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PubMed2003

Roles of land use resolution and unit-area load rates in assessment of diffuse nutrient emissions.

In contrast to its counterparts in Europe and North America, the Australian National Pollutant Inventory (NPI) includes estimates of aggregated emissions of nutrients (total nitrogen and total phosphorus) from catchments and facilities. Sparse or inadequate data limit the extent to which nutrient exports may be estimated from direct observations. The paucity of data for calibration and simulation limits the use of sophisticated models in most Australian catchments. Therefore, a simple unit-area load model-Catchment Management Support System (CMSS)-was selected to estimate aggregated catchment emissions for the NPI. Estimates from models like CMSS are sensitive to spatial and categorical resolution of land uses identified within the catchment and to nutrient generation rates selected for each land use category. Using three Hawkesbury-Nepean subcatchments, we show that while high spatial resolution of land use mapping is useful, only four or five major land use categories with carefully selected generation rates were required to estimate potential nutrient exports sufficiently well and to determine subcatchments contributing most. Nutrient emission estimates proved to be highly dependent on selection of generation rates so a bootstrap technique was adopted to reduce subjectivity and to improve estimates of confidence limits. This led to a specification of new generation rates for Natural, Unimproved pasture, Rural and Urban land uses and to establishment of uncertainty limits.

Agriculture↗
PubMed2004

Extensive distribution of liposomes in rodent brains and brain tumors following convection-enhanced delivery.

Liposomes labeled with various markers were subjected to local-regional administration with either direct injection or convection-enhanced delivery (CED) into rodent brains and brain tumor models. Direct injection of liposomes containing attached or encapsulated fluorochromes and/or encapsulated gold particles indicated that tissue localization of liposomes could be sensitively and specifically detected in the central nervous system (CNS). When CED was applied, liposomes achieved extensive and efficient distribution within normal mouse brains. Co-infusion of mannitol further increased tissue penetration of liposomes. Liposomes were also loaded with gadodiamide to monitor their CNS distribution in rats by magnetic resonance imaging (MRI). CED-infused liposomes were readily seen on MRI scans as large regions of intense signal at 2 h, and more diffuse regions at 24 h. Finally, labeled liposomes were infused via CED into tumor tissue in glioma xenograft models in rodent hosts. In intracranial U-87 glioma xenografts, CED-infused liposomes had distributed throughout tumor tissue, including extension into surrounding normal tissue. Greater penetration was observed using 40 versus 90 nm liposomes, as well as with mannitol co-infusion. To our knowledge, this is the first report of CED infusion of liposomes into the CNS. We conclude that CED of liposomes in the CNS is a feasible approach, and offers a promising strategy for targeting therapeutic agents to brain tumors.

Animals↗
PubMed2000

A mathematical model of tumour angiogenesis incorporating cellular traction and viscoelastic effects.

Angiogenesis is defined as the outgrowth and formation of new vessels from a pre-existing vascular network (Rakusan, In: Cardiac Growth and Regeneration. Annals of the New York Academy of Sciences, 1995), and is of fundamental importance in understanding the processes by which a tumour achieves vascularization. Diffusible substances, collectively called tumour angiogenesis factors are released from the tumour to elicit a variety of responses from the surrounding tissues, most importantly the migration of endothelial cells (lining neighbouring vessels) towards the tumour. To facilitate locomotion, the cells exert appreciable traction forces upon the interstitial extracellular matrix which, in turn, influences the resulting direction of their migration. In this paper, we examine the role played by cellular traction during cell migration and the corresponding viscoelastic effects of the extracellular matrix.

Cell Movement↗
PubMed1996

Integration of emerging designs for the practice and management of nursing.

Work redesign and shared governance represent two of the most popular administrative innovations in contemporary nursing. Whereas work redesign creates changes in the content of nurses' jobs, shared governance addresses the organizational context within which nurses are employed. Although the content and context of nurses' work are closely interrelated, many organizations have attended to one of these issues, but failed to give consideration to the other. Building on this background, the state of the art in nursing redesign and restructuring is summarized, and emerging directions in job and organizational design are identified.

