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Diffusion tensor imaging in primary brain tumors: reproducible quantitative analysis of corpus callosum infiltration and contralateral involvement using a probabilistic mixture model.

Diffusion tensor imaging (DTI) has been advocated as a promising tool for delineation of the extent of tumor infiltration by primary brain tumors. First reports show conflicting results mainly due to difficulties in reproducible determination of DTI-derived parameters. A novel method based on probabilistic voxel classification for a user-independent analysis of DTI-derived parameters is presented and tested in healthy controls and patients with primary brain tumors. The proposed quantification method proved to be highly reproducible both in healthy controls and patients. Fiber integrity in the corpus callosum (CC) was measured using this quantification method, and the profiles of fractional anisotropy (FA) provided additional information of the possible extent of infiltration of primary brain tumors when compared to conventional imaging. This yielded additional information on the nature of ambiguous contralateral lesions in patients with primary brain tumors. The results show that DTI-derived parameters can be determined reproducibly and may have a strong impact on evaluation of contralateral extent of primary brain tumors.

Adult↗

Stochastic modeling of diffuse pesticide losses from a small agricultural catchment.

The objective of this study was to identify the main sources of variation in pesticide losses at field and catchment scales using the dual permeability model MACRO. Stochastic simulations of the leaching of the herbicide MCPA (4-chloro-2-methylphenoxyacetic acid) were compared with seven years of measured concentrations in a stream draining a small agricultural catchment and one year of measured concentrations at the outlet of a field located within the catchment. MACRO was parameterized from measured probability distributions accounting for spatial variability of soil properties and local pedotransfer functions derived from information gathered in field- and catchment-scale soil surveys. At the field scale, a single deterministic simulation using the means of the input distributions was also performed. The deterministic run failed to reproduce the summer outflows when most leaching occurred, and greatly underestimated pesticide leaching. In contrast, the stochastic simulations successfully predicted the hydrologic response of the field and catchment and there was a good resemblance between the simulations and measured MCPA concentrations at the field outlet. At the catchment scale, the stochastic approach underestimated the concentrations of MCPA in the stream, probably mostly due to point sources, but perhaps also because the distributions used for the input variables did not accurately reflect conditions in the catchment. Sensitivity analyses showed that the most important factors affecting MACRO modeled diffuse MCPA losses from this catchment were soil properties controlling macropore flow, precipitation following application, and organic carbon content.

Agriculture↗

Diffusion theory and drug use.

This paper examines the applicability of the diffusion model to drug use. A variety of studies that employ the diffusion model to examine drug-related behaviour, including the use of alcohol, tobacco and illicit drugs, are discussed. Studies include those that focus on "natural" or spontaneous diffusion and those in which diffusion of a drug or a drug-related intervention is planned. Most studies examined support the application of the diffusion model in the study of drug use. The model is particularly valuable when new substances are introduced to a population or subgroup. The addition of economic and other forms of availability as a determinant of adoption would increase the power of the model. Recommended directions for research are outlined. The diffusion model has been used successfully in the study of drug use for several decades. More rigorous designs would strengthen this type of research and provide direction for policymakers and those involved in public health and education.

Diffusion of Innovation↗

Statistical model for diffusion attenuated MR signal.

A general statistical model that can describe a rather large number of experimental results related to the structure of the diffusion-attenuated MR signal in biological systems is introduced. The theoretical framework relies on a phenomenological model that introduces a distribution function for tissue apparent diffusion coefficients (ADC). It is shown that at least two parameters--the position of distribution maxima (ADC) and the distribution width (sigma)--are needed to describe the MR signal in most regions of a human brain. A substantial distribution width, on the order of 36% of the ADC, was found for practically all brain regions examined. This method of modeling the MR diffusion measurement allows determination of an intrinsic tissue-specific ADC for a given diffusion time independent of the strength of diffusion sensitizing gradients. The model accounts for the previously found biexponential behavior of the diffusion-attenuated MR signal in CNS.

Brain↗

Distributed diffusion-clearance model for transient drug distribution within the skin.

