Stimulus-induced transitions between spike-wave discharges and spindles with the modulation of thalamic reticular nucleus.

PubMed

Fan, Denggui; Wang, Qingyun; Su, Jianzhong; Xi, Hongguang

2017-12-01

It is believed that thalamic reticular nucleus (TRN) controls spindles and spike-wave discharges (SWD) in seizure or sleeping processes. The dynamical mechanisms of spatiotemporal evolutions between these two types of activity, however, are not well understood. In light of this, we first use a single-compartment thalamocortical neural field model to investigate the effects of TRN on occurrence of SWD and its transition. Results show that the increasing inhibition from TRN to specific relay nuclei (SRN) can lead to the transition of system from SWD to slow-wave oscillation. Specially, it is shown that stimulations applied in the cortical neuronal populations can also initiate the SWD and slow-wave oscillation from the resting states under the typical inhibitory intensity from TRN to SRN. Then, we expand into a 3-compartment coupled thalamocortical model network in linear and circular structures, respectively, to explore the spatiotemporal evolutions of wave states in different compartments. The main results are: (i) for the open-ended model network, SWD induced by stimulus in the first compartment can be transformed into sleep-like slow UP-DOWN and spindle states as it propagates into the downstream compartments; (ii) for the close-ended model network, weak stimulations performed in the first compartment can result in the consistent experimentally observed spindle oscillations in all three compartments; in contrast, stronger periodic single-pulse stimulations applied in the first compartment can induce periodic transitions between SWD and spindle oscillations. Detailed investigations reveal that multi-attractor coexistence mechanism composed of SWD, spindles and background state underlies these state evolutions. What's more, in order to demonstrate the state evolution stability with respect to the topological structures of neural network, we further expand the 3-compartment coupled network into 10-compartment coupled one, with linear and circular structures, and nearest-neighbor (NN) coupled network as well as its realization of small-world (SW) topology via random rewiring, respectively. Interestingly, for the cases of linear and circular connetivities, qualitatively similar results were obtained in addition to the more irregularity of firings. However, SWD can be eventually transformed into the consistent low-amplitude oscillations for both NN and SW networks. In particular, SWD evolves into the slow spindling oscillations and background tonic oscillations within the NN and SW network, respectively. Our modeling and simulation studies highlight the effect of network topology in the evolutions of SWD and spindling oscillations, which provides new insights into the mechanisms of cortical seizures development.

Switching from a unicellular to multicellular organization in an Aspergillus niger hypha.

PubMed

Bleichrodt, Robert-Jan; Hulsman, Marc; Wösten, Han A B; Reinders, Marcel J T

2015-03-03

Pores in fungal septa enable cytoplasmic streaming between hyphae and their compartments. Consequently, the mycelium can be considered unicellular. However, we show here that Woronin bodies close ~50% of the three most apical septa of growing hyphae of Aspergillus niger. The incidence of closure of the 9th and 10th septa was even ≥94%. Intercompartmental streaming of photoactivatable green fluorescent protein (PA-GFP) was not observed when the septa were closed, but open septa acted as a barrier, reducing the mobility rate of PA-GFP ~500 times. This mobility rate decreased with increasing septal age and under stress conditions, likely reflecting a regulatory mechanism affecting septal pore diameter. Modeling revealed that such regulation offers effective control of compound concentration between compartments. Modeling also showed that the incidence of septal closure in A. niger had an even stronger impact on cytoplasmic continuity. Cytoplasm of hyphal compartments was shown not to be in physical contact when separated by more than 4 septa. Together, data show that apical compartments of growing hyphae behave unicellularly, while older compartments have a multicellular organization. The hyphae of higher fungi are compartmentalized by porous septa that enable cytosolic streaming. Therefore, it is believed that the mycelium shares cytoplasm. However, it is shown here that the septa of Aspergillus niger are always closed in the oldest part of the hyphae, and therefore, these compartments are physically isolated from each other. In contrast, only part of the septa is closed in the youngest part of the hyphae. Still, compartments in this hyphal part are physically isolated when separated by more than 4 septa. Even open septa act as a barrier for cytoplasmic mixing. The mobility rate through such septa reduces with increasing septal age and under stress conditions. Modeling shows that the septal pore width is set such that its regulation offers maximal control of compound concentration levels within the compartments. Together, we show for the first time that Aspergillus hyphae switch from a unicellular to multicellular organization. Copyright © 2015 Bleichrodt et al.

The relationships between half-life (t1/2) and mean residence time (MRT) in the two-compartment open body model.

PubMed

Sobol, Eyal; Bialer, Meir

2004-05-01

In the one-compartment model following i.v. administration the mean residence time (MRT) of a drug is always greater than its half-life (t(1/2)). However, following i.v. administration, drug plasma concentration (C) versus time (t) is best described by a two-compartment model or a two exponential equation:C=Ae(-alpha t)+Be(-beta t), where A and B are concentration unit-coefficients and alpha and beta are exponential coefficients. The relationships between t(1/2) and MRT in the two-compartment model have not been explored and it is not clear whether in this model too MRT is always greater than t(1/2). In the current paper new equations have been developed that describe the relationships between the terminal t(1/2) (or t(1/2 beta)) and MRT in the two-compartment model following administration of i.v. bolus, i.v. infusion (zero order input) and oral administration (first order input). A critical value (CV) equals to the quotient of (1-ln2) and (1-beta/alpha) (CV=(1-ln2)/(1-beta/alpha)=0.307/(1-beta/alpha)) has been derived and was compared with the fraction (f(1)) of drug elimination or AUC (AUC-area under C vs t curve) associated with the first exponential term of the two-compartment equation (f(1)=A/alpha/AUC). Following i.v. bolus, CV ranges between a minimal value of 0.307 (1-ln2) and infinity. As long as f(1)t(1/2) and vice versa, and when f(1)=CV, then MRT=t(1/2). Following i.v. infusion and oral administration the denominator of the CV equation does not change but its numerator increases to (0.307+beta T/2) (T-infusion duration) and (0.307+beta/ka) (ka-absorption rate constant), respectively. Examples of various drugs are provided. For every drug that after i.v. bolus shows two-compartment disposition kinetics the following conclusions can be drawn (a) When f(1)<0.307, then f(1)t(1/2). (b) When beta/alpha>ln2, then CV>1>f(1) and thus(,) MRT>t(1/2). (c) When ln2>beta/alpha>(ln4-1), then 1>CV>0.5 and thus, in order for t(1/2)>MRT, f(1) has to be greater than its complementary fraction f(2) (f(1)>f(2)). (d) When beta/alpha<(ln4-1), it is possible that t(1/2)>MRT even when f(2)>f(1), as long as f(1)>CV. (e) As beta gets closer to alpha, CV approaches its maximal value (infinity) and therefore, the chances of MRT>t(1/2) are growing. (f) As beta becomes smaller compared with alpha, beta/alpha approaches zero, the denominator approaches unity and consequently, CV gets its minimal value and thus, the chances of t(1/2)>MRT are growing. (g) Following zero and first order input MRT increases compared with i.v. bolus and so does CV and thus, the chances of MRT>t(1/2) are growing. Copyright 2004 John Wiley & Sons, Ltd.

Numerical calculation on a two-step subdiffusion behavior of lateral protein movement in plasma membranes

NASA Astrophysics Data System (ADS)

Sumi, Tomonari; Okumoto, Atsushi; Goto, Hitoshi; Sekino, Hideo

2017-10-01

A two-step subdiffusion behavior of lateral movement of transmembrane proteins in plasma membranes has been observed by using single-molecule experiments. A nested double-compartment model where large compartments are divided into several smaller ones has been proposed in order to explain this observation. These compartments are considered to be delimited by membrane-skeleton "fences" and membrane-protein "pickets" bound to the fences. We perform numerical simulations of a master equation using a simple two-dimensional lattice model to investigate the heterogeneous diffusion dynamics behavior of transmembrane proteins within plasma membranes. We show that the experimentally observed two-step subdiffusion process can be described using fence and picket models combined with decreased local diffusivity of transmembrane proteins in the vicinity of the pickets. This allows us to explain the two-step subdiffusion behavior without explicitly introducing nested double compartments.

Fluid circulation determined in the isolated bovine lens.

PubMed

Candia, Oscar A; Mathias, Richard; Gerometta, Rosana

2012-10-11

In 1997, a theoretical model was developed that predicted the existence of an internal, Na(+)-driven fluid circulation from the poles to the equator of the lens. In the present work, we demonstrate with a novel system that fluid movement can be measured across the polar and equatorial surface areas of isolated cow lenses. We have also determined the effects of ouabain and reduced bath [Na(+)]. Lenses were isolated in a chamber with three compartments separated by two thin O-rings. Each compartment, anterior (A), equatorial (E), and posterior (P), was connected to a vertical capillary graduated in 0.25 μL. Capillary levels were read every 15 minutes. The protocols consisted of 2 hours in either open circuit or short circuit. The effects of ouabain and low-Na(+) solutions were determined under open circuit. In 21 experiments, the E capillary increased at a mean rate of 0.060 μL/min while the A and P levels decreased at rates of 0.044 and 0.037 μL/min, respectively, closely accounting for the increase in E. The first-hour flows under short circuit were approximately 40% larger than those in open-circuit conditions. The first-hour flows were always larger than those during the second hour. Preincubation of lenses with either ouabain or low-[Na(+)] solutions resulted in reduced rates of fluid transport. When KCl was used to replace NaCl, a transitory stimulation of fluid transport occurred. These experiments support that a fluid circulation consistent with the 1997 model is physiologically active.

33 CFR 183.605 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

...” means gasoline. “Open to the atmosphere” means a compartment that has at least 15 square inches of open area directly exposed to the atmosphere for each cubic foot of net compartment volume. [CGD 76-082, 44...

33 CFR 183.605 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

...” means gasoline. “Open to the atmosphere” means a compartment that has at least 15 square inches of open area directly exposed to the atmosphere for each cubic foot of net compartment volume. [CGD 76-082, 44...

33 CFR 183.605 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

...” means gasoline. “Open to the atmosphere” means a compartment that has at least 15 square inches of open area directly exposed to the atmosphere for each cubic foot of net compartment volume. [CGD 76-082, 44...

33 CFR 183.605 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

...” means gasoline. “Open to the atmosphere” means a compartment that has at least 15 square inches of open area directly exposed to the atmosphere for each cubic foot of net compartment volume. [CGD 76-082, 44...

33 CFR 183.605 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

...” means gasoline. “Open to the atmosphere” means a compartment that has at least 15 square inches of open area directly exposed to the atmosphere for each cubic foot of net compartment volume. [CGD 76-082, 44...

The Influence of Articular Cartilage Thickness Reduction on Meniscus Biomechanics

PubMed Central

Łuczkiewicz, Piotr; Daszkiewicz, Karol; Chróścielewski, Jacek; Witkowski, Wojciech; Winklewski, Pawel J.

2016-01-01

Objective Evaluation of the biomechanical interaction between meniscus and cartilage in medial compartment knee osteoarthritis. Methods The finite element method was used to simulate knee joint contact mechanics. Three knee models were created on the basis of knee geometry from the Open Knee project. We reduced the thickness of medial cartilages in the intact knee model by approximately 50% to obtain a medial knee osteoarthritis (OA) model. Two variants of medial knee OA model with congruent and incongruent contact surfaces were analysed to investigate the influence of congruency. A nonlinear static analysis for one compressive load case was performed. The focus of the study was the influence of cartilage degeneration on meniscal extrusion and the values of the contact forces and contact areas. Results In the model with incongruent contact surfaces, we observed maximal compressive stress on the tibial plateau. In this model, the value of medial meniscus external shift was 95.3% greater, while the contact area between the tibial cartilage and medial meniscus was 50% lower than in the congruent contact surfaces model. After the non-uniform reduction of cartilage thickness, the medial meniscus carried only 48.4% of load in the medial compartment in comparison to 71.2% in the healthy knee model. Conclusions We have shown that the change in articular cartilage geometry may significantly reduce the role of meniscus in load transmission and the contact area between the meniscus and cartilage. Additionally, medial knee OA may increase the risk of meniscal extrusion in the medial compartment of the knee joint. PMID:27936066

Cross-disciplinary links in environmental systems science: Current state and claimed needs identified in a meta-review of process models.

PubMed

Ayllón, Daniel; Grimm, Volker; Attinger, Sabine; Hauhs, Michael; Simmer, Clemens; Vereecken, Harry; Lischeid, Gunnar

2018-05-01

Terrestrial environmental systems are characterised by numerous feedback links between their different compartments. However, scientific research is organized into disciplines that focus on processes within the respective compartments rather than on interdisciplinary links. Major feedback mechanisms between compartments might therefore have been systematically overlooked so far. Without identifying these gaps, initiatives on future comprehensive environmental monitoring schemes and experimental platforms might fail. We performed a comprehensive overview of feedbacks between compartments currently represented in environmental sciences and explores to what degree missing links have already been acknowledged in the literature. We focused on process models as they can be regarded as repositories of scientific knowledge that compile findings of numerous single studies. In total, 118 simulation models from 23 model types were analysed. Missing processes linking different environmental compartments were identified based on a meta-review of 346 published reviews, model intercomparison studies, and model descriptions. Eight disciplines of environmental sciences were considered and 396 linking processes were identified and ascribed to the physical, chemical or biological domain. There were significant differences between model types and scientific disciplines regarding implemented interdisciplinary links. The most wide-spread interdisciplinary links were between physical processes in meteorology, hydrology and soil science that drive or set the boundary conditions for other processes (e.g., ecological processes). In contrast, most chemical and biological processes were restricted to links within the same compartment. Integration of multiple environmental compartments and interdisciplinary knowledge was scarce in most model types. There was a strong bias of suggested future research foci and model extensions towards reinforcing existing interdisciplinary knowledge rather than to open up new interdisciplinary pathways. No clear pattern across disciplines exists with respect to suggested future research efforts. There is no evidence that environmental research would clearly converge towards more integrated approaches or towards an overarching environmental systems theory. Copyright © 2017 Elsevier B.V. All rights reserved.

Critical analysis of the discrepancy between V(beta) and V(ss) for drugs exhibiting different two-compartment disposition profiles.

PubMed

Sobol, Eyal; Bialer, Meir

2005-03-01

It is well known that in the two-compartment open body model the values of apparent volume of distribution (V(beta)) and volume of distribution at steady state (V(ss)) are never identical. There are at least two conditions when V(beta) significantly overestimates V(ss). The first is when most of a drug is eliminated relatively rapidly but a small fraction of the dose persists and gives rise to an extremely long half-life. The second is when a drug is rapidly cleared from the central compartment with a short half-life. The primary purpose of the current paper was to investigate how different two-compartment disposition profiles affect the magnitude of difference between V(beta) and V(ss). Novel equations have been developed that relate the V(beta)/V(ss) ratio to f1 (fraction of drug elimination associated with the distributive phase) and to beta/alpha (ratio of the exponential coefficients). This paper demonstrates mathematically that an increasing value of f1 is associated with a greater divergence between V(beta) and V(ss). A similar relationship was also found for the divergence between the terminal half-life (t(1/2beta)) and the mean residence time (MRT). An increase in the beta/alpha ratio results in a substantial decrease of this discrepancy and provides a maximal possible value, or an upper limit to the V(beta)/V(ss) ratio. The newly derived equations along with their graphical presentation may serve as an excellent predictive tool for checking the accuracy of the experimentally obtained values of V(beta) and V(ss). Copyright 2004 John Wiley & Sons, Ltd.

DISTING: A web application for fast algorithmic computation of alternative indistinguishable linear compartmental models.

PubMed

Davidson, Natalie R; Godfrey, Keith R; Alquaddoomi, Faisal; Nola, David; DiStefano, Joseph J

2017-05-01

We describe and illustrate use of DISTING, a novel web application for computing alternative structurally identifiable linear compartmental models that are input-output indistinguishable from a postulated linear compartmental model. Several computer packages are available for analysing the structural identifiability of such models, but DISTING is the first to be made available for assessing indistinguishability. The computational algorithms embedded in DISTING are based on advanced versions of established geometric and algebraic properties of linear compartmental models, embedded in a user-friendly graphic model user interface. Novel computational tools greatly speed up the overall procedure. These include algorithms for Jacobian matrix reduction, submatrix rank reduction, and parallelization of candidate rank computations in symbolic matrix analysis. The application of DISTING to three postulated models with respectively two, three and four compartments is given. The 2-compartment example is used to illustrate the indistinguishability problem; the original (unidentifiable) model is found to have two structurally identifiable models that are indistinguishable from it. The 3-compartment example has three structurally identifiable indistinguishable models. It is found from DISTING that the four-compartment example has five structurally identifiable models indistinguishable from the original postulated model. This example shows that care is needed when dealing with models that have two or more compartments which are neither perturbed nor observed, because the numbering of these compartments may be arbitrary. DISTING is universally and freely available via the Internet. It is easy to use and circumvents tedious and complicated algebraic analysis previously done by hand. Copyright © 2017 Elsevier B.V. All rights reserved.

Two-compartment modeling of tissue microcirculation revisited.

PubMed

Brix, Gunnar; Salehi Ravesh, Mona; Griebel, Jürgen

2017-05-01

Conventional two-compartment modeling of tissue microcirculation is used for tracer kinetic analysis of dynamic contrast-enhanced (DCE) computed tomography or magnetic resonance imaging studies although it is well-known that the underlying assumption of an instantaneous mixing of the administered contrast agent (CA) in capillaries is far from being realistic. It was thus the aim of the present study to provide theoretical and computational evidence in favor of a conceptually alternative modeling approach that makes it possible to characterize the bias inherent to compartment modeling and, moreover, to approximately correct for it. Starting from a two-region distributed-parameter model that accounts for spatial gradients in CA concentrations within blood-tissue exchange units, a modified lumped two-compartment exchange model was derived. It has the same analytical structure as the conventional two-compartment model, but indicates that the apparent blood flow identifiable from measured DCE data is substantially overestimated, whereas the three other model parameters (i.e., the permeability-surface area product as well as the volume fractions of the plasma and interstitial distribution space) are unbiased. Furthermore, a simple formula was derived to approximately compute a bias-corrected flow from the estimates of the apparent flow and permeability-surface area product obtained by model fitting. To evaluate the accuracy of the proposed modeling and bias correction method, representative noise-free DCE curves were analyzed. They were simulated for 36 microcirculation and four input scenarios by an axially distributed reference model. As analytically proven, the considered two-compartment exchange model is structurally identifiable from tissue residue data. The apparent flow values estimated for the 144 simulated tissue/input scenarios were considerably biased. After bias-correction, the deviations between estimated and actual parameter values were (11.2 ± 6.4) % (vs. (105 ± 21) % without correction) for the flow, (3.6 ± 6.1) % for the permeability-surface area product, (5.8 ± 4.9) % for the vascular volume and (2.5 ± 4.1) % for the interstitial volume; with individual deviations of more than 20% being the exception and just marginal. Increasing the duration of CA administration only had a statistically significant but opposite effect on the accuracy of the estimated flow (declined) and intravascular volume (improved). Physiologically well-defined tissue parameters are structurally identifiable and accurately estimable from DCE data by the conceptually modified two-compartment model in combination with the bias correction. The accuracy of the bias-corrected flow is nearly comparable to that of the three other (theoretically unbiased) model parameters. As compared to conventional two-compartment modeling, this feature constitutes a major advantage for tracer kinetic analysis of both preclinical and clinical DCE imaging studies. © 2017 American Association of Physicists in Medicine.

Gamma time-dependency in Blaxter's compartmental model.

NASA Technical Reports Server (NTRS)

Matis, J. H.

1972-01-01

A new two-compartment model for the passage of particles through the gastro-intestinal tract of ruminants is proposed. In this model, a gamma distribution of lifetimes is introduced in the first compartment; thereby, passage from that compartment becomes time-dependent. This modification is strongly suggested by the physical alteration which certain substances, e.g. hay particles, undergo in the digestive process. The proposed model is applied to experimental data.

Compartment A4 hold at midplatform level, view from starboard to ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Compartment A-4 hold at mid-platform level, view from starboard to port shows protective deck framing and underside of armor plate. Open wood ceiling aids in circulating air. Note ventilation duct for fresh air at center of photograph. Open hatch penetrates protective deck and leads to bread room, compartment A-102. (012) - USS Olympia, Penn's Landing, 211 South Columbus Boulevard, Philadelphia, Philadelphia County, PA

Refrigerator with anti-sweat hot liquid loop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woolley, S.J.; Cushing, D.S.; Jenkins, T.E.

A cabinet assembly for a refrigerator having a freezer compartment ontop with two top front corners, a fresh food compartment on the bottom, a mullion partition between the compartments and a hot liquid anti-sweat loop is described comprising; an outer sheet metal shell having a top panel, side panels and a front face, a brace located at each of the two top front corners of the cabinet and having two formed sections at right angles to each other and each section is formed as an inwardly open U-shaped channel having a base, a first leg and a second leg spacedmore » apart and integrally joined to the base, fastening means for rigidly attaching each of the second leg of the corner braces to the flange of the third wall of the front face, and means to secure a portion of the hot liquid anti-sweat loop to the braces.« less

Imitation by combination: preschool age children evidence summative imitation in a novel problem-solving task.

PubMed

Subiaul, Francys; Krajkowski, Edward; Price, Elizabeth E; Etz, Alexander

2015-01-01

Children are exceptional, even 'super,' imitators but comparatively poor independent problem-solvers or innovators. Yet, imitation and innovation are both necessary components of cumulative cultural evolution. Here, we explored the relationship between imitation and innovation by assessing children's ability to generate a solution to a novel problem by imitating two different action sequences demonstrated by two different models, an example of imitation by combination, which we refer to as "summative imitation." Children (N = 181) from 3 to 5 years of age and across three experiments were tested in a baseline condition or in one of six demonstration conditions, varying in the number of models and opening techniques demonstrated. Across experiments, more than 75% of children evidenced summative imitation, opening both compartments of the problem box and retrieving the reward hidden in each. Generally, learning different actions from two different models was as good (and in some cases, better) than learning from 1 model, but the underlying representations appear to be the same in both demonstration conditions. These results show that summative imitation not only facilitates imitation learning but can also result in new solutions to problems, an essential feature of innovation and cumulative culture.

Mathematical models for the diffusion magnetic resonance signal abnormality in patients with prion diseases.

PubMed

Figini, Matteo; Alexander, Daniel C; Redaelli, Veronica; Fasano, Fabrizio; Grisoli, Marina; Baselli, Giuseppe; Gambetti, Pierluigi; Tagliavini, Fabrizio; Bizzi, Alberto

2015-01-01

In clinical practice signal hyperintensity in the cortex and/or in the striatum on magnetic resonance (MR) diffusion-weighted images (DWIs) is a marker of sporadic Creutzfeldt-Jakob Disease (sCJD). MR diagnostic accuracy is greater than 90%, but the biophysical mechanisms underpinning the signal abnormality are unknown. The aim of this prospective study is to combine an advanced DWI protocol with new mathematical models of the microstructural changes occurring in prion disease patients to investigate the cause of MR signal alterations. This underpins the later development of more sensitive and specific image-based biomarkers. DWI data with a wide a range of echo times and diffusion weightings were acquired in 15 patients with suspected diagnosis of prion disease and in 4 healthy age-matched subjects. Clinical diagnosis of sCJD was made in nine patients, genetic CJD in one, rapidly progressive encephalopathy in three, and Gerstmann-Sträussler-Scheinker syndrome in two. Data were analysed with two bi-compartment models that represent different hypotheses about the histopathological alterations responsible for the DWI signal hyperintensity. A ROI-based analysis was performed in 13 grey matter areas located in affected and apparently unaffected regions from patients and healthy subjects. We provide for the first time non-invasive estimate of the restricted compartment radius, designed to reflect vacuole size, which is a key discriminator of sCJD subtypes. The estimated vacuole size in DWI hyperintense cortex was in the range between 3 and 10 µm that is compatible with neuropathology measurements. In DWI hyperintense grey matter of sCJD patients the two bi-compartment models outperform the classic mono-exponential ADC model. Both new models show that T2 relaxation times significantly increase, fast and slow diffusivities reduce, and the fraction of the compartment with slow/restricted diffusion increases compared to unaffected grey matter of patients and healthy subjects. Analysis of the raw DWI signal allows us to suggest the following acquisition parameters for optimized detection of CJD lesions: b = 3000 s/mm(2) and TE = 103 ms. In conclusion, these results provide the first in vivo estimate of mean vacuole size, new insight on the mechanisms of DWI signal changes in prionopathies and open the way to designing an optimized acquisition protocol to improve early clinical diagnosis and subtyping of sCJD.

Body composition in elderly people: effect of criterion estimates on predictive equations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumgartner, R.N.; Heymsfield, S.B.; Lichtman, S.

1991-06-01

The purposes of this study were to determine whether there are significant differences between two- and four-compartment model estimates of body composition, whether these differences are associated with aqueous and mineral fractions of the fat-free mass (FFM); and whether the differences are retained in equations for predicting body composition from anthropometry and bioelectric resistance. Body composition was estimated in 98 men and women aged 65-94 y by using a four-compartment model based on hydrodensitometry, {sup 3}H{sub 2}O dilution, and dual-photon absorptiometry. These estimates were significantly different from those obtained by using Siri's two-compartment model. The differences were associated significantly (Pmore » less than 0.0001) with variation in the aqueous fraction of FFM. Equations for predicting body composition from anthropometry and resistance, when calibrated against two-compartment model estimates, retained these systematic errors. Equations predicting body composition in elderly people should be calibrated against estimates from multicompartment models that consider variability in FFM composition.« less

Anxiolytic effects of environmental enrichment attenuate sex-related anxiogenic effects of scopolamine in rats.

PubMed

Hughes, Robert N; Otto, Maria T

2013-01-10

In groups of four same-sexed animals, PVG/c hooded rats were housed for 4.5 months in standard or enriched cages containing several objects that could be explored and manipulated. On separate occasions, each rat then experienced two consecutive daily trials in an open field, a light-dark box or a Y maze with arm inserts that enabled an acquisition trial comprising one black and one white arm to be changed for a retention trial consisting of two black arms. Before their trials in the open field and light-dark box, and following each acquisition trial in the Y maze, the rats received an intraperitoneal injection of 2 mg/kg scopolamine or isotonic saline. In the open field, enrichment led to higher levels of ambulation, walking, rearing and occupancy of the center of the apparatus and shorter emergence latencies from the dark into the light compartment of the light-dark box accompanied by more entries of this compartment. Enrichment also increased entries of and time spent in the changed (or novel) Y-maze arm only for male rats treated with scopolamine. The drug decreased rearing and increased grooming in the open field as well as increasing emergence latencies and decreasing entries of and the time spent on the light compartment of the light-dark box. The main results were interpreted as enrichment having attenuated anxiogenic effects of the behavioral testing and the action of scopolamine for male (but not female) rats in their choices of the novel arm in the Y maze. Copyright © 2012 Elsevier Inc. All rights reserved.

Unrecognized anterior compartment syndrome following ankle fracture surgery: a case report.

PubMed

Seyahi, Aksel; Uludag, Serkan; Akman, Senol; Demirhan, Mehmet

2009-01-01

A 35-year-old male sustained a lateral malleolar fracture while playing football. The fracture was treated by open reduction and internal fixation with a tourniquet. The next day, the patient returned with pain and swelling of the ankle and was admitted again to the hospital with a suspected diagnosis of cellulitis. Ten hours later, the patient developed the symptoms of anterior compartment syndrome. Emergency open fasciotomy of the anterior compartment was performed. The retrospective analysis of the patient's history was suggestive of a predisposition to an exercise-induced compartment syndrome. We think that exertional increase of the compartmental pressure before the injury and the tourniquet used during surgery contributed together to the development of compartment syndrome. Physicians should be vigilant in identifying the features of compartment syndrome when managing patients injured during a sporting activity.

19 CFR 123.24 - Sealing of conveyances or compartments.

Code of Federal Regulations, 2011 CFR

2011-04-01

... in the same manner as less than load or compartment lots; (3) Live animals identifiable by specific... of the parties in interest, in unsealed conveyances or compartments. (b) Seals to be affixed. The carrier shall affix blue in-transit seals to all openings of conveyances and compartments containing in...

Fluid Circulation Determined in the Isolated Bovine Lens

PubMed Central

Candia, Oscar A.; Mathias, Richard; Gerometta, Rosana

2012-01-01

Purpose. In 1997, a theoretical model was developed that predicted the existence of an internal, Na+-driven fluid circulation from the poles to the equator of the lens. In the present work, we demonstrate with a novel system that fluid movement can be measured across the polar and equatorial surface areas of isolated cow lenses. We have also determined the effects of ouabain and reduced bath [Na+]. Methods. Lenses were isolated in a chamber with three compartments separated by two thin O-rings. Each compartment, anterior (A), equatorial (E), and posterior (P), was connected to a vertical capillary graduated in 0.25 μL. Capillary levels were read every 15 minutes. The protocols consisted of 2 hours in either open circuit or short circuit. The effects of ouabain and low-Na+ solutions were determined under open circuit. Results. In 21 experiments, the E capillary increased at a mean rate of 0.060 μL/min while the A and P levels decreased at rates of 0.044 and 0.037 μL/min, respectively, closely accounting for the increase in E. The first-hour flows under short circuit were approximately 40% larger than those in open-circuit conditions. The first-hour flows were always larger than those during the second hour. Preincubation of lenses with either ouabain or low-[Na+] solutions resulted in reduced rates of fluid transport. When KCl was used to replace NaCl, a transitory stimulation of fluid transport occurred. Conclusions. These experiments support that a fluid circulation consistent with the 1997 model is physiologically active. PMID:22969071

19 CFR 123.24 - Sealing of conveyances or compartments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... loads or lots in the same manner as less than load or compartment lots; (3) Live animals identifiable by... the expense of the parties in interest, in unsealed conveyances or compartments. (b) Seals to be affixed. The carrier shall affix blue in-transit seals to all openings of conveyances and compartments...

Population pharmacokinetic analysis of clopidogrel in healthy Jordanian subjects with emphasis optimal sampling strategy.

PubMed

Yousef, A M; Melhem, M; Xue, B; Arafat, T; Reynolds, D K; Van Wart, S A

2013-05-01

Clopidogrel is metabolized primarily into an inactive carboxyl metabolite (clopidogrel-IM) or to a lesser extent an active thiol metabolite. A population pharmacokinetic (PK) model was developed using NONMEM(®) to describe the time course of clopidogrel-IM in plasma and to design a sparse-sampling strategy to predict clopidogrel-IM exposures for use in characterizing anti-platelet activity. Serial blood samples from 76 healthy Jordanian subjects administered a single 75 mg oral dose of clopidogrel were collected and assayed for clopidogrel-IM using reverse phase high performance liquid chromatography. A two-compartment (2-CMT) PK model with first-order absorption and elimination plus an absorption lag-time was evaluated, as well as a variation of this model designed to mimic enterohepatic recycling (EHC). Optimal PK sampling strategies (OSS) were determined using WinPOPT based upon collection of 3-12 post-dose samples. A two-compartment model with EHC provided the best fit and reduced bias in C(max) (median prediction error (PE%) of 9.58% versus 12.2%) relative to the basic two-compartment model, AUC(0-24) was similar for both models (median PE% = 1.39%). The OSS for fitting the two-compartment model with EHC required the collection of seven samples (0.25, 1, 2, 4, 5, 6 and 12 h). Reasonably unbiased and precise exposures were obtained when re-fitting this model to a reduced dataset considering only these sampling times. A two-compartment model considering EHC best characterized the time course of clopidogrel-IM in plasma. Use of the suggested OSS will allow for the collection of fewer PK samples when assessing clopidogrel-IM exposures. Copyright © 2013 John Wiley & Sons, Ltd.

How tibiofemoral alignment and contact locations affect predictions of medial and lateral tibiofemoral contact forces.

PubMed

Lerner, Zachary F; DeMers, Matthew S; Delp, Scott L; Browning, Raymond C

2015-02-26

Understanding degeneration of biological and prosthetic knee joints requires knowledge of the in-vivo loading environment during activities of daily living. Musculoskeletal models can estimate medial/lateral tibiofemoral compartment contact forces, yet anthropometric differences between individuals make accurate predictions challenging. We developed a full-body OpenSim musculoskeletal model with a knee joint that incorporates subject-specific tibiofemoral alignment (i.e. knee varus-valgus) and geometry (i.e. contact locations). We tested the accuracy of our model and determined the importance of these subject-specific parameters by comparing estimated to measured medial and lateral contact forces during walking in an individual with an instrumented knee replacement and post-operative genu valgum (6°). The errors in the predictions of the first peak medial and lateral contact force were 12.4% and 11.9%, respectively, for a model with subject-specific tibiofemoral alignment and contact locations determined through radiographic analysis, vs. 63.1% and 42.0%, respectively, for a model with generic parameters. We found that each degree of tibiofemoral alignment deviation altered the first peak medial compartment contact force by 51N (r(2)=0.99), while each millimeter of medial-lateral translation of the compartment contact point locations altered the first peak medial compartment contact force by 41N (r(2)=0.99). The model, available at www.simtk.org/home/med-lat-knee/, enables the specification of subject-specific joint alignment and compartment contact locations to more accurately estimate medial and lateral tibiofemoral contact forces in individuals with non-neutral alignment. Copyright © 2015 Elsevier Ltd. All rights reserved.

How Tibiofemoral Alignment and Contact Locations Affect Predictions of Medial and Lateral Tibiofemoral Contact Forces

PubMed Central

Lerner, Zachary F.; DeMers, Matthew S.; Delp, Scott L.; Browning, Raymond C.

2015-01-01

Understanding degeneration of biological and prosthetic knee joints requires knowledge of the in-vivo loading environment during activities of daily living. Musculoskeletal models can estimate medial/lateral tibiofemoral compartment contact forces, yet anthropometric differences between individuals make accurate predictions challenging. We developed a full-body OpenSim musculoskeletal model with a knee joint that incorporates subject-specific tibiofemoral alignment (i.e. knee varus-valgus) and geometry (i.e. contact locations). We tested the accuracy of our model and determined the importance of these subject-specific parameters by comparing estimated to measured medial and lateral contact forces during walking in an individual with an instrumented knee replacement and post-operative genu valgum (6°). The errors in the predictions of the first peak medial and lateral contact force were 12.4% and 11.9%, respectively, for a model with subject-specific tibiofemoral alignment and contact locations determined via radiographic analysis, vs. 63.1% and 42.0%, respectively, for a model with generic parameters. We found that each degree of tibiofemoral alignment deviation altered the first peak medial compartment contact force by 51N (r2=0.99), while each millimeter of medial-lateral translation of the compartment contact point locations altered the first peak medial compartment contact force by 41N (r2=0.99). The model, available at www.simtk.org/home/med-lat-knee/, enables the specification of subject-specific joint alignment and compartment contact locations to more accurately estimate medial and lateral tibiofemoral contact forces in individuals with non-neutral alignment. PMID:25595425

On dependency properties of the ISIs generated by a two-compartmental neuronal model.

PubMed

Benedetto, Elisa; Sacerdote, Laura

2013-02-01

One-dimensional leaky integrate and fire neuronal models describe interspike intervals (ISIs) of a neuron as a renewal process and disregarding the neuron geometry. Many multi-compartment models account for the geometrical features of the neuron but are too complex for their mathematical tractability. Leaky integrate and fire two-compartment models seem a good compromise between mathematical tractability and an improved realism. They indeed allow to relax the renewal hypothesis, typical of one-dimensional models, without introducing too strong mathematical difficulties. Here, we pursue the analysis of the two-compartment model studied by Lansky and Rodriguez (Phys D 132:267-286, 1999), aiming of introducing some specific mathematical results used together with simulation techniques. With the aid of these methods, we investigate dependency properties of ISIs for different values of the model parameters. We show that an increase of the input increases the strength of the dependence between successive ISIs.

ROCKET PORT CLOSURE

DOEpatents

Mattingly, J.T.