Clinical Competence↗
PubMed2004

Impact of nitrogen reduction measures on nitrogen surplus, income and production of German agriculture.

Among the numerous non-point sources of diffuse water pollution with nitrogen, agriculture is counted one of the main sources. The agricultural policies of the Agenda 2000 and a decoupling of direct payments for farmers from their production decisions are exemplarily evaluated as nitrogen reduction measures using the Regional Agricultural and Environmental Information System RAUMIS. The results show that until the target year 2010 the risk of diffuse pollution of water bodies with nitrogen is a regional problem in Germany. These problems are neither mitigated by the policies of Agenda 2000 nor by a decoupling of direct payments from production decisions of farmers. While total nitrogen surplus reduces considerably after a decoupling of direct payments due to decreases of land-use the nitrogen surplus on the remaining cultivated area increases resulting from structural changes. Granting the same amount of direct payments to farmers in both policy alternatives the agricultural sector income would be higher after a decoupling of direct payments opposed to the Agenda 2000 resulting from a more efficient allocation of inputs.

Agriculture↗
PubMed2005

Resolving fiber crossing using advanced fast marching tractography based on diffusion tensor imaging.

Magnetic resonance diffusion tensor tractography is a powerful tool for the non-invasive depiction of the white matter architecture in the human brain. However, due to limitations in the underlying tensor model, the technique is often unable to reconstruct correct trajectories in heterogeneous fiber arrangements, such as axonal crossings. A novel tractography method based on fast marching (FM) is proposed which is capable of resolving fiber crossings and also permits trajectories to branch. It detects heterogeneous fiber arrangements by incorporating information from the entire diffusion tensor. The FM speed function is adapted to the local tensor characteristics, allowing in particular to maintain the front evolution direction in crossing situations. In addition, the FM's discretization error is reduced by increasing the number of considered possible front evolution directions. The performance of the technique is demonstrated in artificial data and in the healthy human brain. Comparisons with standard FM tractography and conventional line propagation algorithms show that, in the presence of interfering structures, the proposed method is more accurate in reconstructing trajectories. The in vivo results illustrate that the elucidated major white matter pathways are consistent with known anatomy and that multiple crossings and tract branching are handled correctly.

Algorithms↗
PubMed1986

Comparison between the iontophoretic and passive transport of thyrotropin releasing hormone across excised nude mouse skin.

Thyrotropin releasing hormone [L-proglutamyl-L-histidyl-L-proline amide (TRH)], a tripeptide with molecular weight of 362 and a pKa of 6.2, was used as a model peptide for in vitro passive and iontophoretic diffusion cell studies using excised dorsal nude mouse skin. The results indicate that both the charged and uncharged TRH fluxes across the excised tissue were greater than those obtained by passive diffusion alone. The steady-state flux of both the uncharged and charged TRH was directly proportional to the applied current density, with flux being greater for the uncharged TRH. Additional studies on the transport of methylene blue indicate that transport may be occurring through pores, and that positive ions are preferentially passed through the skin. These results imply that the steady-state flux of TRH is primarily due to a direct, electrically induced ion motion and convection. A practical implication of these results is that it may be possible to enhance and control the transdermal delivery of peptides.

Animals↗
PubMed1981

Active transport of urea across the skin of the euryhaline toad, Bufo viridis.

Urea is accumulated in considerable amounts (greater than 100 mM) in the blood of the euryhaline toad Bufo viridis, under conditions of adaptation to high salinities. Salt adaptation increases active transport of urea (inward direction) in the skin, which was measured in vitro. The active transport of urea is insensitive to ADH, and was inhibited nearly 50% by 0.5 mM phloretin. This transport system is different from the facilitated diffusion of urea which has been studied extensively in the toad urinary bladder, and may offer a simple model system for the study of active urea transport.

Animals↗
PubMed2006

In vitro studies of intestinal permeability and hepatic and intestinal metabolism of 8-prenylnaringenin, a potent phytoestrogen from hops (Humulus lupulus L.).

