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PubMed2006

The emergence and diffusion of DNA microarray technology.

UNLABELLED: The network model of innovation widely adopted among researchers in the economics of science and technology posits relatively porous boundaries between firms and academic research programs and a bi-directional flow of inventions, personnel, and tacit knowledge between sites of university and industry innovation. Moreover, the model suggests that these bi-directional flows should be considered as mutual stimulation of research and invention in both industry and academe, operating as a positive feedback loop. One side of this bi-directional flow--namely; the flow of inventions into industry through the licensing of university-based technologies--has been well studied; but the reverse phenomenon of the stimulation of university research through the absorption of new directions emanating from industry has yet to be investigated in much detail. We discuss the role of federal funding of academic research in the microarray field, and the multiple pathways through which federally supported development of commercial microarray technologies have transformed core academic research fields. RESULTS AND CONCLUSION: Our study confirms the picture put forward by several scholars that the open character of networked economies is what makes them truly innovative. In an open system innovations emerge from the network. The emergence and diffusion of microarray technologies we have traced here provides an excellent example of an open system of innovation in action. Whether they originated in a startup company environment that operated like a think-tank, such as Affymax, the research labs of a large firm, such as Agilent, or within a research university, the inventors we have followed drew heavily on knowledge resources from all parts of the network in bringing microarray platforms to light. Federal funding for high-tech startups and new industrial development was important at several phases in the early history of microarrays, and federal funding of academic researchers using microarrays was fundamental to transforming the research agendas of several fields within academe. The typical story told about the role of federal funding emphasizes the spillovers from federally funded academic research to industry. Our study shows that the knowledge spillovers worked both ways, with federal funding of non-university research providing the impetus for reshaping the research agendas of several academic fields.

Journal Article↗
PubMedDate not supplied

A two layer model for the effects of blood contact on membrane transport in artificial organs.

The performance of many artificial organs can be strongly affected by the transport characteristics of the semi-permeable membranes used in these devices, but there is little data on the effects of blood contact on membrane transport properties. Experimental data were obtained for the solute flux through cellulosic, polyacrylonitrile, and polyethersulfone membranes using polydispersed dextrans. Blood contact had a very large effect on diffusive solute transport through the asymmetric polyethersulfone membranes, but only a small effect on diffusion through the symmetric AN69 and Cuprophan membranes. In contrast, blood contact caused a similar reduction in convective solute transport (sieving) through both the polyethersulfone and AN69 membranes. Convective transport through the blood contacted membranes was also dependent on the flow direction, with greater transport obtained when the membrane was oriented with the blood contacted surface downstream. These data were analyzed using a two layer membrane model consisting of an upper layer of blood cells and proteins adsorbed to the surface of the native membrane. This model accurately accounted for the different effects of blood contact on convection and diffusion, as well as the observed asymmetry in convective solute transport. These results have important implications for the analysis of solute transport in artificial organs.

Acrylic Resins↗
PubMed2005

[Analysis on the multi-distribution and the major influencing factors on severe acute respiratory syndrome in Beijing].

OBJECTIVE: To analyse the multi-dimension nature of severe acute respiratory syndrome (SARS) transmission. METHODS: Based on the data of SARS in 2003 and the geographic information system of Beijing, as well as under the broad range of the theorems and techniques of data-driven and model-driven knowledge mining, hierarchical techniques were used to test the hot spots. Wavelet technique was also used to decompose Moran's I frequency to survey the spatial clustering process of SARS. For factors analysis, BW test was used to distinguish factors which influencing SARS process. In temporal aspects, susceptive-infective-removal model (SIR) without Taylor expansion was solved by a genetic-simulated annealing algorithm, that directly provided a new approach to obtain epidemic parameters from the SIR model. RESULTS: Different order of spatial hot spots were noticed and the clustering were relevant with the means of transportation. Diffusion dynamics were changed along with the temporal process of SARS. Regarding factor analysis, geographic relationship, population density, the amount of doctors and hospitals appeared to be the key elements influencing the transmission of SARS. The predictable number of SARS cases evolving with time were also calculated. CONCLUSIONS: Cluster detection of close contacts of SARS infective in Beijing revealed the spatial characters of urban population flow and having important implications in the prevention and control of this communicable diseases. Some human and physical environment factors played statistical significant roles in different periods during SARS epidemics. An efficient algorithm was developed to solve SIR model directly, enabling the estimation of epidemic parameters from SIR and early forecast.