Quantitative predictions of molecular transport rates through the skin are key to the development of topically applied and transdermally delivered drugs, as well as risk assessment associated with dermal exposure. Most research to date has focused on correlations for the permeability of the stratum corneum, and transient diffusion models that oversimplify vascular clearance processes in terms of a perfect-removal boundary condition at an artificially introduced lower boundary. Considerations of the spatially distributed nature and action of blood vessels have usually been limited to the steady-state case. This article describes a more comprehensive transient model of percutaneous absorption formulated in terms of volumetric dispersion and clearance coefficients reflecting the spatial distribution of vascular processes. The model was implemented through an analysis of published experimental results on in vivo permeation of salicylic acid (SA) in de-epidermized rat skin. With regard to the characterization of SA in rat dermis ("de") in vivo, it was found that: (i) SA is likely to have a dermal effective partition coefficient (relative to pH 7.4 aqueous buffer "pH7.4") around unity (K(de/pH7.4) = 0.9 +/- 0.3); (ii) vascular processes seem not to increase drug dispersion significantly beyond molecular diffusion [D(de) approximately (D(de))(mol) = (8 +/- 3) . 10(-7) cm(2) s(-1)]; and (iii) vascular clearance is characterized by a rate coefficient k(de) = (7 +/- 2) . 10(-4) s(-1). Application of a whole-skin variant of the model (including the stratum corneum and viable epidermis) allowed realistic predictions to be made of transient subsurface concentration levels after application from a finite dose.

Animals↗

Small intrapulmonary artery lung prototypes. Mathematical modeling of gas transfer.

Two diffusion models have been developed to analyze gas transfer data previously measured in an intravascular artificial lung consisting of a central gas supply catheter from which are tethered a large number of blind-ended microporous fibers of equal length. A convective-diffusion model (CD) describes the countercurrent transfer of a binary gas pair when gas is supplied at constant pressure conditions, and a well mixed (WM) cycled pressure model predicts transfer when the gas supply pressure is time cycled between compression and vacuum conditions. Regression of gas to gas and liquid to gas excretion data with the CD model resulted in estimates of the liquid phase mass transfer coefficient kAI. Because these values were intermediate between the kAI expected for flow parallel to a cylinder and for flow normal to a cylinder, gas transfer was influenced by both the tethered region of the fiber that was nearly perpendicular to the axis of the test section and the free end of the fiber that rested along the wall of the test section. With a time cycled gas supply pressure, the enhanced carbon dioxide and oxygen excretion predicted by the WM model was similar to the data, but a loss in transfer efficiency with fiber length was not accounted for by the theory.

Algorithms↗

Quantitative aspects of a unified model of diffusion mediated receptor--cyclase coupling.

A quantitative model is presented of diffusion mediated coupling of adenylate cyclase to multivalent plasma membrane receptors which accounts for a wide range of phenomena including non linear occupation-activation plots with either positive or negative second derivatives, spare receptors, silent receptors, and negative and positive binding cooperativity. A non linear least square fit of the predicted equation for cyclase activation to available data predicts translational diffusion coefficients in the range of (10(-10) - 10(-11))cm2/s.

Adenylyl Cyclases↗

The role of diffusion in the photoresponse of an extraretinal photoreceptor of Aplysia.