1963-02-12

This invention provides a simple pressure-actuated closure whereby windowless observation ports are opened to the atmosphere at preselected altitudes. The closure comprises a disk which seals a windowless observation port in rocket hull. An evacuated instrument compartment is affixed to the rocket hull adjacent the inner surface of the disk, while the outer disk surface is exposed to the atmosphere through which the rocket is traveling. The pressure differential between the evacuated instrument compartment and the relatively high pressure external atmosphere forces the disk against the edge of the observation port, thereby effecting a tight seai. The instrument compartment is evacuated to a pressure equal to the atmospheric pressure existing at the altitude at which it is desiretl that the closure should open. When the rocket reaches this preselected altitude, the inwardly directed atmospheric force on the disk is just equaled by the residual air pressure force within the instrument compartment. Consequently, the closure disk falls away and uncovers the open observation port. The separation of the disk from the rocket hull actuates a switch which energizes the mechanism of a detecting instrument disposed within the instrument compartment. (AE C)

Ages and transit times as important diagnostics of model performance for predicting C allocation in ecosystem models

NASA Astrophysics Data System (ADS)

Ceballos-Núñez, Verónika; Richardson, Andrew; Sierra, Carlos

2017-04-01

The global carbon cycle is strongly controlled by the source/sink strength of vegetation as well as the capacity of terrestrial ecosystems to retain this carbon. However, it is uncertain how some vegetation dynamics such as the allocation of carbon to different ecosystem compartments should be represented in models. The assumptions behind model structures may result in highly divergent model predictions. Here, we asses model performance by calculating the age of the carbon in the system and in each compartment, and the overall transit time of C in the system. We used these diagnostics to assess the influence of three different carbon allocation schemes on the rates of C cycling in vegetation. First, we used published measurements of ecosystem C compartments from the Harvard Forest Environmental Measurement Site to find the best set of parameters for the different model structures. Second, we calculated C stocks, respiration fluxes, radiocarbon values, ages, and transit times. We found a good fit of the three model structures to the available data, but the time series of C in foliage and wood need to be complemented with other ecosystem compartments in order to reduce the high parameter collinearity that we observed and reduce model equifinality. Differences in model structures had a small impact on predicting ecosystem C compartments, but overall they resulted in very different predictions of age and transit time distributions. In particular, the inclusion of a storage compartment had an important impact on predicting system ages and transit times. In the case of the models with 1 or 2 storage compartments, the age of carbon in the system and in each of the compartments was distributed more towards younger ages than in the model that had no storage; the mean system age of these two models with storage was 80 years younger than in the model without storage. As expected from these age distributions, the mean transit time for the two models with storage compartments was 50 years faster than for the model without storage. These results suggest that ages and transit times, which can be indirectly measured using isotope tracers, serve as important diagnostics of model structure and could largely help to reduce uncertainties in model predictions. Furthermore, by considering age and transit times of C in vegetation compartments as distributions, not only their mean values, we obtain additional insights on the temporal dynamics of carbon use, storage, and allocation to plant parts, which not only depends on the rate at which this C is transferred in and out of the compartments, but also on the stochastic nature of the process itself.

Imitation by combination: preschool age children evidence summative imitation in a novel problem-solving task

PubMed Central

Subiaul, Francys; Krajkowski, Edward; Price, Elizabeth E.; Etz, Alexander

2015-01-01

Children are exceptional, even ‘super,’ imitators but comparatively poor independent problem-solvers or innovators. Yet, imitation and innovation are both necessary components of cumulative cultural evolution. Here, we explored the relationship between imitation and innovation by assessing children’s ability to generate a solution to a novel problem by imitating two different action sequences demonstrated by two different models, an example of imitation by combination, which we refer to as “summative imitation.” Children (N = 181) from 3 to 5 years of age and across three experiments were tested in a baseline condition or in one of six demonstration conditions, varying in the number of models and opening techniques demonstrated. Across experiments, more than 75% of children evidenced summative imitation, opening both compartments of the problem box and retrieving the reward hidden in each. Generally, learning different actions from two different models was as good (and in some cases, better) than learning from 1 model, but the underlying representations appear to be the same in both demonstration conditions. These results show that summative imitation not only facilitates imitation learning but can also result in new solutions to problems, an essential feature of innovation and cumulative culture. PMID:26441782

Evaluation of kinetic parameters of natural phytoalexin in resveratrol orally administered in wine to rats.

PubMed

Bertelli, A A; Giovannini, L; Stradi, R; Urien, S; Tillement, J P; Bertelli, A

1998-01-01

In view of the increasing interest in the biological activity of resveratrol, one of the components of red wine which is considered to be one of the main ingredients responsible for the beneficial effect of wine on human health, we have studied plasma kinetics and tissue bioavailability of this compound after red wine oral administration in rats. Plasma pharmacokinetics after oral administration of resveratrol could be described by an open one- or two-compartment model. Tissue concentrations show a significant cardiac bioavailability, and a strong affinity for the liver and kidneys.

A human cadaver fascial compartment pressure measurement model.

PubMed

Messina, Frank C; Cooper, Dylan; Huffman, Gretchen; Bartkus, Edward; Wilbur, Lee

2013-10-01

Fresh human cadavers provide an effective model for procedural training. Currently, there are no realistic models to teach fascial compartment pressure measurement. We created a human cadaver fascial compartment pressure measurement model and studied its feasibility with a pre-post design. Three faculty members, following instructions from a common procedure textbook, used a standard handheld intra-compartment pressure monitor (Stryker(®), Kalamazoo, MI) to measure baseline pressures ("unembalmed") in the anterior, lateral, deep posterior, and superficial posterior compartments of the lower legs of a fresh human cadaver. The right femoral artery was then identified by superficial dissection, cannulated distally towards the lower leg, and connected to a standard embalming machine. After a 5-min infusion, the same three faculty members re-measured pressures ("embalmed") of the same compartments on the cannulated right leg. Unembalmed and embalmed readings for each compartment, and baseline readings for each leg, were compared using a two-sided paired t-test. The mean baseline compartment pressures did not differ between the right and left legs. Using the embalming machine, compartment pressure readings increased significantly over baseline for three of four fascial compartments; all in mm Hg (±SD): anterior from 40 (±9) to 143 (±44) (p = 0.08); lateral from 22 (±2.5) to 160 (±4.3) (p < 0.01); deep posterior from 34 (±7.9) to 161 (±15) (p < 0.01); superficial posterior from 33 (±0) to 140 (±13) (p < 0.01). We created a novel and measurable fascial compartment pressure measurement model in a fresh human cadaver using a standard embalming machine. Set-up is minimal and the model can be incorporated into teaching curricula. Copyright © 2013 Elsevier Inc. All rights reserved.

Estimation of pharmacokinetic parameters from non-compartmental variables using Microsoft Excel.

PubMed

Dansirikul, Chantaratsamon; Choi, Malcolm; Duffull, Stephen B

2005-06-01

This study was conducted to develop a method, termed 'back analysis (BA)', for converting non-compartmental variables to compartment model dependent pharmacokinetic parameters for both one- and two-compartment models. A Microsoft Excel spreadsheet was implemented with the use of Solver and visual basic functions. The performance of the BA method in estimating pharmacokinetic parameter values was evaluated by comparing the parameter values obtained to a standard modelling software program, NONMEM, using simulated data. The results show that the BA method was reasonably precise and provided low bias in estimating fixed and random effect parameters for both one- and two-compartment models. The pharmacokinetic parameters estimated from the BA method were similar to those of NONMEM estimation.

Application of separable parameter space techniques to multi-tracer PET compartment modeling.

PubMed

Zhang, Jeff L; Michael Morey, A; Kadrmas, Dan J

2016-02-07

Multi-tracer positron emission tomography (PET) can image two or more tracers in a single scan, characterizing multiple aspects of biological functions to provide new insights into many diseases. The technique uses dynamic imaging, resulting in time-activity curves that contain contributions from each tracer present. The process of separating and recovering separate images and/or imaging measures for each tracer requires the application of kinetic constraints, which are most commonly applied by fitting parallel compartment models for all tracers. Such multi-tracer compartment modeling presents challenging nonlinear fits in multiple dimensions. This work extends separable parameter space kinetic modeling techniques, previously developed for fitting single-tracer compartment models, to fitting multi-tracer compartment models. The multi-tracer compartment model solution equations were reformulated to maximally separate the linear and nonlinear aspects of the fitting problem, and separable least-squares techniques were applied to effectively reduce the dimensionality of the nonlinear fit. The benefits of the approach are then explored through a number of illustrative examples, including characterization of separable parameter space multi-tracer objective functions and demonstration of exhaustive search fits which guarantee the true global minimum to within arbitrary search precision. Iterative gradient-descent algorithms using Levenberg-Marquardt were also tested, demonstrating improved fitting speed and robustness as compared to corresponding fits using conventional model formulations. The proposed technique overcomes many of the challenges in fitting simultaneous multi-tracer PET compartment models.

Application of separable parameter space techniques to multi-tracer PET compartment modeling

NASA Astrophysics Data System (ADS)

Zhang, Jeff L.; Morey, A. Michael; Kadrmas, Dan J.

2016-02-01

Multi-tracer positron emission tomography (PET) can image two or more tracers in a single scan, characterizing multiple aspects of biological functions to provide new insights into many diseases. The technique uses dynamic imaging, resulting in time-activity curves that contain contributions from each tracer present. The process of separating and recovering separate images and/or imaging measures for each tracer requires the application of kinetic constraints, which are most commonly applied by fitting parallel compartment models for all tracers. Such multi-tracer compartment modeling presents challenging nonlinear fits in multiple dimensions. This work extends separable parameter space kinetic modeling techniques, previously developed for fitting single-tracer compartment models, to fitting multi-tracer compartment models. The multi-tracer compartment model solution equations were reformulated to maximally separate the linear and nonlinear aspects of the fitting problem, and separable least-squares techniques were applied to effectively reduce the dimensionality of the nonlinear fit. The benefits of the approach are then explored through a number of illustrative examples, including characterization of separable parameter space multi-tracer objective functions and demonstration of exhaustive search fits which guarantee the true global minimum to within arbitrary search precision. Iterative gradient-descent algorithms using Levenberg-Marquardt were also tested, demonstrating improved fitting speed and robustness as compared to corresponding fits using conventional model formulations. The proposed technique overcomes many of the challenges in fitting simultaneous multi-tracer PET compartment models.

2D hydrodynamic simulations of a variable length gas target for density down-ramp injection of electrons into a laser wakefield accelerator

NASA Astrophysics Data System (ADS)

Kononenko, O.; Lopes, N. C.; Cole, J. M.; Kamperidis, C.; Mangles, S. P. D.; Najmudin, Z.; Osterhoff, J.; Poder, K.; Rusby, D.; Symes, D. R.; Warwick, J.; Wood, J. C.; Palmer, C. A. J.

2016-09-01

In this work, two-dimensional (2D) hydrodynamic simulations of a variable length gas cell were performed using the open source fluid code OpenFOAM. The gas cell was designed to study controlled injection of electrons into a laser-driven wakefield at the Astra Gemini laser facility. The target consists of two compartments: an accelerator and an injector section connected via an aperture. A sharp transition between the peak and plateau density regions in the injector and accelerator compartments, respectively, was observed in simulations with various inlet pressures. The fluid simulations indicate that the length of the down-ramp connecting the sections depends on the aperture diameter, as does the density drop outside the entrance and the exit cones. Further studies showed, that increasing the inlet pressure leads to turbulence and strong fluctuations in density along the axial profile during target filling, and consequently, is expected to negatively impact the accelerator stability.

Compartmental analysis of [11C]flumazenil kinetics for the estimation of ligand transport rate and receptor distribution using positron emission tomography.

PubMed

Koeppe, R A; Holthoff, V A; Frey, K A; Kilbourn, M R; Kuhl, D E

1991-09-01

The in vivo kinetic behavior of [11C]flumazenil ([11C]FMZ), a non-subtype-specific central benzodiazepine antagonist, is characterized using compartmental analysis with the aim of producing an optimized data acquisition protocol and tracer kinetic model configuration for the assessment of [11C]FMZ binding to benzodiazepine receptors (BZRs) in human brain. The approach presented is simple, requiring only a single radioligand injection. Dynamic positron emission tomography data were acquired on 18 normal volunteers using a 60- to 90-min sequence of scans and were analyzed with model configurations that included a three-compartment, four-parameter model, a three-compartment, three-parameter model, with a fixed value for free plus nonspecific binding; and a two-compartment, two-parameter model. Statistical analysis indicated that a four-parameter model did not yield significantly better fits than a three-parameter model. Goodness of fit was improved for three- versus two-parameter configurations in regions with low receptor density, but not in regions with moderate to high receptor density. Thus, a two-compartment, two-parameter configuration was found to adequately describe the kinetic behavior of [11C]FMZ in human brain, with stable estimates of the model parameters obtainable from as little as 20-30 min of data. Pixel-by-pixel analysis yields functional images of transport rate (K1) and ligand distribution volume (DV"), and thus provides independent estimates of ligand delivery and BZR binding.

Pharmacokinetics of diclofenac and its interaction with enrofloxacin in sheep.

PubMed

Rahal, Anu; Kumar, Amit; Ahmad, A H; Malik, J K

2008-06-01

The pharmacokinetics of diclofenac was investigated in sheep given diclofenac alone (1mgkg(-1), i.v. or i.m.) and in combination with enrofloxacin (5mgkg(-1), i.v.). The plasma concentration-time data following i.v. administration of diclofenac was best described by a two compartment open pharmacokinetic model. The elimination half-life (t(1/2beta)), area under concentration-time-curve (AUC), volume of distribution (Vd(area)), mean residence time (MRT) and total body clearance (Cl(B)) were 1.03+/-0.18h, 12.17+/-1.98microg h ml(-1), 0.14+/-0.02Lkg(-1), 1.36+/-0.16h and 0.10+/-0.02Lkg(-1)h(-1), respectively. Following i.m. administration of diclofenac alone and in conjunction with enrofloxacin, the plasma concentration-time data best fitted to a one compartment open model. The t(1/2beta), AUC, Vd(area), MRT and Cl(B) were 1.33+/-0.10h, 7.32+/-1.01microg h mL(-1), 0.13+/-0.01Lkg(-1) and 0.07+/-0.01Lkg(-1)h(-1), respectively. Co-administration of enrofloxacin did not affect Vd(area) and MRT but absorption rate constant (K(a)), beta, t1/2Ka, t1/2beta, AUC, AUMC, Cl(B) and bioavailability (F) were significantly increased. This may be due to direct inhibition of cytochrome P(450) isozymes by enrofloxacin. A dose of 1.4mgkg(-1) of diclofenac administered every 6h may be appropriate for use in sheep.

Modeling the Pharmacokinetics of Perfluorooctanoic Acid (PFOA) During Gestation and Lactation in Mice

EPA Science Inventory

To address the pharmacokinetics of PFOA during gestation and lactation, a biologically supported dynamic model was developed. A two compartment system linked via placental blood flow described gestation, while milk production linked the dam to a pup litter compartment during lact...

A Three Component Model to Estimate Sensible Heat Flux Over Sparse Shrubs in Nevada

USGS Publications Warehouse

Chehbouni, A.; Nichols, W.D.; Njoku, E.G.; Qi, J.; Kerr, Y.H.; Cabot, F.

1997-01-01

It is now recognized that accurate partitioning of available energy into sensible and latent heat flux is crucial to understanding surface-atmosphere interactions. This issue is more complicated in arid and semi-arid regions where the relative contribution to surface fluxes from the soil and vegetation may vary significantly throughout the day and throughout the season. The objective of this paper is to present a three-component model to estimate sensible heat flux over heterogeneous surfaces. The surface was represented with two adjacent compartments. The first compartment is made up of two components, shrubs and shaded soil; the second compartment consists of bare, unshaded soil. Data collected at two different sites in Nevada during the summers of 1991 and 1992 were used to evaluate model performance. The results show that the present model is sufficiently general to yield satisfactory results for both sites.

Application of separable parameter space techniques to multi-tracer PET compartment modeling

PubMed Central

Zhang, Jeff L; Morey, A Michael; Kadrmas, Dan J

2016-01-01

Multi-tracer positron emission tomography (PET) can image two or more tracers in a single scan, characterizing multiple aspects of biological functions to provide new insights into many diseases. The technique uses dynamic imaging, resulting in time-activity curves that contain contributions from each tracer present. The process of separating and recovering separate images and/or imaging measures for each tracer requires the application of kinetic constraints, which are most commonly applied by fitting parallel compartment models for all tracers. Such multi-tracer compartment modeling presents challenging nonlinear fits in multiple dimensions. This work extends separable parameter space kinetic modeling techniques, previously developed for fitting single-tracer compartment models, to fitting multi-tracer compartment models. The multi-tracer compartment model solution equations were reformulated to maximally separate the linear and nonlinear aspects of the fitting problem, and separable least-squares techniques were applied to effectively reduce the dimensionality of the nonlinear fit. The benefits of the approach are then explored through a number of illustrative examples, including characterization of separable parameter space multi-tracer objective functions and demonstration of exhaustive search fits which guarantee the true global minimum to within arbitrary search precision. Iterative gradient-descent algorithms using Levenberg–Marquardt were also tested, demonstrating improved fitting speed and robustness as compared to corresponding fits using conventional model formulations. The proposed technique overcomes many of the challenges in fitting simultaneous multi-tracer PET compartment models. PMID:26788888

Dual-input two-compartment pharmacokinetic model of dynamic contrast-enhanced magnetic resonance imaging in hepatocellular carcinoma.

PubMed

Yang, Jian-Feng; Zhao, Zhen-Hua; Zhang, Yu; Zhao, Li; Yang, Li-Ming; Zhang, Min-Ming; Wang, Bo-Yin; Wang, Ting; Lu, Bao-Chun

2016-04-07

To investigate the feasibility of a dual-input two-compartment tracer kinetic model for evaluating tumorous microvascular properties in advanced hepatocellular carcinoma (HCC). From January 2014 to April 2015, we prospectively measured and analyzed pharmacokinetic parameters [transfer constant (Ktrans), plasma flow (Fp), permeability surface area product (PS), efflux rate constant (kep), extravascular extracellular space volume ratio (ve), blood plasma volume ratio (vp), and hepatic perfusion index (HPI)] using dual-input two-compartment tracer kinetic models [a dual-input extended Tofts model and a dual-input 2-compartment exchange model (2CXM)] in 28 consecutive HCC patients. A well-known consensus that HCC is a hypervascular tumor supplied by the hepatic artery and the portal vein was used as a reference standard. A paired Student's t-test and a nonparametric paired Wilcoxon rank sum test were used to compare the equivalent pharmacokinetic parameters derived from the two models, and Pearson correlation analysis was also applied to observe the correlations among all equivalent parameters. The tumor size and pharmacokinetic parameters were tested by Pearson correlation analysis, while correlations among stage, tumor size and all pharmacokinetic parameters were assessed by Spearman correlation analysis. The Fp value was greater than the PS value (FP = 1.07 mL/mL per minute, PS = 0.19 mL/mL per minute) in the dual-input 2CXM; HPI was 0.66 and 0.63 in the dual-input extended Tofts model and the dual-input 2CXM, respectively. There were no significant differences in the kep, vp, or HPI between the dual-input extended Tofts model and the dual-input 2CXM (P = 0.524, 0.569, and 0.622, respectively). All equivalent pharmacokinetic parameters, except for ve, were correlated in the two dual-input two-compartment pharmacokinetic models; both Fp and PS in the dual-input 2CXM were correlated with Ktrans derived from the dual-input extended Tofts model (P = 0.002, r = 0.566; P = 0.002, r = 0.570); kep, vp, and HPI between the two kinetic models were positively correlated (P = 0.001, r = 0.594; P = 0.0001, r = 0.686; P = 0.04, r = 0.391, respectively). In the dual input extended Tofts model, ve was significantly less than that in the dual input 2CXM (P = 0.004), and no significant correlation was seen between the two tracer kinetic models (P = 0.156, r = 0.276). Neither tumor size nor tumor stage was significantly correlated with any of the pharmacokinetic parameters obtained from the two models (P > 0.05). A dual-input two-compartment pharmacokinetic model (a dual-input extended Tofts model and a dual-input 2CXM) can be used in assessing the microvascular physiopathological properties before the treatment of advanced HCC. The dual-input extended Tofts model may be more stable in measuring the ve; however, the dual-input 2CXM may be more detailed and accurate in measuring microvascular permeability.

Population pharmacokinetics of telapristone (CDB-4124) and its active monodemethylated metabolite CDB-4453, with a mixture model for total clearance.

PubMed

Morris, Denise; Podolski, Joseph; Kirsch, Alan; Wiehle, Ronald; Fleckenstein, Lawrence

2011-12-01

Telapristone is a selective progesterone antagonist that is being developed for the long-term treatment of symptoms associated with endometriosis and uterine fibroids. The population pharmacokinetics of telapristone (CDB-4124) and CDB-4453 was investigated using nonlinear mixed-effects modeling. Data from two clinical studies (n = 32) were included in the analysis. A two-compartment (parent) one compartment (metabolite) mixture model (with two populations for apparent clearance) with first-order absorption and elimination adequately described the pharmacokinetics of telapristone and CDB-4453. Telapristone was rapidly absorbed with an absorption rate constant (Ka) of 1.26 h(-1). Moderate renal impairment resulted in a 74% decrease in Ka. The population estimates for oral clearance (CL/F) for the two populations were 11.6 and 3.34 L/h, respectively, with 25% of the subjects being allocated to the high-clearance group. Apparent volume of distribution for the central compartment (V2/F) was 37.4 L, apparent inter-compartmental clearance (Q/F) was 21.9 L/h, and apparent peripheral volume of distribution for the parent (V4/F) was 120 L. The ratio of the fraction of telapristone converted to CDB-4453 to the distribution volume of CDB-4453 (Fmet(est)) was 0.20/L. Apparent volume of distribution of the metabolite compartment (V3/F) was fixed to 1 L and apparent clearance of the metabolite (CLM/F) was 2.43 L/h. A two-compartment parent-metabolite model adequately described the pharmacokinetics of telapristone and CDB-4453. The clearance of telapristone was separated into two populations and could be the result of metabolism via polymorphic CYP3A5.

Identification of FBXO25-interacting Proteins Using an Integrated Proteomics Approach

PubMed Central

Teixeira, Felipe R.; Yokoo, Sami; Gartner, Carlos G.; Manfiolli, Adriana O.; Baqui, Munira M. A.; Assmann, Eliana M.; Maragno, Ana Leticia G. C.; Yu, Huijun; de Lanerolle, Primal; Kobarg, Jörg; Gygi, Steven P.; Gomes, Marcelo D.

2011-01-01

FBXO25 is one of 68 human F-box proteins that serve as specificity factors for a family of ubiquitin ligases composed of Skp1, Rbx1, Cullin1 and F-box protein (SCF1) that are involved in targeting proteins for destruction across the ubiquitin proteasome system. We recently reported that the FBXO25 protein accumulates in novel subnuclear structures named FBXO25-associated nuclear domains (FANDs). Combining two-step affinity purification followed by mass spectrometry with a classical two-hybrid screen, we identified 132 novel potential FBXO25 interacting partners. One of the identified proteins, β-actin, physically interacts through its N-terminus with FBXO25 and is enriched in the FBXO25 nuclear compartments. Inhibitors of actin polymerization promote a significant disruption of FANDs, indicating that they are compartments influenced by the organizational state of actin in the nucleus. Furthermore, FBXO25 antibodies interfered with RNA polymerase II transcription in vitro. Our results open new perspectives for the understanding of this novel compartment and its nuclear functions. PMID:20473970

The dynamical analysis of modified two-compartment neuron model and FPGA implementation

NASA Astrophysics Data System (ADS)

Lin, Qianjin; Wang, Jiang; Yang, Shuangming; Yi, Guosheng; Deng, Bin; Wei, Xile; Yu, Haitao

2017-10-01

The complexity of neural models is increasing with the investigation of larger biological neural network, more various ionic channels and more detailed morphologies, and the implementation of biological neural network is a task with huge computational complexity and power consumption. This paper presents an efficient digital design using piecewise linearization on field programmable gate array (FPGA), to succinctly implement the reduced two-compartment model which retains essential features of more complicated models. The design proposes an approximate neuron model which is composed of a set of piecewise linear equations, and it can reproduce different dynamical behaviors to depict the mechanisms of a single neuron model. The consistency of hardware implementation is verified in terms of dynamical behaviors and bifurcation analysis, and the simulation results including varied ion channel characteristics coincide with the biological neuron model with a high accuracy. Hardware synthesis on FPGA demonstrates that the proposed model has reliable performance and lower hardware resource compared with the original two-compartment model. These investigations are conducive to scalability of biological neural network in reconfigurable large-scale neuromorphic system.

STS-88 Mission Highlights Resources Tape. Tape B

NASA Technical Reports Server (NTRS)

1999-01-01

The STS-88 flight crew, Commander Robert D. Cabana, Pilot Frederick W. Sturckow, and Mission Specialists Nancy J. Currie, James H. Newman, Jerry L. Ross, and Sergei Krikalev present a video overview of their space flight. Tape two of three includes the installation of an S-Band to help monitor the UNITY Connecting Module, the opening of UNITY's hatch, the opening of the main compartment hatch to ZARYA Control Module, and the repair of the inflight maintenance system.

Lower limb compartment syndrome following laparoscopic colorectal surgery: a review.

PubMed

Rao, M M; Jayne, D

2011-05-01

  In spite of recent advances in technology and technique, laparoscopic colorectal surgery is associated with increased operating times when compared with open surgery. This increases the risk of acute lower limb compartment syndrome. The aim of this review was to gain a better understanding of postoperative lower limb compartment syndrome following laparoscopic colorectal surgery and to suggest strategies to avoid its occurrence. A MEDLINE search was performed using the keywords 'compartment syndrome', 'laparoscopic surgery' and 'Lloyd-Davies position' between 1970 and 2008. All relevant articles were retrieved and reviewed. A total of 54 articles were retrieved. Of the 30 articles in English, five were reviews, six were original articles and 19 were case reports, of which only one was following laparoscopic colorectal surgery. The remaining 24 were non-English articles. Of these, two were reviews and 22 were case reports, of which only one was following laparoscopic colorectal surgery. The incidence of acute compartment syndrome following laparoscopic colorectal surgery is unknown. The following are believed to be risk factors for acute lower limb compartment syndrome: the Lloyd-Davies operating position with exaggerated Trendelenburg tilt, prolonged operative times and improper patient positioning. Simple strategies are suggested to reduce its occurrence. Simple preventative measures have been identified which may help to reduce the incidence of acute lower limb compartment syndrome. However, if suspected, timely surgical intervention with four-compartment fasciotomy remains the standard of care. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

Coupling volume-excluding compartment-based models of diffusion at different scales: Voronoi and pseudo-compartment approaches

PubMed Central

Taylor, P. R.; Baker, R. E.; Simpson, M. J.; Yates, C. A.

2016-01-01

Numerous processes across both the physical and biological sciences are driven by diffusion. Partial differential equations are a popular tool for modelling such phenomena deterministically, but it is often necessary to use stochastic models to accurately capture the behaviour of a system, especially when the number of diffusing particles is low. The stochastic models we consider in this paper are ‘compartment-based’: the domain is discretized into compartments, and particles can jump between these compartments. Volume-excluding effects (crowding) can be incorporated by blocking movement with some probability. Recent work has established the connection between fine- and coarse-grained models incorporating volume exclusion, but only for uniform lattices. In this paper, we consider non-uniform, hybrid lattices that incorporate both fine- and coarse-grained regions, and present two different approaches to describe the interface of the regions. We test both techniques in a range of scenarios to establish their accuracy, benchmarking against fine-grained models, and show that the hybrid models developed in this paper can be significantly faster to simulate than the fine-grained models in certain situations and are at least as fast otherwise. PMID:27383421

Pharmacokinetics of doxycycline in laying hens after intravenous and oral administration.

PubMed

Yang, F; Si, H B; Wang, Y Q; Zhao, Z S; Zhou, B H; Hao, X Q

2016-08-01

The pharmacokinetics of doxycycline in laying hens was investigated after a single intravenous (IV) or an oral (PO) dose at 20 mg/kg body weight. The concentrations of doxycycline in plasma samples were determined by high-performance liquid chromatography with an ultraviolet detector, and pharmacokinetic parameters were calculated using a compartmental model method. The disposition of doxycycline after one single IV injection was best described by a two-compartment open model and the main pharmacokinetic parameters were as follows: volume of distribution (Vd) was 865.15 ± 127.64 ml/kg, distribution rate constant (α) was (2.28 ± 0.38) 1/h, elimination rate constant (β) was 0.08 ± 0.02 1/h and total body clearance (Cl) was104.11 ± 18.32 ml/h/kg, while after PO administration, the concentration versus time curve was best described by a one-compartment open model and absorption rate constant (Ka), peak concentration (Cmax), time to reach Cmax (tmax) and absolute bioavailability (F) were 2.55 ± 1.40 1/h, 5.88 ± 0.70 μg/ml, 1.73 ± 0.75 h and 52.33%, respectively. The profile of doxycycline exhibited favourable pharmacokinetic characteristics in laying hens, such as quick absorption and slow distribution and elimination, though oral bioavailability was relatively low. A multiple-dosing regimen (a dose of 20 mg/kg/d for 3 consecutive days) of doxycycline was recommended to treat infections in laying hens. But a further study should be conducted to determine the withdrawal time of doxycycline in eggs.

A physiology-based parametric imaging method for FDG-PET data

NASA Astrophysics Data System (ADS)

Scussolini, Mara; Garbarino, Sara; Sambuceti, Gianmario; Caviglia, Giacomo; Piana, Michele

2017-12-01

Parametric imaging is a compartmental approach that processes nuclear imaging data to estimate the spatial distribution of the kinetic parameters governing tracer flow. The present paper proposes a novel and efficient computational method for parametric imaging which is potentially applicable to several compartmental models of diverse complexity and which is effective in the determination of the parametric maps of all kinetic coefficients. We consider applications to [18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET) data and analyze the two-compartment catenary model describing the standard FDG metabolization by an homogeneous tissue and the three-compartment non-catenary model representing the renal physiology. We show uniqueness theorems for both models. The proposed imaging method starts from the reconstructed FDG-PET images of tracer concentration and preliminarily applies image processing algorithms for noise reduction and image segmentation. The optimization procedure solves pixel-wise the non-linear inverse problem of determining the kinetic parameters from dynamic concentration data through a regularized Gauss-Newton iterative algorithm. The reliability of the method is validated against synthetic data, for the two-compartment system, and experimental real data of murine models, for the renal three-compartment system.

Compartmental modeling with nitrogen-15 to determine effects of degree of fat saturation on intraruminal N recycling.

PubMed

Oldick, B S; Firkins, J L; Kohn, R A

2000-09-01

Two- and three-compartment models were developed to describe N kinetics within the rumen using three Holstein heifers and one nonlactating Holstein cow fitted with ruminal and duodenal cannulas. A 4 x 4 Latin square design included a control diet containing no supplemental fat and diets containing 4.85% of diet dry matter as partially hydrogenated tallow (iodine value = 13), tallow (iodine value = 51), or animal-vegetable fat (iodine value = 110). Effects of fat on intraruminal N recycling and relationships between intraruminal N recycling and ruminal protozoa concentration or the efficiency of microbial protein synthesis were determined. A pulse dose of 15(NH4)2SO4 was introduced into the ruminal NH3 N pool, and samples were taken over time from the ruminal NH3 N and nonammonia N pools. For the three-compartment model, precipitates of nonammonia N after trichloroacetic acid and ethanol extraction were defined as slowly turning over nonammonia N; rapidly turning over nonammonia N was determined by difference. Curves of 15N enrichment were fit to models with two (NH3 N and nonammonia N) or three (NH3 N, rapidly turning over nonammonia N, and slowly turning over nonammonia N) compartments using the software SAAM II. Because the three-compartment model did not remove a small systematic bias or improve the fit of the data, the two-compartment model was used to provide measurements of intraruminal N recycling. Intraruminal NH3 N recycling (45% for control) decreased linearly as fat unsaturation increased (50.2, 43.0, and 41.7% for partially hydrogenated tallow, tallow, and animal-vegetable fat, respectively). Intraruminal nitrogen recycling was not correlated with efficiency of microbial protein synthesis or ruminal protozoa counts.

Effect of open wedge high tibial osteotomy on the lateral tibiofemoral compartment in sheep. Part II: standard and overcorrection do not cause articular cartilage degeneration.

PubMed

Ziegler, Raphaela; Goebel, Lars; Cucchiarini, Magali; Pape, Dietrich; Madry, Henning

2014-07-01

To evaluate whether medial open wedge high tibial osteotomy (HTO) results in structural changes in the articular cartilage in the lateral tibiofemoral compartment of adult sheep. Three experimental groups received biplanar osteotomies of the right proximal tibiae: (a) closing wedge HTO (4.5° of tibial varus), (b) opening wedge HTO (4.5° tibial valgus; standard correction), and (c) opening wedge HTO (9.5° of valgus; overcorrection), each of which was compared to the contralateral knees that only received an arthrotomy. After 6 months, the macroscopic and microscopic characteristics of the articular cartilage of the lateral tibiofemoral compartment were assessed. The articular cartilage in the central region of the lateral tibial plateau in sheep had a higher safranin O staining intensity and was 4.6-fold thicker than in the periphery (covered by the lateral meniscus). No topographical variation in the type-II collagen immunoreactivity was seen. All lateral tibial plateaus showed osteoarthritic changes in regions not covered by the lateral meniscus. No osteoarthritis was seen in the peripheral submeniscal regions of the lateral tibial plateau and the lateral femoral condyle. Opening wedge HTO resulting in both standard and overcorrection was not associated with significant macroscopic and microscopic structural changes between groups in the articular cartilage of the lateral tibial plateau and femoral condyle after 6 months in vivo. Opening wedge HTO resulting in both standard and overcorrection is a safe procedure for the articular cartilage in an intact lateral tibiofemoral compartment of adult sheep at 6 months postoperatively.

A three-compartment model of osmotic water exchange in the lung microvasculature.

PubMed

Seale, K T; Harris, T R

2000-08-01

A bolus injection of hypertonic NaCl into the pulmonary arterial circulation of an isolated perfused dog lung causes the osmotic movement of water first into, and then out of the capillary. The associated changes in blood constituent concentrations and density are referred to as the osmotic transient (OT). Measurement of the sound conduction velocity of effluent blood during an OT is a highly sensitive way to monitor water movement between the vascular and extravascular spaces. It was our objective to develop a mathematical model that adequately describes this transient change in the sound conduction velocity and evaluate its application under conditions of homogeneous and heterogeneous capillary flow distributions. The model accounts for osmotic water exchange between the capillary and two parallel extravascular compartments, and includes as parameters the osmotic conductances (sigmaK1 ,sigmaK2) of the two compartments. The osmotic conductance parameters incorporate the filtration coefficient for water and reflection coefficient for salt for the two pathways of water exchange. The partition of total extravascular lung water (EVLW) between the two extravascular compartments is a third parameter of the model. The homogeneous model parameter estimates (per gram wet lung weight +/-95% confidence limits) from the best-fit analysis of a typical curve were sigmaK1=2.15 +/-0.07, sigmaK2 = 0.03 + 0.00 [ml h(-1) (mosmol/liter)(-1) g(-1)] and V1 = 23.83+/-0.12 ml, with a coefficient of variation (CV) of 0.08. The heterogeneous parameter estimates for a capillary transit time distribution with mean transit time (MTTc) = 1.72 s, and relative dispersion (RDc) = 0.35 were KI = 2.38+/-0.05, or K2 = 0.03+/-0.00 [ml h(-1) (mosmol/liter)(-1) g(-1)], V1 = 23.91+/-0.08 ml, and CV=0.05. EVLW was 42.1 ml for both models. We conclude that the three-compartment mathematical model adequately describes a typical OT under both homogeneous and heterogeneous blood flow assumptions.

A biophysical observation model for field potentials of networks of leaky integrate-and-fire neurons.

PubMed

Beim Graben, Peter; Rodrigues, Serafim

2012-01-01

We present a biophysical approach for the coupling of neural network activity as resulting from proper dipole currents of cortical pyramidal neurons to the electric field in extracellular fluid. Starting from a reduced three-compartment model of a single pyramidal neuron, we derive an observation model for dendritic dipole currents in extracellular space and thereby for the dendritic field potential (DFP) that contributes to the local field potential (LFP) of a neural population. This work aligns and satisfies the widespread dipole assumption that is motivated by the "open-field" configuration of the DFP around cortical pyramidal cells. Our reduced three-compartment scheme allows to derive networks of leaky integrate-and-fire (LIF) models, which facilitates comparison with existing neural network and observation models. In particular, by means of numerical simulations we compare our approach with an ad hoc model by Mazzoni et al. (2008), and conclude that our biophysically motivated approach yields substantial improvement.

A biophysical observation model for field potentials of networks of leaky integrate-and-fire neurons

PubMed Central

beim Graben, Peter; Rodrigues, Serafim

2013-01-01

We present a biophysical approach for the coupling of neural network activity as resulting from proper dipole currents of cortical pyramidal neurons to the electric field in extracellular fluid. Starting from a reduced three-compartment model of a single pyramidal neuron, we derive an observation model for dendritic dipole currents in extracellular space and thereby for the dendritic field potential (DFP) that contributes to the local field potential (LFP) of a neural population. This work aligns and satisfies the widespread dipole assumption that is motivated by the “open-field” configuration of the DFP around cortical pyramidal cells. Our reduced three-compartment scheme allows to derive networks of leaky integrate-and-fire (LIF) models, which facilitates comparison with existing neural network and observation models. In particular, by means of numerical simulations we compare our approach with an ad hoc model by Mazzoni et al. (2008), and conclude that our biophysically motivated approach yields substantial improvement. PMID:23316157

Pharmacokinetic studies of the recombinant chicken interferon-α in broiler chickens.