Algorithms↗
PubMed2000

Effects of heterogeneous structure and diffusion permeability of body tissues on decompression gas bubble dynamics.

To gain insight into the special nature of gas bubbles that may form in astronauts, aviators and divers, we developed a mathematical model which describes the following: 1) the dynamics of extravascular bubbles formed in intercellular cavities of a hypothetical tissue undergoing decompression; and 2) the dynamics of nitrogen tension in a thin layer of intercellular fluid and in a thick layer of cells surrounding the bubbles. This model is based on the assumption that, due to limited cellular membrane permeability for gas, a value of effective nitrogen diffusivity in the massive layer of cells in the radial direction is essentially lower compared to conventionally accepted values of nitrogen diffusivity in water and body tissues. Due to rather high nitrogen diffusivity in intercellular fluid, a bubble formed just at completion of fast one-stage reduction of ambient pressure almost instantly grows to the size determined by the initial volume of the intercellular cavity, surface tension of the fluid, the initial nitrogen tension in the tissue, and the level of final pressure. The rate of further bubble growth and maximum bubble size depend on comparatively low effective nitrogen diffusivity in the cell layer, the tissue perfusion rate, the initial nitrogen tension in the tissue, and the final ambient pressure. The tissue deformation pressure performs its conservative action on bubble dynamics only in a limited volume of tissue (at a high density of formed bubbles). Our model is completely consistent with the available data concerning the random latency times to the onset of decompression sickness (DCS) symptoms associated with hypobaric decompressions simulating extravehicular activity. We believe that this model could be used as a theoretical basis for development of more adequate methods for the DCS risk prediction.

Atmospheric Pressure↗
PubMed2006

Evaluation of a diffusion-driven mechanism for substrate ubiquitination by the SCF-Cdc34 ubiquitin ligase complex.

Release of ubiquitin-charged Cdc34 from the SCF ubiquitin ligase followed by diffusion-driven collision with substrate has been proposed to underlie ubiquitination of the canonical SCF substrate Sic1. Cdc34 F72V, reported to be defective in dissociation from SCF, served as key validation. Here, we test predictions of this "hit-and-run" hypothesis. We find that Cdc34 F72V is generally defective in SCF-mediated activation but, contrary to expectation, does not compete with wild-type Cdc34 in vitro or in vivo and can fulfill the physiological role of Cdc34 with only moderate delay in Sic1 turnover. Whereas a hit-and-run mechanism might explain how Cdc34 can transfer ubiquitin to the ends of growing ubiquitin chains on SCF-bound substrates, molecular modeling suggests that an E2 docked to SCF can do so without dissociating. We propose that interactions between Cdc34 approximately Ub and SCF directly activate ubiquitin transfer within a substrate-SCF-Cdc34 approximately Ub ternary complex.

Anaphase-Promoting Complex-Cyclosome↗
PubMed2004

Analytical error propagation in diffusion anisotropy calculations.

PURPOSE: To develop an analytical formalism describing how noise and selection of diffusion-weighting scheme propagate through the diffusion tensor imaging (DTI) computational chain into variances of the diffusion tensor elements, and errors in the relative anisotropy (RA) and fractional anisotropy (FA) indices. MATERIALS AND METHODS: Singular-value decomposition (SVD) was used to determine the tensor variances, with diffusion-weighting scheme and measurement noise incorporated into the design matrix. Anisotropy errors were then derived using propagation of error. To illustrate the applications of the model, 12 data sets were acquired from each human subject, over a range of b-values (500-2500 seconds/mm2) and diffusion-weighting gradient directions (N = 6-55). The mean RA and FA values and their respective errors were calculated within a region of interest (ROI) in the splenium. The RA and FA errors as a function of b-value and N were evaluated, and a number of diffusion-weighting schemes were assessed based on a new metric, sum of diffusion tensor variances. RESULTS: When the acquisition time was held constant, the sum of the diffusion tensor variances decreased as N increased. The same trend was also observed for several diffusion-weighting schemes with constant condition number when noise in the diffusion-weighted (DW) images was assumed unity. Errors in both FA and RA increased with b-value and decreased with N. The FA error in the splenium was approximately threefold smaller than RA error, irrespective of b-value or N. CONCLUSION: The condition number may not adequately characterize the noise sensitivity for a given diffusion-weighting scheme. Signal averaging may not be as effective as increasing N, especially when N is small (e.g., N < 13). Due to its smaller error, FA is preferred over RA for quantitative DTI applications.