PURPOSE: The absorption potential and metabolism of 8-prenylnaringenin (8-PN) from hops (Humulus lupulus L.) were investigated. 8-PN is a potent estrogen with the potential to be used for the relief of menopausal symptoms in women. METHODS: Monolayers of the human intestinal epithelial cancer cell line Caco-2 and human hepatocytes were incubated with 8-PN to model its intestinal absorption and hepatic metabolism, respectively. RESULTS: The apparent permeability coefficients for 8-PN in the apical-to-basolateral and basolateral-to-apical directions of a Caco-2 monolayer were 5.2 +/- 0.7 x 10(-5) and 4.9 +/- 0.5 x 10(-5) cm/s, respectively, indicating good intestinal absorption via passive diffusion. Both glucuronide and sulfate conjugates of 8-PN were detected in the Caco-2 cell incubations. The 4'-O-glucuronide was the predominant Caco-2 cell metabolite, followed by 7-O-sulfate and 4'-O-sulfate. Both phase I and phase II metabolites of 8-PN were formed by human hepatocytes. The 7-O-glucuronide was the most abundant hepatocyte metabolite, and no sulfate conjugates were detected. Incubations with various cDNA-expressed UDP-glucuronosyltransferases indicated that the isozymes UGT1A1, UGT1A6, UGT1A8, and UGT1A9 were responsible for glucuronidation of 8-PN. CONCLUSIONS: Although orally administered 8-PN should be readily absorbed from the intestine, its bioavailability should be reduced significantly by intestinal and hepatic metabolism.

Caco-2 Cells↗
PubMed2001

Surface Kinetics of Copper Oxidation Investigated by In Situ Ultra-high Vacuum Transmission Electron Microscopy.

We review our studies of the initial oxidation stages of Cu(001) thin films as investigated by in situ ultra-high vacuum transmission electron microscopy. We present our observations of surface reconstruction and the nucleation to coalescence of copper oxide during in situ oxidation in O2. We have proposed a semi-quantitative model, where oxygen surface diffusion is the dominant mechanism of the initial oxidation stages of Cu. We have also investigated the effect of water vapor on copper oxidation. We have observed that the presence of water vapor in the oxidizing atmosphere retards the rate of Cu oxidation and Cu2O is reduced when exposed directly to steam.

Journal Article↗
PubMed1986

Flow-induced anisotropy in the susceptibility of a particle suspension.

The initial susceptibility, or low-field high-frequency permeability, of a rod-like particle suspension or polymer solution can become anisotropic when the particles or molecules interact with a magnetic field in a directional manner and are nonrandomly oriented by certain types of flow field. This is the alignment that leads to thixotropy and deviatoric stresses during rheological measurements on these fluids. A general expression for the particle order parameter and the fluid permeability in terms of Legendre polynomials is derived by calculating the ensemble average over all possible orientation angles. This is an integral containing the orientation angle-dependent orientation probability function. The example case of single-domain magnetic particles suspended in extensional flow of a newtonian fluid is examined by using the following well-known models: chain-of-spheres model for the magnetic properties of a particle and the Kirkwood-Auer theory for the orientation probability function. From this, the particle orientation in the flow direction downstream from a sharp circular convergence is predicted to dramatically increase with an increase in the ratio of the extension rate to the particle rotary diffusion coefficient. Consequently, the measured permeability of the fluid is predicted to decrease parallel to, and to increase perpendicular to, the flow direction.

Journal Article↗
PubMedDate not supplied

The effect of vasospasm on perfusion radionuclide imaging in experimental pulmonary embolism.

Experiments were conducted to further evaluate previously observed discrepancies between postembolic perfusion scans and angiograms, and the relationship of these discrepancies to pulmonary vasospasm. Nonresorbable emboli were formed from Ivalon, muscle, or heated autologous clot. Scans and angiograms were compared at 24-hour intervals for two to eight days. During the first two days after embolism, angiographic-scan discrepancies occurred in most dogs, characterized by decreased size of scintigraphically demonstrated perfusion defects at the same times that the angiogram showed stable or even progressive obstruction. This discordant behavior of scan and angiogram is thought to reflect subsidence of postembolic vasospasm. In the 17 experimental dogs, 13 showed evidence of vasospasm, and four did not. In those that developed spasm, direct angiographic evidence of such spasm was present in all but one, manifest as diffuse constriction of small arteries and diminished parenchymal stain in vascular beds that were not directly obstructed mechanically. Although spasm diminished rapidly during the first 6 hours, there was continued and appreciable further resolution for over 48 hours in some dogs. This study reconfirms the frequent existence of vasospasm in three different embolic models, and indicates subsidence of spasm over a much longer time frame than was formerly supposed. Regression of spasm over an interval of several days suggests that perfusion scans should be performed clinically as soon as possible after a suspected embolic episode, prior to subsidence of spasm, in order to exploit the added sensitivity provided by spasm.

