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PubMed2006

Diffusion-limited binding to a site on the wall of a membrane channel.

The authors develop a theory of diffusion-controlled reactions with a site located on the wall of a cylindrical membrane channel that connects two reservoirs containing diffusing particles which are trapped by the site at the first contact. An expression for the Laplace transform of the rate coefficient, kt, is derived assuming that the size of the site is small compared to the channel radius. The expression is used to find the stationary value of the rate coefficient, kinfinity, as a function of the length and radius of the channel, the radius of the site, and its position inside the channel (distances from the two ends of the channel) as well as the particle diffusion constants in the bulk and in the channel. Their derivation is based on the one-dimensional description of the particle motion in the channel, which is generalized to include binding to the site into consideration. The validity of the approximate one-dimensional description of diffusion and binding was checked by three-dimensional Brownian dynamics simulations. They found that the one-dimensional description works reasonably well when the size of the site does not exceed 0.2 of the channel radius.

Binding Sites↗
PubMed1999

Permeability of single nuclear pores.

In this first application of optical single transporter recording (OSTR), a recently established technique for optically monitoring the activity of single transporters in membrane patches (Tschödrich-Rotter and Peters. 1998. J. Microsc. 192:114-125), the passive permeability of the nuclear pore complex (NPC) was measured for a homologous series of hydrophilic probe molecules. Nuclei were isolated from Xenopus oocytes and firmly attached to filters containing small cylindrical pores. Transport through membrane patches spanning filter pores was measured by scanning microphotolysis. Thus the permeability coefficients of single NPCs were determined for fluorescently labeled dextrans of approximately 4, 10, and 20 kDa. Dextrans of >/=40 kDa could not permeate the NPC. The data were consistent with a model in which the NPC contains a single diffusion channel. By application of established theories for the restricted diffusion through small pores, the diffusion channel was approximated as a cylinder with a radius of 4.4-6.1 nm (mean 5. 35 nm). Because the transport rate constant of the single NPC was known, the equivalent length of the channel could be also determined and was found to be 40-50 nm (mean 44.5 nm). The symmetry of the NPC implies that a singular component such as the diffusion channel is located at the center of the NPC. Therefore a common transport pathway apparently mediates both passive and signal-dependent transport. To test this hypothesis, measurements of signal-dependent transport and of the mutual effects signal-dependent and passive transport may exert on each other are in progress.

Animals↗
PubMed2003

De-airing of a cardiothoracic wound cavity model with carbon dioxide: theory and comparison of a gas diffuser with conventional tubes.

OBJECTIVES: To compare the efficiency of a new gas diffuser with conventional tubes for carbon dioxide (CO(2)) de-airing of a cardiothoracic wound cavity model, and to analyze how insufflation flow, outflow velocity, and diffusion affect de-airing. DESIGN: Technical study in vitro. SETTING: A nonventilated room at a University Hospital. INTERVENTIONS: De-airing by CO(2) insufflation via 3 methods was studied in a symmetric cardiothoracic wound model. MEASUREMENTS AND MAIN RESULTS: The studied insufflation devices were 2 open-ended tubes with an inner diameter of 2.5 mm and (1/4)-in (6.35 mm), respectively, and a gas diffuser (ie, a 2.5-mm tube with a diffuser at the end). CO(2) flows of 2.5, 5, 7.5, and 10 L/min were used. De-airing was assessed by measurement of remaining air content in a set of systematically distributed measuring points in the model. Three-, 2-, and 1-way analysis of variance all revealed significant interaction of device, flow, and depth on air content (p < 0.001). With tubes, the mean air content was 18% to 96% at the studied flows. With the gas diffuser, the mean air content in the cavity was below 0.2% at flows of 5 to 10 L/min. There was an exponential relation between calculated outflow velocity and air content. At a flow of 2.5 L/min, diffusion attenuated de-airing. CONCLUSION: These data imply that de-airing of a cardiothoracic wound by CO(2) insufflation depends on flow and outflow velocity. To compensate for diffusion with ambient air, the CO(2) flow should be >/= 5 L/min, and the outflow velocity should be about 0.1 m/s or less to avoid turbulence in the wound. This is only attainable with a gas diffuser.

Adult↗
PubMed1979

Divalent cation-induced aggregation of chromaffin granule membranes.