PubMed

Zhao, Jun; Yu, Hai-Yang; Zhang, Jun-Ling; Wang, Xing-Man; Li, Jin-Pei; Hu, Tao; Hu, Yong; Wang, Ming-Li; Shen, Yong-Zhou; Xu, Jing-Dong; Han, Guo-Xiang; Chen, Jason

2017-02-14

In this study, 24 male and female broiler chickens at 30-day-old were divided into three groups with 8 animals in each group. The animals were administered with recombinant chicken interferon-α (rChIFN-α) at a dose of 1.0 × 10 6 IU/kg intravenously, intramuscularly or subcutaneously, respectively. Serum samples were collected at different time points post administration, and the titers of rChIFN-α in the blood were determined by cytopathic effect inhibition assay. The results showed that the pharmacokinetic characteristics of rChIFN-α by intramuscular injection and subcutaneous injection were fitted to one compartment open model, and the T max was 3.21 ± 0.79 hr and 3.95 ± 0.85 hr, respectively, and the elimination half-life (T 1/2 ) was 6.20 ± 2.77 hr and 5.03 ± 3.70 hr, respectively. In contrast, the pharmacokinetics of rChIFN-α via intravenous injection was in line with the open model of two-compartment and was eliminated in the first order, and the elimination half-life (T 1/2 ) was 4.61 ± 0.84 hr. In addition, compared with those in the intravenous group and the subcutaneous group, the bioavailability of rChIFN-α in the intramuscular group was 82.80%. In conclusion, rChIFN-α was rapidly absorbed and slowly eliminated after intramuscular administration of single dose of rChIFN-α aqueous formulations. Thus, rChIFN-α can be used as a commonly-used therapeutic agent.

SimpleBox 4.0: Improving the model while keeping it simple….

PubMed

Hollander, Anne; Schoorl, Marian; van de Meent, Dik

2016-04-01

Chemical behavior in the environment is often modeled with multimedia fate models. SimpleBox is one often-used multimedia fate model, firstly developed in 1986. Since then, two updated versions were published. Based on recent scientific developments and experience with SimpleBox 3.0, a new version of SimpleBox was developed and is made public here: SimpleBox 4.0. In this new model, eight major changes were implemented: removal of the local scale and vegetation compartments, addition of lake compartments and deep ocean compartments (including the thermohaline circulation), implementation of intermittent rain instead of drizzle and of depth dependent soil concentrations, adjustment of the partitioning behavior for organic acids and bases as well as of the value for enthalpy of vaporization. In this paper, the effects of the model changes in SimpleBox 4.0 on the predicted steady-state concentrations of chemical substances were explored for different substance groups (neutral organic substances, acids, bases, metals) in a standard emission scenario. In general, the largest differences between the predicted concentrations in the new and the old model are caused by the implementation of layered ocean compartments. Undesirable high model complexity caused by vegetation compartments and a local scale were removed to enlarge the simplicity and user friendliness of the model. Copyright © 2016 Elsevier Ltd. All rights reserved.

Population pharmacokinetic analysis of carboxyhaemoglobin concentrations in adult cigarette smokers.

PubMed

Cronenberger, Carol; Mould, Diane R; Roethig, Hans-Juergen; Sarkar, Mohamadi

2008-01-01

To develop a population-based model to describe and predict the pharmacokinetics of carboxyhaemoglobin (COHb) in adult smokers. Data from smokers of different conventional cigarettes (CC) in three open-label, randomized studies were analysed using NONMEM (version V, Level 1.1). COHb concentrations were determined at baseline for two cigarettes [Federal Trade Commission (FTC) tar 11 mg; CC1, or FTC tar 6 mg; CC2]. On day 1, subjects were randomized to continue smoking their original cigarettes, switch to a different cigarette (FTC tar 1 mg; CC3), or stop smoking. COHb concentrations were measured at baseline and on days 3 and 8 after randomization. Each cigarette was treated as a unit dose assuming a linear relationship between the number of cigarettes smoked and measured COHb percent saturation. Model building used standard methods. Model performance was evaluated using nonparametric bootstrapping and predictive checks. The data were described by a two-compartment model with zero-order input and first-order elimination with endogenous COHb. Model parameters included elimination rate constant (k(10)), central volume of distribution (Vc/F), rate constants between central and peripheral compartments (k(12) and k(21)), baseline COHb concentrations (c0), and relative fraction of carbon monoxide absorbed (F1). The median (range) COHb half-lives were 1.6 h (0.680-2.76) and 30.9 h (7.13-367) (alpha and beta phases, respectively). F1 increased with increasing cigarette tar content and age, whereas k(12) increased with ideal body weight. A robust model was developed to predict COHb concentrations in adult smokers and to determine optimum COHb sampling times in future studies.

Treatment model of dengue hemorrhagic fever infection in human body

NASA Astrophysics Data System (ADS)

Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

2014-03-01

The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

Kinetic modeling of benzodiazepine receptor binding with PET and high specific activity [(11)C]Iomazenil in healthy human subjects.

PubMed

Bremner, J D; Horti, A; Staib, L H; Zea-Ponce, Y; Soufer, R; Charney, D S; Baldwin, R

2000-01-01

Quantitation of the PET benzodiazepine receptor antagonist, [(11)C]Iomazenil, using low specific activity radioligand was recently described. The purpose of this study was to quantitate benzodiazepine receptor binding in human subjects using PET and high specific activity [(11)C]Iomazenil. Six healthy human subjects underwent PET imaging following a bolus injection of high specific activity (>100 Ci/mmol) [(11)C]iomazenil. Arterial samples were collected at multiple time points after injection for measurement of unmetabolized total and nonprotein-bound parent compound in plasma. Time activity curves of radioligand concentration in brain and plasma were analyzed using two and three compartment model. Kinetic rate constants of transfer of radioligand between plasma, nonspecifically bound brain tissue, and specifically bound brain tissue compartments were fitted to the model. Values for fitted kinetic rate constants were used in the calculation of measures of benzodiazepine receptor binding, including binding potential (the ratio of receptor density to affinity), and product of BP and the fraction of free nonprotein-bound parent compound (V(3)'). Use of the three compartment model improved the goodness of fit in comparison to the two compartment model. Values for kinetic rate constants and measures of benzodiazepine receptor binding, including BP and V(3)', were similar to results obtained with the SPECT radioligand [(123)I]iomazenil, and a prior report with low specific activity [(11)C]Iomazenil. Kinetic modeling using the three compartment model with PET and high specific activity [(11)C]Iomazenil provides a reliable measure of benzodiazepine receptor binding. Synapse 35:68-77, 2000. Published 2000 Wiley-Liss, Inc.

Ages and transit times as important diagnostics of model performance for predicting carbon dynamics in terrestrial vegetation models

NASA Astrophysics Data System (ADS)

Ceballos-Núñez, Verónika; Richardson, Andrew D.; Sierra, Carlos A.

2018-03-01

The global carbon cycle is strongly controlled by the source/sink strength of vegetation as well as the capacity of terrestrial ecosystems to retain this carbon. These dynamics, as well as processes such as the mixing of old and newly fixed carbon, have been studied using ecosystem models, but different assumptions regarding the carbon allocation strategies and other model structures may result in highly divergent model predictions. We assessed the influence of three different carbon allocation schemes on the C cycling in vegetation. First, we described each model with a set of ordinary differential equations. Second, we used published measurements of ecosystem C compartments from the Harvard Forest Environmental Measurement Site to find suitable parameters for the different model structures. And third, we calculated C stocks, release fluxes, radiocarbon values (based on the bomb spike), ages, and transit times. We obtained model simulations in accordance with the available data, but the time series of C in foliage and wood need to be complemented with other ecosystem compartments in order to reduce the high parameter collinearity that we observed, and reduce model equifinality. Although the simulated C stocks in ecosystem compartments were similar, the different model structures resulted in very different predictions of age and transit time distributions. In particular, the inclusion of two storage compartments resulted in the prediction of a system mean age that was 12-20 years older than in the models with one or no storage compartments. The age of carbon in the wood compartment of this model was also distributed towards older ages, whereas fast cycling compartments had an age distribution that did not exceed 5 years. As expected, models with C distributed towards older ages also had longer transit times. These results suggest that ages and transit times, which can be indirectly measured using isotope tracers, serve as important diagnostics of model structure and could largely help to reduce uncertainties in model predictions. Furthermore, by considering age and transit times of C in vegetation compartments as distributions, not only their mean values, we obtain additional insights into the temporal dynamics of carbon use, storage, and allocation to plant parts, which not only depends on the rate at which this C is transferred in and out of the compartments but also on the stochastic nature of the process itself.

Physiological water model development

NASA Technical Reports Server (NTRS)

Doty, Susan

1993-01-01

The water of the human body can be categorized as existing in two main compartments: intracellular water and extracellular water. The intracellular water consists of all the water within the cells and constitutes over half of the total body water. Since red blood cells are surrounded by plasma, and all other cells are surrounded by interstitial fluid, the intracellular compartment has been subdivided to represent these two cell types. The extracellular water, which includes all of the fluid outside of the cells, can be further subdivided into compartments which represent the interstitial fluid, circulating blood plasma, lymph, and transcellular water. The interstitial fluid surrounds cells outside of the vascular system whereas plasma is contained within the blood vessels. Avascular tissues such as dense connective tissue and cartilage contain interstitial water which slowly equilibrates with tracers used to determine extracellular fluid volume. For this reason, additional compartments are sometimes used to represent these avascular tissues. The average size of each compartment, in terms of percent body weight, has been determined for adult males and females. These compartments and the forces which cause flow between them are presented. The kidneys, a main compartment, receive about 25 percent of the cardiac output and filters out a fluid similar to plasma. The composition of this filtered fluid changes as it flows through the kidney tubules since compounds are continually being secreted and reabsorbed. Through this mechanism, the kidneys eliminate wastes while conserving body water, electrolytes, and metabolites. Since sodium accounts for over 90 percent of the cations in the extracellular fluid, and the number of cations is balanced by the number of anions, considering the renal handling sodium and water only should sufficiently describe the relationship between the plasma compartment and kidneys. A kidney function model is presented which has been adapted from a previous model of normal renal function in man. To test the validity of the proposed kidney model, results predicted by the model will be compared to actual data involving injected or ingested fluids and subsequent urine flow rates. Comparison of the model simulation to actual data following the ingestion of 1 liter of water is shown. The model simulation is also shown with actual data following the intravenous infusion of hypertonic saline.

Granular fountains: convection cascade in a compartmentalized granular gas.

PubMed

van der Meer, Devaraj; van der Weele, Ko; Reimann, Peter

2006-06-01

This paper extends the two-compartment granular fountain [D. van der Meer, P. Reimann, K. van der Weele, and D. Lohse, Phys. Rev. Lett. 92, 184301 (2004)] to an arbitrary number of compartments: the tendency of a granular gas to form clusters is exploited to generate spontaneous convective currents, with particles going down in the well-filled compartments and going up in the diluted ones. We focus upon the bifurcation diagram of the general -compartment system, which is constructed using a dynamical flux model and which proves to agree quantitatively with results from molecular dynamics simulations.

Stochastic Model of Vesicular Sorting in Cellular Organelles

NASA Astrophysics Data System (ADS)

Vagne, Quentin; Sens, Pierre

2018-02-01

The proper sorting of membrane components by regulated exchange between cellular organelles is crucial to intracellular organization. This process relies on the budding and fusion of transport vesicles, and should be strongly influenced by stochastic fluctuations, considering the relatively small size of many organelles. We identify the perfect sorting of two membrane components initially mixed in a single compartment as a first passage process, and we show that the mean sorting time exhibits two distinct regimes as a function of the ratio of vesicle fusion to budding rates. Low ratio values lead to fast sorting but result in a broad size distribution of sorted compartments dominated by small entities. High ratio values result in two well-defined sorted compartments but sorting is exponentially slow. Our results suggest an optimal balance between vesicle budding and fusion for the rapid and efficient sorting of membrane components and highlight the importance of stochastic effects for the steady-state organization of intracellular compartments.

Analytical solutions to compartmental indoor air quality models with application to environmental tobacco smoke concentrations measured in a house.

PubMed

Ott, Wayne R; Klepeis, Neil E; Switzer, Paul

2003-08-01

This paper derives the analytical solutions to multi-compartment indoor air quality models for predicting indoor air pollutant concentrations in the home and evaluates the solutions using experimental measurements in the rooms of a single-story residence. The model uses Laplace transform methods to solve the mass balance equations for two interconnected compartments, obtaining analytical solutions that can be applied without a computer. Environmental tobacco smoke (ETS) sources such as the cigarette typically emit pollutants for relatively short times (7-11 min) and are represented mathematically by a "rectangular" source emission time function, or approximated by a short-duration source called an "impulse" time function. Other time-varying indoor sources also can be represented by Laplace transforms. The two-compartment model is more complicated than the single-compartment model and has more parameters, including the cigarette or combustion source emission rate as a function of time, room volumes, compartmental air change rates, and interzonal air flow factors expressed as dimensionless ratios. This paper provides analytical solutions for the impulse, step (Heaviside), and rectangular source emission time functions. It evaluates the indoor model in an unoccupied two-bedroom home using cigars and cigarettes as sources with continuous measurements of carbon monoxide (CO), respirable suspended particles (RSP), and particulate polycyclic aromatic hydrocarbons (PPAH). Fine particle mass concentrations (RSP or PM3.5) are measured using real-time monitors. In our experiments, simultaneous measurements of concentrations at three heights in a bedroom confirm an important assumption of the model-spatial uniformity of mixing. The parameter values of the two-compartment model were obtained using a "grid search" optimization method, and the predicted solutions agreed well with the measured concentration time series in the rooms of the home. The door and window positions in each room had considerable effect on the pollutant concentrations observed in the home. Because of the small volumes and low air change rates of most homes, indoor pollutant concentrations from smoking activity in a home can be very high and can persist at measurable levels indoors for many hours.

Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans.

PubMed

van Eijkeren, Jan C H; Olie, J Daniël N; Bradberry, Sally M; Vale, J Allister; de Vries, Irma; Meulenbelt, Jan; Hunault, Claudine C

2016-11-01

No kinetic models presently exist which simulate the effect of chelation therapy on lead blood concentrations in lead poisoning. Our aim was to develop a kinetic model that describes the kinetics of dimercaptosuccinic acid (DMSA; succimer), a commonly used chelating agent, that could be used in developing a lead chelating model. This was a kinetic modelling study. We used a two-compartment model, with a non-systemic gastrointestinal compartment (gut lumen) and the whole body as one systemic compartment. The only data available from the literature were used to calibrate the unknown model parameters. The calibrated model was then validated by comparing its predictions with measured data from three different experimental human studies. The model predicted total DMSA plasma and urine concentrations measured in three healthy volunteers after ingestion of DMSA 10 mg/kg. The model was then validated by using data from three other published studies; it predicted concentrations within a factor of two, representing inter-human variability. A simple kinetic model simulating the kinetics of DMSA in humans has been developed and validated. The interest of this model lies in the future potential to use it to predict blood lead concentrations in lead-poisoned patients treated with DMSA.

The pseudo-compartment method for coupling partial differential equation and compartment-based models of diffusion.

PubMed

Yates, Christian A; Flegg, Mark B

2015-05-06

Spatial reaction-diffusion models have been employed to describe many emergent phenomena in biological systems. The modelling technique most commonly adopted in the literature implements systems of partial differential equations (PDEs), which assumes there are sufficient densities of particles that a continuum approximation is valid. However, owing to recent advances in computational power, the simulation and therefore postulation, of computationally intensive individual-based models has become a popular way to investigate the effects of noise in reaction-diffusion systems in which regions of low copy numbers exist. The specific stochastic models with which we shall be concerned in this manuscript are referred to as 'compartment-based' or 'on-lattice'. These models are characterized by a discretization of the computational domain into a grid/lattice of 'compartments'. Within each compartment, particles are assumed to be well mixed and are permitted to react with other particles within their compartment or to transfer between neighbouring compartments. Stochastic models provide accuracy, but at the cost of significant computational resources. For models that have regions of both low and high concentrations, it is often desirable, for reasons of efficiency, to employ coupled multi-scale modelling paradigms. In this work, we develop two hybrid algorithms in which a PDE in one region of the domain is coupled to a compartment-based model in the other. Rather than attempting to balance average fluxes, our algorithms answer a more fundamental question: 'how are individual particles transported between the vastly different model descriptions?' First, we present an algorithm derived by carefully redefining the continuous PDE concentration as a probability distribution. While this first algorithm shows very strong convergence to analytical solutions of test problems, it can be cumbersome to simulate. Our second algorithm is a simplified and more efficient implementation of the first, it is derived in the continuum limit over the PDE region alone. We test our hybrid methods for functionality and accuracy in a variety of different scenarios by comparing the averaged simulations with analytical solutions of PDEs for mean concentrations. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Excellent Field Emission Properties of Short Conical Carbon Nanotubes Prepared by Microwave Plasma Enhanced CVD Process

PubMed Central

2008-01-01

Randomly oriented short and low density conical carbon nanotubes (CNTs) were prepared on Si substrates by tubular microwave plasma enhanced chemical vapor deposition process at relatively low temperature (350–550 °C) by judiciously controlling the microwave power and growth time in C2H2 + NH3gas composition and Fe catalyst. Both length as well as density of the CNTs increased with increasing microwave power. CNTs consisted of regular conical compartments stacked in such a way that their outer diameter remained constant. Majority of the nanotubes had a sharp conical tip (5–20 nm) while its other side was either open or had a cone/pear-shaped catalyst particle. The CNTs were highly crystalline and had many open edges on the outer surface, particularly near the joints of the two compartments. These films showed excellent field emission characteristics. The best emission was observed for a medium density film with the lowest turn-on and threshold fields of 1.0 and 2.10 V/μm, respectively. It is suggested that not only CNT tip but open edges on the body also act as active emission sites in the randomly oriented geometry of such periodic structures.

Cranial airways and the integration between the inner and outer facial skeleton in humans.

PubMed

Bastir, Markus; Rosas, Antonio

2013-10-01

The cranial airways are in the center of the human face. Therefore variation in the size and shape of these central craniofacial structures could have important consequences for the surrounding midfacial morphology during development and evolution. Yet such interactions are unclear because one school of thought, based on experimental and developmental evidence, suggests a relative independence (modularity) of these two facial compartments, whereas another one assumes tight morphological integration. This study uses geometric morphometrics of modern humans (N = 263) and 40 three-dimensional-landmarks of the skeletal nasopharynx and nasal cavity and outer midfacial skeleton to analyze these questions in terms of modularity. The sizes of all facial compartments were all strongly correlated. Shape integration was high between the cranial airways and the outer midfacial skeleton and between the latter and the anterior airway openings (skeletal regions close to and including piriform aperture). However, no shape integration was detected between outer midface and posterior airway openings (nasopharynx and choanae). Similarly, no integration was detected between posterior and anterior airway openings. This may reflect functional modularization of nasal cavity compartments related to respiratory physiology and differential developmental interactions with the face. Airway size likely relates to the energetics of the organism, whereas airways shape might be more indicative of respiratory physiology and climate. Although this hypothesis should be addressed in future steps, here we suggest that selection on morphofunctional characteristics of the cranial airways could have cascading effects for the variation, development, and evolution of the human face. Copyright © 2013 Wiley Periodicals, Inc.

Simulation of the inhibition of microbial sulfate reduction in a two-compartment upflow bioreactor subjected to molybdate injection.

PubMed

de Jesus, E B; de Andrade Lima, L R P

2016-08-01

Souring of oil fields during secondary oil recovery by water injection occurs mainly due to the action of sulfate-reducing bacteria (SRB) adhered to the rock surface in the vicinity of injection wells. Upflow packed-bed bioreactors have been used in petroleum microbiology because of its similarity to the oil field near the injection wells or production. However, these reactors do not realistically describe the regions near the injection wells, which are characterized by the presence of a saturated zone and a void region close to the well. In this study, the hydrodynamics of the two-compartment packing-free/packed-bed pilot bioreactor that mimics an oil reservoir was studied. The packed-free compartment was modeled using a continuous stirred tank model with mass exchange between active and stagnant zones, whereas the packed-bed compartment was modeled using a piston-dispersion-exchange model. The proposed model adequately represents the hydrodynamic of the packed-free/packed-bed bioreactor while the simulations provide important information about the characteristics of the residence time distribution (RTD) curves for different sets of model parameters. Simulations were performed to represent the control of the sulfate-reducing bacteria activity in the bioreactor with the use of molybdate in different scenarios. The simulations show that increased amounts of molybdate cause an effective inhibition of the souring sulfate-reducing bacteria activity.

Aircraft Material Fire Test Handbook

DTIC Science & Technology

1990-09-01

becomes extinguished for any period that exceeds 3 sec. A circuit for a satisfactory device is sketched in Figure 5-4. 5.3.8.2 Upper Pilot Burner An...34A model 470 Series Power controller manufactured by Eurotherm, a Model 3AEV 1B IOC I Triac manufactured by General Electric Co, or equivalent have...Compartment (galley or lavatory module ) An enclosure or shell structure with access provisions, such as a waste chute opening or doors, designed for

A new, open-source, multi-modality digital breast phantom

NASA Astrophysics Data System (ADS)

Graff, Christian G.

2016-03-01

An anthropomorphic digital breast phantom has been developed with the goal of generating random voxelized breast models that capture the anatomic variability observed in vivo. This is a new phantom and is not based on existing digital breast phantoms or segmentation of patient images. It has been designed at the outset to be modality agnostic (i.e., suitable for use in modeling x-ray based imaging systems, magnetic resonance imaging, and potentially other imaging systems) and open source so that users may freely modify the phantom to suit a particular study. In this work we describe the modeling techniques that have been developed, the capabilities and novel features of this phantom, and study simulated images produced from it. Starting from a base quadric, a series of deformations are performed to create a breast with a particular volume and shape. Initial glandular compartments are generated using a Voronoi technique and a ductal tree structure with terminal duct lobular units is grown from the nipple into each compartment. An additional step involving the creation of fat and glandular lobules using a Perlin noise function is performed to create more realistic glandular/fat tissue interfaces and generate a Cooper's ligament network. A vascular tree is grown from the chest muscle into the breast tissue. Breast compression is performed using a neo-Hookean elasticity model. We show simulated mammographic and T1-weighted MRI images and study properties of these images.

Tracing compartment exchange by NMR diffusometry: Water in lithium-exchanged low-silica X zeolites

NASA Astrophysics Data System (ADS)

Lauerer, A.; Kurzhals, R.; Toufar, H.; Freude, D.; Kärger, J.

2018-04-01

The two-region model for analyzing signal attenuation in pulsed field gradient (PFG) NMR diffusion studies with molecules in compartmented media implies that, on their trajectory, molecules get from one region (one type of compartment) into the other one with a constant (i.e. a time-invariant) probability. This pattern has proved to serve as a good approach for considering guest diffusion in beds of nanoporous host materials, with the two regions ("compartments") identified as the intra- and intercrystalline pore spaces. It is obvious, however, that the requirements of the application of the two-region model are not strictly fulfilled given the correlation between the covered diffusion path lengths in the intracrystalline pore space and the probability of molecular "escape" from the individual crystallites. On considering water diffusion in lithium-exchanged low-silica X zeolite, we are now assuming a different position since this type of material is known to offer "traps" in the trajectories of the water molecules. Now, on attributing the water molecules in the traps and outside of the traps to these two types of regions, we perfectly comply with the requirements of the two-region model. We do, moreover, benefit from the option of high-resolution measurements owing to the combination of magic angle spinning (MAS) with PFG NMR. Data analysis via the two-region model under inclusion of the influence of nuclear magnetic relaxation yields satisfactory agreement between experimental evidence and theoretical estimates. Limitations in accuracy are shown to result from the fact that mass transfer outside of the traps is too complicated for being adequately reflected by simple Fick's laws with but one diffusivity.

A matlab framework for estimation of NLME models using stochastic differential equations: applications for estimation of insulin secretion rates.

PubMed

Mortensen, Stig B; Klim, Søren; Dammann, Bernd; Kristensen, Niels R; Madsen, Henrik; Overgaard, Rune V

2007-10-01

The non-linear mixed-effects model based on stochastic differential equations (SDEs) provides an attractive residual error model, that is able to handle serially correlated residuals typically arising from structural mis-specification of the true underlying model. The use of SDEs also opens up for new tools for model development and easily allows for tracking of unknown inputs and parameters over time. An algorithm for maximum likelihood estimation of the model has earlier been proposed, and the present paper presents the first general implementation of this algorithm. The implementation is done in Matlab and also demonstrates the use of parallel computing for improved estimation times. The use of the implementation is illustrated by two examples of application which focus on the ability of the model to estimate unknown inputs facilitated by the extension to SDEs. The first application is a deconvolution-type estimation of the insulin secretion rate based on a linear two-compartment model for C-peptide measurements. In the second application the model is extended to also give an estimate of the time varying liver extraction based on both C-peptide and insulin measurements.

Reaction time for trimolecular reactions in compartment-based reaction-diffusion models

NASA Astrophysics Data System (ADS)

Li, Fei; Chen, Minghan; Erban, Radek; Cao, Yang

2018-05-01

Trimolecular reaction models are investigated in the compartment-based (lattice-based) framework for stochastic reaction-diffusion modeling. The formulae for the first collision time and the mean reaction time are derived for the case where three molecules are present in the solution under periodic boundary conditions. For the case of reflecting boundary conditions, similar formulae are obtained using a computer-assisted approach. The accuracy of these formulae is further verified through comparison with numerical results. The presented derivation is based on the first passage time analysis of Montroll [J. Math. Phys. 10, 753 (1969)]. Montroll's results for two-dimensional lattice-based random walks are adapted and applied to compartment-based models of trimolecular reactions, which are studied in one-dimensional or pseudo one-dimensional domains.

Lateral Opening-wedge Distal Femoral Osteotomy: Pain Relief, Functional Improvement, and Survivorship at 5 Years.

PubMed

Cameron, James I; McCauley, Julie C; Kermanshahi, Arash Y; Bugbee, William D

2015-06-01

Distal femoral varus osteotomy may be used to treat valgus knee malalignment or to protect a knee compartment in which cartilage restoration surgery (such as osteochondral or meniscus allografting) has been performed. Medial closing-wedge osteotomy has demonstrated good success in treatment of osteoarthritis in published series, but few studies have evaluated distal femoral lateral opening-wedge osteotomy in terms of correction of deformity, pain and function, and survivorship. (1) Does lateral opening-wedge osteotomy lead to accurate correction? (2) What pain and function levels do patients experience after lateral opening-wedge osteotomy? (3) What are the nonunion, complication, and reoperation rates after lateral opening-wedge osteotomy? Between 2000 and 2010, we performed 40 distal femoral osteotomies. Two knees (two patients) underwent a medial closing-wedge osteotomy and were excluded from the present study. Thirty-eight knees (97%) in 36 patients were lateral opening-wedge varus-producing osteotomies; of those, 31 knees (82%) in 30 patients had followup at a minimum of 2 years (mean, 5 years; SD, 2; range, 2-12 years) and comprised the study population. The indications for osteotomy included symptomatic lateral compartment arthritis with clinical valgus deformity or a cartilage or meniscal defect in the lateral compartment with clinical valgus alignment. The study population was stratified into two groups based on reason for osteotomy: patients with isolated symptomatic lateral compartment arthritis (arthritis group; 19 knees [61%]) and patients who underwent joint preservation procedures including osteochondral allograft transplantation or meniscal allograft transplantation (joint preservation group; 12 knees [39%]). Data collection from our institution's osteotomy database included patient demographics, lower extremity coronal alignment, and operative details. Pain and function were measured preoperatively and postoperatively using the International Knee Documentation Committee (IKDC) score. Time to radiographic union, complications, and reoperations were recorded. Twenty-one of 31 knees had postoperative radiographic data available for review. Of these, seven of 15 knees in the arthritis group and three of six knees in the joint preservation group were within the correction goal of ± 3° from neutral mechanical alignment. In the arthritis group, the mean IKDC total score improved from 47 (SD, 15) preoperatively to 67 (SD, 10) postoperatively. In the joint preservation group, the mean IKDC total score improved from 36 (SD, 12) preoperatively to 62 (SD, 18) postoperatively. One nonunion occurred in the arthritis group. No postoperative complications were experienced. Ten knees in the arthritis group and six knees in the joint preservation group had additional surgery after the osteotomy, consisting primarily of hardware removal, arthroscopy for cartilage-related conditions, or conversion to arthroplasty. Survivorship at 5 years, with conversion to arthroplasty as the endpoint, was 74% in the arthritis group and 92% in the joint preservation group. Lateral opening-wedge distal femoral osteotomy was less accurate in correction of valgus deformity than expected, but the procedure was associated with improved knee pain and function scores. Our clinical and radiographic results are comparable to published series evaluating medial closing-wedge distal femoral osteotomy. Achieving our desired correction of ± 3° from neutral alignment was clinically difficult. An improved method of preoperative templating and refinement of the intraoperative technique may improve this. Future studies with more patients and longer followup will provide clarity on this topic. Level IV, therapeutic study.

Staged minimally invasive plate osteosynthesis of proximal tibial fractures with acute compartment syndrome.

PubMed

Kim, Joon-Woo; Oh, Chang-Wug; Oh, Jong-Keon; Kyung, Hee-Soo; Park, Kyeong-Hyeon; Kim, Hee-June; Jung, Jae-Wook; Jung, Young-Soo

2017-06-01

High-energy proximal tibial fractures often accompany compartment syndrome and are usually treated by fasciotomy with external fixation followed by secondary plating. However, the initial soft tissue injury may affect bony union, the fasciotomy incision or external fixator pin sites may lead to postoperative wound infections, and the staged procedure itself may adversely affect lower limb function. We assess the results of staged minimally invasive plate osteosynthesis (MIPO) for proximal tibial fractures with acute compartment syndrome. Twenty-eight patients with proximal tibial fractures accompanied by acute compartment syndrome who underwent staged MIPO and had a minimum of 12 months follow-up were enrolled. According to the AO/OTA classification, 6 were 41-A, 15 were 41-C, 2 were 42-A and 5 were 42-C fractures; this included 6 cases of open fractures. Immediate fasciotomy was performed once compartment syndrome was diagnosed and stabilization of the fracture followed using external fixation. After the soft tissue condition normalized, internal conversion with MIPO was done on an average of 37 days (range, 9-158) after index trauma. At the time of internal conversion, the external fixator pin site grades were 0 in 3 cases, 1 in 12 cases, 2 in 10 cases and 3 in 3 cases, as described by Dahl. Radiographic assessment of bony union and alignment and a functional assessment using the Knee Society Score and American Orthopedic Foot and Ankle Society (AOFAS) score were carried out. Twenty-six cases achieved primary bony union at an average of 18.5 weeks. Two cases of nonunion healed after autogenous bone grafting. The mean Knee Society Score and the AOFAS score were 95 and 95.3 respectively, at last follow-up. Complications included 1 case of osteomyelitis in a patient with a grade IIIC open fracture and 1 case of malunion caused by delayed MIPO due to poor wound conditions. Duration of external fixation and the external fixator pin site grade were not related to the occurrence of infection. Staged MIPO for proximal tibial fractures with acute compartment syndrome may achieve satisfactory bony union and functional results, while decreasing deep infections and soft tissue complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacokinetic Studies of Oxathio-Heterocycle Fused Chalcones.

PubMed

Okoniewska, Krystyna; Konieczny, Marek T; Lemke, Krzysztof; Grabowski, Tomasz

2017-02-01

Chalcone constitutes one of the most used molecular frameworks in medicinal chemistry and its derivatives exhibit a broad spectrum of biological activities. Low absolute bioavailability, poor distribution, intensive metabolism and elimination of chalcones are the main problems in designing new drugs based on their structure. One of the fundamental steps in evaluation of drug candidates is a comparative analysis of pharmacokinetic parameters. The aim of the studies was the pharmacokinetic characterization of the selected oxathio-heterocycle fused chalcones. The pharmacokinetic parameters of 19 compounds were reported. The analyzed chalcones were examined after a single intravenous administration to forty 7-week-old mature male rats of Wistar stock. Pharmacokinetic analysis was performed independently using SHAM (slopes, highest, amounts, and moments) and the two-compartment model. Basic physiochemical parameters were calculated. The bioanalytical methods were validated in terms of repeatability, linearity, accuracy, precision, and selectivity. The pharmacokinetics of the examined group of chalcones are compatible with the two-compartment model. The physicochemical characteristics of this group are quite homogeneous. The kinetics of the examined chalcones are indicative of a distribution to the tissue compartment with the predominance of a rate constant from central to peripheral compartments (k 12 ) over the rate constant from peripheral to central compartments (k 21 ). The elimination from the central compartment (k 10 ) is higher than the transfer from the central compartment to the tissues (k 10  > k 12 ) in almost all examined cases. The presented group of compounds may form a starting point for studies into drugs treating autoimmune diseases of the gastro-intestinal tract.

An experimental approach towards the development of an in vitro cortical-thalamic co-culture model.

PubMed

Kanagasabapathi, Thirukumaran T; Massobrio, Paolo; Tedesco, Mariateresa; Martinoia, Sergio; Wadman, Wytse J; Decré, Michel M J

2011-01-01

In this paper, we propose an experimental approach to develop an in vitro dissociated cortical-thalamic co-culture model using a dual compartment neurofluidic device. The device has two compartments separated by 10 μm wide and 3 μm high microchannels. The microchannels provide a physical isolation of neurons allowing only neurites to grow between the compartments. Long-term viable co-culture was maintained in the compartmented device, neurite growth through the microchannels was verified using immunofluorescence staining, and electrophysiological recordings from the co-culture system was investigated. Preliminary analysis of spontaneous activities from the co-culture shows a distinctively different firing pattern associated with cultures of individual cell types and further analysis is proposed for a deeper understanding of the dynamics involved in the network connectivity in such a co-culture system.

TUBEWALL: a passive solar thermo-siphoning, field-fabricated, water storage wall system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moore, F.; Hemker, P.

1980-01-01

The basic component of TUBEWALL is a water-filled thin-wall cylindrical tube with an insulating foam vertical partition insert that divides the inside of the tube into a thin collector water compartment (solar side) and a larger storage water compartment (room side). The two compartments are connected at the top and bottom by means of circulation holes in the foam partition. When the sun strikes the solar side of the tube, the thin layer of collector water is heated, thermosiphons through the top opening in the partition into the larger storage compartment on the room side, and is replaced with coolmore » water drawn from the bottom of the storage through the bottom hole in the partition. Night back-siphonage is prevented by a thin flap valve over the top circulation hole. The tubes may by used between wall studs having a low-cost fiberglass/tedlar double glazing. The tubes can be covered on the room side with drywall and heat transferred to the living space by indirect radiation, and either natural air convection through top and bottom vent slots or by fan. Alternatively, the tubes can be left exposed for direct radiation.« less

A recycling model of the biokinetics of systemic tellurium.

PubMed

Giussani, Augusto

2014-11-01

To develop a compartmental model of the systemic biokinetics of tellurium required for calculating the internal dose and interpreting bioassay measurements after incorporation of radioactive tellurium. The compartmental model for tellurium was developed with the software SAAM II v. 2.0 (©The Epsilon Group, Charlottesville, Virginia, USA). Model parameters were determined on the basis of published retention and excretion data in humans and animals. The model consists of two blood compartments, one compartment each for liver, kidneys, thyroid, four compartments for bone tissues and a generic compartment for the soft tissues. The model predicts a rapid urinary excretion of systemic tellurium: 45% in the first 24 h and 84% after 50 d. Faecal excretion amounts to 0.4% after 3 d and 9% after 50 d. Whole body retention is 55% after one day, and 2.8% after 100 d. These values as well as the retained fractions in the single organs are reasonably consistent with the available human and animal data (studies with swine and guinea pigs). The proposed model gives a realistic description of the available biokinetic data for tellurium and will be adopted by the International Commission on Radiological Protection for applications in internal dosimetry.

49 CFR 176.182 - Conditions for handling on board ship.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Class 1 (explosive) materials. During electrical storms, cargo operations must be halted and all hatches...) All hatches and cargo ports opening into a compartment in which Class 1 (explosive) materials are stowed must be kept closed except during loading and unloading of the compartment. After loading, hatches...

49 CFR 176.182 - Conditions for handling on board ship.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Class 1 (explosive) materials. During electrical storms, cargo operations must be halted and all hatches...) All hatches and cargo ports opening into a compartment in which Class 1 (explosive) materials are stowed must be kept closed except during loading and unloading of the compartment. After loading, hatches...

49 CFR 176.182 - Conditions for handling on board ship.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Class 1 (explosive) materials. During electrical storms, cargo operations must be halted and all hatches...) All hatches and cargo ports opening into a compartment in which Class 1 (explosive) materials are stowed must be kept closed except during loading and unloading of the compartment. After loading, hatches...

49 CFR 176.182 - Conditions for handling on board ship.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Class 1 (explosive) materials. During electrical storms, cargo operations must be halted and all hatches...) All hatches and cargo ports opening into a compartment in which Class 1 (explosive) materials are stowed must be kept closed except during loading and unloading of the compartment. After loading, hatches...

View forward in starboard engine room, compartment C1. Note starboard ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View forward in starboard engine room, compartment C-1. Note starboard engine thrust bearing in open housing at bottom center of photograph; note main circulation pump, main steam chest at top of photo. (065) - USS Olympia, Penn's Landing, 211 South Columbus Boulevard, Philadelphia, Philadelphia County, PA

75 FR 81 - Special Conditions: Boeing Model 787-8 Airplane; Overhead Flightcrew Rest Compartment Occupiable...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-04

..., explain the reason for any recommended change, and include supporting data. We ask that you send us two... changes to the approved OFCR compartment configuration that affect crewmember emergency egress or any other procedures affecting safety of the occupying crewmembers or related emergency training will...