Adult↗
PubMed1998

Motion in a stochastic layer described by symbolic dynamics.

The motion in the stochastic layer surrounding an island can be studied by using the standard map: This problem is of direct relevance to the diffusion of magnetic field lines in a tokamak. In a previous work it was shown that this process can be adequately modelled by a continuous time random walk (CTRW) describing transitions of the running point between three basins representing, respectively, trapped motion around the island, and passing motion above or below the island. The sticking property of the island deeply modifies the nature of the transport process, leading to subdiffusive behavior. In the present work it is shown that the motion can be analyzed in terms of a symbolic dynamics which leads to the possibility of an automatic measurement of the data necessary for the construction of the CTRW. The logical features of the procedure are described, and the method is applied to an analysis of long time series, thus completing the results of the previous work. (c) 1998 American Institute of Physics.

Journal Article↗
PubMed2002

Computer modelling of radiation-induced bystander effect.

Radiation-induced genomic instability and bystander effects are now well established consequences of exposure of living cells to ionising radiation. It has been observed that cells not directly hit by radiation tracks may still exhibit radiation effects. We present a quantitative modelling of the radiation-induced bystander effect based on a diffusion model of spreading the bystander signal. The model assumes the bystander factor to be aprotein of low molecular weight, given out by the hit cell, diffusing in the medium and reacting with non-hit cells. The model calculations successfully predict the results of cell survival in an irradiated conditioned medium. The model predicts the shape of dose-effect relationship for cell survival and oncogenic transformation induced by broad-beam and micro-beam irradiation by alpha-particles.

Bystander Effect↗
PubMed2005

Asymmetric nanodiffusion.

The asymmetric diffusion through conical nanopores is described by the diffusional model. Diffusion is several times faster; when the concentration gradient points from the wide towards the narrow opening of the cone than in the opposite direction. The asymmetric diffusion appears either when the diffusion coefficient depends on the concentration or when the diffusing substances interact with the channel (i.e., ions moving through channels with charged walls). These results suggest that asymmetric nanopores can act as molecular (ionic) filters which could be used for retrieving the molecules of a given component from solutions in which its concentration fluctuates strongly, and only occasionally attains high values.

Journal Article↗
PubMedDate not supplied

Boundary integral method for bioluminescence tomography.

Bioluminescence tomography (BLT) allows in vivo localization and quantification of bioluminescent sources inside a small animal to reveal various molecular and cellular activities. We develop a reconstruction method to identify such a bioluminescent source distribution using the boundary integral method. Based on the diffusion model of the photon propagation in the biological tissue, this method incorporates a priori knowledge to define the permissible source region, and establish a direct linear relationship between measured body surface data and an unknown bioluminescent source distribution to enhance numerical stability and efficiency. The feasibility of the proposed BLT algorithm is demonstrated in heterogeneous mouse chest phantom studies.

Algorithms↗
PubMed2006

Dual diffusion model for single-cell recording data from the superior colliculus in a brightness-discrimination task.

Monkeys made saccades to one of two peripheral targets based on the brightness of a central stimulus. Task difficulty was manipulated by varying the ratio of stimulus black-and-white pixels. Correct response probability for two monkeys varied directly with difficulty. Deep layer SC neurons exhibited robust presaccadic activity the magnitude of which was unaffected by task difficulty when the stimulus specified a saccade toward a target within the neuron's response field. Activity after stimuli specifying saccades to targets outside the response field was affected by task difficulty, increasing as the task became more difficult. A quantitative model derived from studies of human decision-making was fit to the behavioral data. The model assumes that information from the stimulus drives two independent diffusion processes. Simulated paths from the model were compared with neuron activity, assuming that firing rate is linearly related to position in the accumulation process. The firing rate data show delayed availability of discriminative information for fast, intermediate, and slow decisions when activity is aligned on the stimulus and very small differences in discriminative information when aligned on the saccade. The model produces exactly these patterns of results. The accumulation process is highly variable, allowing the process both to make errors, as is the case for the behavioral performance, and also to account for the firing rate results. Thus the dual diffusion model provides a quantitative account for both the behavior in a simple decision-making task as well as the patterns of activity in competing populations of neurons.

Animals↗
PubMedDate not supplied

Peritoneal transport of glucose in rat.