Angiography↗
PubMed2006

Diffusion tensor magnetic resonance imaging tractography in cognitive disorders.

PURPOSE OF REVIEW: The advent of novel techniques for tracing connections in vivo, such as diffusion tensor magnetic resonance imaging tractography, allows us, for the first time in the human brain, to study the microstructural integrity of white matter fibres and perform virtual dissections of large scale neurocognitive networks. This review will outline the advantages and limitations of applying diffusion tensor magnetic resonance imaging to the study of cognitive and behavioural disorders in neurology and psychiatry. RECENT FINDINGS: Diffusion tensor magnetic resonance imaging has been used to re-explore the anatomy of white matter tracts in the living human brain and to create connectional models of brain function. Beyond its application to classical disconnection syndromes, diffusion tensor magnetic resonance imaging is becoming an important tool to extend the disconnectionist paradigm to neurodevelopmental and neurodegenerative disorders. SUMMARY: For the first time, we are able to correlate disconnecting lesions with clinical symptoms in vivo and test the disconnection mechanism directly in cognitive disorders. With diffusion tensor magnetic resonance imaging tractography alone and in combination with other magnetic resonance imaging techniques, researchers are able to detect abnormalities in white matter that are not visible with conventional magnetic resonance imaging.

Anisotropy↗
PubMed2001

Mobility of polymer chains confined at a free surface.

Dynamic secondary ion mass spectrometry was used to investigate the chain mobility of polystyrene (MW ranging from 4.3 to 957 kg/mol) at the free surface. The data show that the diffusion coefficient was reduced relative to the bulk value within a distance, d < or = 4R(g), from the surface and scaled as 1/N(2.5) at fixed d. These results are in excellent agreement with self-consistent field calculations of the surface segmental distribution and provide the first direct confirmation of various theoretical models that predict asymmetric segmental fluctuation which arises from surface induced orientation of polymer chains.

Journal Article↗
PubMed1994

A fiber matrix model for the growth of macromolecular leakage spots in the arterial intima.

A new model is presented for the growth of cellular level macromolecular leakage spots in the arterial intima. The theoretical approach differs from the recent study by Yuan et al. [19] in that it directly models and calculates the intimal transport parameters based on Frank and Fogelman's [22] ultrastructural observations of the extracellular subendothelial proteoglycan matrix that their rapid freeze etching technique preserves (see Addendum). Using a heterogeneous fiber matrix theory, which includes proteoglycan and collagen components, the model predicts that the Darcy permeability Kp and macromolecular diffusivity D of the subendothelial intima is two orders of magnitude larger than the corresponding values measured in the media, and supports the observations in Lark et al. [24] that the proteoglycan structure of the intima differs greatly from that of the media. Numerical results show that convection parallel to the endothelium is a very significant transport mechanism for macromolecules in the intima in a large region of roughly 200 microns diameter surrounding the leaky cleft. The predictions of the new model for the early-time spread of the advancing convective-diffusive front from the leakage spots in the intima are in close agreement with our experimental measurements for the growth of HRP spots in [20]. The regions of high concentration surrounding the leaky cell, however, are much more limited and cover an area that is typically equivalent to 20 cells. This prediction is consistent with the recent measurements of Truskey et al. for LDL spot size in rabbit aorta [21] and the hypothesis advanced in [19] that there is a colocalization of subendothelial liposome growth and cellular level leakage. Finally, comparison of predicted and experimentally-measured average LDL concentration in leakage spots strongly suggests that there is significant local molecular sieving at the interface between the fenestral openings in the internal elastic lamina and the media.