75 FR 75 - Special Conditions: Boeing Model 787-8 Airplane; Overhead Crew Rest Compartment

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-04

..., explain the reason for any recommended change, and include supporting data. We ask that you send us two...-site operational evaluation. Any changes to the approved OCR compartment configuration that affect crewmember emergency egress or any other procedures affecting safety of the occupying crewmembers or related...

Analysis of blind identification methods for estimation of kinetic parameters in dynamic medical imaging

NASA Astrophysics Data System (ADS)

Riabkov, Dmitri

Compartment modeling of dynamic medical image data implies that the concentration of the tracer over time in a particular region of the organ of interest is well-modeled as a convolution of the tissue response with the tracer concentration in the blood stream. The tissue response is different for different tissues while the blood input is assumed to be the same for different tissues. The kinetic parameters characterizing the tissue responses can be estimated by blind identification methods. These algorithms use the simultaneous measurements of concentration in separate regions of the organ; if the regions have different responses, the measurement of the blood input function may not be required. In this work it is shown that the blind identification problem has a unique solution for two-compartment model tissue response. For two-compartment model tissue responses in dynamic cardiac MRI imaging conditions with gadolinium-DTPA contrast agent, three blind identification algorithms are analyzed here to assess their utility: Eigenvector-based Algorithm for Multichannel Blind Deconvolution (EVAM), Cross Relations (CR), and Iterative Quadratic Maximum Likelihood (IQML). Comparisons of accuracy with conventional (not blind) identification techniques where the blood input is known are made as well. The statistical accuracies of estimation for the three methods are evaluated and compared for multiple parameter sets. The results show that the IQML method gives more accurate estimates than the other two blind identification methods. A proof is presented here that three-compartment model blind identification is not unique in the case of only two regions. It is shown that it is likely unique for the case of more than two regions, but this has not been proved analytically. For the three-compartment model the tissue responses in dynamic FDG PET imaging conditions are analyzed with the blind identification algorithms EVAM and Separable variables Least Squares (SLS). A method of identification that assumes that FDG blood input in the brain can be modeled as a function of time and several parameters (IFM) is analyzed also. Nonuniform sampling SLS (NSLS) is developed due to the rapid change of the FDG concentration in the blood during the early postinjection stage. Comparisons of accuracy of EVAM, SLS, NSLS and IFM identification techniques are made.

GLUT4 Retention in Adipocytes Requires Two Intracellular Insulin-regulated Transport Steps

PubMed Central

Zeigerer, Anja; Lampson, Michael A.; Karylowski, Ola; Sabatini, David D.; Adesnik, Milton; Ren, Mindong; McGraw, Timothy E.

2002-01-01

Insulin regulates glucose uptake into fat and muscle by modulating the distribution of the GLUT4 glucose transporter between the surface and interior of cells. The GLUT4 trafficking pathway overlaps with the general endocytic recycling pathway, but the degree and functional significance of the overlap are not known. In this study of intact adipocytes, we demonstrate, by using a compartment-specific fluorescence-quenching assay, that GLUT4 is equally distributed between two intracellular pools: the transferrin receptor-containing endosomes and a specialized compartment that excludes the transferrin receptor. These pools of GLUT4 are in dynamic communication with one another and with the cell surface. Insulin-induced redistribution of GLUT4 to the surface requires mobilization of both pools. These data establish a role for the general endosomal system in the specialized, insulin-regulated trafficking of GLUT4. Trafficking through the general endosomal system is regulated by rab11. Herein, we show that rab11 is required for the transport of GLUT4 from endosomes to the specialized compartment and for the insulin-induced translocation to the cell surface, emphasizing the importance of the general endosomal pathway in the specialized trafficking of GLUT4. Based on these findings we propose a two-step model for GLUT4 trafficking in which the general endosomal recycling compartment plays a specialized role in the insulin-regulated traffic of GLUT4. This compartment-based model provides the framework for understanding insulin-regulated trafficking at a molecular level. PMID:12134080

GLUT4 retention in adipocytes requires two intracellular insulin-regulated transport steps.

PubMed

Zeigerer, Anja; Lampson, Michael A; Karylowski, Ola; Sabatini, David D; Adesnik, Milton; Ren, Mindong; McGraw, Timothy E

2002-07-01

Insulin regulates glucose uptake into fat and muscle by modulating the distribution of the GLUT4 glucose transporter between the surface and interior of cells. The GLUT4 trafficking pathway overlaps with the general endocytic recycling pathway, but the degree and functional significance of the overlap are not known. In this study of intact adipocytes, we demonstrate, by using a compartment-specific fluorescence-quenching assay, that GLUT4 is equally distributed between two intracellular pools: the transferrin receptor-containing endosomes and a specialized compartment that excludes the transferrin receptor. These pools of GLUT4 are in dynamic communication with one another and with the cell surface. Insulin-induced redistribution of GLUT4 to the surface requires mobilization of both pools. These data establish a role for the general endosomal system in the specialized, insulin-regulated trafficking of GLUT4. Trafficking through the general endosomal system is regulated by rab11. Herein, we show that rab11 is required for the transport of GLUT4 from endosomes to the specialized compartment and for the insulin-induced translocation to the cell surface, emphasizing the importance of the general endosomal pathway in the specialized trafficking of GLUT4. Based on these findings we propose a two-step model for GLUT4 trafficking in which the general endosomal recycling compartment plays a specialized role in the insulin-regulated traffic of GLUT4. This compartment-based model provides the framework for understanding insulin-regulated trafficking at a molecular level.

Polymersome nanoreactors for enzymatic ring-opening polymerization.

PubMed

Nallani, Madhavan; de Hoog, Hans-Peter M; Cornelissen, Jeroen J L M; Palmans, Anja R A; van Hest, Jan C M; Nolte, Roeland J M

2007-12-01

Polystyrene-polyisocyanopeptide (PS-PIAT) polymersomes containing CALB in two different locations, one in the aqueous inner compartment and one in the bilayer, were investigated for enzymatic ring-opening polymerization of lactones in water. It is shown that the monomers 8-octanolactone and dodecalactone yield oligomers with this polymersome system. It is also observed that the polymerization activity is dependent on the position of the enzyme in the polymersome. SEM investigations show that the polymersome structures were destabilized during the polymerization. Further investigations show that the vesicular morphology of the polymersomes was destabilized only in the case of polymer product formation.

49 CFR 176.205 - Under deck stowage requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... electrical power line in the hold or compartment must be protected by a strong metal covering to prevent... (flammable gas) materials. (6) Full and efficient hatch covers must be used. Tarpaulins, if fitted, must be... from the hold or compartment. The fire screen must completely cover the open area. It must consist of...

Dictyostelium LvsB has a regulatory role in endosomal vesicle fusion

PubMed Central

Falkenstein, Kristin; De Lozanne, Arturo

2014-01-01

ABSTRACT Defects in human lysosomal-trafficking regulator (Lyst) are associated with the lysosomal disorder Chediak–Higashi syndrome. The absence of Lyst results in the formation of enlarged lysosome-related compartments, but the mechanism for how these compartments arise is not well established. Two opposing models have been proposed to explain Lyst function. The fission model describes Lyst as a positive regulator of fission from lysosomal compartments, whereas the fusion model identifies Lyst as a negative regulator of fusion between lysosomal vesicles. Here, we used assays that can distinguish between defects in vesicle fusion versus fission. We compared the phenotype of Dictyostelium discoideum cells defective in LvsB, the ortholog of Lyst, with that of two known fission defect mutants (μ3- and WASH-null mutants). We found that the temporal localization characteristics of the post-lysosomal marker vacuolin, as well as vesicular acidity and the fusion dynamics of LvsB-null cells are distinct from those of both μ3- and WASH-null fission defect mutants. These distinctions are predicted by the fusion defect model and implicate LvsB as a negative regulator of vesicle fusion. PMID:25086066

Early full weight-bearing versus 6-week partial weight-bearing after open wedge high tibial osteotomy leads to earlier improvement of the clinical results: a prospective, randomised evaluation.

PubMed

Schröter, S; Ateschrang, A; Löwe, W; Nakayama, H; Stöckle, U; Ihle, C

2017-01-01

Open wedge high tibial osteotomy is a widespread treatment option in patients with varus malalignment and medial compartment osteoarthritis. There is no standardised protocol for post-operative rehabilitation available. The purpose of this study was to compare two post-operative rehabilitation protocols and to evaluate the clinical outcome of early full weight-bearing after open wedge HTO. One hundred and twenty consecutive patients with varus malalignment and medial compartment osteoarthritis received an open wedge HTO using an angular locking plate fixation between December 2008 and December 2011. All patients were assigned randomly into one of two groups with different post-operative rehabilitation protocols (11-day vs. 6-week 20-kg partial weight-bearing). Clinical outcome was evaluated using established instruments (Lequesne, Lysholm, HSS and IKDC scores) preoperatively, 6, 12 and 18 months post-operatively. Deformity analysis was performed preoperatively and during follow-up. All clinical scores showed a significant pre- to post-operative improvement. After 6 months, there was a higher improvement in the group of early full weight-bearing. The difference between preoperative and 6-month follow-up for the group with early full weight-bearing and for the group with 20-kg PWB for 6 weeks was 28 ± 26 and 18 ± 22, respectively, for the Lysholm score and -5.0 ± 5.1 and -3.0 ± 3.6, respectively, for the Lequesne score. Early full weight-bearing (11-day 20-kg partial weight-bearing) after open wedge HTO without bone graft leads to earlier improvement of the clinical results and can be recommended for post-operative rehabilitation after open wedge HTO and fixation with an angular locking plate. Therapeutic study, Level I.

A novel single compartment in vitro model for electrophysiological research using the perfluorocarbon FC-770.

PubMed

Choudhary, M; Clavica, F; van Mastrigt, R; van Asselt, E

2016-06-20

Electrophysiological studies of whole organ systems in vitro often require measurement of nerve activity and/or stimulation of the organ via the associated nerves. Currently two-compartment setups are used for such studies. These setups are complicated and require two fluids in two separate compartments and stretching the nerve across one chamber to the other, which may damage the nerves. We aimed at developing a simple single compartment setup by testing the electrophysiological properties of FC-770 (a perfluorocarbon) for in vitro recording of bladder afferent nerve activity and electrical stimulation of the bladder. Perflurocarbons are especially suitable for such a setup because of their high oxygen carrying capacity and insulating properties. In male Wistar rats, afferent nerve activity was recorded from postganglionic branches of the pelvic nerve in vitro, in situ and in vivo. The bladder was stimulated electrically via the efferent nerves. Organ viability was monitored by recording spontaneous contractions of the bladder. Additionally, histological examinations were done to test the effect of FC-770 on the bladder tissue. Afferent nerve activity was successfully recorded in a total of 11 rats. The bladders were stimulated electrically and high amplitude contractions were evoked. Histological examinations and monitoring of spontaneous contractions showed that FC-770 maintained organ viability and did not cause damage to the tissue. We have shown that FC-770 enables a simple, one compartment in vitro alternative for the generally used two compartment setups for whole organ electrophysiological studies.

Convergence of methods for coupling of microscopic and mesoscopic reaction-diffusion simulations

NASA Astrophysics Data System (ADS)

Flegg, Mark B.; Hellander, Stefan; Erban, Radek

2015-05-01

In this paper, three multiscale methods for coupling of mesoscopic (compartment-based) and microscopic (molecular-based) stochastic reaction-diffusion simulations are investigated. Two of the three methods that will be discussed in detail have been previously reported in the literature; the two-regime method (TRM) and the compartment-placement method (CPM). The third method that is introduced and analysed in this paper is called the ghost cell method (GCM), since it works by constructing a "ghost cell" in which molecules can disappear and jump into the compartment-based simulation. Presented is a comparison of sources of error. The convergent properties of this error are studied as the time step Δt (for updating the molecular-based part of the model) approaches zero. It is found that the error behaviour depends on another fundamental computational parameter h, the compartment size in the mesoscopic part of the model. Two important limiting cases, which appear in applications, are considered: Δt → 0 and h is fixed; Δt → 0 and h → 0 such that √{ Δt } / h is fixed. The error for previously developed approaches (the TRM and CPM) converges to zero only in the limiting case (ii), but not in case (i). It is shown that the error of the GCM converges in the limiting case (i). Thus the GCM is superior to previous coupling techniques if the mesoscopic description is much coarser than the microscopic part of the model.

In vitro differentiation of bone marrow stromal cells into neurons and glial cells and differential protein expression in a two-compartment bone marrow stromal cell/neuron co-culture system.

PubMed

Qi, Xu; Shao, Ming; Peng, Haisheng; Bi, Zhenggang; Su, Zhiqiang; Li, Hulun

2010-07-01

This study was performed to establish a bone marrow stromal cell (BMSC)/neuron two-compartment co-culture model in which differentiation of BMSCs into neurons could occur without direct contact between the two cell types, and to investigate protein expression changes during differentiation of this entirely BMSC-derived population. Cultured BMSCs isolated from Wistar rats were divided into three groups: BMSC culture, BMSC/neuron co-culture and BMSC/neuron two-compartment co-culture. Cells were examined for neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) expression. The electrophysiological behavior of the BMSCs was examined using patch clamping. Proteins that had significantly different expression levels in BMSCs cultured alone and co-cultured with neurons were studied using a protein chip-mass spectroscopy technique. Expression of NSE and GFAP were significantly higher in co-culture cells than in two-compartment co-culture cells, and significantly higher in both co-culture groups than in BMSCs cultured alone. Five proteins showed significant changes in expression during differentiation: TIP39_RAT and CALC_RAT underwent increases, and INSL6_RAT, PNOC_RAT and PCSK1_RAT underwent decreases in expression. We conclude that BMSCs can differentiate into neurons during both contact co-culture with neurons and two-compartment co-culture with neurons. The rate at which BMSCs differentiated into neurons was higher in contact co-culture than in non-contact co-culture.

14 CFR 25.365 - Pressurized compartment loads.

Code of Federal Regulations, 2011 CFR

2011-01-01

... multiplied by a factor of 1.33 for airplanes to be approved for operation to 45,000 feet or by a factor of 1.67 for airplanes to be approved for operation above 45,000 feet, omitting other loads. (e) Any... an engine disintegration; (2) Any opening in any pressurized compartment up to the size Ho in square...

A model describing diffusion in prostate cancer.

PubMed

Gilani, Nima; Malcolm, Paul; Johnson, Glyn

2017-07-01

Quantitative diffusion MRI has frequently been studied as a means of grading prostate cancer. Interpretation of results is complicated by the nature of prostate tissue, which consists of four distinct compartments: vascular, ductal lumen, epithelium, and stroma. Current diffusion measurements are an ill-defined weighted average of these compartments. In this study, prostate diffusion is analyzed in terms of a model that takes explicit account of tissue compartmentalization, exchange effects, and the non-Gaussian behavior of tissue diffusion. The model assumes that exchange between the cellular (ie, stromal plus epithelial) and the vascular and ductal compartments is slow. Ductal and cellular diffusion characteristics are estimated by Monte Carlo simulation and a two-compartment exchange model, respectively. Vascular pseudodiffusion is represented by an additional signal at b = 0. Most model parameters are obtained either from published data or by comparing model predictions with the published results from 41 studies. Model prediction error is estimated using 10-fold cross-validation. Agreement between model predictions and published results is good. The model satisfactorily explains the variability of ADC estimates found in the literature. A reliable model that predicts the diffusion behavior of benign and cancerous prostate tissue of different Gleason scores has been developed. Magn Reson Med 78:316-326, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Analysis of steady-state flow and advective transport in the eastern Snake River Plain aquifer system, Idaho

USGS Publications Warehouse

Ackerman, D.J.

1995-01-01

Quantitative estimates of ground-water flow directions and traveltimes for advective flow were developed for the regional aquifer system of the eastern Snake River Plain, Idaho. The work included: (1) descriptions of compartments in the aquifer that function as intermediate and regional flow systems, (2) descriptions of pathlines for flow originating at or near the water table, and (3) quantitative estimates of traveltimes for advective transport originating at or near the water table. A particle-tracking postprocessing program was used to compute pathlines on the basis of output from an existing three-dimensional steady-state flow model. The flow model uses 1980 conditions to approximate average annual conditions for 1950-80. The advective transport model required additional information about the nature of flow across model boundaries, aquifer thickness, and porosity. Porosity of two types of basalt strata has been reported for more than 1,500 individual cores from test holes, wells, and outcrops near the south side of the Idaho National Engineering Laboratory. The central 80 percent of samples had porosities of 0.08 to 0.25, the central 50 percent of samples, O. 11 to 0.21. Calibration of the model involved choosing a value for porosity that yielded the best solution. Two radiologic contaminants, iodine-129 and tritium, both introduced to the flow system about 40 years ago, are relatively conservative tracers. Iodine- 129 was considered to be more useful because of a lower analytical detection limit, longer half-life, and longer flow path. The calibration value for porosity was 0.21. Most flow in the aquifer is contained within a regional-scale compartment and follows paths that discharge to the Snake River downstream from Milner Dam. Two intermediate-scale compartments exist along the southeast side of the aquifer and near Mud Lake.One intermediate-scale compartment along the southeast side of the aquifer discharges to the Snake River near American Fails Reservoir and covers an area of nearly 1,000 square miles. This compartment, which receives recharge from an area of intensive surface-water irrigation, is apparently fairly stable. The other intermediate-scale compartment near Mud Lake covers an area of 300 square miles. The stability and size of this compartment are uncertain, but are assumed to be in a state of change. Traveltimes for advective flow from the water table to discharge points in the regional compartment ranged from 12 to 350 years for 80 percent of the particles; in the intermediate-scale flow compartment near American Falls Reservoir, from 7 to 60 years for 80 percent of the particles; and in the intermediate-scale compartment near Mud Lake, from 25 to 100 years for 80 percent of the particles. Traveltimes are sensitive to porosity and assumptions regarding the importance of the strength of internal sinks, which represent ground-water pumpage. A decrease in porosity results in shorter traveltimes but not a uniform decrease in traveltime, because the porosity and thickness is different in each model layer. Most flow was horizontal and occurred in the top 500 feet of the aquifer. An important limitation of the model is the assumption of steady-state flow. The most recent trend in the flow system has been a decrease in recharge since 1987 because of an extended drought and changes in land use. A decrease in flow through the system will result in longer traveltimes than those predicted for a greater flow. Because the interpretation of the model was limited to flow on a larger scale, and did not consider individual wells or well fields, the interpretations were not seriously limited by the discretization of well discharge. The interpretations made from this model also were limited by the discretization of the major discharge areas. Near discharge areas, pathlines might not be representative at the resolution of the grid. Most improvement in the estimates of ground-waterflow directions and travelt

Geophysical Imprints of the Geodynamic Evolution of Moesia Following the Black Sea Opening

NASA Astrophysics Data System (ADS)

Besutiu, Lucian

2014-05-01

Genesis of the two types of the Moesia basement (the so called Walachian, and Dobrogean sectors) along with the complex fault system affecting its cover and basement are still debated issues. Besides, there are two other intriguing aspects raised by the seismicity map of Romania: the sub-crustal events in the bending zone of East Carpathians, and the crust seismicity of the eastern Moesian Plate (MoP). Both the intermediate-depth earthquakes within full intra-continental environment and the intense craton seismicity are unusual aspects, and their apparent association difficult to explain. The paper proposes an integrated geodynamic model of MoP able to justify its current tectonics and both the crustal events in front of Carpathians, and the intermediate-depth earthquakes in the Vrancea zone within the frame of a unique geodynamic process. It starts from the idea that tectonic and geodynamic evolution of the E MoP and the bending zone of East Carpathians has been strongly affected by the opening of the W Black Sea basin, and is currently maintained by active rifting in SW Arabian Plate. The model is supported by geophysical and geodetic evidence. Unlike some previous geology-based models assuming that Black Sea opened during a singular geodynamic event (northward subduction of the Neo-Tethys Ocean floor), the pattern of the gravity and geomagnetic field, along with off-shore seismics bring convincing evidence on the distinct timing of the W and E Black Sea basins opening. Fingerprints of the lithosphere expelled by the W Black Sea rifting in the NW inland may be seen in the distribution of compression (P) wave velocity. In-depth development of NW striking major faults (splitting MoP into numerous vertical compartments) is also well revealed by seismic tomography (e.g. Peceneaga-Camena Fault, as the limit between MoP and East European Plate (EEP), still separates two distinct P wave velocity domains at 150 km depth). A second major fault system was created by the downward bending of MoP pushed towards vertical edge of Intra-Alpine Plate. It seems that W Black Sea opening also created the necessary environment for a FFT unstable triple junction within the bending zone of East Carpathians (VTJ), to which intermediate-depth earthquakes should be associated through thermo-baric accommodation phenomena occurring within the lithosphere sunken into the upper mantle. The triangle-shape and in-depth increase of the lateral extension of the VTJ high velocity seismic body are revealed by the high accuracy P wave tomography performed within Vrancea zone. Current geodetic and geophysical monitoring in the area has suggested a close link between crust and intermediate-depth seismic events. The intensification in tectonic forces may firstly led to the intensification of crust seismicity in the Carpathians foreland (by provoking slips between the MoP vertical compartments), followed, after a time-span depending on the force intensity and upper mantle viscosity, by VTJ sinking and consequent intermediate-depth seismic events in the Vrancea zone.

Membrane rupture generates single open membrane sheets during vaccinia virus assembly.

PubMed

Chlanda, Petr; Carbajal, Maria Alejandra; Cyrklaff, Marek; Griffiths, Gareth; Krijnse-Locker, Jacomine

2009-07-23

The biogenesis and dynamics of cellular membranes are governed by fusion and fission processes that ensure the maintenance of closed compartments. These principles also apply to viruses during acquisition of their envelope. Based on conventional electron microscopy (EM), however, it has been proposed that poxviruses assemble from membranes made de novo with "free" ends in the cytoplasm. Here, we analyze the origin and structure of poxvirus membranes in a close-to-native state and in three dimensions by using cryopreservation and electron tomography (ET). By cryo-EM, the precursor membrane of poxviruses appears as an open membrane sheet stabilized by a protein scaffold. ET shows that this membrane is derived from pre-existing cellular membranes that rupture to generate an open compartment, rather than being made de novo. Thus, poxvirus infection represents an excellent system to study how cytoplasmic membranes can form open sheets by a process distinct from well-defined mechanisms of membrane biogenesis.

Parameter estimation using weighted total least squares in the two-compartment exchange model.

PubMed

Garpebring, Anders; Löfstedt, Tommy

2018-01-01

The linear least squares (LLS) estimator provides a fast approach to parameter estimation in the linearized two-compartment exchange model. However, the LLS method may introduce a bias through correlated noise in the system matrix of the model. The purpose of this work is to present a new estimator for the linearized two-compartment exchange model that takes this noise into account. To account for the noise in the system matrix, we developed an estimator based on the weighted total least squares (WTLS) method. Using simulations, the proposed WTLS estimator was compared, in terms of accuracy and precision, to an LLS estimator and a nonlinear least squares (NLLS) estimator. The WTLS method improved the accuracy compared to the LLS method to levels comparable to the NLLS method. This improvement was at the expense of increased computational time; however, the WTLS was still faster than the NLLS method. At high signal-to-noise ratio all methods provided similar precisions while inconclusive results were observed at low signal-to-noise ratio. The proposed method provides improvements in accuracy compared to the LLS method, however, at an increased computational cost. Magn Reson Med 79:561-567, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Towards an improved understanding of processes controlling absorption efficiency and biomagnification of organic chemicals by fish.

PubMed

Xiao, Ruiyang; Arnot, Jon A; MacLeod, Matthew

2015-11-01

Dietary exposure is considered the dominant pathway for fish exposed to persistent, hydrophobic chemicals in the environment. Here we present a dynamic, fugacity-based three-compartment bioaccumulation model that describes the fish body as one compartment and the gastrointestinal tract (GIT) as two compartments. The model simulates uptake from the GIT by passive diffusion and micelle-mediated diffusion, and chemical degradation in the fish and the GIT compartments. We applied the model to a consistent measured dietary uptake and depuration dataset for rainbow trout (n=215) that is comprised of chlorinated benzenes, biphenyls, dioxins, diphenyl ethers, and polycyclic aromatic hydrocarbons (PAHs). Model performance relative to the measured data is statistically similar regardless of whether micelle-mediated diffusion is included; however, there are considerable uncertainties in modeling this process. When degradation in the GIT is assumed to be negligible, modeled chemical elimination rates are similar to measured rates; however, predicted concentrations of the PAHs are consistently higher than measurements by up to a factor of 20. Introducing a kinetic limit on chemical transport from the fish compartment to the GIT and increasing the rate constant for degradation of PAHs in tissues of the liver and/or GIT are required to achieve good agreement between the modelled and measured concentrations for PAHs. Our results indicate that the apparent low absorption efficiency of PAHs relative to the chemicals with similar hydrophobicity is attributable to biotransformation in the liver and/or the GIT. Our results provide process-level insights about controls on the extent of bioaccumulation of chemicals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Estimating fat-free mass in elite-level male rowers: a four-compartment model validation of laboratory and field methods.

PubMed

Kendall, Kristina L; Fukuda, David H; Hyde, Parker N; Smith-Ryan, Abbie E; Moon, Jordon R; Stout, Jeffrey R

2017-04-01

The purpose of this study was to investigate the accuracy of fat-free mass (FFM) estimates from two-compartment (2C) models including air displacement plethysmography (ADP), ultrasound (US), near-infrared interactance (NIR), and the Jackson and Pollock skinfold equation (SKF) against a criterion four-compartment (4C) model in elite male rowers. Twenty-three elite-level male rowers (mean± SD; age 24.6 ± 2.2 years; stature: 191.4 ± 7.2 cm; mass: 87.2 ± 11.2 kg) participated in this investigation. All body composition assessments were performed on the same day in random order, except for hydrostatic weighing (HW), which was measured last. FFM was evaluated using a 4C model, which included total body water from bioimpedance spectroscopy, body volume from HW, and total body bone mineral via dual-energy X-ray absorptiometry. The major findings of the study were that the 2C models evaluated overestimated FFM and should be considered with caution for the assessment of FFM in elite male rowers. Future studies should use multiple-compartment models, with measurement of TBW and bone mineral content, for the estimation of FFM.

Numerical analysis of air-flow and temperature field in a passenger car compartment

NASA Astrophysics Data System (ADS)

Kamar, Haslinda Mohamed; Kamsah, Nazri; Mohammad Nor, Ahmad Miski

2012-06-01

This paper presents a numerical study on the temperature field inside a passenger's compartment of a Proton Wira saloon car using computational fluid dynamics (CFD) method. The main goal is to investigate the effects of different glazing types applied onto the front and rear windscreens of the car on the distribution of air-temperature inside the passenger compartment in the steady-state conditions. The air-flow condition in the passenger's compartment is also investigated. Fluent CFD software was used to develop a three-dimensional symmetrical model of the passenger's compartment. Simplified representations of the driver and one rear passenger were incorporated into the CFD model of the passenger's compartment. Two types of glazing were considered namely clear insulated laminated tint (CIL) with a shading coefficient of 0.78 and green insulated laminate tint (GIL) with a shading coefficient of 0.5. Results of the CFD analysis were compared with those obtained when the windscreens are made up of clear glass having a shading coefficient of 0.86. Results of the CFD analysis show that for a given glazing material, the temperature of the air around the driver is slightly lower than the air around the rear passenger. Also, the use of GIL glazing material on both the front and rear windscreens significantly reduces the air temperature inside the passenger's compartment of the car. This contributes to a better thermal comfort condition to the occupants. Swirling air flow condition occurs in the passenger compartment. The air-flow intensity and velocity are higher along the side wall of the passenger's compartment compared to that along the middle section of the compartment. It was also found that the use of glazing materials on both the front and rear windscreen has no significant effects on the air-flow condition inside the passenger's compartment of the car.

Multi-compartmental modeling of SORLA’s influence on amyloidogenic processing in Alzheimer’s disease

PubMed Central

2012-01-01

Background Proteolytic breakdown of the amyloid precursor protein (APP) by secretases is a complex cellular process that results in formation of neurotoxic Aβ peptides, causative of neurodegeneration in Alzheimer’s disease (AD). Processing involves monomeric and dimeric forms of APP that traffic through distinct cellular compartments where the various secretases reside. Amyloidogenic processing is also influenced by modifiers such as sorting receptor-related protein (SORLA), an inhibitor of APP breakdown and major AD risk factor. Results In this study, we developed a multi-compartment model to simulate the complexity of APP processing in neurons and to accurately describe the effects of SORLA on these processes. Based on dose–response data, our study concludes that SORLA specifically impairs processing of APP dimers, the preferred secretase substrate. In addition, SORLA alters the dynamic behavior of β-secretase, the enzyme responsible for the initial step in the amyloidogenic processing cascade. Conclusions Our multi-compartment model represents a major conceptual advance over single-compartment models previously used to simulate APP processing; and it identified APP dimers and β-secretase as the two distinct targets of the inhibitory action of SORLA in Alzheimer’s disease. PMID:22727043

3D printed multi-compartment capsular devices for two-pulse oral drug delivery.

PubMed

Maroni, A; Melocchi, A; Parietti, F; Foppoli, A; Zema, L; Gazzaniga, A

2017-12-28

In the drug delivery area, versatile therapeutic systems intended to yield customized combinations of drugs, drug doses and release kinetics have drawn increasing attention, especially because of the advantages that personalized pharmaceutical treatments would offer. In this respect, a previously proposed capsular device able to control the release performance based on its design and composition, which could extemporaneously be filled, was improved to include multiple separate compartments so that differing active ingredients or formulations may be conveyed. The compartments, which may differ in thickness and composition, resulted from assembly of two hollow halves through a joint also acting as a partition. The systems were manufactured by fused deposition modeling (FDM) 3D printing, which holds special potential for product personalization, and injection molding (IM) that would enable production on a larger scale. Through combination of compartments having wall thickness of 600 or 1200μm, composed of promptly soluble, swellable/erodible or enteric soluble polymers, devices showing two-pulse release patterns, consistent with the nature of the starting materials, were obtained. Systems fabricated using the two techniques exhibited comparable performance, thus proving the prototyping ability of FDM versus IM. Copyright © 2017 Elsevier B.V. All rights reserved.

3-D architecture modeling using high-resolution seismic data and sparse well control: Example from the Mars {open_quotes}Pink{close_quotes} reservoir, Mississippi Canyon Area, Gulf of Mexico

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapin, M.A.; Tiller, G.M.; Mahaffie, M.J.

1996-12-31

Economic considerations of the deep-water turbidite play, in the Gulf of Mexico and elsewhere, require large reservoir volumes to be drained by relatively few, very expensive wells. Deep-water development projects to date have been planned on the basis of high-quality 3-D seismic data and sparse well control. The link between 3-D seismic, well control, and the 3-D geological and reservoir architecture model are demonstrated here for Pliocene turbidite sands of the {open_quotes}Pink{close_quotes} reservoir, Prospect Mars, Mississippi Canyon Areas 763 and 807, Gulf of Mexico. This information was used to better understand potential reservoir compartments for development well planning.

Design of vaccination and fumigation on Host-Vector Model by input-output linearization method

NASA Astrophysics Data System (ADS)

Nugraha, Edwin Setiawan; Naiborhu, Janson; Nuraini, Nuning

2017-03-01

Here, we analyze the Host-Vector Model and proposed design of vaccination and fumigation to control infectious population by using feedback control especially input-output liniearization method. Host population is divided into three compartments: susceptible, infectious and recovery. Whereas the vector population is divided into two compartment such as susceptible and infectious. In this system, vaccination and fumigation treat as input factors and infectious population as output result. The objective of design is to stabilize of the output asymptotically tend to zero. We also present the examples to illustrate the design model.

The usage of a three-compartment model to investigate the metabolic differences between hepatic reductase null and wild-type mice.

PubMed

Hill, Lydia; Chaplain, Mark A J; Wolf, Roland; Kapelyukh, Yury

2017-03-01

The Cytochrome P450 (CYP) system is involved in 90% of the human body's interactions with xenobiotics and due to this, it has become an area of avid research including the creation of transgenic mice. This paper proposes a three-compartment model which is used to explain the drug metabolism in the Hepatic Reductase Null (HRN) mouse developed by the University of Dundee (Henderson, C. J., Otto, D. M. E., Carrie, D., Magnuson, M. A., McLaren, A. W., Rosewell, I. and Wolf, C. R. (2003) Inactivation of the hepatic cytochrome p450 system by conditional deletion of hepatic cytochrome p450 reductase. J. Biol. Chem. , 13480-13486). The model is compared with a two-compartment model using experimental data from studies using wild-type and HRN mice. This comparison allowed for metabolic differences between the two types of mice to be isolated. The three sets of drug data (Gefitinib, Midazolam and Thalidomide) showed that the transgenic mouse has a decreased rate of metabolism. © The authors 2015. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Review of Van earthquakes form an orthopaedic perspective: a multicentre retrospective study.

PubMed

Guner, Savas; Guner, Sukriye Ilkay; Isik, Yasemin; Gormeli, Gokay; Kalender, Ali Murat; Turktas, Ugur; Gokalp, Mehmet Ata; Gozen, Abdurrahim; Isik, Mustafa; Ozkan, Sezai; Turkozu, Tulin; Karadas, Sevdegul; Ceylan, Mehmet Fethi; Ediz, Levent; Bulut, Mehmet; Gunes, Yusuf; Gormeli, Ayse; Erturk, Cemil; Eseoglu, Metehan; Dursun, Recep

2013-01-01

This is a descriptive analysis, of victims of Turkey's October 23, 2011 and November 21, 2011 Van earthquakes. The goal of this study is investigated the injury profile of the both earthquakes in relation to musculoskeletal trauma. We retrospectively reviewed medical records of 3,965 patients admitted to in seven hospitals. A large share of these injuries were soft tissue injuries, followed by fractures, crush injuries, crush syndromes, nerve injuries, vascular injuries, compartment syndrome and joint dislocations. A total of 73 crush injuries were diagnosed and 31 of them were developed compartment syndrome. The patients with closed undisplaced fractures were treated with casting braces. For closed unstable fractures with good skin and soft-tissue conditions, open reduction and internal fixation was performed. All patients with open fracture had an external fixator applied after adequate debridement. Thirty one of 40 patients with compartment syndrome were treated by fasciotomy. For twelve of them, amputation was necessary. The most common procedure performed was debridement, followed by open reduction and internal fixation and closed reduction-casting, respectively. The results of this study may provide the basis for future development of strategy to optimise attempts at rescue and plan treatment of survivors with musculoskeletal injuries after earthquakes.

A Hybrid Windkessel Model of Blood Flow in Arterial Tree Using Velocity Profile Method

NASA Astrophysics Data System (ADS)

Aboelkassem, Yasser; Virag, Zdravko

2016-11-01

For the study of pulsatile blood flow in the arterial system, we derived a coupled Windkessel-Womersley mathematical model. Initially, a 6-elements Windkessel model is proposed to describe the hemodynamics transport in terms of constant resistance, inductance and capacitance. This model can be seen as a two compartment model, in which the compartments are connected by a rigid pipe, modeled by one inductor and resistor. The first viscoelastic compartment models proximal part of the aorta, the second elastic compartment represents the rest of the arterial tree and aorta can be seen as the connection pipe. Although the proposed 6-elements lumped model was able to accurately reconstruct the aortic pressure, it can't be used to predict the axial velocity distribution in the aorta and the wall shear stress and consequently, proper time varying pressure drop. We then modified this lumped model by replacing the connection pipe circuit elements with a vessel having a radius R and a length L. The pulsatile flow motions in the vessel are resolved instantaneously along with the Windkessel like model enable not only accurate prediction of the aortic pressure but also wall shear stress and frictional pressure drop. The proposed hybrid model has been validated using several in-vivo aortic pressure and flow rate data acquired from different species such as, humans, dogs and pigs. The method accurately predicts the time variation of wall shear stress and frictional pressure drop. Institute for Computational Medicine, Dept. Biomedical Engineering.

Hydrogen gas relief valve

DOEpatents

Whittlesey, Curtis C.

1985-01-01

An improved battery stack design for an electrochemical system having at least one cell from which a gas is generated and an electrolyte in communication with the cell is described. The improved battery stack design features means for defining a substantially closed compartment for containing the battery cells and at least a portion of the electrolyte for the system, and means in association with the compartment means for selectively venting gas from the interior of the compartment means in response to the level of the electrolyte within the compartment means. The venting means includes a relief valve having a float member which is actuated in response to the level of the electrolyte within the compartment means. This float member is adapted to close the relief valve when the level of the electrolyte is above a predetermined level and open the relief valve when the level of electrolyte is below this predetermined level.

Comparing models for perfluorooctanoic acid pharmacokinetics using Bayesian analysis.