OBJECTIVE: To evaluate the convective transport characteristics of glucose and the effect of high glucose and insulin during experimental peritoneal dialysis in rat. METHODS: Male Sprague-Dawley rats weighing 300-400 g were used in this study. Mannitol (5%) was used as osmotic agent. Glucose was added to dialysis solution to yield a concentration of 100 mg/dL (group 1) or 300 mg/dL (group 2). Mannitol solution (5%) containing the same concentration of electrolytes and lactate but without glucose was used as control (group 3). In group 2, blood sugar was maintained at approximately 300 mg/dL by continuous intravenous infusion of 25% glucose solution and 0.9% NaCl solution. A 2-hour dwell study was performed with 30 mL of test solutions. Intraperitoneal volume was calculated by volume marker (18.5 kBq of 131I-human radioiodinated serum albumin, RISA) dilution with corrections made for the elimination of RISA from the peritoneal cavity (K(E)) and sample volume. The diffusive mass transport coefficient (K(BD)) and sieving coefficient (S(BRF)) were calculated by using the Babb-Randerson-Farrell model. S was also calculated directly by using isocratic methods (S(I)). The peritoneal fluid absorption rate (K(E)) was taken into account for the calculation of S(I). RESULTS: Intraperitoneal volume was significantly higher in group 2 compared with groups 1 and 3. Peritoneal fluid absorption rate, K(E), was similar in all three groups. S(BRF) and S(I) for glucose were significantly lower in group 2 compared with groups 1 and 3. S(BRF) for glucose in group 2 was below zero and S(I) near zero. K(BD) for glucose was significantly higher in group 2 than in groups 1 and 3. Plasma and dialysate concentrations of insulin increased during the initial hour and then decreased to the baseline value in groups 1 and 3, while in group 2 it continuously increased. CONCLUSION: Significantly lower sieving coefficients for glucose in the high glucose and high insulin group suggest that transport mechanisms other than simple passive transport are involved in peritoneal glucose transport, and that high glucose per se and/or high insulin may be important factors that determine glucose transport characteristics.

Animals↗
PubMed1988

Theoretical aspects of stripe formation in relation to Drosophila segmentation.

Many aspects of Drosophila segmentation can be discussed in one-dimensional terms as a linear pattern of repeated elements or cell states. But the initial metameric pattern seen in the expression of pair-rule genes is fully two-dimensional, i.e. a pattern of stripes. Several lines of evidence suggest a kinetic mechanism acting globally during the syncytial blastoderm stage may be responsible for generating this pattern. The requirement that the mechanism should produce stripes, not spots or some other periodic pattern, imposes preconditions on this act, namely (1) sharp anterior and posterior boundaries that delimit the pattern-forming region, and (2) an axial asymmetrizing influence in the form of an anteroposterior gradient. Models for Drosophila segmentation generally rely on the gradient to provide positional information in the form of concentration thresholds that cue downstream elements of a hierarchical control system. This imposes restrictions on how such models cope with experimental disturbances to the gradient. A shallower gradient, for example, means fewer pattern elements. This need not be the case if the gradient acts through a kinetic mechanism like reaction-diffusion that involves the whole system. It is then the overall direction of the gradient that is important rather than specific concentration values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Alteration of pore properties of Escherichia coli OmpF induced by mutation of key residues in anti-loop 3 region.

The Escherichia coli OmpF pore is governed by an internal constriction consisting of the negatively charged loop 3 folded into the lumen and the positively charged barrel wall located on the opposite side across the pore, 'anti-loop 3'. To investigate the role of anti-loop 3 in solute diffusion, four site-directed mutations, K16A, K16D, R132A and R132D, were introduced into this eyelet region. The mutant porins were expressed efficiently and inserted into the outer membrane, and the thermal stabilities of the resulting trimers were determined. Diffusion of cefepime, a recently developed cephalosporin, was analysed in vivo. In vitro studies were performed on purified porins reconstituted in planar lipid bilayers to measure conductance, selectivity and voltage closure, as well as in liposomes for patch-clamp and sugar-swelling assays. All substitutions modified the ion-channel parameters, and minor conformational changes in the OmpF eyelet region were predicted from modelling studies. Our data show that Lys-16, and to a lesser extent Arg-132, are involved in voltage-gating and pore selectivity via their side-chain charges. Substitution K16D, which causes a severe decrease in critical voltage (V(c)), may generate a channel susceptible to membrane potential, which perturbs cefepime diffusion. These results suggest that the Lys-16 residue plays an important role in the process of diffusion through the OmpF lumen.