1. Membrane currents produced by flashes and steps of light (photo-current) were recorded from the ventral photoresponsive neurone of Aplysia californica. The effects of background illumination and changes in temperature were also examined. 2. The falling phase of the response wave form may be separated into two components with time constants of 10--12 sec and 50 sec. 3. Background illumination reduced the response amplitude to light impulses without appreciably altering the response wave form. 4. Lowering the temperature greatly reduced the amplitude of the photo-current with a Q10 of 2.91 (25--15 degrees C) and greatly prolonged the duration of the response. 5. Because of the relatively large distance between the plasma membrane and the pigmented cytoplasmic lipochondria where light is absorbed, a diffusion-based model with Ca as the internal-transmitter (Andresen & Brown, 1979) was developed. 6. In this model diffusion of Ca2+ released from the lipochondria upon photon absorption is slowed by the reversible uptake of Ca2+ at cytoplasmic binding sites. Ca2+ interacts with sites at the plasma membrane to increase GK and Ca2+ levels are subsequently restored by irreversible uptake processes. Ca2+ release and its adsorption and desorption from the more numerous plasma membrane binding sites were assumed to be instantaneous with respect to the duration of the light-evoked response. 7. The linearized model equations adequately predict the experimental response wave forms, the effects of temperature, and saturation of the steady-state amplitude--stimulus relationship. Aside from amplitude scaling, no curve-fitting was used. 8. The model also gives realistic values for the cytoplasmic diffusion coefficient of Ca and the net rate of Ca efflux required to restore dark Ca activity.

Animals↗

Application of the mass transfer model for describing nonequilibrium transport of HOCs through natural geosorbents.

Column experiments of nonsorbing and sorbing solutes were conducted in sandy aquifer material. Results of the column experiments were analyzed using a numerical nonequilibrium mass transfer model (designated as dispersed flow, film and particle diffusion model, DF-FPDM), an equilibrium advection-dispersion model (designated as dispersed flow, local equilibrium model, DF-LEM) as well as a nonequilibrium two region (mobile-immobile) advection-diffusion model (designated as homogeneous solid diffusion model, HSDM). Results of the analyses revealed that in all experiments the experimental BTCs are much better predicted by the DF-FPDM than by DF-LEM and HSDM. The relative influence of different processes (film diffusion, intraparticle diffusion and dispersion) can be identified by dimensionless mass transfer parameters N(F), N(S) and N(D). Their plausibility can be compared with the well-known advection-dispersion-based equilibrium model. In general, spreading and asymmetry of sorbing solute BTCs can be explained with the DF-LEM and HSDM, but the identification of different processes and their influence on the total transport processes can only be ascertained with a model like DF-FPDM.

Diffusion↗

Efficacy of beta-lactam and inhibitor combinations in a diffusion chamber model in rabbits.

Using a diffusion chamber in rabbits, we evaluated therapy with the combination of ceftriaxone plus the beta-lactamase inhibitor tazobactam in comparison with ceftriaxone alone. One sensitive and one resistant strain of Escherichia coli, Enterobacter cloacae and Klebsiella pneumoniae were inoculated into one of the six diffusion chambers, implanted in the same animal. In order to simulate pharmacokinetics in humans, both substances were administered in decreasing doses. Ceftriaxone was given 0, 2, 4 and 6 h after infection in dosages of 45, 35, 25 and 15 mg/kg of body weight, while tazobactam was administered either in one dose at 0 h, or divided into two doses at 0 and 1 h or 0 and 4 h, or divided into three doses at 0, 1 and 4 h after infection. The ratio of ceftriaxone:tazobactam was fixed at 8:1. Ceftriaxone, in combination with tazobactam, given in one dose immediately after infection showed a significant reduction in bacterial count. All other combinations of ceftriaxone and tazobactam did not differ from ceftriaxone in monotherapy. Co-administration of the beta-lactamase inhibitor tazobactam significantly enhanced the activity of ceftriaxone against all three tested species.

Animals↗

Rapid modeling of diffuse reflectance of light in turbid slabs.

An efficient and accurate hybrid model of the Monte Carlo technique and the diffusion theory was developed to simulate the diffuse reflectance of light in a turbid slab due to an infinitely narrow light beam. The narrow beam was normally incident on the top surface of the slab. The hybrid model was accurate in modeling the diffuse reflectance near the light source, where the diffusion theory was most inaccurate. The hybrid model was much faster than a pure Monte Carlo method by a factor as great as several hundred, depending on the optical properties, the thickness of the slab, and the settings of the hybrid and the Monte Carlo computations. The computation speed of the hybrid model was insensitive to the optical properties of the medium, in contrast to the pure Monte Carlo technique. The diffusion theory was accurate in modeling both the diffuse reflectance far from the source and the diffuse transmittance. The hybrid model and the diffusion theory should be used in conjunction for efficient and accurate computation of diffuse reflectance and diffuse transmittance.