PubMed

Wambaugh, John F; Barton, Hugh A; Setzer, R Woodrow

2008-12-01

Selecting the appropriate pharmacokinetic (PK) model given the available data is investigated for perfluorooctanoic acid (PFOA), which has been widely analyzed with an empirical, one-compartment model. This research examined the results of experiments [Kemper R. A., DuPont Haskell Laboratories, USEPA Administrative Record AR-226.1499 (2003)] that administered single oral or iv doses of PFOA to adult male and female rats. PFOA concentration was observed over time; in plasma for some animals and in fecal and urinary excretion for others. There were four rats per dose group, for a total of 36 males and 36 females. Assuming that the PK parameters for each individual within a gender were drawn from the same, biologically varying population, plasma and excretion data were jointly analyzed using a hierarchical framework to separate uncertainty due to measurement error from actual biological variability. Bayesian analysis using Markov Chain Monte Carlo (MCMC) provides tools to perform such an analysis as well as quantitative diagnostics to evaluate and discriminate between models. Starting from a one-compartment PK model with separate clearances to urine and feces, the model was incrementally expanded using Bayesian measures to assess if the expansion was supported by the data. PFOA excretion is sexually dimorphic in rats; male rats have bi-phasic elimination that is roughly 40 times slower than that of the females, which appear to have a single elimination phase. The male and female data were analyzed separately, keeping only the parameters describing the measurement process in common. For male rats, including excretion data initially decreased certainty in the one-compartment parameter estimates compared to an analysis using plasma data only. Allowing a third, unspecified clearance improved agreement and increased certainty when all the data was used, however a significant amount of eliminated PFOA was estimated to be missing from the excretion data. Adding an additional PK compartment reduced the unaccounted-for elimination to amounts comparable to the cage wash. For both sexes, an MCMC estimate of the appropriateness of a model for a given data type, the Deviance Information Criterion, indicated that this two-compartment model was better suited to describing PFOA PK. The median estimate was 142.1 +/- 37.6 ml/kg for the volume of the primary compartment and 1.24 +/- 1.1 ml/kg/h for the clearances of male rats and 166.4 +/- 46.8 ml/kg and 30.3 +/- 13.2 ml/kg/h, respectively for female rats. The estimates for the second compartment differed greatly with gender-volume 311.8 +/- 453.9 ml/kg with clearance 3.2 +/- 6.2 for males and 1400 +/- 2507.5 ml/kg and 4.3 +/- 2.2 ml/kg/h for females. The median estimated clearance was 12 +/- 6% to feces and 85 +/- 7% to urine for male rats and 8 +/- 6% and 77 +/- 9% for female rats. We conclude that the available data may support more models for PFOA PK beyond two-compartments and that the methods employed here will be generally useful for more complicated, including PBPK, models.

Population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1 receptor agonist (recombinant exendin-4, rE-4) in Chinese patients with type 2 diabetes mellitus
.

PubMed

Zang, Yan-Nan; Zhang, Min-Jie; Wang, Yi-Tong; Wang, Chen; Wang, Qian; Zheng, Qing-Shan; Ji, Li-Nong; Guo, Wei; Fang, Yi

2017-08-01

To investigate the population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1 receptor agonist (rE-4) in Chinese patients with type 2 diabetes mellitus (T2DM) for plasma concentration estimation and individualized treatment. Twelve patients with T2DM were enrolled to receive subcutaneous injections of rE-4 at 5 µg twice daily for 84 days. Administration dosage was adjusted from 5 µg to 10 µg twice daily at day 29 in case of glycated albumin (GA) ≥ 17%. The population pharmacokinetic model was developed in the nonlinear mixed-effects modeling software NONMEM. The data were best described by a two-compartment model with first-order absorption and elimination. The outcome parameters were as follows: apparent clearance (CL/F) 6.67 L/h, apparent distribution volume of central compartment (V_c/F) 19.4 L, absorption rate constant (K_a) 1.39 h^-1, apparent distribution volume of peripheral compartment (V_p/F) 22.6 L, intercompartmental clearance (Q/F) 1.28 L/h. The interindividual variabilities for CL/F, V_c/F, K_a, and Q/F were 64.4%, 57.7%, 45.5%, and 153.3%, respectively. The intra-individual variability of proportional error model was 41.7%. No covariate was screened out that showed significant influence on the model parameters. The established two-compartment model with first-order absorption and elimination successfully described the pharmacokinetic characteristics of rE-4 in Chinese patients with T2DM.
.

The role of the bi-compartmental stem cell niche in delaying cancer

NASA Astrophysics Data System (ADS)

Shahriyari, Leili; Komarova, Natalia L.

2015-10-01

In recent years, by using modern imaging techniques, scientists have found evidence of collaboration between different types of stem cells (SCs), and proposed a bi-compartmental organization of the SC niche. Here we create a class of stochastic models to simulate the dynamics of such a heterogeneous SC niche. We consider two SC groups: the border compartment, S1, is in direct contact with transit-amplifying (TA) cells, and the central compartment, S2, is hierarchically upstream from S1. The S1 SCs differentiate or divide asymmetrically when the tissue needs TA cells. Both groups proliferate when the tissue requires SCs (thus maintaining homeostasis). There is an influx of S2 cells into the border compartment, either by migration, or by proliferation. We examine this model in the context of double-hit mutant generation, which is a rate-limiting step in the development of many cancers. We discover that this type of a cooperative pattern in the stem niche with two compartments leads to a significantly smaller rate of double-hit mutant production compared with a homogeneous, one-compartmental SC niche. Furthermore, the minimum probability of double-hit mutant generation corresponds to purely symmetric division of SCs, consistent with the literature. Finally, the optimal architecture (which minimizes the rate of double-hit mutant production) requires a large proliferation rate of S1 cells along with a small, but non-zero, proliferation rate of S2 cells. This result is remarkably similar to the niche structure described recently by several authors, where one of the two SC compartments was found more actively engaged in tissue homeostasis and turnover, while the other was characterized by higher levels of quiescence (but contributed strongly to injury recovery). Both numerical and analytical results are presented.

Towards a rechargeable alcohol biobattery

NASA Astrophysics Data System (ADS)

Addo, Paul K.; Arechederra, Robert L.; Minteer, Shelley D.

This research focused on the transition of biofuel cell technology to rechargeable biobatteries. The bioanode compartment of the biobattery consisted of NAD-dependent alcohol dehydrogenase (ADH) immobilized into a carbon composite paste with butyl-3-methylimidazolium chloride (BMIMCl) ionic liquid serving as the electrolyte. Ferrocene was added to shuttle electrons to/from the electrode surface/current collector. The bioanode catalyzed the oxidation of ethanol to acetaldehyde in discharge mode. This bioanode was coupled to a cathode that consisted of Prussian Blue in a carbon composite paste with Nafion 212 acting as the separator between the two compartments. The biobattery can be fabricated in a charged mode with ethanol and have an open circuit potential of 0.8 V in the original state prior to charging or in the discharged mode with acetaldehyde and have an open circuit potential of 0.05 V. After charging it has an open circuit potential of 1.2 V and a maximum power density of 13.0 μW cm -3 and a maximum current density of 35.0 μA cm -3, respectively. The stability and efficiency of the biobattery were studied by cycling continuously at a discharging current of 0.4 mA and the results obtained showed reasonable stability over 50 cycles. This is a new type of secondary battery inspired by the metabolic processes of the living cell, which is an effective energy conversion system.

N-acetyltransferase genotypes and the pharmacokinetics and tolerability of para-aminosalicylic acid in patients with drug-resistant pulmonary tuberculosis.

PubMed

Sy, Sherwin K B; de Kock, Lizanne; Diacon, Andreas H; Werely, Cedric J; Xia, Huiming; Rosenkranz, Bernd; van der Merwe, Lize; Donald, Peter R

2015-07-01

The aim of this study was to examine the relationships between N-acetyltransferase genotypes, pharmacokinetics, and tolerability of granular slow-release para-aminosalicylic acid (GSR-PAS) in tuberculosis patients. The study was a randomized, two-period, open-label, crossover design wherein each patient received 4 g GSR-PAS twice daily or 8 g once daily alternately. The PAS concentration-time profiles were modeled by a one-compartment disposition model with three transit compartments in series to describe its absorption. Patients' NAT1 and NAT2 genotypes were determined by sequencing and restriction enzyme analysis, respectively. The number of daily vomits was modeled by a Poisson probability mass function. Comparisons of other tolerability measures by regimens, gender, and genotypes were evaluated by a linear mixed-effects model. The covariate effects associated with efavirenz, gender, and NAT1*3, NAT1*14, and NAT2*5 alleles corresponded to 25, 37, -17, -48, and -27% changes, respectively, in oral clearance of PAS. The NAT1*10 allele did not influence drug clearance. The time above the MIC of 1 mg/liter was significantly different between the two regimens but not influenced by the NAT1 or NAT2 genotypes. The occurrence and intensity of intolerance differed little between regimens. Four grams of GSR-PAS twice daily but not 8 g once daily ensured concentrations exceeding the MIC (1 mg/liter) throughout the dosing interval; PAS intolerance was not related to maximum PAS concentrations over the doses studied and was not more frequent after once-daily dosing. We confirm that the slow phenotype conferred by the NAT1*14 and NAT1*3 alleles resulted in higher PAS exposure but found no evidence of increased activity of the NAT1*10 allele. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Initial high-resolution microscopic mapping of active and inactive regulatory sequences proves non-random 3D arrangements in chromatin domain clusters.

PubMed

Cremer, Marion; Schmid, Volker J; Kraus, Felix; Markaki, Yolanda; Hellmann, Ines; Maiser, Andreas; Leonhardt, Heinrich; John, Sam; Stamatoyannopoulos, John; Cremer, Thomas

2017-08-07

The association of active transcription regulatory elements (TREs) with DNAse I hypersensitivity (DHS[+]) and an 'open' local chromatin configuration has long been known. However, the 3D topography of TREs within the nuclear landscape of individual cells in relation to their active or inactive status has remained elusive. Here, we explored the 3D nuclear topography of active and inactive TREs in the context of a recently proposed model for a functionally defined nuclear architecture, where an active and an inactive nuclear compartment (ANC-INC) form two spatially co-aligned and functionally interacting networks. Using 3D structured illumination microscopy, we performed 3D FISH with differently labeled DNA probe sets targeting either sites with DHS[+], apparently active TREs, or DHS[-] sites harboring inactive TREs. Using an in-house image analysis tool, DNA targets were quantitatively mapped on chromatin compaction shaped 3D nuclear landscapes. Our analyses present evidence for a radial 3D organization of chromatin domain clusters (CDCs) with layers of increasing chromatin compaction from the periphery to the CDC core. Segments harboring active TREs are significantly enriched at the decondensed periphery of CDCs with loops penetrating into interchromatin compartment channels, constituting the ANC. In contrast, segments lacking active TREs (DHS[-]) are enriched toward the compacted interior of CDCs (INC). Our results add further evidence in support of the ANC-INC network model. The different 3D topographies of DHS[+] and DHS[-] sites suggest positional changes of TREs between the ANC and INC depending on their functional state, which might provide additional protection against an inappropriate activation. Our finding of a structural organization of CDCs based on radially arranged layers of different chromatin compaction levels indicates a complex higher-order chromatin organization beyond a dichotomic classification of chromatin into an 'open,' active and 'closed,' inactive state.

46 CFR 171.017 - One and two compartment standards of flooding.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false One and two compartment standards of flooding. 171.017... standards of flooding. (a) One compartment standard of flooding. A vessel is designed to a one compartment standard of flooding if the margin line is not submerged when the total buoyancy between each set of two...

46 CFR 171.017 - One and two compartment standards of flooding.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false One and two compartment standards of flooding. 171.017... standards of flooding. (a) One compartment standard of flooding. A vessel is designed to a one compartment standard of flooding if the margin line is not submerged when the total buoyancy between each set of two...

46 CFR 171.017 - One and two compartment standards of flooding.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false One and two compartment standards of flooding. 171.017... standards of flooding. (a) One compartment standard of flooding. A vessel is designed to a one compartment standard of flooding if the margin line is not submerged when the total buoyancy between each set of two...

46 CFR 171.017 - One and two compartment standards of flooding.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false One and two compartment standards of flooding. 171.017... standards of flooding. (a) One compartment standard of flooding. A vessel is designed to a one compartment standard of flooding if the margin line is not submerged when the total buoyancy between each set of two...

46 CFR 171.017 - One and two compartment standards of flooding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false One and two compartment standards of flooding. 171.017... standards of flooding. (a) One compartment standard of flooding. A vessel is designed to a one compartment standard of flooding if the margin line is not submerged when the total buoyancy between each set of two...

Negative pressure wound therapy-assisted dermatotraction for the closure of large open wounds in a patient with non-clostridial gas gangrene.

PubMed

Ishida, Kenichiro; Noborio, Mitsuhiro; Nishimura, Tetsuro; Ieki, Yohei; Shimahara, Yumiko; Sogabe, Taku; Ehara, Naoki; Saoyama, Yuki; Sadamitsu, Daikai

2016-04-01

A 53-year-old woman developed septic shock associated with non-clostridial gas gangrene. She presented to the emergency department with two large open wounds on both thighs and in her sacral region. Non-enhanced computed tomography showed air density in contact with the right iliopsoas, which extended to the posterior compartment of the thigh. We made repeated efforts at surgical debridement of the wound with resection of necrotic tissues. Using negative pressure wound therapy-assisted dermatotraction, the pus pockets and the wound dehiscence decreased in size. Using this method we were successful in achieving delayed closure without skin grafts. Negative pressure wound therapy can be an effective treatment for large and infected open contoured wounds. Negative pressure wound therapy-assisted dermatotraction might be beneficial for poorly healing, large, open wounds in patients in poor condition and with insufficient reserve to tolerate reconstructive surgery.

Compartment models of the diffusion MR signal in brain white matter: a taxonomy and comparison.

PubMed

Panagiotaki, Eleftheria; Schneider, Torben; Siow, Bernard; Hall, Matt G; Lythgoe, Mark F; Alexander, Daniel C

2012-02-01

This paper aims to identify the minimum requirements for an accurate model of the diffusion MR signal in white matter of the brain. We construct a taxonomy of multi-compartment models of white matter from combinations of simple models for the intra- and the extra-axonal spaces. We devise a new diffusion MRI protocol that provides measurements with a wide range of imaging parameters for diffusion sensitization both parallel and perpendicular to white matter fibres. We use the protocol to acquire data from two fixed rat brains, which allows us to fit, study and compare the different models. The study examines a total of 47 analytic models, including several well-used models from the literature, which we place within the taxonomy. The results show that models that incorporate intra-axonal restriction, such as ball and stick or CHARMED, generally explain the data better than those that do not, such as the DT or the biexponential models. However, three-compartment models which account for restriction parallel to the axons and incorporate pore size explain the measurements most accurately. The best fit comes from combining a full diffusion tensor (DT) model of the extra-axonal space with a cylindrical intra-axonal component of single radius and a third spherical compartment of non-zero radius. We also measure the stability of the non-zero radius intra-axonal models and find that single radius intra-axonal models are more stable than gamma distributed radii models with similar fitting performance. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluation of the maternal-fetal transfer of granisetron in an ex vivo placenta perfusion model.

PubMed

Julius, Justin M; Tindall, Andrew; Moise, Kenneth J; Refuerzo, Jerrie S; Berens, Pamela D; Smith, Judith A

2014-11-01

The objective of this study was to estimate maternal-fetal transplacental passage of granisetron in an ex vivo placental perfusion model. Term human placentas (N=8) were collected immediately after delivery. A single cotyledon from each placenta was perfused granisetron concentration to mimic systemic maternal peak plasma concentrations following either IV (50ng/mL) or transdermal administration (5ng/mL). To assess drug transfer and accumulation, samples were collected from maternal and fetal compartments. In the 50ng/mL open model, the mean transport fraction was 0.21±0.08 with clearance index of 0.53±0.66. Fetal peak concentrations achieved was 5.6±6.6ng/mL with mean accumulation of 5.35±6.4ng/mL. No drug was detected in the fetal compartment with the 5ng/mL models. Transplacental passage of granisetron was inconsistent at the 50ng/mL concentration that achieved with IV dosing. However, there consistently was no detectable passage in all the placentas evaluated of the granisetron at 5ng/mL concentration that would be achieved after transdermal patch administration. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of CYP2C19 genotypes on the pharmacokinetic/pharmacodynamic relationship of rabeprazole after a single oral dose in healthy Chinese volunteers.

PubMed

Sheng, Yu-Cheng; Wang, Kun; He, Ying-Chun; Yang, Juan; Zheng, Qing-Shan

2010-11-01

To explore the pharmacokinetic/pharmacodynamic relationship of rabeprazole and the role of CYP2C19 genotypes after a single oral dose in healthy Chinese volunteers by a population approach. Plasma concentration time profile data and intragastric pH values of 19 genotyped healthy male adults after a single oral dose of rabeprazole in an open label randomized fashion were used for this population analysis. Simulation technology was performed to examine the rabeprazole response in subjects with different CYP2C19 genotypes to further investigate the effect of acid inhibition. The pharmacokinetics of rabeprazole was characterized by a two-compartment model with first order absorption and with an absorption lag-time. The results show that clearance of rabeprazole was affected by CYP2C19 genotypes (average clearances of homEM, hetEM, and PM were 13.9, 11.5, and 8.74 L·h(-1) respectively). An effect compartment with a sigmoidal Emax model was considered more rational for analyzing the relationship between rabeprazole concentrations and intragastric pH values. Simulated results suggest that rabeprazole 20 mg once daily for PMs is sufficient, but might be administered more frequently for other genotypes in treating gastro-esophageal reflux disease. The CYP2C19 genotype played a considerable role in the pharmacokinetic characteristics of rabeprazole, and this might need to be taken into account for clinical use.

Population pharmacokinetic analysis of carboxyhaemoglobin concentrations in adult cigarette smokers

PubMed Central

Cronenberger, Carol; Mould, Diane R; Roethig, Hans-Juergen; Sarkar, Mohamadi

2008-01-01

AIMS To develop a population-based model to describe and predict the pharmacokinetics of carboxyhaemoglobin (COHb) in adult smokers. METHODS Data from smokers of different conventional cigarettes (CC) in three open-label, randomized studies were analysed using NONMEM (version V, Level 1.1). COHb concentrations were determined at baseline for two cigarettes [Federal Trade Commission (FTC) tar 11 mg; CC1, or FTC tar 6 mg; CC2]. On day 1, subjects were randomized to continue smoking their original cigarettes, switch to a different cigarette (FTC tar 1 mg; CC3), or stop smoking. COHb concentrations were measured at baseline and on days 3 and 8 after randomization. Each cigarette was treated as a unit dose assuming a linear relationship between the number of cigarettes smoked and measured COHb percent saturation. Model building used standard methods. Model performance was evaluated using nonparametric bootstrapping and predictive checks. RESULTS The data were described by a two-compartment model with zero-order input and first-order elimination with endogenous COHb. Model parameters included elimination rate constant (k10), central volume of distribution (Vc/F), rate constants between central and peripheral compartments (k12 and k21), baseline COHb concentrations (c0), and relative fraction of carbon monoxide absorbed (F1). The median (range) COHb half-lives were 1.6 h (0.680–2.76) and 30.9 h (7.13–367) (α and β phases, respectively). F1 increased with increasing cigarette tar content and age, whereas k12 increased with ideal body weight. CONCLUSION A robust model was developed to predict COHb concentrations in adult smokers and to determine optimum COHb sampling times in future studies. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT The pharmacokinetics of carboxyhaemoglobin have been reported previously, primarily with regard to poisoning and toxicity. Most of these reports have involved noncompartmental analysis of data obtained where the actual dose of carbon monoxide was not known. WHAT THIS STUDY ADDS This study presents a comprehensive population pharmacokinetic model for carboxyhaemoglobin in adult cigarette smokers. Since carboxyhaemoglobin is a marker of cigarette smoke exposure, model-based evaluations can be used for simulation and other evaluations of the kinetics of this agent. PMID:17764477

Distribution of creatinine following intravenous and oral administration to rats.

PubMed

Watanabe, J; Hirate, J; Iwamoto, K; Ozeki, S

1981-05-01

To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

Abdominal intra-compartment syndrome - a non-hydraulic model of abdominal compartment syndrome due to post-hepatectomy hemorrhage in a man with a localized frozen abdomen due to extensive adhesions: a case report.

PubMed

Bressan, Alexsander K; Kirkpatrick, Andrew W; Ball, Chad G

2016-09-15

Postoperative hemorrhage is a significant cause of morbidity and mortality following liver resection. It typically presents early within the postoperative period, and conservative management is possible in the majority of cases. We present a case of late post-hepatectomy hemorrhage associated with overt abdominal compartment syndrome resulting from a localized functional compartment within the abdomen. A 68-year-old white man was readmitted with sudden onset of upper abdominal pain, vomiting, and hemodynamic instability 8 days after an uneventful hepatic resection for metachronous colon cancer metastasis. A frozen abdomen with adhesions due to complicated previous abdominal surgeries was encountered at the first intervention, but the surgery itself and initial recovery were otherwise unremarkable. Prompt response to fluid resuscitation at admission was followed by a computed tomography of his abdomen that revealed active arterial hemorrhage in the liver resection site and hemoperitoneum (estimated volume <2 L). Selective arteriography successfully identified and embolized a small bleeding branch of his right hepatic artery. He remained hemodynamically stable, but eventually developed overt abdominal compartment syndrome. Surgical exploration confirmed a small volume of ascites and blood clots (1.2 L) under significant pressure in his supramesocolic region, restricted by his frozen lower abdomen, which we evacuated. Dramatic improvement in his ventilatory pressure was immediate. His abdomen was left open and a negative pressure device was placed for temporary abdominal closure. The fascia was formally closed after 48 hours. He was discharged home at postoperative day 6. Intra-abdominal pressure and radiologic findings of intra-abdominal hemorrhage should be carefully interpreted in patients with extensive intra-abdominal adhesions. A high index of suspicion and detailed understanding of abdominal compartment mechanics are paramount for the timely diagnosis of abdominal compartment syndrome in these patients. Clinicians should be aware that abnormal anatomy (such as adhesions) coupled with localized pathophysiology (such as hemorrhage) can create a so-named abdominal intra-compartment syndrome requiring extra vigilance to diagnose.

Reinforcing properties of the substance P C-fragment analog DiMe-C7 in Carassius auratus.

PubMed

Mattioli, R; Coelho, J; Martins, A

1996-04-01

The aim of the present study was to investigate whether two substance P (SP) fragments have reinforcing effects in Carassius auratus when the fish were tested in a place-preference experimental model. Fish were placed in a 3-compartment box in which one compartment gives access to two others that are not connected. The time spent in each compartment was recorded for 10 min in order to determine which one was preferred. Twenty-four hours later the fish were given one of the following ip treatments: 1) group VEH (N = 12), injected with teleost saline, 2) group DiMe-C7 (N = 12), injected with 33 micrograms/kg DiMe-C7, and 3) group SP1-7 (N = 12), injected with 167 micrograms/kg SP1-7. Immediately after treatment the fish were kept for 30 min in the compartment that was the least preferred on the day before and this procedure was repeated for 3 days. On the fifth day the fish were retested for 10 min to determine the time spent in each compartment. Two-way analysis of variance with treatments and testing as factors indicated a main effect (P < 0.0025) as well as a testing effect (P < 0.009). The post-hoc Scheffé multiple comparison test indicated that only the DiMe-C7 group presented an increase in the time spent in the paired compartment after treatment. We suggest that the C-terminal fragment of SP has reinforcing effects in Carassius auratus.

A Modified Tri-Exponential Model for Multi-b-value Diffusion-Weighted Imaging: A Method to Detect the Strictly Diffusion-Limited Compartment in Brain

PubMed Central

Zeng, Qiang; Shi, Feina; Zhang, Jianmin; Ling, Chenhan; Dong, Fei; Jiang, Biao

2018-01-01

Purpose: To present a new modified tri-exponential model for diffusion-weighted imaging (DWI) to detect the strictly diffusion-limited compartment, and to compare it with the conventional bi- and tri-exponential models. Methods: Multi-b-value diffusion-weighted imaging (DWI) with 17 b-values up to 8,000 s/mm2 were performed on six volunteers. The corrected Akaike information criterions (AICc) and squared predicted errors (SPE) were calculated to compare these three models. Results: The mean f0 values were ranging 11.9–18.7% in white matter ROIs and 1.2–2.7% in gray matter ROIs. In all white matter ROIs: the AICcs of the modified tri-exponential model were the lowest (p < 0.05 for five ROIs), indicating the new model has the best fit among these models; the SPEs of the bi-exponential model were the highest (p < 0.05), suggesting the bi-exponential model is unable to predict the signal intensity at ultra-high b-value. The mean ADCvery−slow values were extremely low in white matter (1–7 × 10−6 mm2/s), but not in gray matter (251–445 × 10−6 mm2/s), indicating that the conventional tri-exponential model fails to represent a special compartment. Conclusions: The strictly diffusion-limited compartment may be an important component in white matter. The new model fits better than the other two models, and may provide additional information. PMID:29535599

Structural Design Strategies for Improved Small Overlap Crashworthiness Performance.

PubMed

Mueller, Becky C; Brethwaite, Andrew S; Zuby, David S; Nolan, Joseph M

2014-11-01

In 2012, the Insurance Institute for Highway Safety (IIHS) began a 64 km/h small overlap frontal crash test consumer information test program. Thirteen automakers already have redesigned models to improve test performance. One or more distinct strategies are evident in these redesigns: reinforcement of the occupant compartment, use of energy-absorbing fender structures, and the addition of engagement structures to induce vehicle lateral translation. Each strategy influences vehicle kinematics, posing additional challenges for the restraint systems. The objective of this two-part study was to examine how vehicles were modified to improve small overlap test performance and then to examine how these modifications affect dummy response and restraint system performance. Among eight models tested before and after design changes, occupant compartment intrusion reductions ranged from 6 cm to 45 cm, with the highest reductions observed in models with the largest number of modifications. All redesigns included additional occupant compartment reinforcement, one-third added structures to engage the barrier, and two modified a shotgun load path. Designs with engagement structures produced greater glance-off from the barrier and exhibited lower delta Vs but experienced more lateral outboard motion of the dummy. Designs with heavy reinforcement of the occupant compartment had higher vehicle accelerations and delta V. In three cases, these apparent trade-offs were not well addressed by concurrent changes in restraint systems and resulted in increased injury risk compared with the original tests. Among the 36 models tested after design changes, the extent of design changes correlated to structural performance. Half of the vehicles with the lowest intrusion levels incorporated aspects of all three design strategies. Vehicle kinematics and dummy and restraint system characteristics were similar to those observed in the before/after pairs. Different combinations of structural improvement strategies for improving small overlap test performance were found to be effective in reducing occupant compartment intrusion and improving dummy kinematics in the IIHS small overlap test with modest weight increase.

Evaluation of an I-box wind tunnel model for assessment of behavioral responses of blow flies.

PubMed

Moophayak, Kittikhun; Sukontason, Kabkaew L; Kurahashi, Hiromu; Vogtsberger, Roy C; Sukontason, Kom

2013-11-01

The behavioral response of flies to olfactory cues remains the focus of many investigations, and wind tunnels have sometimes been employed for assessment of this variable in the laboratory. In this study, our aim was to design, construct, and operate a new model of I-box wind tunnel with improved efficacy, highlighting the use of a new wind tunnel model to investigate the behavioral response of the medically important blow fly, Chrysomya megacephala (Fabricius). The I-box dual-choice wind tunnel designed for this study consists of seven conjoined compartments that resulted in a linear apparatus with clear glass tunnel of 30 × 30 × 190 cm ended both sides with wooden "fan compartments" which are equipped with adjustable fans as wind source. The clear glass tunnel consisted of two "stimulus compartments" with either presence or absence (control) of bait; two "trap compartments" where flies were attracted and allowed to reside; and one central "release compartment" where flies were introduced. Wind tunnel experiments were carried out in a temperature-controlled room, with a room light as a light source and a room-ventilated fan as odor-remover from tunnel out. Evaluation of testing parameters revealed that the highest attractive index was achieved with the use of 300 g of 1-day tainted pork scrap (pork meat mixed with offal) as bait in wind tunnel settings wind speed of 0.58 m/s, during 1.00-5.00 PM with light intensity of 341.33 lux from vertical light and 135.93 lux from horizontal light for testing a group of 60 flies. In addition, no significant response of well-fed and 24 h staved flies to this bait under these conditions was found. Results of this study supported this new wind tunnel model as a suitable apparatus for investigation of behavioral response of blow flies to bait chemical cues in the laboratory.

Influence of throat configuration and fish density on escapement of channel catfish from hoop nets

USGS Publications Warehouse

Porath, Mark T.; Pape, Larry D.; Richters, Lindsey K.

2011-01-01

In recent years, several state agencies have adopted the use of baited, tandemset hoop nets to assess lentic channel catfish Ictalurus punctatus populations. Some level of escapement from the net is expected because an opening exists in each throat of the net, although factors influencing rates of escapement from hoop nets have not been quantified. We conducted experiments to quantify rates of escapement and to determine the influence of throat configuration and fish density within the net on escapement rates. An initial experiment to determine the rate of escapement from each net compartment utilized individually tagged channel catfish placed within the entrance (between the two throats) and cod (within the second throat) compartments of a single hoop net for overnight sets. From this experiment, the mean rate (±SE) of channel catfish escaping was 4.2% (±1.5) from the cod (cod throat was additionally restricted from the traditionally manufactured product), and 74% (±4.2) from the entrance compartments. In a subsequent experiment, channel catfish were placed only in the cod compartment with different throat configurations (restricted or unrestricted) and at two densities (low [6 fish per net] and high [60 fish per net]) for overnight sets to determine the influence of fish density and throat configuration on escapement rates. Escapement rates between throat configurations were doubled at low fish density (13.3 ± 5.4% restricted versus 26.7 ± 5.6% unrestricted) and tripled at high fish density (14.3 ± 4.9% restricted versus 51.9 ± 5.0% unrestricted). These results suggest that retention efficiency is high from cod compartments with restricted throat entrances. However, managers and researchers need to be aware that modification to the cod throats (restrictions) is needed for hoop nets ordered from manufacturers. Managers need to be consistent in their use and reporting of cod end throat configurations when using this gear.

Multi-Algorithm Particle Simulations with Spatiocyte.

PubMed

Arjunan, Satya N V; Takahashi, Koichi

2017-01-01

As quantitative biologists get more measurements of spatially regulated systems such as cell division and polarization, simulation of reaction and diffusion of proteins using the data is becoming increasingly relevant to uncover the mechanisms underlying the systems. Spatiocyte is a lattice-based stochastic particle simulator for biochemical reaction and diffusion processes. Simulations can be performed at single molecule and compartment spatial scales simultaneously. Molecules can diffuse and react in 1D (filament), 2D (membrane), and 3D (cytosol) compartments. The implications of crowded regions in the cell can be investigated because each diffusing molecule has spatial dimensions. Spatiocyte adopts multi-algorithm and multi-timescale frameworks to simulate models that simultaneously employ deterministic, stochastic, and particle reaction-diffusion algorithms. Comparison of light microscopy images to simulation snapshots is supported by Spatiocyte microscopy visualization and molecule tagging features. Spatiocyte is open-source software and is freely available at http://spatiocyte.org .

Two compartment model of diazepam biotransformation in an organotypical culture of primary human hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acikgoez, Ali; Department of Surgery, Universitaet Leipzig, Liebig Str. 20, D-04103 Leipzig; Karim, Najibulla

2009-01-15

Drug biotransformation is one of the most important parameters of preclinical screening tests for the registration of new drug candidates. Conventional existing tests rely on nonhuman models which deliver an incomplete metabolic profile of drugs due to the lack of proper CYP450 expression as seen in human liver in vivo. In order to overcome this limitation, we used an organotypical model of human primary hepatocytes for the biotransformation of the drug diazepam with special reference to metabolites in both the cell matrix phase and supernatant and its interaction of three inducers (phenobarbital, dexamethasone, aroclor 1254) in different time responses (1,more » 2, 4, 8, 24 h). Phenobarbital showed the strongest inducing effect in generating desmethyldiazepam and induced up to a 150 fold increase in oxazepam-content which correlates with the increased availability of the precursor metabolites (temazepam and desmethyldiazepam). Aroclor 1254 and dexamethasone had the strongest inducing effect on temazepam and the second strongest on oxazepam. The strong and overlapping inductive role of phenobarbital strengthens the participation of CYP2B6 and CYP3A in diazepam N-demethylation and CYP3A in temazepam formation. Aroclor 1254 preferentially generated temazepam due to the interaction with CYP3A and potentially CYP2C19. In parallel we represented these data in the form of a mathematical model with two compartments explaining the dynamics of diazepam metabolism with the effect of these other inducers in human primary hepatocytes. The model consists of ten differential equations, with one for each concentration c{sub i,j} (i = diazepam, temazepam, desmethyldiazepam, oxazepam, other metabolites) and one for each compartment (j = cell matrix phase, supernatant), respectively. The parameters p{sub k} (k = 1, 2, 3, 4, 13) are rate constants describing the biotransformation of diazepam and its metabolites and the other parameters (k = 5, 6, 7, 8, 9, 10, 11, 12, 14, 15) explain the concentration changes in the two compartments.« less

Compartment A19, paint & oils locker from bulkhead #9 aft ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Compartment A-19, paint & oils locker from bulkhead #9 aft to forward; wood storage shelves at center of photograph are for storing containers. Sea valve at lower right is on the starboard side. This would be opened if it was necessary to scuttle the vessel. Heavy frame marked "A-2" supports armored protective deck. (03) - USS Olympia, Penn's Landing, 211 South Columbus Boulevard, Philadelphia, Philadelphia County, PA

Hydrophilic solute transport across the rat blood-brain barrier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucchesi, K.J.

1987-01-01

Brain capillary permeability-surface area products (PS) of hydrophilic solutes ranging in size from 180 to 5,500 Daltons were measured in rats according to the method of Ohno, Pettigrew and Rapoport. The distribution volume of 70 KD dextran at 10 minutes after i.v. injection was also measured to determine the residual volume of blood in brain tissue at the time of sacrifice. Small test solutes were injected in pairs in order to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. This issue was examined in rats whose blood-brain barrier (BBB)more » was presumed to be intact (untreated) and in rats that received intracarotid infusions to open the BBB (isosmotic salt (ISS) and hyperosmolar arabinose). Ohno PS values of {sup 3}H-inulin and {sup 14}C-L-glucose in untreated rats were found to decrease as the labelling time was lengthened. This was evidence that a rapidly equilibrating compartment exists between blood and brain that renders the Ohno two-compartment model inadequate for computing true transfer rate constants. When the data were reanalyzed using a multi-compartment graphical analysis, solutes with different molecular radii were found to enter the brain at approximately equal rates. Furthermore, unidirectional transport is likely to be initiated by solute adsorption to a glycocalyx coat on the luminal surface of brain capillary endothelium. Apparently, more inulin than L-glucose was adsorbed, which may account for its slightly faster transfer across the BBB. After rats were treated with intracarotid infusions of ISS or hyperosmolar arabinose, solute PS values were significantly increased, but the ratio of PS for each of the solute pairs approached that of their free-diffusion coefficients.« less

Dynamics of tax evasion through an epidemic-like model

NASA Astrophysics Data System (ADS)

Brum, Rafael M.; Crokidakis, Nuno

In this work, we study a model of tax evasion. We considered a fixed population divided in three compartments, namely honest tax payers, tax evaders and a third class between the mentioned two, which we call susceptibles to become evaders. The transitions among those compartments are ruled by probabilities, similarly to a model of epidemic spreading. These probabilities model social interactions among the individuals, as well as the government’s fiscalization. We simulate the model on fully-connected graphs, as well as on scale-free and random complex networks. For the fully-connected and random graph cases, we observe that the emergence of tax evaders in the population is associated with an active-absorbing nonequilibrium phase transition, that is absent in scale-free networks.

Population Pharmacokinetics and Exploratory Pharmacodynamics of Lorazepam in Pediatric Status Epilepticus.

PubMed

Gonzalez, Daniel; Chamberlain, James M; Guptill, Jeffrey T; Cohen-Wolkowiez, Michael; Harper, Barrie; Zhao, Jian; Capparelli, Edmund V

2017-08-01

Lorazepam is one of the preferred agents used for intravenous treatment of status epilepticus (SE). We combined data from two pediatric clinical trials to characterize the population pharmacokinetics of intravenous lorazepam in infants and children aged 3 months to 17 years with active SE or a history of SE. We developed a population pharmacokinetic model for lorazepam using the NONMEM software. We then assessed exploratory exposure-response relationships using the overall efficacy and safety study endpoints, and performed dosing simulations. A total of 145 patients contributed 439 pharmacokinetic samples. The median (range) age and dose were 5.4 years (0.3-17.8) and 0.10 mg/kg (0.02-0.18), respectively. A two-compartment pharmacokinetic model with allometric scaling described the data well. In addition to total body weight (WT), younger age was associated with slightly higher weight-normalized clearance (CL). The following relationships characterized the typical values for the central compartment volume (V1), CL, peripheral compartment volume (V2), and intercompartmental CL (Q), using individual subject WT (kg) and age (years): V1 (L) = 0.879*WT; CL (L/h) = 0.115*(Age/4.7) 0.133 *WT 0.75 ; V2 (L) = 0.542*V1; Q (L/h) = 1.45*WT 0.75 . No pharmacokinetic parameters were associated with clinical outcomes. Simulations suggest uniform pediatric dosing (0.1 mg/kg, to a maximum of 4 mg) can be used to achieve concentrations of 50-100 ng/mL in children with SE, which have been previously associated with effective seizure control. The population pharmacokinetics of lorazepam were successfully described using a sparse sampling approach and a two-compartment model in pediatric patients with active SE.

