with rotational-isomeric-state models but is inconsistent with results from more elaborate atomistic models that take packing effects into account.
The Probabilistic Neural Network (PNN) and its close relative, the Generalized Regression Neural Network (GRNN), are presented as simple yet powerful neural network techniques for use in Quantitative Structure-Activity Relationship (QSAR) and Quantitative Structure-Property Relationship (QSPR) studies. The PNN methodology is applicable to classification problems, and the GRNN is applicable to continuous function mapping problems. The basic underlying theory behind these probability-based methods is presented along with two applications of the PNN/GRNN methodology. The PNN model presented identifies molecules as potential soluble epoxide hydrolase inhibitors using a binary classification scheme. The GRNN model presented predicts the aqueous solubility of nitrogen- and oxygen-containing small organic molecules. For each application, the network inputs consist of a small set of descriptors that encode structural features at the molecular level. Each of these studies has also been previously addressed in this research group using more traditional techniques such as k-nearest neighbor classification, multiple linear regression, and multilayer feed-forward neural networks. In each case, the predictive power of the PNN and GRNN models was found to be comparable to that of the more traditional techniques but requiring significantly fewer input descriptors.
Conformational energies of histamine and 4-methylhistamine monocations are calculated using the EHT molecular orbital procedure; the results are expressed as potential energy surfaces in which bond rotations (theta1 for ring-Cbeta, theta2 for Cbeta-Calpha) are measured along the axes, and energy variation is indicated by contours. Using the classical Boltzmann partition function and Simpson's rule for normalization, corresponding probability surfaces are generated which take account of the potential surface entropy. Comparing the two surfaces provides regions which are within a given probability contour of histamine but outside this contour for 4-methylhistamine. Thus, at the 99% probability level, three conformational regions defined by the bond rotation angles are indicated as possible "H1-essential" conformations of histamine: viz. trans (theta1=290-330 degrees, theta2=150-210 degrees) and gauche (theta1=260-280 degrees, theta2=30-90 degrees and theta1=290-320 degrees, theta2=270-320 degrees). This procedure provides a quantitative basis for comparison with other histamine derivatives and may have a general value for studying relationships between conformation and biological activity of closely related small molecules.
Reduced-dimensionality quantum reactive scattering calculations for the C(3P) + C2H2 reaction have been carried out in order to understand the product branching dynamics of cyclic-C3H + H and linear-C3H + H. Our model treats only two degrees of freedom but can explicitly describe both of the C3H isomer product channels. The lowest triplet potential energy surface has been obtained by the hybrid density-functional method at the B3LYP/6-31G(d,p) level of theory. The calculated reaction probabilities were found to be dominated by resonance consistent with the complex-formation potential, and the results show that cyclic-C3H is preferentially formed via the cyclic-C3H2 intermediate produced by insertion of C(3P) into the CC bond. We have found that the isomerization from the cyclic-C3H2 to linear-C3H2 intermediate is suppressed by a barrier separating potential wells corresponding to these two intermediates. It has also been found that the energy dependence of the calculated total reaction cross section is in good agreement with the result of crossed molecular beam experiments.
Monte Carlo techniques were used to evaluate the flow of molecules through an ideal orifice (effusion) as predicted by isotropy-failure theory. Binary collisions of molecules were treated using classical mechanics with random numbers used for molecular speeds, directions, and recoil angles. Isotropy-failure theory was applied to give the dependence on pressure of the gas. Isotropy-failure theory assumes that the probability of escape is increased by the absence of the container wall where the orifice is located. The simulation was performed for Ar at 1000 K for 10(7) collisions. The simulation provided the number of molecules and their speeds in the orifice direction as a function of the isotropy-failure parameter domega/2pi (related to the Knudsen number defined as the mean-free path divided by orifice diameter). As domega/2pi increased (Knudsen number decreased, pressure increased) the transmission probability of the orifice increased, and the average speed of molecules escaping along the orifice normal increased. The results are compared to experimental results for the orifice transmission probability and speed distribution.