Diffusion↗

Localized interaction of the polyamine methylspermidine with double-helical DNA as monitored by 1H NMR self-diffusion measurements.

The 1H NMR pulsed field gradient self-diffusion method has been used to measure the diffusion coefficient of the polyamine analogue methylspermidine (completely N-methylated spermidine) in DNA solution, as a function of the concentration ratio of methylspermidine to DNA phosphate. Three different DNA's have been investigated: d(GC)4 (8 base pairs), core length calf thymus DNA (approximately 120 base pairs), and sonicated high molecular weight calf thymus DNA (average 7500 base pairs). For a constant ratio of methylspermidine to DNA phosphate, the diffusion coefficient decreases with increasing DNA length. Moreover, at low concentration ratios the diffusion coefficient of methylspermidine approaches a limiting value that is close to that of the DNA molecule. The experimental data are well reproduced by a two-state diffusion model. In this model the diffusion coefficient of the polyamine is a population-weighted average of polyamine associated with DNA (with a diffusion coefficient given by that of the DNA molecule) and polyamine free in solution.

Animals↗

Statistical procedures for spatiotemporal neuronal data with applications to optical recording of the auditory cortex.

This article presents new procedures for multisite spatiotemporal neuronal data analysis. A new statistical model - the diffusion model - is considered, whose parameters can be estimated from experimental data thanks to mean-field approximations. This work has been applied to optical recording of the guinea pig's auditory cortex (layers II-III). The rates of innovation and internal diffusion inside the stimulated area have been estimated. The results suggest that the activity of the layer balances between the alternate predominance of its innovation process and its internal process.

Animals↗

Diffusion-based model to predict the conservation of gratings recorded in poly(vinyl alcohol)-acrylamide photopolymer.

Photopolymers are interesting materials for use in recording information in holography. We study the holographic behavior and stability of volume holograms recorded in poly(vinyl alcohol)--acrylamide photopolymers with and without a cross linker. Using a first-harmonic diffusion model, we analyze the residual monomer that remains when volume diffraction gratings are recorded in photopolymer materials. The importance of this residual monomer to the stability of the gratings is evaluated.

Journal Article↗

Conditional Diffusion Model-Based Method for Annotation of Antibiotic Resistance Gene Properties.

The crisis of bacterial antibiotic resistance, which has led to a decline in the effectiveness of antibiotics originally used to combat bacterial infections, has emerged as an urgent challenge for public health. Antibiotic resistance genes (ARGs) are one of the key reasons for bacteria to develop resistance to antibiotics. Therefore, accurately identifying and annotating the critical properties of ARGs is of great importance for addressing the antibiotic resistance emergency. Although existing deep learning models demonstrate remarkable effectiveness in extracting local features from sequence data, they still face limitations in the capacity to further gain the enriched latent representations within the data. To address the critical challenge of extracting higher-quality representations from ARGs sequence data, we propose a novel ARGs properties annotation method based on the conditional diffusion model which is used to learn latent representations through domain-specific knowledge injection. Specifically, during the conditional information integration phase, we systematically incorporate ARGs' domain knowledge to guide the diffusion process in generating high-quality latent representations. To overcome information redundancy caused by direct concatenation of conditional information and intermediate features, we design a cross-attention mechanism that enables feature fusion between heterogeneous information sources, thereby enhancing further the quality of obtained representations. Experimental results on widely used data sets demonstrate the framework's effectiveness in achieving superior prediction performance compared to existing methods.

Anti-Bacterial Agents↗

Diffusion epidemic models with incubation and crisscross dynamics.

A diffusion age-structured epidemic model is analyzed. The model describes an epidemic in a host-vector two-population system. Each population is diffusing in a spatial region. Each population is divided into susceptible, incubating, and infectious subclasses. The incubating and infectious subclasses in each population are determined by a structure variable corresponding to age since infection. The model consists of a system of nonlinear partial differential equations with crisscross dynamics. The existence, uniqueness, and asymptotic behavior of solutions are analyzed.