Animals↗
PubMed1976

Energy cost of galactoside transport to Escherichia coli.

Energy reserves of Escherichia coli can be depleted by our previously reported procedure to a level such that even the "downhill" transport of o-nitrophenyl-beta-D-galactopyranoside (ONPG) is completely dependent upon the exogenous energy supply. The ONPG concentration is high externally to the cells and is low intracellular because of the action of cytoplasmic beta-galactosidase. In the present work, depleted cell suspensions have been infused at low, steady rates with glucose and other energy sources while measurements of transport were being made. Comparing the rate of ONPG transport with the rate of introduction of glucose under conditions where the chosen glucose infusion rate limits transport, we find that 89 molecules of ONPG are transported per molecule of fully oxidized glucose. This transport yield is constant over a 6.5-fold range in rate of glucose addition. This constancy over a range of infusion rates implies that transport is the major cellular function under these special conditions. The yield value if 89 is in the agreement with the predicitions of 76 from Mitchell's chemiosmotic theory and constitutes an independent proff of its validity, since all the other proposed mechanisms of engery coupling predict much smaller yields. The lag from the start of glucose infusion into the reaction cuvette, to the extrapolated time at which a steady rate of transport and concomitant hydrolysis are achieved, is short (approximately 1 min). Similarly, the time after the infusion is stopped until the rate of transport returns to the background rate is also short. The latter implies that the energy metabolism is directed almost entirely to transport and/or other ongoing cellular processes and not to repair or renewal of an energy-independent, facilitated diffusion system.

Biological Transport, Active↗
PubMed1995

Polarity and transport properties of rabbit kidney proximal tubule cells on collagen IV-coated porous membranes.

A high degree of functional polarity has been obtained in primary cultures of rabbit kidney proximal tubule cells grown on collagen IV-coated porous membranes. Tight confluency was attained 6 days after seeding and maintained for at least 6 more days, as shown by analysis of paracellular inulin diffusion. From day 6 onward, L-lactate, ammonia, and D-glucose concentration gradient and a pH difference of approximately 1 unit developed between the two nutrient medium compartments. Confluent monolayers expressed organic ion transport properties higher than those formerly reported for other cell models. Transcellular transport of 20 microM tetraethylammonium was directed from basal to apical compartment and was specifically inhibited by mepiperphenidol (1 mM). Unidirectional transport of 2.4 microM p-aminohippurate also occurred from basal to apical compartment, was saturable, and specifically inhibited by probenecid (1 mM). These results suggest that rabbit kidney proximal tubule cells, cultured under the experimental conditions described here, may be a useful model for the in vitro study of highly polarized renal transport processes.

Ammonia↗
PubMed1996

Ligand recognition by murine anti-DNA autoantibodies. II. Genetic analysis and pathogenicity.

Although anti-DNA autoantibodies are an important hallmark of lupus, the relationships among anti-DNA structure, reactivity, and pathogenicity have not been fully elucidated. To further investigate these relationships, we compare the variable genes and primary structure of eight anti-DNA mAbs previously obtained from an MRL/MpJ-lpr/lpr mouse along with the ability of three representative mAbs to induce nephritis in nonautoimmune mice using established adoptive transfer protocols. One monospecific anti-single-stranded (ss) DNA (11F8) induces severe diffuse proliferative glomerulonephritis in nonautoimmune mice whereas another anti-ssDNA with apparently similar in vitro binding properties (9F11) and an anti-double-stranded DNA (4B2) are essentially benign. These results establish a murine model of anti-DNA-induced glomerular injury resembling the severe nephritis seen in lupus patients and provide direct evidence that anti-ssDNA can be more pathogenic than anti-double-stranded DNA. In vitro binding experiments using both protein-DNA complexes and naive kidney tissue indicate that glomerular localization of 11F8 may occur by recognition of a planted antigen in vivo. Binding to this antigen is DNase sensitive which suggests that DNA or a DNA-containing molecule is being recognized.

Amino Acid Sequence↗