Quasiclassical trajectory calculations are used to investigate the dynamics of the OH(v) + NO(2) --> HONO(2) --> OH(v') + NO(2) recombination/dissociation reaction on an analytic potential energy surface (PES) that gives good agreement with the known structure and vibrational frequencies of nitric acid. The calculated recombination rate constants depend only weakly on temperature and on the initial vibrational energy level of OH(v). The magnitude of the recombination rate constant is sensitive to the potential function describing the newly formed bond and to the switching functions in the PES that attenuate inter-mode interactions at long range. The lifetime of the nascent excited HONO(2) depends strongly not only on its internal energy but also on the identity of the initial state, in disagreement with statistical theory. This disagreement is probably due to the effects of slow intramolecular vibrational energy redistribution (IVR) from the initially excited OH stretching mode. The vibrational energy distribution of product OH(v') radicals is different from statistical distributions, a result consistent with the effects of slow IVR. Nonetheless, the trajectory results predict that vibrational deactivation of OH(v) via the HONO(2) transient complex is approximately 90% efficient, almost independent of initial OH(v) vibrational level, in qualitative agreement with recent experiments. Tests are also carried out using the HONO(2) PES, but assuming the weaker O-O bond strength found in HOONO (peroxynitrous acid). In this case, the predicted vibrational deactivation efficiencies are significantly lower and depend strongly on the initial vibrational state of OH(v), in disagreement with experiments. This disagreement suggests that the actual HOONO PES may contain more inter-mode coupling than found in the present model PES, which is based on HONO(2). For nitric acid, the measured vibrational deactivation rate constant is a useful proxy for the recombination rate, but IVR randomization of energy is not complete, suggesting that the efficacy of the proxy method must be evaluated on a case-by-case basis.
PURPOSE: To investigate the influence of various nonreducing disaccharides and sugar alcohols on the inactivation kinetics of recombinant factor VIII SQ (r-VIII SQ) in aqueous solution not containing albumin as a stabiliser. METHODS: The stability of r-VIII SQ was followed using measurement of activity (VIII:C) and HPLC gel filtration at different temperatures. The thermal stability was investigated using differential scanning calorimetry (DSC). RESULTS: The decline in VIII:C followed pseudo-first order kinetics. However, the Arrhenius plot was not linear for formulations without carbohydrate, demonstrating a distinct, reproducible curvature. The reaction rate at 5 degrees C was faster than expected from the Arrhenius kinetics. The energy of activation (Ea) for formulations without added carbohydrates, derived from the linear part of the Arrhenius plot, varied between 77 and 86 kJ/mole in the temperature range 20-37 degrees C. The addition of 600 mg/ml sucrose increased the Ea to 104 kJ/mole. DSC measurements showed that Tm' was 64.2 +/- 0.2 degrees C for r-VIII SQ without stabiliser. This value increased linearly with increasing concentrations of carbohydrate. This stabilising effect is most probably explained by the theory of preferential hydration. CONCLUSIONS: The inactivation kinetics of r-VIII SQ in aqueous solution without addition of carbohydrates followed pseudo-first order kinetics but the Arrhenius plot was nonlinear. Sucrose and sorbitol both had highly stabilising effects on r-VIII SQ at concentrations above 300 mg/ml. The preparation containing 600 mg/ml sucrose was stable for at least 12 months at 5 degrees C and 6 months at 25 degrees C.
The relation between biomedical knowledge and clinical knowledge is discussed by comparing their respective structures. The knowledge of a disease as a biological phenomenon is constructed by the interaction of facts and theories from the main biomedical disciplines: epidemiology, diagnostics, clinical trial, therapy development and pathogenesis. Although these facts and theories are based on probabilities and extrapolations, the interaction provides a reliable and coherent structure, comparable to a Kuhnian paradigma. In the structure of clinical knowledge, i.e. knowledge of the patient with the disease, not only biomedical knowledge contributes to the structure but also economic and social relations, ethics and personal experience. However, the interaction between each of the participating "knowledges" in clinical knowledge is not based on mutual dependency and accumulation of different arguments from each, as in biomedical knowledge, but on competition and partial exclusion. Therefore, the structure of biomedical knowledge is different from that of clinical knowledge. This difference is used as the basis for a discussion in which the place of technology, evidence-based medicine and the gap between scientific and clinical knowledge are evaluated.
According to the discrepancy-attribution hypothesis (B. W. A. Whittlesea & L. D. Williams, 1998), people experience a feeling of familiarity when they perceive their processing to be surprising, but for an indefinite reason. This hypothesis has been successful in explaining several illusions of familiarity. Here, it is applied to the prototype-familiarity effect, an illusion of remembering that occurs when people are shown prototype words after studying lists of associates. The experiments showed that studying associates enhances semantic, but not perceptual, processing of prototypes. They also showed that claims of recognizing prototypes can be modified by presenting them in predictive or incongruous contexts at test. The evidence suggests that the effect results from an evaluation process that monitors the coherence of processing.
Veridical memory for presented list words and false memory for nonpresented but related items were tested using the Deese/Roediger and McDermott paradigm. The strength and density of preexisting connections among the list words, and from the list words to the critical items, were manipulated. The likelihood of producing false memories in free recall varied with the strength of connections from the list words to the critical items but was inversely related to the density of the interconnections among the list words. In contrast, veridical recall of list words was positively related to the density of the interconnections. A final recognition test showed that both false and veridical memories were more likely when the list words were more densely interconnected. The results are discussed in terms of an associative model of memory, Processing Implicit and Explicit Representations (PIER 2) that describes the influence of implicitly activated preexisting information on memory performance.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.