Animal Exposure During Burn Tests

NASA Technical Reports Server (NTRS)

Gaume, J. G.

1978-01-01

An animal exposure test system (AETS) was designed and fabricated for the purpose of collecting physiological and environmental (temperature) data from animal subjects exposed to combustion gases in large scale fire tests. The AETS consisted of an open wire mesh, two-compartment cage, one containing an exercise wheel for small rodents, and the other containing one rat instrumented externally for electrocardiogram (ECG) and respiration. Cage temperature is measured by a thermistor located in the upper portion of the rat compartment. Animal activity is monitored by the ECG and the records indicate an increase in EMG (electromyograph) noise super-imposed by the increased activity of the torso musculature. Examples of the recordings are presented and discussed as to their significance regarding toxicity of fire gases and specific events occurring during the test. The AETS was shown to be a useful tool in screening materials for the relative toxicity of their outgassing products during pyrolysis and combustion.

Kinetic characteristic of phenanthrene sorption in aged soil amended with biochar

NASA Astrophysics Data System (ADS)

Kim, Chanyang; Kim, Yong-Seong; Hyun, Seunghun

2015-04-01

Biochar has been recently highlighted as an amendment that affects yield of the crops by increasing pH, cation exchange capacity and water retention, and reduces the lability of contaminants by increasing sorption capacity in the soil system. Biochar's physico-chemical properties, high CEC, surfaces containing abundant micropores and macropores, and various types of functional groups, play important roles in enhancing sorption capacity of contaminants. Aging through a natural weathering process might change physico-chemical properties of biochar amended in soils, which can affect the sorption behavior of contaminants. Thus, in this study, the sorption characteristics of phenanthrene (PHE) on biochar-amended soils were studied with various types of chars depending on aging time. To do this, 1) soil was amended with sludge waste char (SWC), wood char (WC), and municipal waste char (MWC) during 0, 6, and 12 month. Chars were applied to soil at 1% and 2.5% (w/w) ratio. 2) Several batch kinetic and equilibrium studies were conducted. One-compartment first order and two-compartment first order model apportioning the fraction of fast and slow sorbing were selected for kinetic models. Where, qt is PHE concentration in biochar-amended soils at each time t, qeis PHE concentration in biochar-amended soils at equilibrium. ff is fastly sorbing fraction and (1-ff) is slowly sorbing fraction. k is sorption rate constant from one-compartment first order model, k1 and k2 are sorption rate constant from two-compartment first order model, t is time (hr). The equilibrium sorption data were fitted with Fruendlich and Langmuir equation. 3) Change in physico-chemical properties of biochar-amended soils was investigated with aging time. Batch equilibrium sorption results suggested that sorbed amount of PHE on WC was greater than SWC and MWC. The more char contents added to soil, the greater sorption capacity of PHE. Sorption equilibrium was reached after 4 hours and equilibrium pH ranged from 6.5 to 8.0. Sorption capacity was reduced with aging time. From kinetic results, two-compartment first order model was more suitable than one-compartment first order model. Fast sorption site of biochar-amended soils dominated total sorption process (i.e., Fraction of fast sorption site ranged from 0.55 to 0.96). Reduced sorption capacity with aging time could be attributed to changes in physico-chemical properties of biochar-amended soils (e.g., reduced pores and increased hydrophilic carboxyl and carbonyl functional groups). Verification is FI-IR and SSA. It is assumed that biochar is a suitable material for PHE contaminated soil in order to reduce the lability of PHE. However, aging effects would lessen biochar benefit for reducing the sorption capacity of PHE by forming hydrophilic functional group and reducing pores.

Simulation of radiofrequency ablation in real human anatomy.

PubMed

Zorbas, George; Samaras, Theodoros

2014-12-01

The objective of the current work was to simulate radiofrequency ablation treatment in computational models with realistic human anatomy, in order to investigate the effect of realistic geometry in the treatment outcome. The body sites considered in the study were liver, lung and kidney. One numerical model for each body site was obtained from Duke, member of the IT'IS Virtual Family. A spherical tumour was embedded in each model and a single electrode was inserted into the tumour. The same excitation voltage was used in all cases to underline the differences in the resulting temperature rise, due to different anatomy at each body site investigated. The same numerical calculations were performed for a two-compartment model of the tissue geometry, as well as with the use of an analytical approximation for a single tissue compartment. Radiofrequency ablation (RFA) therapy appears efficient for tumours in liver and lung, but less efficient in kidney. Moreover, the time evolution of temperature for a realistic geometry differs from that for a two-compartment model, but even more for an infinite homogenous tissue model. However, it appears that the most critical parameters of computational models for RFA treatment planning are tissue properties rather than tissue geometry. Computational simulations of realistic anatomy models show that the conventional technique of a single electrode inside the tumour volume requires a careful choice of both the excitation voltage and treatment time in order to achieve effective treatment, since the ablation zone differs considerably for various body sites.

Comparison of software tools for kinetic evaluation of chemical degradation data.

PubMed

Ranke, Johannes; Wöltjen, Janina; Meinecke, Stefan

2018-01-01

For evaluating the fate of xenobiotics in the environment, a variety of degradation or environmental metabolism experiments are routinely conducted. The data generated in such experiments are evaluated by optimizing the parameters of kinetic models in a way that the model simulation fits the data. No comparison of the main software tools currently in use has been published to date. This article shows a comparison of numerical results as well as an overall, somewhat subjective comparison based on a scoring system using a set of criteria. The scoring was separately performed for two types of uses. Uses of type I are routine evaluations involving standard kinetic models and up to three metabolites in a single compartment. Evaluations involving non-standard model components, more than three metabolites or more than a single compartment belong to use type II. For use type I, usability is most important, while the flexibility of the model definition is most important for use type II. Test datasets were assembled that can be used to compare the numerical results for different software tools. These datasets can also be used to ensure that no unintended or erroneous behaviour is introduced in newer versions. In the comparison of numerical results, good agreement between the parameter estimates was observed for datasets with up to three metabolites. For the now unmaintained reference software DegKinManager/ModelMaker, and for OpenModel which is still under development, user options were identified that should be taken care of in order to obtain results that are as reliable as possible. Based on the scoring system mentioned above, the software tools gmkin, KinGUII and CAKE received the best scores for use type I. Out of the 15 software packages compared with respect to use type II, again gmkin and KinGUII were the first two, followed by the script based tool mkin, which is the technical basis for gmkin, and by OpenModel. Based on the evaluation using the system of criteria mentioned above and the comparison of numerical results for the suite of test datasets, the software tools gmkin, KinGUII and CAKE are recommended for use type I, and gmkin and KinGUII for use type II. For users that prefer to work with scripts instead of graphical user interfaces, mkin is recommended. For future software evaluations, it is recommended to include a measure for the total time that a typical user needs for a kinetic evaluation into the scoring scheme. It is the hope of the authors that the publication of test data, source code and overall rankings foster the evolution of useful and reliable software in the field.

Modelling the delay between pharmacokinetics and EEG effects of morphine in rats: binding kinetic versus effect compartment models.

PubMed

de Witte, Wilhelmus E A; Rottschäfer, Vivi; Danhof, Meindert; van der Graaf, Piet H; Peletier, Lambertus A; de Lange, Elizabeth C M

2018-05-18

Drug-target binding kinetics (as determined by association and dissociation rate constants, k on and k off ) can be an important determinant of the kinetics of drug action. However, the effect compartment model is used most frequently instead of a target binding model to describe hysteresis. Here we investigate when the drug-target binding model should be used in lieu of the effect compartment model. The utility of the effect compartment (EC), the target binding kinetics (TB) and the combined effect compartment-target binding kinetics (EC-TB) model were tested on either plasma (EC PL , TB PL and EC-TB PL ) or brain extracellular fluid (ECF) (EC ECF , TB ECF and EC-TB ECF ) morphine concentrations and EEG amplitude in rats. It was also analyzed when a significant shift in the time to maximal target occupancy (Tmax TO ) with increasing dose, the discriminating feature between the TB and EC model, occurs in the TB model. All TB models assumed a linear relationship between target occupancy and drug effect on the EEG amplitude. All three model types performed similarly in describing the morphine pharmacodynamics data, although the EC model provided the best statistical result. The analysis of the shift in Tmax TO (∆Tmax TO ) as a result of increasing dose revealed that ∆Tmax TO is decreasing towards zero if the k off is much smaller than the elimination rate constant or if the target concentration is larger than the initial morphine concentration. The results for the morphine PKPD modelling and the analysis of ∆Tmax TO indicate that the EC and TB models do not necessarily lead to different drug effect versus time curves for different doses if a delay between drug concentrations and drug effect (hysteresis) is described. Drawing mechanistic conclusions from successfully fitting one of these two models should therefore be avoided. Since the TB model can be informed by in vitro measurements of k on and k off , a target binding model should be considered more often for mechanistic modelling purposes.

Whole-body mathematical model for simulating intracranial pressure dynamics

NASA Technical Reports Server (NTRS)

Lakin, William D. (Inventor); Penar, Paul L. (Inventor); Stevens, Scott A. (Inventor); Tranmer, Bruce I. (Inventor)

2007-01-01

A whole-body mathematical model (10) for simulating intracranial pressure dynamics. In one embodiment, model (10) includes 17 interacting compartments, of which nine lie entirely outside of intracranial vault (14). Compartments (F) and (T) are defined to distinguish ventricular from extraventricular CSF. The vasculature of the intracranial system within cranial vault (14) is also subdivided into five compartments (A, C, P, V, and S, respectively) representing the intracranial arteries, capillaries, choroid plexus, veins, and venous sinus. The body's extracranial systemic vasculature is divided into six compartments (I, J, O, Z, D, and X, respectively) representing the arteries, capillaries, and veins of the central body and the lower body. Compartments (G) and (B) include tissue and the associated interstitial fluid in the intracranial and lower regions. Compartment (Y) is a composite involving the tissues, organs, and pulmonary circulation of the central body and compartment (M) represents the external environment.

Coupled effect of chemotaxis and growth on microbial distributions in organic-amended aquifer sediments: Observations from laboratory and field studies

USGS Publications Warehouse

Wang, M.; Ford, R.M.; Harvey, R.W.

2008-01-01

The inter-relationship of growth and chemotactic response exhibited by two common soil-inhabiting bacteria was investigated to determine its impact on bacterial migration. Filter-chambers were used to simulate aquifer sediments characterized by vertical gradients of organic contaminants in both artificial groundwater flow systems in the laboratory and within the screened intervals of observation wells in a sandy aquifer. A labile model contaminant (acetate) was added to the top compartments of the three-part chambers, whereas bacteria with a demonstrated propensity to grow on and chemotactically respond to acetate were introduced to the lower compartments, The motility and chemotactic response of Pseudomonas putida F1 resulted in 40 to 110% greater abundances in the upper compartments and concomitant 22 to 70% depletions in the lower compartments relative to the nonchemotactic controls over 2 days. Bacteria were in greatest abundance within the sand plug that separated the upper and lower compartments where sharp acetate gradients induced a strong chemotactic response. This observation was consistent with predictions from a mathematical model. In agreement with the laboratory results, the down-well filter-chamber incubations with Pseudomonas stutzeri in the aquifer indicated that 91% fewer bacteria resided in the lower compartment than the control experiment without acetate at 15 h. The combination of chemotaxis and growth greatly accelerated the migration of bacteria toward and subsequent abundance at the higher acetate concentration. ?? 2008 American Chemical Society.

Radiofrequency ablation: importance of background tissue electrical conductivity--an agar phantom and computer modeling study.

PubMed

Solazzo, Stephanie A; Liu, Zhengjun; Lobo, S Melvyn; Ahmed, Muneeb; Hines-Peralta, Andrew U; Lenkinski, Robert E; Goldberg, S Nahum

2005-08-01

To determine whether radiofrequency (RF)-induced heating can be correlated with background electrical conductivity in a controlled experimental phantom environment mimicking different background tissue electrical conductivities and to determine the potential electrical and physical basis for such a correlation by using computer modeling. The effect of background tissue electrical conductivity on RF-induced heating was studied in a controlled system of 80 two-compartment agar phantoms (with inner wells of 0.3%, 1.0%, or 36.0% NaCl) with background conductivity that varied from 0.6% to 5.0% NaCl. Mathematical modeling of the relationship between electrical conductivity and temperatures 2 cm from the electrode (T2cm) was performed. Next, computer simulation of RF heating by using two-dimensional finite-element analysis (ETherm) was performed with parameters selected to approximate the agar phantoms. Resultant heating, in terms of both the T2cm and the distance of defined thermal isotherms from the electrode surface, was calculated and compared with the phantom data. Additionally, electrical and thermal profiles were determined by using the computer modeling data and correlated by using linear regression analysis. For each inner compartment NaCl concentration, a negative exponential relationship was established between increased background NaCl concentration and the T2cm (R2= 0.64-0.78). Similar negative exponential relationships (r2 > 0.97%) were observed for the computer modeling. Correlation values (R2) between the computer and experimental data were 0.9, 0.9, and 0.55 for the 0.3%, 1.0%, and 36.0% inner NaCl concentrations, respectively. Plotting of the electrical field generated around the RF electrode identified the potential for a dramatic local change in electrical field distribution (ie, a second electrical peak ["E-peak"]) occurring at the interface between the two compartments of varied electrical background conductivity. Linear correlations between the E-peak and heating at T2cm (R2= 0.98-1.00) and the 50 degrees C isotherm (R2= 0.99-1.00) were established. These results demonstrate the strong relationship between background tissue conductivity and RF heating and further explain electrical phenomena that occur in a two-compartment system.

Opening-wedge high tibial osteotomy with a locked low-profile plate: surgical technique.

PubMed

Kolb, Werner; Guhlmann, Hanno; Windisch, Christoph; Koller, Heiko; Grützner, Paul; Kolb, Klaus

2010-09-01

High tibial osteotomy has been recognized as a beneficial treatment for osteoarthritis of the medial compartment of the knee. The purpose of this prospective study was to assess the short-term results of opening-wedge high tibial osteotomies with locked plate fixation. From September 2002 to November 2005, fifty-one consecutive medial opening-wedge high tibial osteotomies were performed. The mean age of the patients at the time of the index operation was forty-nine years. The preoperative and postoperative factors analyzed included the grade of arthritis of the tibiofemoral compartment (the Ahlbäck radiographic grade), the anatomic tibiofemoral angle, patellar height, the Hospital for Special Surgery rating system score, and the Lysholm and Gillquist knee score. Postoperatively, one superficial wound infection occurred. Fifty of the fifty-one osteotomies healed after an average period of 12.9 weeks (range, eight to sixteen weeks) without bone grafts. A nonunion developed in a sixty-two-year-old patient who was a cigarette smoker. The average postoperative tibiofemoral angle was 9° of valgus. Forty-nine patients were followed for a mean of fifty-two months. The average score on the Hospital for Special Surgery rating system was 86 points at the time of the most recent follow-up. The rating was excellent in twenty-eight patients (57%), good in twelve (24%), fair in four (8%), and poor in five (10%). The average score on the Lysholm and Gillquist knee-scoring scale was 83 points. According to these scores, the outcome was excellent in nine patients (18%), good in thirty-one (63%), fair in three (6%), and poor in six (12%). Four knees failed after an average of thirty-six months. Our results suggest that an opening-wedge high tibial osteotomy with locked plate fixation allows a correct valgus angle to be achieved with good short-term results.

MELiSSA third compartment: Nitrosomonas europaea and Nitrobacter winogradskyi axenic cultures in bioreactors

NASA Astrophysics Data System (ADS)

Cruvellier, Nelly; Lasseur, Christophe; Poughon, Laurent; Creuly, Catherine; Dussap, Gilles

Nitrogen is a key element for the life and its balance on Earth is regulated by the nitrogen cycle. This loop includes several steps among which nitrification that permits the transformation of the ammonium into nitrate. The MELiSSA loop is an artificial ecosystem designed for life support systems (LSS). It is based on the carbon and nitrogen cycles and the recycling of the non-edible part of the higher plants and the waste produced by the crew. In this order, all the wastes are collected in the first compartment to degrade them into organic acids and CO2. These compounds are joining the second compartment which is a photoheterotrophic compartment where at the outlet an organic-free medium containing ammonium is produced. This solution will be the substrate of the third compartment where nitrification is done. This compartment has to oxidize the ammonium into nitrate, and this biological reaction needs two steps. In the MELiSSA loop, the nitrification is carried out by two bacteria: Nitrosomonas europaea ATCC® 19718™ which is oxidizing ammonia into nitrite and Nitrobacter winogradskyi ATCC® 25391™ which is producing nitrate from nitrite in the third compartment. These two bacteria are growing in axenic conditions on a fixed bed bioreactor filled with Biostyr® beads. The nitrogen compounds are controlled by Ionic Chromatography and colorimetric titration for each sample. The work presented here deals with the culture of both bacteria in pure cultures and mixed cultures in stirred and aerated bioreactors of different volumes. The first aim of our work is the characterization of the bacteria growth in bioreactors and in the nitrifying fixed-bed column. The experimental results confirm that the growth is slow; the maximal growth rate in suspended cultures is 0.054h-1 for Nitrosomonas europaea and 0.022h-1 for Nitrobacter winogradskyi. Mixed cultures are difficult to control and operate but one could be done for more than 500 hours. The characterization of the bacteria will be used to calibrate the nitrification model which will be the basis of the control model for managing the nitrification process in the MELiSSA loop. The experimental results highlighted the use of online measurement of base addition and oxygen consumption as possible parameters for the control of the nitrification process. Keywords: Nitrosomonas europaea, Nitrobacter winogradskyi, MELiSSA, bioreactor

Transport of fluid and solutes in the body I. Formulation of a mathematical model.

PubMed

Gyenge, C C; Bowen, B D; Reed, R K; Bert, J L

1999-09-01

A compartmental model of short-term whole body fluid, protein, and ion distribution and transport is formulated. The model comprises four compartments: a vascular and an interstitial compartment, each with an embedded cellular compartment. The present paper discusses the assumptions on which the model is based and describes the equations that make up the model. Fluid and protein transport parameters from a previously validated model as well as ionic exchange parameters from the literature or from statistical estimation [see companion paper: C. C. Gyenge, B. D. Bowen, R. K. Reed, and J. L. Bert. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1228-H1240, 1999] are used in formulating the model. The dynamic model has the ability to simulate 1) transport across the capillary membrane of fluid, proteins, and small ions and their distribution between the vascular and interstitial compartments; 2) the changes in extracellular osmolarity; 3) the distribution and transport of water and ions associated with each of the cellular compartments; 4) the cellular transmembrane potential; and 5) the changes of volume in the four fluid compartments. The validation and testing of the proposed model against available experimental data are presented in the companion paper.

Statistical Exposé of a Multiple-Compartment Anaerobic Reactor Treating Domestic Wastewater.

PubMed

Pfluger, Andrew R; Hahn, Martha J; Hering, Amanda S; Munakata-Marr, Junko; Figueroa, Linda

2018-06-01

  Mainstream anaerobic treatment of domestic wastewater is a promising energy-generating treatment strategy; however, such reactors operated in colder regions are not well characterized. Performance data from a pilot-scale, multiple-compartment anaerobic reactor taken over 786 days were subjected to comprehensive statistical analyses. Results suggest that chemical oxygen demand (COD) was a poor proxy for organics in anaerobic systems as oxygen demand from dissolved inorganic material, dissolved methane, and colloidal material influence dissolved and particulate COD measurements. Additionally, univariate and functional boxplots were useful in visualizing variability in contaminant concentrations and identifying statistical outliers. Further, significantly different dissolved organic removal and methane production was observed between operational years, suggesting that anaerobic reactor systems may not achieve steady-state performance within one year. Last, modeling multiple-compartment reactor systems will require data collected over at least two years to capture seasonal variations of the major anaerobic microbial functions occurring within each reactor compartment.

Evaluation of pharmacokinetic models for perfusion imaging with dynamic contrast-enhanced magnetic resonance imaging in porcine skeletal muscle using low-molecular-weight contrast agents.

PubMed

Hindel, Stefan; Papanastasiou, Giorgos; Wust, Peter; Maaß, Marc; Söhner, Anika; Lüdemann, Lutz

2018-06-01

Pharmacokinetic models for perfusion quantification with a low-molecular-weight contrast agent (LMCA) in skeletal muscle using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were evaluated. Tissue perfusion was measured in seven regions of interest (ROIs) placed in the total hind leg supplied by the femoral artery in seven female pigs. DCE-MRI was performed using a 3D gradient echo sequence with k-space sharing. The sequence was acquired twice, first after LMCA and then after blood pool contrast agent injection. Blood flow was augmented by continuous infusion of the vasodilator adenosine into the femoral artery, resulting in up to four times increased blood flow. The results obtained with several LMCA models were compared with those of a two-compartment blood pool model (2CBPM) consisting of a capillary and an arteriolar compartment. Measurements performed with a Doppler flow probe placed at the femoral artery served as ground truth. The two-compartment exchange model extended by an arteriolar compartment (E2CXM) showed the highest fit quality of all LMCA models and the most significant correlation with the Doppler measurements, r = 0.78 (P < 0.001). The best correspondence between the capillary perfusion measurements of the LMCA models and those of the 2CBPM was found with the E2CXM (slope of the regression line equal to 1, r = 0.85, P < 0.001). The results for the clinical patient data corresponded very well with the results obtained in the animal experiments. Double-contrast agent DCE-MRI in combination with the E2CXM yields the most reliable results and can be used in clinical routine. Magn Reson Med 79:3154-3162, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Promotion of Testa Rupture during Garden Cress Germination Involves Seed Compartment-Specific Expression and Activity of Pectin Methylesterases1[OPEN

PubMed Central

Scheler, Claudia; Weitbrecht, Karin; Pearce, Simon P.; Hampstead, Anthony; Büttner-Mainik, Annette; Lee, Kieran J.D.; Voegele, Antje; Oracz, Krystyna; Dekkers, Bas J.W.; Wang, Xiaofeng; Wood, Andrew T.A.; Bentsink, Leónie; King, John R.; Knox, J. Paul; Holdsworth, Michael J.; Müller, Kerstin; Leubner-Metzger, Gerhard

2015-01-01

Pectin methylesterase (PME) controls the methylesterification status of pectins and thereby determines the biophysical properties of plant cell walls, which are important for tissue growth and weakening processes. We demonstrate here that tissue-specific and spatiotemporal alterations in cell wall pectin methylesterification occur during the germination of garden cress (Lepidium sativum). These cell wall changes are associated with characteristic expression patterns of PME genes and resultant enzyme activities in the key seed compartments CAP (micropylar endosperm) and RAD (radicle plus lower hypocotyl). Transcriptome and quantitative real-time reverse transcription-polymerase chain reaction analysis as well as PME enzyme activity measurements of separated seed compartments, including CAP and RAD, revealed distinct phases during germination. These were associated with hormonal and compartment-specific regulation of PME group 1, PME group 2, and PME inhibitor transcript expression and total PME activity. The regulatory patterns indicated a role for PME activity in testa rupture (TR). Consistent with a role for cell wall pectin methylesterification in TR, treatment of seeds with PME resulted in enhanced testa permeability and promoted TR. Mathematical modeling of transcript expression changes in germinating garden cress and Arabidopsis (Arabidopsis thaliana) seeds suggested that group 2 PMEs make a major contribution to the overall PME activity rather than acting as PME inhibitors. It is concluded that regulated changes in the degree of pectin methylesterification through CAP- and RAD-specific PME and PME inhibitor expression play a crucial role during Brassicaceae seed germination. PMID:25429110

Hot and Cool Spots of Primary Production, Respiration and 15N Nitrate and Ammonium Uptake: Spatial Heterogeneity in Tropical Streams and Rivers

NASA Astrophysics Data System (ADS)

Dodds, W. K.; Tromboni, F.; Neres-Lima, V.; Zandoná, E.; Moulton, T. P.

2016-12-01

While whole-stream measures of metabolism and uptake have become common methods to characterize biogeochemical transport and processing, less is known about how nitrogen (N) uptake, gross primary production (GPP) and ecosystem respiration (ER) covary among different stream substrata as smaller scales. We measured 15N ammonium and nitrate uptake seperately, and GPP and ER of ecosystem compartments (leaves, epilithon, sand-associated biota and macrophytes) in closed circulating chambers in three streams/ rivers of varied size. The streams drain pristine Brazilian Atlantic Rainforest watersheds and are all within a few km of eachother. The smallest stream had dense forest canopy cover; the largest river was almost completely open. GPP could not be detected in the closed canopy stream. Epilithon (biofilms on rocks) was a dominant compartment for GPP and N uptake in the two open streams, and macrophytes rivaled epilithon GPP and N uptake rates in the most open stream. Even though leaves covered only 1-3% of the stream bottom, they could account for around half of all the ER in the streams but almost no N uptake. Sand had minimal rates of N uptake, GPP and R associated with it in all streams due to relatively low organic material content. The data suggest that N uptake, GPP and ER of different substrata are not closely linked over relatively small spatial (dm) scales, and that different biogeochemical processes may map to different hot and cool spots for ecosystem rates.

The impact of pH inhomogeneities on CHO cell physiology and fed-batch process performance - two-compartment scale-down modelling and intracellular pH excursion.

PubMed

Brunner, Matthias; Braun, Philipp; Doppler, Philipp; Posch, Christoph; Behrens, Dirk; Herwig, Christoph; Fricke, Jens

2017-07-01

Due to high mixing times and base addition from top of the vessel, pH inhomogeneities are most likely to occur during large-scale mammalian processes. The goal of this study was to set-up a scale-down model of a 10-12 m 3 stirred tank bioreactor and to investigate the effect of pH perturbations on CHO cell physiology and process performance. Short-term changes in extracellular pH are hypothesized to affect intracellular pH and thus cell physiology. Therefore, batch fermentations, including pH shifts to 9.0 and 7.8, in regular one-compartment systems are conducted. The short-term adaption of the cells intracellular pH are showed an immediate increase due to elevated extracellular pH. With this basis of fundamental knowledge, a two-compartment system is established which is capable of simulating defined pH inhomogeneities. In contrast to state-of-the-art literature, the scale-down model is included parameters (e.g. volume of the inhomogeneous zone) as they might occur during large-scale processes. pH inhomogeneity studies in the two-compartment system are performed with simulation of temporary pH zones of pH 9.0. The specific growth rate especially during the exponential growth phase is strongly affected resulting in a decreased maximum viable cell density and final product titer. The gathered results indicate that even short-term exposure of cells to elevated pH values during large-scale processes can affect cell physiology and overall process performance. In particular, it could be shown for the first time that pH perturbations, which might occur during the early process phase, have to be considered in scale-down models of mammalian processes. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A general multiple-compartment model for the transport of trace elements through animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Assimakopoulos, P.A.; Ioannides, K.G.; Pakou, A.A.

1991-08-01

Multiple-compartment models employed in the analysis of trace element transport in animals are often based on linear differential equations which relate the rate of change of contaminant (or contaminant concentration) in each compartment to the amount of contaminant (or contaminant concentration) in every other compartment in the system. This has the serious disadvantage of mixing intrinsic physiological properties with the geometry of the animal. The basic equations on which the model presented here is developed are derived from the actual physical process under way and are capable of separating intrinsic physiological properties from geometry. It is thus expected that ratemore » coefficients determined through this model will be applicable to a wider category of physiologically similar animals. A specific application of the model for the study of contamination of sheep--or indeed for any ruminant--is presented, and the temporal evolution of contaminant concentration in the various compartments of the animal is calculated. The application of this model to a system of compartments with changing geometry is also presented.« less

Population Pharmacokinetics and Dosing Regimen Optimization of Meropenem in Cerebrospinal Fluid and Plasma in Patients with Meningitis after Neurosurgery

PubMed Central

Lu, Cheng; Zhang, Yuyi; Chen, Mingyu; Zhong, Ping; Chen, Yuancheng; Yu, Jicheng; Wu, Xiaojie; Wu, Jufang

2016-01-01

Meropenem is used to manage postneurosurgical meningitis, but its population pharmacokinetics (PPK) in plasma and cerebrospinal fluid (CSF) in this patient group are not well-known. Our aims were to (i) characterize meropenem PPK in plasma and CSF and (ii) recommend favorable dosing regimens in postneurosurgical meningitis patients. Eighty-two patients were enrolled to receive meropenem infusions of 2 g every 8 h (q8h), 1 g q8h, or 1 g q6h for at least 3 days. Serial blood and CSF samples were collected, and concentrations were determined and analyzed via population modeling. Probabilities of target attainment (PTA) were predicted via Monte Carlo simulations, using the target of unbound meropenem concentrations above the MICs for at least 40% of dosing intervals in plasma and at least of 50% or 100% of dosing intervals in CSF. A two-compartment model plus another CSF compartment best described the data. The central, intercentral/peripheral, and intercentral/CSF compartment clearances were 22.2 liters/h, 1.79 liters/h, and 0.01 liter/h, respectively. Distribution volumes of the central and peripheral compartments were 17.9 liters and 3.84 liters, respectively. The CSF compartment volume was fixed at 0.13 liter, with its clearance calculated by the observed drainage amount. The multiplier for the transfer from the central to the CSF compartment was 0.172. Simulation results show that the PTAs increase as infusion is prolonged and as the daily CSF drainage volume decreases. A 4-hour infusion of 2 g q8h with CSF drainage of less than 150 ml/day, which provides a PTA of >90% for MICs of ≤8 mg/liter in blood and of ≤0.5 mg/liter or 0.25 mg/liter in CSF, is recommended. (This study has been registered at ClinicalTrials.gov under identifier NCT02506686.) PMID:27572392

Effect of gradient pulse duration on MRI estimation of the diffusional kurtosis for a two-compartment exchange model

NASA Astrophysics Data System (ADS)

Jensen, Jens H.; Helpern, Joseph A.

2011-06-01

Hardware constraints typically require the use of extended gradient pulse durations for clinical applications of diffusion-weighted magnetic resonance imaging (DW-MRI), which can potentially influence the estimation of diffusion metrics. Prior studies have examined this effect for the apparent diffusion coefficient. This study employs a two-compartment exchange model in order to assess the gradient pulse duration sensitivity of the apparent diffusional kurtosis (ADK), a quantitative index of diffusional non-Gaussianity. An analytic expression is derived and numerically evaluated for parameter ranges relevant to DW-MRI of brain. It is found that the ADK differs from the true diffusional kurtosis by at most a few percent. This suggests that ADK estimates for brain may be robust with respect to changes in pulse gradient duration.

A compartmental model of uranium in human hair for protracted ingestion of natural uranium in drinking water.

PubMed

Li, W B; Karpas, Z; Salonen, L; Kurttio, P; Muikku, M; Wahl, W; Höllriegl, V; Hoeschen, C; Oeh, U

2009-06-01

To predict uranium in human hair due to chronic exposure through drinking water, a compartment representing human hair was added into the uranium biokinetic model developed by the International Commission on Radiological Protection (ICRP). The hair compartmental model was used to predict uranium excretion in human hair as a bioassay indicator due to elevated uranium intakes. Two excretion pathways, one starting from the compartment of plasma and the other from the compartment of intermediate turnover soft tissue, are assumed to transfer uranium to the compartment of hair. The transfer rate was determined from reported uranium contents in urine and in hair, taking into account the hair growth rate of 0.1 g d(-1). The fractional absorption in the gastrointestinal tract of 0.6% was found to fit best to describe the measured uranium levels among the users of drilled wells in Finland. The ingestion dose coefficient for (238)U, which includes its progeny of (234)Th, (234m)Pa, and (234)Pa, was calculated equal to 1.3 x 10(-8) Sv Bq(-1) according to the hair compartmental model. This estimate is smaller than the value of 4.5 x 10(-8) Sv Bq(-1) published by ICRP for the members of the public. In this new model, excretion of uranium through urine is better represented when excretion to the hair compartment is accounted for and hair analysis can provide a means for assessing the internal body burden of uranium. The model is applicable for chronic exposure as well as for an acute exposure incident. In the latter case, the hair sample can be collected and analyzed even several days after the incident, whereas urinalysis requires sample collection shortly after the exposure. The model developed in this study applies to ingestion intakes of uranium.

Direct reconstruction in CT-analogous pharmacokinetic diffuse fluorescence tomography: two-dimensional simulative and experimental validations

NASA Astrophysics Data System (ADS)

Wang, Xin; Zhang, Yanqi; Zhang, Limin; Li, Jiao; Zhou, Zhongxing; Zhao, Huijuan; Gao, Feng

2016-04-01

We present a generalized strategy for direct reconstruction in pharmacokinetic diffuse fluorescence tomography (DFT) with CT-analogous scanning mode, which can accomplish one-step reconstruction of the indocyanine-green pharmacokinetic-rate images within in vivo small animals by incorporating the compartmental kinetic model into an adaptive extended Kalman filtering scheme and using an instantaneous sampling dataset. This scheme, compared with the established indirect and direct methods, eliminates the interim error of the DFT inversion and relaxes the expensive requirement of the instrument for obtaining highly time-resolved date-sets of complete 360 deg projections. The scheme is validated by two-dimensional simulations for the two-compartment model and pilot phantom experiments for the one-compartment model, suggesting that the proposed method can estimate the compartmental concentrations and the pharmacokinetic-rates simultaneously with a fair quantitative and localization accuracy, and is well suitable for cost-effective and dense-sampling instrumentation based on the highly-sensitive photon counting technique.

Robotic Sow

NASA Technical Reports Server (NTRS)

1987-01-01

In swine farming 15 to 25 percent of piglets die before weaning, and that poses a serious economic problem for hog producers. Sometimes a sow will accidentally crush her piglets or she will reject or abuse a piglet. Frequently a litter is oversized and the sow cannot accommodate all her piglets for nursing or is just unable to lactate due to physical disorders. Farmatic Inc.'s mechanical mother pig comes in two models, one with eight artificial nipples and another with 16. Shortly before feeding time the automated sow releases a prescribed amount of formula from a refrigerated compartment into a warming chamber, where milk is heated to the desired temperature. At feeding time a heat lamp simulating a sow's body warmth is automatically turned on and the machine emits rhythmic grunts like a mother pig summoning her piglets. As piglets scamper to their mechanical mother, a panel across the front opens to expose the row of nipples.

Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration.

PubMed

Rawlins, M D; Henderson, D B; Hijab, A R

1977-04-20

Plasma paracetamol concentrations were measured in 6 volunteers after single intravenous (1000 mg) and oral (500 mg, 1000 mg and 2000 mg) doses of the drug. Paracetamol levels declined multiphasically with a mean clearance after intravenous administration of 352 +/- 40 ml/min. A two-compartment open model appeared to describe the decline adequately. Comparison of the areas under the plasma concentration-time curves (AUC) indicated that oral bioavailability increased from 0.63 +/- 0.02 after 500 mg, to 0.89 +/- 0.04 and 0.87 +/- 0.08 after 1000 mg and 2000 mg, respectively. As a consequence of the incomplete bioavailability of paracetamol, as well as its multicompartmental distribution, accurate estimates of its distribution volume and clearance cannot be obtained if the drug is given orally. However, an estimate of its total plasma clearance may be derived from the AUC after a 500 mg oral dose.

Geometric properties-dependent neural synchrony modulated by extracellular subthreshold electric field

NASA Astrophysics Data System (ADS)

Wei, Xile; Si, Kaili; Yi, Guosheng; Wang, Jiang; Lu, Meili

2016-07-01

In this paper, we use a reduced two-compartment neuron model to investigate the interaction between extracellular subthreshold electric field and synchrony in small world networks. It is observed that network synchronization is closely related to the strength of electric field and geometric properties of the two-compartment model. Specifically, increasing the electric field induces a gradual improvement in network synchrony, while increasing the geometric factor results in an abrupt decrease in synchronization of network. In addition, increasing electric field can make the network become synchronous from asynchronous when the geometric parameter is set to a given value. Furthermore, it is demonstrated that network synchrony can also be affected by the firing frequency and dynamical bifurcation feature of single neuron. These results highlight the effect of weak field on network synchrony from the view of biophysical model, which may contribute to further understanding the effect of electric field on network activity.

Hepatic function imaging using dynamic Gd-EOB-DTPA enhanced MRI and pharmacokinetic modeling.