Arginine↗
PubMed1995

A diffusion-reaction model of nerve regeneration.

The process of peripheral nerve regeneration has been modeled using 5 populations of mathematical variables to represent the biological activities of Wallerian degeneration, fibrin matrix development, Schwann cell activity, elongating neurites, and neovascularization. The mathematical model provided simulations of nerve regeneration following transection and crush injuries that correspond with growth behaviors quantified in biological experiments. Neovascularization was spatiotemporally quantified in nerve regeneration chambers and following nerve crush injury in order to test the simulations of the mathematical model. The vasculature in both the chamber and following nerve crush responded as predicted by the model, increasing beyond normal levels to a peak only to decrease back to normal. This behavior appeared as a traveling wave in the proximal-distal direction preceeding the major thrust of neuritic outgrowth suggesting that development of the vasculature is a rate-limiting step in nerve regeneration.

Animals↗
PubMed2003

Aging dynamics in globular proteins: summary and analysis of experimental results and simulation by a modified trap model.

Recent results of spectral diffusion experiments by spectral hole-burning techniques carried out at cryogenic temperatures on various monomeric heme proteins unequivocally show interesting new features of conformational dynamics of globular proteins that were not emphasized in the literature until now. These new aspects of the protein dynamics are anomalous diffusion and the aging effect. Here, using the similarities between proteins and glassy systems, we present a model which can interpret the line broadening and-through this effect-the aging phenomenon as well. Leaving untouched the widely accepted energy landscape (EL) concept for the general description of protein dynamics, we concentrate on the bottom of the funnel-like EL, because this part corresponds to the native state(s) at low temperature. We suggest that the overall shape of the EL at the lowest energy range is rather smooth, but on a finer scale it consists of traps. The dynamics is defined by sequential jumps among these traps and the process is described by a Master equation, where the hopping rate only depends on the parameters of the starting state. This model was adapted to interpret the common results of spectral diffusion experiments. We tested our model in the simplest case by computer simulation, and it shows excellent agreement with the experimental data. To our knowledge this is the first work where a theoretical interpretation of the aging dynamics of proteins is directly and quantitatively related to the experimental observations. We also show that the model, after the generalization that the traps are hierarchically organized, is in accordance with the concept of other well-known EL models.

Biophysical Phenomena↗
PubMed1996

Gamma sterilization of UHMWPE articular implants: an analysis of the oxidation problem. Ultra High Molecular Weight Poly Ethylene.

Gamma irradiation of Ultrahigh Molecular Weight Polyethylene (UHMWPE) leads to long-lived free radicals which react with oxygen. Diffusion of oxygen, occurring over months or years, controlled by the permeability characteristics of the polymer, results in progressive oxidation, breaking of polymer chains, alteration of the crystalline portion of the polymer, and deterioration of the mechanical properties of the polymer. This paper reviews the observations in the literature on this issue and then presents a conceptual model concerning the interplay of radical diffusion, oxygen diffusion, non-uniform permeability, and free-radically driven chain reactions in order to explain these observations. The suggested model is based on literature that is available on the oxidation of linear polyethylenes during and after irradiation. The model directs the attention of researchers in the field of orthopaedic implants to the complexity of the process and the variety of issues and parameters to be considered while studying the long-term effects of radiation sterilization on UHMWPE.

Biopolymers↗
PubMed2003

An enhanced cosmic-ray flux towards zeta Persei inferred from a laboratory study of the H3+-e- recombination rate.

The H3+ molecular ion plays a fundamental role in interstellar chemistry, as it initiates a network of chemical reactions that produce many molecules. In dense interstellar clouds, the H3+ abundance is understood using a simple chemical model, from which observations of H3+ yield valuable estimates of cloud path length, density and temperature. But observations of diffuse clouds have suggested that H3+ is considerably more abundant than expected from the chemical models. Models of diffuse clouds have, however, been hampered by the uncertain values of three key parameters: the rate of H3+ destruction by electrons (e-), the electron fraction, and the cosmic-ray ionization rate. Here we report a direct experimental measurement of the H3+ destruction rate under nearly interstellar conditions. We also report the observation of H3+ in a diffuse cloud (towards Persei) where the electron fraction is already known. From these, we find that the cosmic-ray ionization rate along this line of sight is 40 times faster than previously assumed. If such a high cosmic-ray flux is ubiquitous in diffuse clouds, the discrepancy between chemical models and the previous observations of H3+ can be resolved.

Journal Article↗