Divalent cations induce the aggregation of chromaffin granule ghosts (CG membranes) at millimolar concentrations. Monovalent cations produce the same effect at 100-fold higher concentrations. The kinetics of the dimerization phase were followed by light-scattering changes observed in stopped-flow rapid mixing experiments. The rate constant for Ca2+-induced dimerization (kapp) is 0.86-1.0 x 10(9) M-1sec-1, based on the "molar" vesicle concentration. This value is close to the values predicted by theory for the case of diffusion-controlled reaction (7.02 x 10(9) M-1sec-1), indicating that there is no energy barrier to dimerization. Arrhenius plots between 10 degrees and 42 degrees C support this; the activation energy observed, +4.4 Kcal, is close to the value (4.6-4.8 Kcal) predicted for diffusion control according to theory. Artificial vesicles prepared from CG lipids were also found to have cation-induced aggregation, but the rates (values of kapp) were less than 1/100 as large as those with native CG membranes. Also, significant differences were found with respect to cation specificity. It is concluded that the slow rates are due to the low probability that the segments of membrane which approach will be matched in polar head group composition and disposition. Thus large numbers of approaches are necessary before matched segments come into aposition. The salient features of the chromaffin granule membrane aggregation mechanism are as follows: (a) In the absence of cations capable of shielding and binding, the membranes are held apart by electrostatic repulsion of their negatively charged surfaces. (b) The divalent and monovalent cation effects on aggregation are due to their ability to shield these charges, allowing a closer approach of the membrane surfaces. (c) The major determinants of the aggregation rates of CG membranes are proteins which protrude from the (phospholipid) surface of the membrane and serve as points of primary contact. Transmembrane contact between these proteins does not require full neutralization of the surface charge and surface potential arising from the negatively charged phospholipids. (d) After contact between proteins is established, the interaction between membranes can be strengthened through transmembrane hydrogen bonding of phosphatidyl ethanolamine polar head groups, divalent cation-mediated salt bridging, and segregation of phosphatidylcholine out of the region of contact.

Adrenal Medulla↗
PubMed2004

Influence of diffusion on the kinetics of excited-state association--dissociation reactions: comparison of theory and simulation.

Several recent theories of the kinetics of diffusion influenced excited-state association--dissociation reactions are tested against accurate Brownian dynamics simulation results for a wide range of parameters. The theories include the relaxation time approximation (RTA), multiparticle kernel decoupling approximations and the so-called kinetic theory. In the irreversible limit, none of these theories reduce to the Smoluchowski result. For the pseudo-first-order target problem, we show how the RTA can be modified so that the resulting formalism does reduce correctly in the irreversible limit. We call this the unified Smoluchowski approximation, because it unites modern theories of reversible reactions with Smoluchowski's theory of irreversible reactions.

Computer Simulation↗
PubMed2003

Characterization of continuously distributed cortical water diffusion rates with a stretched-exponential model.

Experience with diffusion-weighted imaging (DWI) shows that signal attenuation is consistent with a multicompartmental theory of water diffusion in the brain. The source of this so-called nonexponential behavior is a topic of debate, because the cerebral cortex contains considerable microscopic heterogeneity and is therefore difficult to model. To account for this heterogeneity and understand its implications for current models of diffusion, a stretched-exponential function was developed to describe diffusion-related signal decay as a continuous distribution of sources decaying at different rates, with no assumptions made about the number of participating sources. DWI experiments were performed using a spin-echo diffusion-weighted pulse sequence with b-values of 500-6500 s/mm(2) in six rats. Signal attenuation curves were fit to a stretched-exponential function, and 20% of the voxels were better fit to the stretched-exponential model than to a biexponential model, even though the latter model had one more adjustable parameter. Based on the calculated intravoxel heterogeneity measure, the cerebral cortex contains considerable heterogeneity in diffusion. The use of a distributed diffusion coefficient (DDC) is suggested to measure mean intravoxel diffusion rates in the presence of such heterogeneity.

Animals↗
PubMed2006

The diffusion of medical technology, local conditions, and technology re-invention: a comparative case study on coronary stenting.

Innovation of medical technology is a major driving force behind the increase in medical expenditures in developed countries. Previous studies identified that the diffusion of medical technology varied across countries according to the characteristics of regulatory policy and payment systems. Based on Roger's diffusion of innovation theory, this study purported to see how local practice norms, the evolving nature of diffusing technology, and local clinical needs in addition to differences in politico-economic systems would affect the process of innovation diffusion. Taking a case of coronary stenting, an innovative therapeutic technology in early 1990s, we provided a case study of hospital-based data between two teaching high-tech hospitals in Japan and the US for discussion. Stenting began to be widely used in both countries when complementary new technology modified its clinical efficacy, but the diffusion process still differed between the two hospitals due to (1) distinctive payment systems for hospitals and physicians, (2) practice norms in favor of percutaneous intervention rather than bypass surgery that was shaped by payment incentives and cultural attitudes, and (3) local patient's clinical characteristics that the technology had to be tailored for. The case study described the diffusion of stent technology as a dynamic process between patients, physicians, hospitals, health care systems, and technology under global and local conditions.