PubMed

Ning, Jia; Yang, Zhiying; Xie, Sheng; Sun, Yongliang; Yuan, Chun; Chen, Huijun

2017-10-01

To determine whether pharmacokinetic modeling parameters with different output assumptions of dynamic contrast-enhanced MRI (DCE-MRI) using Gd-EOB-DTPA correlate with serum-based liver function tests, and compare the goodness of fit of the different output assumptions. A 6-min DCE-MRI protocol was performed in 38 patients. Four dual-input two-compartment models with different output assumptions and a published one-compartment model were used to calculate hepatic function parameters. The Akaike information criterion fitting error was used to evaluate the goodness of fit. Imaging-based hepatic function parameters were compared with blood chemistry using correlation with multiple comparison correction. The dual-input two-compartment model assuming venous flow equals arterial flow plus portal venous flow and no bile duct output better described the liver tissue enhancement with low fitting error and high correlation with blood chemistry. The relative uptake rate Kir derived from this model was found to be significantly correlated with direct bilirubin (r = -0.52, P = 0.015), prealbumin concentration (r = 0.58, P = 0.015), and prothrombin time (r = -0.51, P = 0.026). It is feasible to evaluate hepatic function by proper output assumptions. The relative uptake rate has the potential to serve as a biomarker of function. Magn Reson Med 78:1488-1495, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Blind identification of the kinetic parameters in three-compartment models

NASA Astrophysics Data System (ADS)

Riabkov, Dmitri Y.; Di Bella, Edward V. R.

2004-03-01

Quantified knowledge of tissue kinetic parameters in the regions of the brain and other organs can offer information useful in clinical and research applications. Dynamic medical imaging with injection of radioactive or paramagnetic tracer can be used for this measurement. The kinetics of some widely used tracers such as [18F]2-fluoro-2-deoxy-D-glucose can be described by a three-compartment physiological model. The kinetic parameters of the tissue can be estimated from dynamically acquired images. Feasibility of estimation by blind identification, which does not require knowledge of the blood input, is considered analytically and numerically in this work for the three-compartment type of tissue response. The non-uniqueness of the two-region case for blind identification of kinetic parameters in three-compartment model is shown; at least three regions are needed for the blind identification to be unique. Numerical results for the accuracy of these blind identification methods in different conditions were considered. Both a separable variables least-squares (SLS) approach and an eigenvector-based algorithm for multichannel blind deconvolution approach were used. The latter showed poor accuracy. Modifications for non-uniform time sampling were also developed. Also, another method which uses a model for the blood input was compared. Results for the macroparameter K, which reflects the metabolic rate of glucose usage, using three regions with noise showed comparable accuracy for the separable variables least squares method and for the input model-based method, and slightly worse accuracy for SLS with the non-uniform sampling modification.

Near Infra-Red Spectroscopy to Reduce Prophylactic Fasciotomies for and Missed Cases of Acute Compartment Syndrome in Soldiers Injured in OEF/OIF

DTIC Science & Technology

2013-10-01

demonstrated that NIRS measurement of hemoglobin oxygen saturation in the tibial compartment provided reliable and sensitive correlation to increases...on 60 healthy participants. Our results indicated that NIRS was able to detect changes in oxygen saturation of muscle with exercise in all 60...Model 41 Introduction 42 Over the last two decades, tissue oxygenation saturation (StO2) measured by near infrared 43 spectroscopy (NIRS) has

Population Pharmacokinetic Modeling as a Tool To Characterize the Decrease in Ciprofloxacin Free Interstitial Levels Caused by Pseudomonas aeruginosa Biofilm Lung Infection in Wistar Rats

PubMed Central

Torres, Bruna G. S.; Helfer, Victória E.; Bernardes, Priscila M.; Macedo, Alexandre José; Nielsen, Elisabet I.; Friberg, Lena E.

2017-01-01

ABSTRACT Biofilm formation plays an important role in the persistence of pulmonary infections, for example, in cystic fibrosis patients. So far, little is known about the antimicrobial lung disposition in biofilm-associated pneumonia. This study aimed to evaluate, by microdialysis, ciprofloxacin (CIP) penetration into the lungs of healthy and Pseudomonas aeruginosa biofilm-infected rats and to develop a comprehensive model to describe the CIP disposition under both conditions. P. aeruginosa was immobilized into alginate beads and intratracheally inoculated 14 days before CIP administration (20 mg/kg of body weight). Plasma and microdialysate were sampled from different animal groups, and the observations were evaluated by noncompartmental analysis (NCA) and population pharmacokinetic (popPK) analysis. The final model that successfully described all data consisted of an arterial and a venous central compartment and two peripheral distribution compartments, and the disposition in the lung was modeled as a two-compartment model structure linked to the venous compartment. Plasma clearance was approximately 32% lower in infected animals, leading to a significantly higher level of plasma CIP exposure (area under the concentration-time curve from time zero to infinity, 27.3 ± 12.1 μg · h/ml and 13.3 ± 3.5 μg · h/ml in infected and healthy rats, respectively). Despite the plasma exposure, infected animals showed a four times lower tissue concentration/plasma concentration ratio (lung penetration factor = 0.44 and 1.69 in infected and healthy rats, respectively), and lung clearance (CLlung) was added to the model for these animals (CLlung = 0.643 liters/h/kg) to explain the lower tissue concentrations. Our results indicate that P. aeruginosa biofilm infection reduces the CIP free interstitial lung concentrations and increases plasma exposure, suggesting that plasma concentrations alone are not a good surrogate of lung concentrations. PMID:28461311

Reprint of: A numerical modelling of gas exchange mechanisms between air and turbulent water with an aquarium chemical reaction

NASA Astrophysics Data System (ADS)

Nagaosa, Ryuichi S.

2014-08-01

This paper proposes a new numerical modelling to examine environmental chemodynamics of a gaseous material exchanged between the air and turbulent water phases across a gas-liquid interface, followed by an aquarium chemical reaction. This study uses an extended concept of a two-compartment model, and assumes two physicochemical substeps to approximate the gas exchange processes. The first substep is the gas-liquid equilibrium between the air and water phases, A(g)⇌A(aq), with Henry's law constant H. The second is a first-order irreversible chemical reaction in turbulent water, A(aq)+H2O→B(aq)+H+ with a chemical reaction rate κA. A direct numerical simulation (DNS) technique has been employed to obtain details of the gas exchange mechanisms and the chemical reaction in the water compartment, while zero velocity and uniform concentration of A is considered in the air compartment. The study uses the different Schmidt numbers between 1 and 8, and six nondimensional chemical reaction rates between 10(≈0) to 101 at a fixed Reynolds number. It focuses on the effects of the Schmidt number and the chemical reaction rate on fundamental mechanisms of the gas exchange processes across the interface.

Multiobjective optimization of cartilage stress for non-invasive, patient-specific recommendations of high tibial osteotomy correction angle - a novel method to investigate alignment correction.

PubMed

Zheng, Keke; Scholes, Corey J; Chen, Junning; Parker, David; Li, Qing

2017-04-01

Medial opening wedge high tibial osteotomy (MOWHTO) is a surgical procedure to treat knee osteoarthritis associated with varus deformity. However, the ideal final alignment of the Hip-Knee-Ankle (HKA) angle in the frontal plane, that maximizes procedural success and post-operative knee function, remains controversial. Therefore, the purpose of this study was to introduce a subject-specific modeling procedure in determining the biomechanical effects of MOWHTO alignment on tibiofemoral cartilage stress distribution. A 3D finite element knee model derived from magnetic resonance imaging of a healthy participant was manipulated in-silico to simulate a range of final HKA angles (i.e. 0.2°, 2.7°, 3.9° and 6.6° valgus). Loading and boundary conditions were assigned based on subject-specific kinematic and kinetic data from gait analysis. Multiobjective optimization was used to identify the final alignment that balanced compressive and shear forces between medial and lateral knee compartments. Peak stresses decreased in the medial and increased in the lateral compartment as the HKA was shifted into valgus, with balanced loading occurring at angles of 4.3° and 2.9° valgus for the femoral and tibial cartilage respectively. The concept introduced here provides a platform for non-invasive, patient-specific preoperative planning of the osteotomy for medial compartment knee osteoarthritis. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Insulin-like growth factor (IGF)-I controls prostate fibromuscular development: IGF-I inhibition prevents both fibromuscular and glandular development in eugonadal mice.

PubMed

Kleinberg, David L; Ruan, Weifeng; Yee, Douglas; Kovacs, Kalman T; Vidal, Sergio

2007-03-01

Although antiandrogen therapy has been shown effective in treating prostatic tumors, it is relatively ineffective in treating benign prostatic hyperplasia (BPH). In an attempt to understand better the role of androgens in the development of the normal prostate and BPH, we studied the relative effects of testosterone and IGF-I on the development of the two compartments of the prostate in castrated IGF-I((-/-)) male mice. Here we report that IGF-I stimulated the development of the fibromuscular compartment, but testosterone inhibited it (stromal epithelial ratio 2.17 vs. 0.83, respectively; P < 0.001). Testosterone also impaired IGF-I induced insulin receptor substrate-1 phosphorylation and cell division, and increased apoptosis in fibromuscular tissue. In sharp contrast IGF-I and testosterone both stimulated the development of the glandular compartment individually and together. The combined effects were either additive or synergistic on compartment size, cell division, insulin receptor substrate-1 phosphorylation, and probasin production. Together they also had a greater inhibitory effect on apoptosis in gland tissue. To determine whether IGF-I inhibition would inhibit both fibromuscular and glandular compartments, we tested the effect of IGF binding protein-1 on prostate development in two different models: castrated Ames dwarf mice and eugonadal normal male mice. IGF binding protein-1 blocked bovine GH-induced fibromuscular and glandular development in both. It also inhibited epithelial cell division and increased apoptosis in both prostate compartments in the eugonadal mice. The observed discordance between IGF-I and testosterone control of prostate compartment development might explain the relative failure of 5alpha-reductase inhibition in BPH and why testosterone inhibition might theoretically reduce gland volume but increase fibromuscular tissue. The work also provides a rationale for considering IGF-I inhibition as therapy for BPH to reduce the size of both prostate compartments.

A multiobjective modeling approach to locate multi-compartment containers for urban-sorted waste

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tralhao, Lino, E-mail: lmlrt@inescc.p; Coutinho-Rodrigues, Joao, E-mail: coutinho@dec.uc.p; Alcada-Almeida, Luis, E-mail: alcada@inescc.p

2010-12-15

The location of multi-compartment sorted waste containers for recycling purposes in cities is an important problem in the context of urban waste management. The costs associated with those facilities and the impacts placed on populations are important concerns. This paper introduces a mixed-integer, multiobjective programming approach to identify the locations and capacities of such facilities. The approach incorporates an optimization model in a Geographical Information System (GIS)-based interactive decision support system that includes four objectives. The first objective minimizes the total investment cost; the second one minimizes the average distance from dwellings to the respective multi-compartment container; the last twomore » objectives address the 'pull' and 'push' characteristics of the decision problem, one by minimizing the number of individuals too close to any container, and the other by minimizing the number of dwellings too far from the respective multi-compartment container. The model determines the number of facilities to be opened, the respective container capacities, their locations, their respective shares of the total waste of each type to be collected, and the dwellings assigned to each facility. The approach proposed was tested with a case study for the historical center of Coimbra city, Portugal, where a large urban renovation project, addressing about 800 buildings, is being undertaken. This paper demonstrates that the models and techniques incorporated in the interactive decision support system (IDSS) can be used to assist a decision maker (DM) in analyzing this complex problem in a realistically sized urban application. Ten solutions consisting of different combinations of underground containers for the disposal of four types of sorted waste in 12 candidate sites, were generated. These solutions and tradeoffs among the objectives are presented to the DM via tables, graphs, color-coded maps and other graphics. The DM can then use this information to 'guide' the IDSS in identifying additional solutions of potential interest. Nevertheless, this research showed that a particular solution with a better objective balance can be identified. The actual sequence of additional solutions generated will depend upon the objectives and preferences of the DM in a specific application.« less

Negative pressure wound therapy‐assisted dermatotraction for the closure of large open wounds in a patient with non‐clostridial gas gangrene

PubMed Central

Noborio, Mitsuhiro; Nishimura, Tetsuro; Ieki, Yohei; Shimahara, Yumiko; Sogabe, Taku; Ehara, Naoki; Saoyama, Yuki; Sadamitsu, Daikai

2015-01-01

Case A 53‐year‐old woman developed septic shock associated with non‐clostridial gas gangrene. She presented to the emergency department with two large open wounds on both thighs and in her sacral region. Non‐enhanced computed tomography showed air density in contact with the right iliopsoas, which extended to the posterior compartment of the thigh. We made repeated efforts at surgical debridement of the wound with resection of necrotic tissues. Outcome Using negative pressure wound therapy‐assisted dermatotraction, the pus pockets and the wound dehiscence decreased in size. Using this method we were successful in achieving delayed closure without skin grafts. Conclusion Negative pressure wound therapy can be an effective treatment for large and infected open contoured wounds. Negative pressure wound therapy‐assisted dermatotraction might be beneficial for poorly healing, large, open wounds in patients in poor condition and with insufficient reserve to tolerate reconstructive surgery. PMID:29123764

Open abdomen critical care management principles: resuscitation, fluid balance, nutrition, and ventilator management

PubMed Central

Chabot, Elizabeth; Nirula, Ram

2017-01-01

The term “open abdomen” refers to a surgically created defect in the abdominal wall that exposes abdominal viscera. Leaving an abdominal cavity temporarily open has been well described for several indications, including damage control surgery and abdominal compartment syndrome. Although beneficial in certain patients, the act of keeping an abdominal cavity open has physiologic repercussions that must be recognized and managed during postoperative care. This review article describes these issues and provides guidelines for the critical care physician managing a patient with an open abdomen. PMID:29766080

The estimation of the rates of lead exchange between body compartments of smelter employees.

PubMed

Behinaein, Sepideh; Chettle, David R; Egden, Lesley M; McNeill, Fiona E; Norman, Geoff; Richard, Norbert; Stever, Susan

2014-07-01

The overwhelming proportion of the mass of lead (Pb) is stored in bone and the residence time of Pb in bone is much longer than that in other tissues. Hence, in a metabolic model that we used to solve the differential equations governing the transfer of lead between body compartments, three main compartments are involved: blood (as a transfer compartment), cortical bone (tibia), and trabecular bone (calcaneus). There is a bidirectional connection between blood and the other two compartments. A grid search chi-squared minimization method was used to estimate the initial values of lead transfer rate values from tibia (λTB) and calcaneus (λCB) to blood of 209 smelter employees whose bone lead measurements are available from 1994, 1999, and 2008, and their blood lead level from 1967 onwards (depending on exposure history from once per month to once per year), and then the initial values of kinematic parameters were used to develop multivariate models in order to express λTB and λCB as a function of employment time, age, body lead contents and their interaction. We observed a significant decrease in the transfer rate of lead from bone to blood with increasing body lead contents. The model was tested by calculating the bone lead concentration in 1999 and 2008, and by comparing those values with the measured ones. A good agreement was found between the calculated and measured tibia/calcaneus lead values. Also, we found that the transfer rate of lead from tibia to blood can be expressed solely as a function of cumulative blood lead index.

Simulation of a proposed emergency outlet from Devils Lake, North Dakota

USGS Publications Warehouse

Vecchia, Aldo V.

2002-01-01

From 1993 to 2001, Devils Lake rose more than 25 feet, flooding farmland, roads, and structures around the lake and causing more than $400 million in damages in the Devils Lake Basin. In July 2001, the level of Devils Lake was at 1,448.0 feet above sea level1, which was the highest lake level in more than 160 years. The lake could continue to rise to several feet above its natural spill elevation to the Sheyenne River (1,459 feet above sea level) in future years, causing extensive additional flooding in the basin and, in the event of an uncontrolled natural spill, downstream in the Red River of the North Basin as well. The outlet simulation model described in this report was developed to determine the potential effects of various outlet alternatives on the future lake levels and water quality of Devils Lake.Lake levels of Devils Lake are controlled largely by precipitation on the lake surface, evaporation from the lake surface, and surface inflow. For this study, a monthly water-balance model was developed to compute the change in total volume of Devils Lake, and a regression model was used to estimate monthly water-balance data on the basis of limited recorded data. Estimated coefficients for the regression model indicated fitted precipitation on the lake surface was greater than measured precipitation in most months, fitted evaporation from the lake surface was less than estimated evaporation in most months, and ungaged inflow was about 2 percent of gaged inflow in most months. Dissolved sulfate was considered to be the key water-quality constituent for evaluating the effects of a proposed outlet on downstream water quality. Because large differences in sulfate concentrations existed among the various bays of Devils Lake, monthly water-balance data were used to develop detailed water and sulfate mass-balance models to compute changes in sulfate load for each of six major storage compartments in response to precipitation, evaporation, inflow, and outflow from each compartment. The storage compartments--five for Devils Lake and one for Stump Lake--were connected by bridge openings, culverts, or natural channels that restricted mixing between compartments. A numerical algorithm was developed to calculate inflow and outflow from each compartment. Sulfate loads for the storage compartments first were calculated using the assumptions that no interaction occurred between the bottom sediments and the water column and no wind- or buoyancy-induced mixing occurred between compartments. However, because the fitted sulfate loads did not agree with the estimated sulfate loads, which were obtained from recorded sulfate concentrations, components were added to the sulfate mass-balance model to account for the flux of sulfate between bottom sediments and the lake and for mixing between storage compartments. Mixing between compartments can occur during periods of open water because of wind and during periods of ice cover because of water-density differences between compartments. Sulfate loads calculated using the sulfate mass-balance model with sediment interaction and mixing between compartments closely matched sulfate loads computed from historical concentrations. The water and sulfate mass-balance models were used to calculate potential future lake levels and sulfate concentrations for Devils Lake and Stump Lake given potential future values of monthly precipitation, evaporation, and inflow. Potential future inputs were generated using a scenario approach and a stochastic approach. In the scenario approach, historical values of precipitation, evaporation, and inflow were repeated in the future for a particular sequence of historical years. In the stochastic approach, a statistical time-series model was developed to randomly generate potential future inputs. The scenario approach was used to evaluate the effectiveness of various outlet alternatives, and the stochastic approach was used to evaluate the hydrologic and water-quality effects of the potential outlet alternatives that were selected on the basis of the scenario analysis. Given potential future lake levels and sulfate concentrations generated using either the scenario or stochastic approach and potential future ambient flows and sulfate concentrations for the Sheyenne River receiving waters, daily outlet discharges could be calculated for virtually any outlet alternative. For the scenario approach, future ambient flows and sulfate concentrations for the Sheyenne River were generated using the same sequence of years used for generating water-balance data for Devils Lake. For the stochastic approach, a procedure was developed for generating daily Sheyenne River flows and sulfate concentrations that were "in-phase" with the generated water-balance data for Devils Lake. Simulation results for the scenario approach indicated that neither of the West Bay outlet alternatives provided effective flood-damage reduction without exceeding downstream water-quality constraints. However, both Pelican Lake outlet alternatives provided significant flood-damage reduction with only minor downstream water-quality changes. The most effective alternative for controlling rising lake levels was a Pelican Lake outlet with a 480-cubic-foot-per-second pump capacity and a 250-milligram-per-liter downstream sulfate constraint. However, this plan is costly because of the high pump capacity and the requirement of a control structure on Highway 19 to control the level of Pelican Lake. A less costly, though less effective for flood-damage reduction, plan is a Pelican Lake outlet with a 300-cubic-foot-per-second pump capacity and a 250-milligram-per-liter downstream sulfate constraint. The plan is less costly because the pump capacity is smaller and because the control structure on Highway 19 is not required. The less costly Pelican Lake alternative with a 450-milligramper- liter downstream sulfate constraint rather than a 250-milligram-per-liter downstream sulfate constraint was identified by the U.S. Army Corps of Engineers as the preferred alternative for detailed design and engineering analysis. Simulation results for the stochastic approach indicated that the geologic history of lake-level fluctuations of Devils Lake for the past 2,500 years was consistent with a climatic history that consisted of two climate states--a wet state, similar to conditions during 1980-99, and a normal state, similar to conditions during 1950-78. The transition times between the wet and normal climatic periods occurred randomly. The average duration of the wet climatic periods was 20 years, and the average duration of the normal climatic periods was 120 years. The stochastic approach was used to generate 10,000 independent sequences of lake levels and sulfate concentrations for Devils Lake for water years 2001-50. Each trace began with the same starting conditions, and the duration of the current wet cycle was generated randomly for each trace. Each trace was generated for the baseline (natural) condition and for the Pelican Lake outlet with a 300-cubic-foot-per-second pump capacity and a 450-milligram-per-liter downstream sulfate constraint. The outlet significantly lowered the probabilities of future lake-level increases within the next 50 years and did not substantially increase the probabilities of reaching low lake levels or poor water-quality conditions during the same period.

A Model for the Estimation of Hepatic Insulin Extraction After a Meal.

PubMed

Piccinini, Francesca; Dalla Man, Chiara; Vella, Adrian; Cobelli, Claudio

2016-09-01

Quantitative assessment of hepatic insulin extraction (HE) after an oral glucose challenge, e.g., a meal, is important to understand the regulation of carbohydrate metabolism. The aim of the current study is to develop a model of system for estimating HE. Nine different models, of increasing complexity, were tested on data of 204 normal subjects, who underwent a mixed meal tolerance test, with frequent measurement of plasma glucose, insulin, and C-peptide concentrations. All these models included a two-compartment model of C-peptide kinetics, an insulin secretion model, a compartmental model of insulin kinetics (with number of compartments ranging from one to three), and different HE descriptions, depending on plasma glucose and insulin. Model performances were compared on the basis of data fit, precision of parameter estimates, and parsimony criteria. The three-compartment model of insulin kinetics, coupled with HE depending on glucose concentration, showed the best fit and a good ability to precisely estimate the parameters. In addition, the model calculates basal and total indices of HE ( HE b and HE tot , respectively), and provides an index of HE sensitivity to glucose ( S G HE ). A new physiologically based HE model has been developed, which allows an improved quantitative description of glucose regulation. The use of the new model provides an in-depth description of insulin kinetics, thus enabling a better understanding of a given subject's metabolic state.

Definition of compartment-based radical surgery in uterine cancer: modified radical hysterectomy in intermediate/high-risk endometrial cancer using peritoneal mesometrial resection (PMMR) by M Höckel translated to robotic surgery.

PubMed

Kimmig, Rainer; Aktas, Bahriye; Buderath, Paul; Wimberger, Pauline; Iannaccone, Antonella; Heubner, Martin

2013-08-16

The technique of compartment-based radical hysterectomy was originally described by M Höckel as total mesometrial resection (TMMR) for standard treatment of stage I and II cervical cancer. However, with regard to the ontogenetically-defined compartments of tumor development (Müllerian) and lymph drainage (Müllerian and mesonephric), compartments at risk may also be defined consistently in endometrial cancer. This is the first report in the literature on the compartment-based surgical approach to endometrial cancer. Peritoneal mesometrial resection (PMMR) with therapeutic lymphadenectomy (tLNE) as an ontogenetic, compartment-based oncologic surgery could be beneficial for patients in terms of surgical radicalness as well as complication rates; it can be standardized for compartment-confined tumors. Supported by M Höckel, PMMR was translated to robotic surgery (rPMMR) and described step-by-step in comparison to robotic TMMR (rTMMR). Patients (n = 42) were treated by rPMMR (n = 39) or extrafascial simple hysterectomy (n = 3) with/without bilateral pelvic and/or periaortic robotic therapeutic lymphadenectomy (rtLNE) for stage I to III endometrial cancer, according to International Federation of Gynecology and Obstetrics (FIGO) classification. Tumors were classified as intermediate/high-risk in 22 out of 40 patients (55%) and low-risk in 18 out of 40 patients (45%), and two patients showed other uterine malignancies. In 11 patients, no adjuvant external radiotherapy was performed, but chemotherapy was applied. No transition to open surgery was necessary. There were no intraoperative complications. The postoperative complication rate was 12% with venous thromboses, (n = 2), infected pelvic lymph cyst (n = 1), transient aphasia (n = 1) and transient dysfunction of micturition (n = 1). The mean difference in perioperative hemoglobin concentrations was 2.4 g/dL (± 1.2 g/dL) and one patient (2.4%) required transfusion. During follow-up (median 17 months), one patient experienced distant recurrence and one patient distant/regional recurrence of endometrial cancer (4.8%), but none developed isolated locoregional recurrence. There were two deaths from endometrial cancer during the observation period (4.8%). We conclude that rPMMR and rtLNE are feasible and safe with regard to perioperative morbidity, thus, it seems promising for the treatment of intermediate/high-risk endometrial cancer in terms of surgical radicalness and complication rates. This could be particularly beneficial for morbidly obese and seriously ill patients.

An empirical investigation of the possibility of adaptability of arbuscular mycorrhizal fungi to new hosts.

PubMed

Koyama, Akihiro; Pietrangelo, Olivia; Sanderson, Laura; Antunes, Pedro M

2017-08-01

Little is known about the adaptive capacity of arbuscular mycorrhizal (AM) fungi to novel hosts. Here we assessed the possibility of two heterospecific AM fungal isolates to adaptively change, in terms of host biomass response, as a function of host plant identity, over the course of a growing season. First, we produced pure inocula of Rhizophagus clarus and Rhizophagus intraradices, each starting from a single spore. Second, we "trained" each isolate individually in a community with two plants, sudangrass (Sorgum bicolour subsp. drummondii) and leek (Aliium ampeloprasum var. porrum), using a dual-compartment system to allow the establishment of a common mycorrhizal network between the two hosts. Third, we conducted a greenhouse experiment to reciprocally test each "trained" clone, obtained from each compartment, either with the same (home), or the other host (away) under two contrasting phosphorus levels. Overall, results did not support adaptive responses of the AM fungi to their hosts (i.e., greater host biomass under "home" relative to "away" conditions), but the opposite (i.e., greater host biomass under "away" relative to "home" conditions) was more frequently observed. These changes in AM fungal symbiotic functioning open the possibility for relatively rapid genetic change of arbuscular mycorrhizal fungi in response to new hosts, which represents one step forward from in vitro experiments.

Tracking of cell nuclei for assessment of in vitro uptake kinetics in ultrasound-mediated drug delivery using fibered confocal fluorescence microscopy.

PubMed

Derieppe, Marc; de Senneville, Baudouin Denis; Kuijf, Hugo; Moonen, Chrit; Bos, Clemens

2014-10-01

Previously, we demonstrated the feasibility to monitor ultrasound-mediated uptake of a cell-impermeable model drug in real time with fibered confocal fluorescence microscopy. Here, we present a complete post-processing methodology, which corrects for cell displacements, to improve the accuracy of pharmacokinetic parameter estimation. Nucleus detection was performed based on the radial symmetry transform algorithm. Cell tracking used an iterative closest point approach. Pharmacokinetic parameters were calculated by fitting a two-compartment model to the time-intensity curves of individual cells. Cells were tracked successfully, improving time-intensity curve accuracy and pharmacokinetic parameter estimation. With tracking, 93 % of the 370 nuclei showed a fluorescence signal variation that was well-described by a two-compartment model. In addition, parameter distributions were narrower, thus increasing precision. Dedicated image analysis was implemented and enabled studying ultrasound-mediated model drug uptake kinetics in hundreds of cells per experiment, using fiber-based confocal fluorescence microscopy.

Change rates and prevalence of a dichotomous variable: simulations and applications.

PubMed

Brinks, Ralph; Landwehr, Sandra

2015-01-01

A common modelling approach in public health and epidemiology divides the population under study into compartments containing persons that share the same status. Here we consider a three-state model with the compartments: A, B and Dead. States A and B may be the states of any dichotomous variable, for example, Healthy and Ill, respectively. The transitions between the states are described by change rates, which depend on calendar time and on age. So far, a rigorous mathematical calculation of the prevalence of property B has been difficult, which has limited the use of the model in epidemiology and public health. We develop a partial differential equation (PDE) that simplifies the use of the three-state model. To demonstrate the validity of the PDE, it is applied to two simulation studies, one about a hypothetical chronic disease and one about dementia in Germany. In two further applications, the PDE may provide insights into smoking behaviour of males in Germany and the knowledge about the ovulatory cycle in Egyptian women.

Estimating changes in mean body temperature for humans during exercise using core and skin temperatures is inaccurate even with a correction factor.

PubMed

Jay, Ollie; Reardon, Francis D; Webb, Paul; Ducharme, Michel B; Ramsay, Tim; Nettlefold, Lindsay; Kenny, Glen P

2007-08-01

Changes in mean body temperature (DeltaT(b)) estimated by the traditional two-compartment model of "core" and "shell" temperatures and an adjusted two-compartment model incorporating a correction factor were compared with values derived by whole body calorimetry. Sixty participants (31 men, 29 women) cycled at 40% of peak O(2) consumption for 60 or 90 min in the Snellen calorimeter at 24 or 30 degrees C. The core compartment was represented by esophageal, rectal (T(re)), and aural canal temperature, and the shell compartment was represented by a 12-point mean skin temperature (T(sk)). Using T(re) and conventional core-to-shell weightings (X) of 0.66, 0.79, and 0.90, mean DeltaT(b) estimation error (with 95% confidence interval limits in parentheses) for the traditional model was -95.2% (-83.0, -107.3) to -76.6% (-72.8, -80.5) after 10 min and -47.2% (-40.9, -53.5) to -22.6% (-14.5, -30.7) after 90 min. Using T(re), X = 0.80, and a correction factor (X(0)) of 0.40, mean DeltaT(b) estimation error for the adjusted model was +9.5% (+16.9, +2.1) to -0.3% (+11.9, -12.5) after 10 min and +15.0% (+27.2, +2.8) to -13.7% (-4.2, -23.3) after 90 min. Quadratic analyses of calorimetry DeltaT(b) data was subsequently used to derive best-fitting values of X for both models and X(0) for the adjusted model for each measure of core temperature. The most accurate model at any time point or condition only accounted for 20% of the variation observed in DeltaT(b) for the traditional model and 56% for the adjusted model. In conclusion, throughout exercise the estimation of DeltaT(b) using any measure of core temperature together with mean skin temperature irrespective of weighting is inaccurate even with a correction factor customized for the specific conditions.

Hepatic sinusoid is not well-stirred: estimation of the degree of axial mixing by analysis of lobular concentration gradients formed during uptake of thyroxine by the perfused rat liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weisiger, R.A.; Mendel, C.M.; Cavalieri, R.R.

1986-03-01

Two general models have been proposed for predicting the effects of metabolism, protein binding, and plasma flow on the removal of drugs by the liver. These models differ in the degree of plasma mixing assumed to exist within each hepatic sinusoid. The venous equilibrium model treats the sinusoid as a single well-stirred compartment, whereas the sinusoidal model effectively breaks up the sinusoid into a large number of sequentially perfused compartments which do not exchange their contents except through plasma flow. As a consequence, the sinusoidal model, but not the venous equilibrium model, predicts that the concentration of highly extracted drugsmore » will decline as the plasma flows through the hepatic lobule. To determine which of these alternative models best describes the hepatic uptake process, we looked for evidence that concentration gradients are formed during the uptake of (/sup 125/I)thyroxine by the perfused rat liver. Autoradiography of tissue slices after perfusion of the portal vein at physiologic flow rates with protein-free buffer containing (/sup 125/I)thyroxine demonstrated a rapid exponential fall in grain density with distance from the portal venule, declining by half for each 8% of the mean length of the sinusoid. Reversing the direction of perfusate flow reversed the direction of the autoradiographic gradients, indicating that they primarily reflect differences in the concentration of thyroxine within the hepatic sinusoids rather than differences in the uptake capacity of portal and central hepatocytes. Analysis of the data using models in which each sinusoid was represented by different numbers of sequentially perfused compartments (1-20) indicated that at least eight compartments were necessary to account for the magnitude of the gradients seen.« less

Electroremediation of PCB contaminated soil combined with iron nanoparticles: Effect of the soil type.

PubMed

Gomes, Helena I; Dias-Ferreira, Celia; Ottosen, Lisbeth M; Ribeiro, Alexandra B

2015-07-01

Polychlorinated biphenyls (PCB) are carcinogenic and persistent organic pollutants that accumulate in soils and sediments. Currently, there is no cost-effective and sustainable remediation technology for these contaminants. In this work, a new combination of electrodialytic remediation and zero valent iron particles in a two-compartment cell is tested and compared to a more conventional combination of electrokinetic remediation and nZVI in a three-compartment cell. In the new two-compartment cell, the soil is suspended and stirred simultaneously with the addition of zero valent iron nanoparticles. Remediation experiments are made with two different historically PCB contaminated soils, which differ in both soil composition and contamination source. Soil 1 is a mix of soils with spills of transformer oils, while Soil 2 is a superficial soil from a decommissioned school where PCB were used as windows sealants. Saponin, a natural surfactant, was also tested to increase the PCB desorption from soils and enhance dechlorination. Remediation of Soil 1 (with highest pH, carbonate content, organic matter and PCB concentrations) obtained the maximum 83% and 60% PCB removal with the two-compartment and the three-compartment cell, respectively. The highest removal with Soil 2 were 58% and 45%, in the two-compartment and the three-compartment cell, respectively, in the experiments without direct current. The pH of the soil suspension in the two-compartment treatment appears to be a determining factor for the PCB dechlorination, and this cell allowed a uniform distribution of the nanoparticles in the soil, while there was iron accumulation in the injection reservoir in the three-compartment cell. Copyright © 2015 Elsevier Ltd. All rights reserved.

The sinonasal communication in the horse: examinations using computerized three-dimensional reformatted renderings of computed-tomography datasets

PubMed Central

2014-01-01

Background Sinusitis is a common disease in the horse. In human medicine it is described, that obstruction of the sinonasal communication plays a major role in the development of sinusitis. To get spatial sense of the equine specific communication ways between the nasal cavity and the paranasal sinuses, heads of 19 horses, aged 2 to 26 years, were analyzed using three-dimensional (3D) reformatted renderings of CT-datasets. Three-dimensional models were generated following manual and semi-automated segmentation. Before segmentation, the two-dimensional (2D) CT-images were verified against corresponding frozen sections of cadaveric heads. Results Three-dimensional analysis of the paranasal sinuses showed the bilateral existence of seven sinus compartments: rostral maxillary sinus, ventral conchal sinus, caudal maxillary sinus, dorsal conchal sinus, frontal sinus, sphenopalatine sinus and middle conchal sinus. The maxillary septum divides these seven compartments into two sinus systems: a rostral paranasal sinus system composed of the rostral maxillary sinus and the ventral conchal sinus and a caudal paranasal sinus system which comprises all other sinuses. The generated 3D models revealed a typically configuration of the sinonasal communication ways. The sinonasal communication started within the middle nasal meatus at the nasomaxillary aperture (Apertura nasomaxillaris), which opens in a common sinonasal channel (Canalis sinunasalis communis). This common sinonasal channel ramifies into a rostral sinonasal channel (Canalis sinunasalis rostralis) and a caudo-lateral sinonasal channel (Canalis sinunasalis caudalis). The rostral sinonasal channel ventilated the rostral paranasal sinus system, the caudo-lateral sinonasal channel opened into the caudal paranasal sinus system. The rostral sinonasal channel was connected to the rostral paranasal sinuses in various ways. Whereas, the caudal channel showed less anatomical variations and was in all cases connected to the caudal maxillary sinus. Volumetric measurements of the sinonasal channels showed no statistically significant differences (P <0.05) between the right and left side of the head. Conclusions Under physiologic conditions both paranasal sinus systems are connected to the nasal cavity by equine specific sinonasal channels. To resolve sinus disease it is aimed to maintain or even reconstruct the normal anatomy of the sinonasal communication by surgical intervention. Therefore, the presented 3D analyses may provide a useful basis. PMID:24646003

STS-35 crewmembers in sleep station compartments on OV-102's middeck

NASA Image and Video Library

1990-12-11

Though they are not actually asleep, three STS-35 crewmembers demonstrate the bunk-style sleep compartments onboard Columbia's, Orbiter Vehicle (OV) 102's, middeck. From top to bottom are Payload Specialist Samuel T. Durrance, Mission Specialist (MS) Jeffrey A. Hoffman, and MS John M. Lounge. At the left is the shuttle amateur radio experiment (SAREX). The crew escape pole (CES) is visible overhead and the open airlock hatch in the foreground. The sleep station is located against the middeck starboard wall.

Shortened acquisition protocols for the quantitative assessment of the 2-tissue-compartment model using dynamic PET/CT 18F-FDG studies.

PubMed

Strauss, Ludwig G; Pan, Leyun; Cheng, Caixia; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2011-03-01

(18)F-FDG kinetics are quantified by a 2-tissue-compartment model. The routine use of dynamic PET is limited because of this modality's 1-h acquisition time. We evaluated shortened acquisition protocols up to 0-30 min regarding the accuracy for data analysis with the 2-tissue-compartment model. Full dynamic series for 0-60 min were analyzed using a 2-tissue-compartment model. The time-activity curves and the resulting parameters for the model were stored in a database. Shortened acquisition data were generated from the database using the following time intervals: 0-10, 0-16, 0-20, 0-25, and 0-30 min. Furthermore, the impact of adding a 60-min uptake value to the dynamic series was evaluated. The datasets were analyzed using dedicated software to predict the results of the full dynamic series. The software is based on a modified support vector machines (SVM) algorithm and predicts the compartment parameters of the full dynamic series. The SVM-based software provides user-independent results and was accurate at predicting the compartment parameters of the full dynamic series. If a squared correlation coefficient of 0.8 (corresponding to 80% explained variance of the data) was used as a limit, a shortened acquisition of 0-16 min was accurate at predicting the 60-min 2-tissue-compartment parameters. If a limit of 0.9 (90% explained variance) was used, a dynamic series of at least 0-20 min together with the 60-min uptake values is required. Shortened acquisition protocols can be used to predict the parameters of the 2-tissue-compartment model. Either a dynamic PET series of 0-16 min or a combination of a dynamic PET/CT series of 0-20 min and a 60-min uptake value is accurate for analysis with a 2-tissue-compartment model.