Chagas Disease↗

A model of diffuse traumatic brain injury in the immature rat.

Diffuse cerebral swelling after severe traumatic brain injury (TBI) develops more commonly in children than adults; however, models of diffuse brain injury in immature animals are lacking. The authors developed a new model of diffuse severe TBI in immature rats by modifying a recently described closed head injury model for adult rats. A total of 105 Sprague-Dawley immature rats (17 days old; average weight 38.5 +/- 5.46 g) were subjected to head impact using variable weights (0 g (sham), 75 g, 100 g, or 125 g) delivered from a height of 2 m onto a metal disk cemented to the intact cranium. Mortality, physiological and neurological parameters (from early reflex recovery to escape), and early histopathological changes were assessed. During the acute period after severe injury (SI) (100 g delivered from a height of 2 m; 50 rats), apnea was frequently observed and the mortality rate was 38%. Neurological recovery was complete in the sham-injured animals (11 rats) by 4.1 +/- 0.23 minutes (mean +/- standard error of the mean), but was delayed in both moderately injured (MI) (75 g/2 m; 11 rats) (14.97 +/- 3.99 minutes) and SI (20.57 +/- 1.31 minutes (p < 0.05)) rats. In the first 24 hours, the sham-injured animals were more active than the injured ones as reflected by a greater net weight gain: 2.9 +/- 1.0 g, 1.2 +/- 1.6 g, and -0.6 +/- 2.1 g in sham-injured, MI, and SI animals, respectively. Immediately after injury, transient hypertension (lasting < 15 seconds) was followed by hypotension (lasting < 3 minutes) and loss of temperature regulation. Both injuries also induced apnea (0.75 +/- 0.7 minutes and 1.27 +/- 0.53 minutes in MI and SI groups, respectively), which either resolved or deteriorated to death. Intubation and assisted ventilation in animals with SI for 9.57 +/- 3.27 minutes in the peritrauma period eliminated mortality (p < 0.05, intubated vs. nonintubated). Histologically, after SI, there was diffuse edema throughout the corpus callosum below the region of injury and in the thalami. Other injuries included neuronal death in the deep nuclei, bilateral disruption of CA3, diffuse subarachnoid hemorrhage, and, in some, ventriculomegaly. Following a diffuse TBI in immature rats, SI produced a mortality rate, neurological deficit, and histological changes similar to those previously reported for an injury resulting from a 450-g weight dropped from 2 m in adult rats. A graded insult was achieved by maintaining the height of the weight drop but varying the weights. Weight loss, acute physiological instability, and acute neurological deficits were also indicative of an SI. Mortality was eliminated when ventilatory support was used during the peritrauma period. This model should be useful in studying the response of the immature rat to diffuse severe TBI.

Animals↗

The effects of transmural transport in the microcirculation: a two gas species model.

Diffusion of oxygen and carbon dioxide across the walls of noncapillary vessels in the microcirculation has been suggested by several studies. The formulation and steady-state solutions to a nine-compartment mathematical model of the microcirculation of skeletal muscle with transmural gas diffusion in all vessels are presented. The simultaneous transport of oxygen and carbon dioxide between arterioles, capillaries, and venules, and connective and muscle tissue at rest and exercise are described. Special attention is paid to the interactions of these gases in blood. This model predicts a longitudinal intravascular gradient in oxygen tension from large to small vessel with the tension at the precapillary vessels relatively insensitive to changes in the input tension. At rest, there is significant small arteriolar oxygen flux. However, during exercise, the precapillary transmural flux of oxygen is only a small fraction of the total metabolic demand. The model predicts large noncapillary fluxes of carbon dioxide, and also that tissue PCO2 is dependent on input tensions. The model also predicts that Bohr shifts due to either changes in input PCO2 or increased precapillary PCO2 due to increased metabolism may cause physiologically significant changes in precapillary PO2. Countercurrent shunting was predicted by the model to be significant only for carbon dioxide.

Animals↗