Aged↗
PubMed2006

An evaluation of how well research reports facilitate the use of findings in practice.

PURPOSE: To analyze how research is reported in journal publications as a potential barrier to use of research findings in practice. DESIGN: Content analysis of 46 reports of diabetes self-management interventions published between 1993 and 2004. METHODS: Data were extracted from the publications using a coding scheme based on concepts from Rogers' theory of the diffusion of innovations. FINDINGS: Authors provided only some of the information potential users need to progress through Roger's stages of adopting an intervention and implementing it in practice. Authors provided only limited information on the target population; frequency, number, and duration of patient contacts; expertise and training required to deliver the intervention; intervention protocol; and the process of adapting and implementing interventions in practice settings. CONCLUSIONS: To close the gap between research and practice, authors should offer more information to help readers decide whether and how to adopt and implement interventions.

Diffusion of Innovation↗
PubMed1989

The neutral theory of molecular evolution and the world view of the neutralists.

The main tenet of the neutral theory is that the great majority of evolutionary changes at the molecular level are caused not by Darwinian selection but by random fixation of selectively neutral (or very nearly neutral) alleles through random sampling drift under continued mutation pressure. The theory also asserts that the majority of protein and DNA polymorphisms are selectively neutral, and that they are maintained in the species by mutational input balanced by random extinction rather than by "balancing selection." The neutral theory is based on simple assumptions. This enabled us to develop mathematical theories (using the diffusion equation method) that can treat these phenomena in quantitative terms and that permit theory to be tested against actual observations. Although the neutral theory has been severely criticized by the neo-Darwinian establishment, supporting evidence has accumulated over the last 20 years. In particular, the recent burst of DNA sequence data helped to strengthen the theory a great deal. I believe that the neutral theory triggered reexamination of the traditional "synthetic theory of evolution." In this paper, I review the present status of the neutral theory, including discussions of such topics as "molecular evolutionary clock," very high evolutionary rates observed in RNA viruses, a deviant coding system found in Mycoplasm together with the concept of mutation-driven neutral evolution, and the origin of life. I also present a worldview based on the conception of what I call "survival of the luckiest."

Animals↗
PubMed2003

Clinical team functioning and IT innovation: a study of the diffusion of a point-of-care online evidence system.

OBJECTIVES: To investigate the association between clinical team functioning and diffusion (awareness, use, and impact) of a 24-hour online evidence retrieval system. To examine the relationships between clinical team characteristics and the adoption of the online evidence system. DESIGN: 18 clinical teams, consisting of 180 clinicians from three Australian hospitals, were identified and studied. Teams were categorized as small ( 15). MEASUREMENTS: Clinical team functioning was assessed using the Team Climate Inventory (TCI). Awareness, use, and impact of an online evidence retrieval system were measured using a self-administered questionnaire. The relationships between TCI scores and awareness, use, and impact were examined using t-tests and one-way ANOVAs. Chi square analyses were used to examine differences between small and large teams. RESULTS were interpreted within a diffusion of innovations framework. RESULTS: Clinical team functioning was not related to awareness or use of the online evidence retrieval system. However, clinical team functioning was significantly associated with the impact of online evidence in terms of reported experience of improved patient care following system use. Clinicians in small teams ( 15) teams. CONCLUSIONS: Team functioning had the greatest impact on the fourth stage of innovation diffusion, the effective use of online evidence for clinical care. This supports Rogers' diffusion of innovation theory, to the effect that different types of communication about an innovation are important at different stages in the diffusion process. Members of small teams were more aware of the system than members of large teams. Team functioning is amenable to improvement through interventions. The findings suggest that the role of team climate in the diffusion of information systems is a promising area for future research.

Analysis of Variance↗
PubMed1982

The pharmacokinetics of antibiotic diffusion in chronic bacterial prostatitis.

Historically chronic bacterial prostatitis in the male human has been relatively resistant to antimicrobial chemotherapy. The pharmacokinetic theory of drug diffusion into the prostate is reviewed. A brief description of the various canine models utilized to quantitate antimicrobial drug diffusion is presented. Specific data concerning the diffusion of various antimicrobial agents are abstracted followed by a brief discussion of mechanistic explanations for the success or failure of drug therapy.

Aminoglycosides↗