Predicting Drug Concentration‐Time Profiles in Multiple CNS Compartments Using a Comprehensive Physiologically‐Based Pharmacokinetic Model

PubMed Central

Yamamoto, Yumi; Välitalo, Pyry A.; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W.; van den Berg, Dirk‐Jan; Hartman, Robin; Wong, Yin Cheong; Danhof, Meindert; van Hasselt, John G. C.

2017-01-01

Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We developed a generic physiologically based pharmacokinetic (PBPK) model for prediction of drug concentrations in physiologically relevant CNS compartments. System‐specific and drug‐specific model parameters were derived from literature and in silico predictions. The model was validated using detailed concentration‐time profiles from 10 drugs in rat plasma, brain extracellular fluid, 2 cerebrospinal fluid sites, and total brain tissue. These drugs, all small molecules, were selected to cover a wide range of physicochemical properties. The concentration‐time profiles for these drugs were adequately predicted across the CNS compartments (symmetric mean absolute percentage error for the model prediction was <91%). In conclusion, the developed PBPK model can be used to predict temporal concentration profiles of drugs in multiple relevant CNS compartments, which we consider valuable information for efficient CNS drug development. PMID:28891201

Emergent central pattern generator behavior in chemical coupled two-compartment models with time delay

NASA Astrophysics Data System (ADS)

Li, Shanshan; Zhang, Guoshan; Wang, Jiang; Chen, Yingyuan; Deng, Bin

2018-02-01

This paper proposes that modified two-compartment Pinsky-Rinzel (PR) neural model can be used to develop the simple form of central pattern generator (CPG). The CPG is called as 'half-central oscillator', which constructed by two inhibitory chemical coupled PR neurons with time delay. Some key properties of PR neural model related to CPG are studied and proved to meet the requirements of CPG. Using the simple CPG network, we first study the relationship between rhythmical output and key factors, including ambient noise, sensory feedback signals, morphological character of single neuron as well as the coupling delay time. We demonstrate that, appropriate intensity noise can enhance synchronization between two coupled neurons. Different output rhythm of CPG network can be entrained by sensory feedback signals. We also show that the morphology of single neuron has strong effect on the output rhythm. The phase synchronization indexes decrease with the increase of morphology parameter's difference. Through adjusting coupled delay time, we can get absolutely phase synchronization and antiphase state of CPG. Those results of simulation show the feasibility of PR neural model as a valid CPG as well as the emergent behaviors of the particularly CPG.

Alveolar ventilation to perfusion heterogeneity and diffusion impairment in a mathematical model of gas exchange

NASA Technical Reports Server (NTRS)

Vidal Melo, M. F.; Loeppky, J. A.; Caprihan, A.; Luft, U. C.

1993-01-01

This study describes a two-compartment model of pulmonary gas exchange in which alveolar ventilation to perfusion (VA/Q) heterogeneity and impairment of pulmonary diffusing capacity (D) are simultaneously taken into account. The mathematical model uses as input data measurements usually obtained in the lung function laboratory. It consists of two compartments and an anatomical shunt. Each compartment receives fractions of alveolar ventilation and blood flow. Mass balance equations and integration of Fick's law of diffusion are used to compute alveolar and blood O2 and CO2 values compatible with input O2 uptake and CO2 elimination. Two applications are presented. The first is a method to partition O2 and CO2 alveolar-arterial gradients into VA/Q and D components. The technique is evaluated in data of patients with chronic obstructive pulmonary disease (COPD). The second is a theoretical analysis of the effects of blood flow variation in alveolar and blood O2 partial pressures. The results show the importance of simultaneous consideration of D to estimate VA/Q heterogeneity in patients with diffusion impairment. This factor plays an increasing role in gas alveolar-arterial gradients as severity of COPD increases. Association of VA/Q heterogeneity and D may produce an increase of O2 arterial pressure with decreasing QT which would not be observed if only D were considered. We conclude that the presented computer model is a useful tool for description and interpretation of data from COPD patients and for performing theoretical analysis of variables involved in the gas exchange process.

Pharmacokinetic properties of intramuscular versus oral syrup paracetamol in Plasmodium falciparum malaria.

PubMed

Wattanakul, Thanaporn; Teerapong, Pramote; Plewes, Katherine; Newton, Paul N; Chierakul, Wirongrong; Silamut, Kamolrat; Chotivanich, Kesinee; Ruengweerayut, Ronnatrai; White, Nicholas J; Dondorp, Arjen M; Tarning, Joel

2016-04-27

Fever is an inherent symptom of malaria in both adults and children. Paracetamol (acetaminophen) is the recommended antipyretic as it is inexpensive, widely available and has a good safety profile, but patients may not be able to take the oral drug reliably. A comparison between the pharmacokinetics of oral syrup and intramuscular paracetamol given to patients with acute falciparum malaria and high body temperature was performed. A randomized, open-label, two-treatment, crossover, pharmacokinetic study of paracetamol dosed orally and intramuscularly was conducted. Twenty-one adult patients with uncomplicated falciparum malaria were randomized to receive a single 600 mg dose of paracetamol either as syrup or intramuscular injection on day 0 followed by a single dose administered by the alternative route on day 1. Paracetamol plasma concentrations were quantified frequently and modelled simultaneously using nonlinear mixed-effects modelling. The final population pharmacokinetic model was used for dose optimization simulations. Relationships between paracetamol concentrations with temperature and parasite half-life were investigated using linear and non-linear regression analyses. The population pharmacokinetic properties of paracetamol were best described by a two-compartment disposition model, with zero-order and first-order absorption for intramuscular and oral syrup administration, respectively. The relative bioavailability of oral syrup was 84.4 % (95 % CI 68.2-95.1 %) compared to intramuscular administration. Dosing simulations showed that 1000 mg of intramuscular or oral syrup administered six-hourly reached therapeutic steady state concentrations for antipyresis, but more favourable concentration-time profiles were achieved with a loading dose of 1500 mg, followed by a 1000 mg maintenance dose. This ensured that maximum therapeutic concentrations were reached rapidly during the first 6 h. No significant relationships between paracetamol concentrations and temperature or parasite half-life were found. Paracetamol plasma concentrations after oral syrup and intramuscular administration in patients with acute falciparum malaria were described successfully by a two-compartment disposition model. Relative oral bioavailability compared to intramuscular dosing was estimated as 84.4 % (95 % CI 68.2-95.1 %). Dosing simulations showed that a loading dose followed by six-hourly dosing intervals reduced the time delay to reach therapeutic drug levels after both routes of administration. The safety and efficacy of loading dose paracetamol antipyretic regimens now needs to be established in larger studies.

Osmosis-Based Pressure Generation: Dynamics and Application

PubMed Central

Li, Suyi; Billeh, Yazan N.; Wang, K. W.; Mayer, Michael

2014-01-01

This paper describes osmotically-driven pressure generation in a membrane-bound compartment while taking into account volume expansion, solute dilution, surface area to volume ratio, membrane hydraulic permeability, and changes in osmotic gradient, bulk modulus, and degree of membrane fouling. The emphasis lies on the dynamics of pressure generation; these dynamics have not previously been described in detail. Experimental results are compared to and supported by numerical simulations, which we make accessible as an open source tool. This approach reveals unintuitive results about the quantitative dependence of the speed of pressure generation on the relevant and interdependent parameters that will be encountered in most osmotically-driven pressure generators. For instance, restricting the volume expansion of a compartment allows it to generate its first 5 kPa of pressure seven times faster than without a restraint. In addition, this dynamics study shows that plants are near-ideal osmotic pressure generators, as they are composed of many small compartments with large surface area to volume ratios and strong cell wall reinforcements. Finally, we demonstrate two applications of an osmosis-based pressure generator: actuation of a soft robot and continuous volume delivery over long periods of time. Both applications do not need an external power source but rather take advantage of the energy released upon watering the pressure generators. PMID:24614529

Data reduction of room tests for zone model validation

Treesearch

M. Janssens; H. C. Tran

1992-01-01

Compartment fire zone models are based on many simplifying assumptions, in particular that gases stratify in two distinct layers. Because of these assumptions, certain model output is in a form unsuitable for direct comparison to measurements made in full-scale room tests. The experimental data must first be reduced and transformed to be compatible with the model...

Microgravity-Induced Physiological Fluid Redistribution: Computational Analysis to Assess Influence of Physiological Parameters

NASA Technical Reports Server (NTRS)

Myers, J. G.; Eke, Chika; Werner, C.; Nelson, E. S.; Mulugeta, L.; Feola, A.; Raykin, J.; Samuels, B.; Ethier, C. R.

2016-01-01

Space flight impacts human physiology in many ways, the most immediate being the marked cephalad (headward) shift of fluid upon introduction into the microgravity environment. This physiological response to microgravity points to the redistribution of blood and interstitial fluid as a major factor in the loss of venous tone and reduction in heart muscle efficiency which impact astronaut performance. In addition, researchers have hypothesized that a reduction in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, is associated with this redistribution of fluid. VIIP arises within several months of beginning space flight and includes a variety of ophthalmic changes including posterior globe flattening, distension of the optic nerve sheath, and kinking of the optic nerve. We utilize a suite of lumped parameter models to simulate microgravity-induced fluid redistribution in the cardiovascular, central nervous and ocular systems to provide initial and boundary data to a 3D finite element simulation of ocular biomechanics in VIIP. Specifically, the lumped parameter cardiovascular model acts as the primary means of establishing how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. The cardiovascular model consists of 16 compartments, including three cerebrospinal fluid (CSF) compartments, three cranial blood compartments, and 10 thoracic and lower limb blood compartments. To assess the models capability to address variations in physiological parameters, we completed a formal uncertainty and sensitivity analysis that evaluated the relative importance of 42 input parameters required in the model on relative compartment flows and compartment pressures. Utilizing the model in a pulsatile flow configuration, the sensitivity analysis identified the ten parameters that most influenced each compartment pressure. Generally, each compartment responded appropriately to parameter variations associated with itself and adjacent compartments. However, several unexpected interactions between components, such as between the choroid plexus and the lower capillaries, were found, and are due to simplifications in the formulation of the model. The analysis illustrates that highly influential parameters and those that have unique influences within the model formulation must be tightly controlled for successful model application.

Neuromuscular partitioning in the extensor carpi radialis longus and brevis based on intramuscular nerve distribution patterns: A three-dimensional modeling study.

PubMed

Ravichandiran, Mayoorendra; Ravichandiran, Nisanthini; Ravichandiran, Kajeandra; McKee, Nancy H; Richardson, Denyse; Oliver, Michele; Agur, Anne M

2012-04-01

Differential activation of specific regions within a skeletal muscle has been linked to the presence of neuromuscular compartments. However, few studies have investigated the extra- or intramuscular innervation throughout the muscle volume of extensor carpi radialis longus (ECRL) and brevis (ECRB). The aim of this study was to determine the presence of neuromuscular partitions in ECRL and ECRB based on the extra- and intramuscular innervation using three-dimensional modeling. The extra- and intramuscular nerve distribution was digitized and reconstructed in 3D in all the muscle volumes using Autodesk Maya in seven formalin embalmed cadaveric specimens (mean age, 75.7 ± 15.2 years). The intramuscular nerve distribution was modeled in all the muscle volumes. ECRL was found to have two neuromuscular compartments, superficial and deep. One branch from the radial nerve proper was found to innervate ECRL. This branch was divided into anterior and posterior branches to the superficial and deep compartments, respectively. Five innervation patterns were identified in ECRB with partitioning of the muscle belly into two, three, or four compartments, in a proximal to distal direction depending on the number of nerve branches entering the muscle belly. The ECRL and ECRB both demonstrated neuromuscular compartmentalization based on intramuscular innervation. According to the partitioning hypothesis, a muscle may be differentially activated depending on the required function of the muscle, thus allowing multifunctional muscles to contribute to a variety of movements. Therefore, the increased number of neuromuscular partitions in ECRB when compared with ECRL could be due to the need for more differential recruitment in the ECRB depending on force requirements. Copyright © 2011 Wiley Periodicals, Inc.

The Hv1 proton channel responds to mechanical stimuli.

PubMed

Pathak, Medha M; Tran, Truc; Hong, Liang; Joós, Béla; Morris, Catherine E; Tombola, Francesco

2016-11-01

The voltage-gated proton channel, Hv1, is expressed in tissues throughout the body and plays important roles in pH homeostasis and regulation of NADPH oxidase. Hv1 operates in membrane compartments that experience strong mechanical forces under physiological or pathological conditions. In microglia, for example, Hv1 activity is potentiated by cell swelling and causes an increase in brain damage after stroke. The channel complex consists of two proton-permeable voltage-sensing domains (VSDs) linked by a cytoplasmic coiled-coil domain. Here, we report that these VSDs directly respond to mechanical stimuli. We find that membrane stretch facilitates Hv1 channel opening by increasing the rate of activation and shifting the steady-state activation curve to less depolarized potentials. In the presence of a transmembrane pH gradient, membrane stretch alone opens the channel without the need for strong depolarizations. The effect of membrane stretch persists for several minutes after the mechanical stimulus is turned off, suggesting that the channel switches to a "facilitated" mode in which opening occurs more readily and then slowly reverts to the normal mode observed in the absence of membrane stretch. Conductance simulations with a six-state model recapitulate all the features of the channel's response to mechanical stimulation. Hv1 mechanosensitivity thus provides a mechanistic link between channel activation in microglia and brain damage after stroke. © 2016 Pathak et al.

Evaluation of conceptual models of natural organic matter (humus) from a consideration of the chemical and biochemical processes of humification

USGS Publications Warehouse

Wershaw, Robert L.

2004-01-01

Natural organic matter (NOM) has been studied for more than 200 years because of its importance in enhancing soil fertility, soil structure, and water-holding capacity and as a carbon sink in the global carbon cycle. Two different types of models have been proposed for NOM: (1) the humic polymer models and (2) the molecular aggregate models. In the humic polymer models, NOM molecules are depicted as large (humic) polymers that have unique chemical structures that are different from those of the precursor plant degradation products. In the molecular aggregate models, NOM is depicted as being composed of molecular aggregates (supramolecular aggregates) of plant degradation products held together by non-covalent bonds. The preponderance of evidence favors the supramolecular aggregate models. These models were developed by studying the properties of NOM extracted from soils and natural waters, and as such, they provide only a very generalized picture of the structure of NOM aggregates in soils and natural waters prior to extraction. A compartmental model, in which the structure of the NOM in each of the compartments is treated separately, should provide a more accurate representation of NOM in soil and sediment systems. The proposed NOM compartments are: (1) partially degraded plant tissue, (2) biomass from microorganisms, (3) organic coatings on mineral grains, (4) pyrolytic carbon, (5) organic precipitates, and (6) dissolved organic matter (DOM) in interstitial water. Within each of these compartments there are NOM supramolecular aggregates that will be dissolved by the solvent systems that are used by researchers for extraction of NOM from soils and sediments. In natural water systems DOM may be considered as existing in two subcompartments: (1) truly dissolved DOM and (2) colloidal DOM.

A Review on Pharmacokinetic Modeling and the Effects of Environmental Stressors on Pharmacokinetics for Operational Medicine: Operational Pharmacokinetics

DTIC Science & Technology

2009-09-01

hypercholesterolemia Two-compartment model Ezzet, Krishna et al. 2001 Antilipemics Statins: simvastatin, rosuvastatin, atorvastatin Treatment of...Pharmacokinetic model* & rosuvastatin Scopus 14 3 PubMed 9 3 Pharmacokinetic model* & atorvastatin Scopus 49 4 Pharmacokinetic model* & zaleplon...Fentanyl & pharmacokinetic & heat 9 2 Fentanyl & pharmacokinetic & cold 4 0 Fentanyl & pharmacokinetic & blood loss 19 5 Atorvastatin

Non-invasive breast biopsy method using GD-DTPA contrast enhanced MRI series and F-18-FDG PET/CT dynamic image series

NASA Astrophysics Data System (ADS)

Magri, Alphonso William

This study was undertaken to develop a nonsurgical breast biopsy from Gd-DTPA Contrast Enhanced Magnetic Resonance (CE-MR) images and F-18-FDG PET/CT dynamic image series. A five-step process was developed to accomplish this. (1) Dynamic PET series were nonrigidly registered to the initial frame using a finite element method (FEM) based registration that requires fiducial skin markers to sample the displacement field between image frames. A commercial FEM package (ANSYS) was used for meshing and FEM calculations. Dynamic PET image series registrations were evaluated using similarity measurements SAVD and NCC. (2) Dynamic CE-MR series were nonrigidly registered to the initial frame using two registration methods: a multi-resolution free-form deformation (FFD) registration driven by normalized mutual information, and a FEM-based registration method. Dynamic CE-MR image series registrations were evaluated using similarity measurements, localization measurements, and qualitative comparison of motion artifacts. FFD registration was found to be superior to FEM-based registration. (3) Nonlinear curve fitting was performed for each voxel of the PET/CT volume of activity versus time, based on a realistic two-compartmental Patlak model. Three parameters for this model were fitted; two of them describe the activity levels in the blood and in the cellular compartment, while the third characterizes the washout rate of F-18-FDG from the cellular compartment. (4) Nonlinear curve fitting was performed for each voxel of the MR volume of signal intensity versus time, based on a realistic two-compartment Brix model. Three parameters for this model were fitted: rate of Gd exiting the compartment, representing the extracellular space of a lesion; rate of Gd exiting a blood compartment; and a parameter that characterizes the strength of signal intensities. Curve fitting used for PET/CT and MR series was accomplished by application of the Levenburg-Marquardt nonlinear regression algorithm. The best-fit parameters were used to create 3D parametric images. Compartmental modeling evaluation was based on the ability of parameter values to differentiate between tissue types. This evaluation was used on registered and unregistered image series and found that registration improved results. (5) PET and MR parametric images were registered through FEM- and FFD-based registration. Parametric image registration was evaluated using similarity measurements, target registration error, and qualitative comparison. Comparing FFD and FEM-based registration results showed that the FEM method is superior. This five-step process constitutes a novel multifaceted approach to a nonsurgical breast biopsy that successfully executes each step. Comparison of this method to biopsy still needs to be done with a larger set of subject data.

123/125I-labelled 2-iodo-L: -phenylalanine and 2-iodo-D: -phenylalanine: comparative uptake in various tumour types and biodistribution in mice.

PubMed

Kersemans, Veerle; Cornelissen, Bart; Kersemans, Ken; Bauwens, Matthias; Dierckx, Rudi A; De Spiegeleer, Bart; Mertens, John; Slegers, Guido

2006-08-01

In vitro in the R1M cell model and in vivo in the R1M tumour-bearing athymic model, both [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine have shown promising results as tumour diagnostic agents for SPECT. In order to compare these two amino acid analogues and to examine whether the observed characteristics could be generalised, both isomers were evaluated in various tumour models. Transport type characterisation in vitro in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M cells with [(123)I]-2-iodo-L: -phenylalanine was performed using the method described by Shotwell et al. Subsequently, [(123)I]-2-iodo-L: -phenylalanine and [(123)I]-2-iodo-D: -phenylalanine tumour uptake and biodistribution were evaluated using dynamic planar imaging and/or dissection in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M inoculated athymic mice. Two-compartment blood modelling of the imaging results was performed. In vitro testing demonstrated that [(123)I]-2-iodo-L: -phenylalanine was transported in all tumour cell lines by LAT1. In all tumour models, the two amino acid analogues showed the same general biodistribution characteristics: high and specific tumour uptake and renal tracer clearance. Two-compartment modelling revealed that the D: -isomer showed a faster blood clearance together with a faster distribution to the peripheral compartment in comparison with [(123)I]-2-iodo-L: -phenylalanine. [(123)I]-2-iodo-L: -phenylalanine and its D: -isomer are promising tumour diagnostic agents for dynamic planar imaging. They showed a high and similar uptake in all tested tumours. [(123)I]-2-iodo-D: -phenylalanine showed better tracer characteristics concerning radiation dose to other organs.

Evaluation of Laminaria-based microbial fuel cells (LbMs) for electricity production.

PubMed

Gadhamshetty, Venkataramana; Belanger, Derek; Gardiner, Carly-Jeanne; Cummings, Anasha; Hynes, Anne

2013-01-01

Marine algae represents a sustainable feedstock in microbial fuel cells (MFCs) due to its low water and energy requirements for cultivation, higher capacity to sequester carbondioxide, and high carbohydrate content. Two-compartment MFCs were evaluated under batch-fed mode using Laminaria saccharina as the model for algae-based electron donor, and mixed microbial consortia as the biocatalyst, in the anode compartment. The Laminaria-based MFCs (LBMs) were studied with three different pretreatment conditions for the L. saccharina: (i) autoclaving (Auto), (ii) microwave irradiation (Micro), and (iii) as received treatment (No-Treat). A control was setup to establish base line performance for two-compartment MFCs using glucose as the electron donor in the anode. The performance of LBMs (250 mW/m(2) and 900 mA/m(2)) was on par with glucose-based MFCs. AC impedance analysis revealed that the charge transfer resistance was at least 50-fold higher than the corresponding ohmic losses in both LBMs and glucose-based MFCs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anatomical Study of Temporal Fat Compartments and its Clinical Application for Temporal Fat Grafting

PubMed Central

Huang, Ru-Lin; Xie, Yun; Wang, Wenjin; Herrler, Tanja; Zhou, Jia; Zhao, Peijuan; Pu, Lee LQ; Li, Qingfeng

2017-01-01

Abstract Background Low satisfaction rates and severe complications are two major limitations for temporal hollowing augmentation using autologous fat grafting. Despite fat compartments in temporal region have been reported, its clinical applied anatomy for fat grafting have not been the subject of studies that show its benefits objectively and statistically. Objectives To investigate temporal fat compartments and relative neurovascular structures in cadavers, developing a safe and effective fat grafting technique for temporal hollowing augmentation. Methods The study was conducted on 8 cadavers (16 temples). The tissue layers, fat compartments, ligaments, and neurovascular structures in the temporal region were analysed. The variables were the number and location of sentinel veins, perforator vessels of the middle temporal vein. Measurements were taken with a digital calliper. Results Two separate fat compartments, the lateral temporal-cheek fat compartment and lateral orbital fat compartment, were found in the subcutaneous layer, and two separate septum compartments, the upper and lower temporal compartment, were found in the loose areolar tissue layer. One sentinel vein and 1 to 6 perforator vessels were found to travel through the subcutaneous tissue layer, traverse the overlapping tissue layers in the lower temporal septum region, and finally join in the middle temporal vein. Conclusions The four fat compartments in the temporal region are ideal receipt sites for fat grafting. The medial border of the junction of the hairline and temporal line is a safe and effective cannula entry site for temporal fat grafting. The anterior half of the lower temporal compartment is a “zone of caution” for temporal fat grafting. PMID:28520850

The structure of bovine mitochondrial adenylate kinase: comparison with isoenzymes in other compartments.

PubMed Central

Schlauderer, G. J.; Schulz, G. E.

1996-01-01

In vertebrates, there are different adenylate kinases in the compartments cytosol, mitochondrial intermembrane space, and mitochondrial matrix. Here, we report the spatial structure of the intermembrane species established in two crystal forms by X-ray diffraction analyses at 1.92 and 2.1 A resolution. In both structures, the enzyme is unligated, and thus in an "open" conformation. The enzyme was prepared from bovine liver, containing at least five variants arisen from posttranscriptional and posttranslational modifications. It could only be crystallized after removing some of these variants. A comparison with the known structures of the adenylate kinases from cytosol and mitochondrial matrix reveals structural differences that should play a role in protein targeting because none of these enzymes contains a cleavable signal peptide. A further comparison with adenylate kinases from Gram-positive bacteria showed that the structural Zn2+ ion of these species is replaced by a strictly conserved assembly of hydrogen bonded residues. PMID:8868479

Chronic exertional compartment syndrome of the superficial posterior compartment: Soleus syndrome.

PubMed

Gross, Christopher E; Parekh, Bela J; Adams, Samuel B; Parekh, Selene G

2015-01-01

Chronic exertional compartment syndrome (CECS) represents the second most-common cause of exertional leg pain with incidence of 27-33%. CECS of the superficial posterior compartment, or soleus syndrome, is rare and has only been discussed briefly in the literature. We discuss the management of two patients with bilateral soleus syndrome or CECS of the superficial posterior compartment.

Two-compartment passive frequency domain cochlea model allowing independent fluid coupling to the tectorial and basilar membranes

PubMed Central

Cormack, John; Liu, Yanju; Nam, Jong-Hoon; Gracewski, Sheryl M.

2015-01-01

The cochlea is a spiral-shaped, liquid-filled organ in the inner ear that converts sound with high frequency selectivity over a wide pressure range to neurological signals that are eventually interpreted by the brain. The cochlear partition, consisting of the organ of Corti supported below by the basilar membrane and attached above to the tectorial membrane, plays a major role in the frequency analysis. In early fluid-structure interaction models of the cochlea, the mechanics of the cochlear partition were approximated by a series of single-degree-of-freedom systems representing the distributed stiffness and mass of the basilar membrane. Recent experiments suggest that the mechanical properties of the tectorial membrane may also be important for the cochlea frequency response and that separate waves may propagate along the basilar and tectorial membranes. Therefore, a two-dimensional two-compartment finite difference model of the cochlea was developed to investigate the independent coupling of the basilar and tectorial membranes to the surrounding liquid. Responses are presented for models using two- or three-degree-of-freedom stiffness, damping, and mass parameters derived from a physiologically based finite element model of the cochlear partition. Effects of changes in membrane and organ of Corti stiffnesses on the individual membrane responses are investigated. PMID:25786927

[Analysis of parameters of serum concentration and pharmacokinetic of liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats].

PubMed

Zha, Lin; Zhao, Yan; Zhu, Hong-Yan; Cai, En-Bo; Liu, Shuang-Li; Yang, He; Zhao, Ying; Gao, Yu-Gang; Zhang, Lian-Xue

2017-05-01

The experiment was aimed to investigate the difference of plasma concentration and pharmacokinetic parameters between liposome and aqueous solution of toatal ginsenoside of ginseng stems and leaves in rats, such as ginsenosides Rg₁, Re, Rf, Rb₁, Rg₂, Rc, Rb₂, Rb₃, Rd. After intravenous injection of liposome and aqueous solution in rats, the blood was taken from the femoral vein to detect the plasma concentration of the above 9 ginsenoside monomers in different time points by using HPLC. The concentration-time curve was obtained and 3p97 pharmacokinetic software was used to get the pharmacokinetic parameters. After the intravenous injection of ginsenosides to rats, nine ginsenosides were detected in plasma. In general, among these ginsenosides, the peak time of the aqueous solution was between 0.05 to 0.083 3 h, and the serum concentration peak of liposome usually appeared after 0.5 h. After software fitting, the aqueous solution of ginsenoside monomers Rg₁, Re, Rf, Rg₂, Rc, Rd, Rb₃ was two-compartment model, and the liposomes were one-compartment model; aqueous solution and liposome of ginsenoside monomers Rb₁ were three-compartment model; aqueous solution of ginsenoside monomers Rb₂ was three-compartment model, and its liposome was one-compartment model. Area under the drug time curve (AUC) of these 9 kinds of saponin liposomes was larger than that of aqueous solution, and the retention time of the liposomes was longer than that of the aqueous solution; the removal rate was slower than that of the aqueous solution, and the half-life was longer than that of the water solution. The results from the experiment showed that by intravenous administration, the pharmacokinetic parameters of two formulations were significantly different from each other; the liposomes could not only remain the drug for a longer time in vivo, but also reduce the elimination rate and increase the treatment efficacy. As compared with the traditional dosage forms, the total ginsenoside of ginseng stems and leaves can improve the sustained release of the drug, which is of great significance for the research and development of new dosage forms of ginsenosides in the future. Copyright© by the Chinese Pharmaceutical Association.

Limitations of the permeability-limited compartment model in estimating vascular permeability and interstitial volume fraction in DCE-MRI.

PubMed

Carreira, Guido Correia; Gemeinhardt, Ole; Gorenflo, Rudolf; Beyersdorff, Dirk; Franiel, Tobias; Plendl, Johanna; Lüdemann, Lutz

2011-06-01

Dynamic contrast-enhanced magnetic resonance imaging commonly uses compartment models to estimate tissue parameters in general and perfusion parameters in particular. Compartment models assume a homogeneous distribution of the injected tracer throughout the compartment volume. Since tracer distribution within a compartment cannot be assessed, the parameters obtained by means of a compartment model might differ from the actual physical values. This work systematically examines the widely used permeability-surface-limited one-compartment model to determine the reliability of the parameters obtained by comparing them with their actual values. A computer simulation was used to model spatial tracer distribution within the interstitial volume using diffusion of contrast agent in tissue. Vascular parameters were varied as well as tissue parameters. The vascular parameters used were capillary radius (4 and 12 μm), capillary permeability (from 0.03 to 3.3 μm/s) and intercapillary distances from 30 to 300 μm. The tissue parameters used were tortuosity (λ), porosity (α) and interstitial volume fraction (v(e)). Our results suggest that the permeability-surface-limited compartment model generally underestimates capillary permeability for capillaries with a radius of 4 μm by factors from ≈0.03 for α=0.04, to ≈ 0.1 for α=0.2, to ≈ 0.5 for α=1.0. An overestimation of actual capillary permeability for capillaries with a radius of 12 μm by a factor of ≥1.3 was found for α=1.0, while α=0.2 yielded an underestimation by a factor of ≈0.3 and α=0.04 by a factor of ≈ 0.03. The interstitial volume fraction, v(e), obtained by the compartment model differed with increasing intercapillary distances and for low vessel permeability, whereas v(e) was found to be estimated approximately accurately for P=0.3 μm/s and P=3.3 μm/s for vessel distances <100 μm. Copyright © 2011 Elsevier Inc. All rights reserved.

Esophageal lesions following button-battery ingestion in children: Analysis of causes and proposals for preventive measures.

PubMed

Lahmar, J; Célérier, C; Garabédian, E N; Couloigner, V; Leboulanger, N; Denoyelle, F

2018-04-01

To study recent cases of esophageal injury due to button-battery ingestion in children presenting in pediatric ENT emergency departments of the Paris area of France (Île-de-France region), in order to propose appropriate preventive measures. A retrospective descriptive single-center study included all children under 15 years of age, presenting in pediatric ENT emergency departments between January 2008 and April 2014 for button-battery ingestion with esophageal impaction requiring emergency removal. Twenty-two boys and 4 girls, with a median age of 25 months, were included. Twenty-five of the 26 batteries had diameters of 20mm or more. Median esophageal impaction time was 7 hours 30 minutes (range, 2 to 72 hours). The complications rate was 23%. Mean hospital stay cost was €38,751 (range, €5130-119,737). The origin of the battery was known in 23 of the 26 cases: remote control without screw-secured compartment (42.3%), open battery pack (15.4%), children's toy (15.3%), camera (7.7%), watch (1 case) and hearing aid without screw-secured compartment (1 case). Esophageal lesions due to ingestion of button-batteries in children are almost always due to batteries larger than 20mm in diameter, mostly from devices with a poorly protected compartment, or batteries that are not individually packaged. These lesions cause serious complications in a quarter of cases and their management entails high health costs. Legislation requiring screw-secured compartments and individual blisters for batteries could have prevented 69.2% of the ingestions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Preliminary Modelling of Mass Flux at the Surface of Plant Leaves within the MELiSSA Higher Plant Compartments

NASA Astrophysics Data System (ADS)

Holmberg, Madeleine; Paille, Christel; Lasseur, Christophe

The ESA project Micro Ecological Life Support System Alternative (MELiSSA) is an ecosystem of micro-organisms and higher plants, constructed with the objective of being operated as a tool to understand artificial ecosystems to be used for a long-term or permanent manned planetary base (e.g. Moon or Mars). The purpose of such a system is to provide for generation of food, water recycling, atmospheric regeneration and waste management within defined standards of quality and reliability. As MELiSSA consists of individual compartments which are connected to each other, the robustness of the system is fully dependent on the control of each compartment, as well as the flow management between them. Quality of consumables and reliability of the ecosystem rely on the knowledge, understanding and control of each of the components. This includes the full understanding of all processes related to the higher plants. To progress in that direction, this paper focuses on the mechanical processes driving the gas and liquid exchanges between the plant leaf and its environment. The process responsible for the mass transfer on the surface of plant leaves is diffusion. The diffusion flux is dependent on the behaviour of the stoma of the leaf and also on the leaf boundary layer (BL). In this paper, the physiology of the leaf is briefly examined in order to relate parameters such as light quality, light quantity, CO2 concentration, temperature, leaf water potential, humidity, vapour pressure deficit (VPD) gradients and pollutants to the opening or closing of stomata. The diffusion process is described theoretically and the description is compared to empirical approaches. The variables of the BL are examined and the effect airflow in the compartment has on the BL is investigated. Also presented is the impact changes in different environmental parameters may have on the fluid exchanges. Finally, some tests, to evaluate the accuracy of the concluded model, are suggested.

[Modelling of phosphorus transfers during haemodialysis].

PubMed

Chazot, Guillaume; Lemoine, Sandrine; Juillard, Laurent

2017-04-01

Chronic kidney disease causes hyperphosphatemia, which is associated with increased cardiovascular risk and mortality. In patients with end-stage renal disease, haemodialysis allows the control of hyperphosphatemia. During a 4-h haemodialysis session, between 600 and 700mg of phosphate are extracted from the plasma, whereas the latter contains only 90mg of inorganic phosphate. The precise origin of phosphates remains unknown. The modelling of phosphorus transfers allows to predict the outcome after changes in dialysis prescription (duration, frequency) with simple two-compartment models and to describe the transfers between the different body compartments with more complex models. Work using 31 P nuclear magnetic resonance spectroscopy performed in animals showed an increase in intracellular phosphate concentration and a decrease in intracellular ATP during a haemodialysis session suggesting an intracellular origin of phosphates. Copyright © 2017. Published by Elsevier Masson SAS.

Oscillations in epidemic models with spread of awareness.

PubMed

Just, Winfried; Saldaña, Joan; Xin, Ying

2018-03-01

We study ODE models of epidemic spreading with a preventive behavioral response that is triggered by awareness of the infection. Previous studies of such models have mostly focused on the impact of the response on the initial growth of an outbreak and the existence and location of endemic equilibria. Here we study the question whether this type of response is sufficient to prevent future flare-ups from low endemic levels if awareness is assumed to decay over time. In the ODE context, such flare-ups would translate into sustained oscillations with significant amplitudes. Our results show that such oscillations are ruled out in Susceptible-Aware-Infectious-Susceptible models with a single compartment of aware hosts, but can occur if we consider two distinct compartments of aware hosts who differ in their willingness to alert other susceptible hosts.

The Role of Water Compartments in the Material Properties of Cortical Bone.

PubMed

Granke, Mathilde; Does, Mark D; Nyman, Jeffry S

2015-09-01

Comprising ~20% of the volume, water is a key determinant of the mechanical behavior of cortical bone. It essentially exists in two general compartments: within pores and bound to the matrix. The amount of pore water-residing in the vascular-lacunar-canalicular space-primarily reflects intracortical porosity (i.e., open spaces within the matrix largely due to Haversian canals and resorption sites) and as such is inversely proportional to most mechanical properties of bone. Movement of water according to pressure gradients generated during dynamic loading likely confers hydraulic stiffening to the bone as well. Nonetheless, bound water is a primary contributor to the mechanical behavior of bone in that it is responsible for giving collagen the ability to confer ductility or plasticity to bone (i.e., allows deformation to continue once permanent damage begins to form in the matrix) and decreases with age along with fracture resistance. Thus, dehydration by air-drying or by solvents with less hydrogen bonding capacity causes bone to become brittle, but interestingly, it also increases stiffness and strength across the hierarchical levels of organization. Despite the importance of matrix hydration to fracture resistance, little is known about why bound water decreases with age in hydrated human bone. Using (1)H nuclear magnetic resonance (NMR), both bound and pore water concentrations in bone can be measured ex vivo because the proton relaxation times differ between the two water compartments, giving rise to two distinct signals. There are also emerging techniques to measure bound and pore water in vivo with magnetic resonance imaging (MRI). The NMR/MRI-derived bound water concentration is positively correlated with both the strength and toughness of hydrated bone and may become a useful clinical marker of fracture risk.

Normal tissue complication probability (NTCP) parameters for breast fibrosis: pooled results from two randomised trials.

PubMed

Mukesh, Mukesh B; Harris, Emma; Collette, Sandra; Coles, Charlotte E; Bartelink, Harry; Wilkinson, Jenny; Evans, Philip M; Graham, Peter; Haviland, Jo; Poortmans, Philip; Yarnold, John; Jena, Raj

2013-08-01

The dose-volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy. We pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n=1410) were used to test the predicted models. 26.8% patients in the Cambridge trial (5 years) and 20.7% patients in the EORTC trial (10 years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50)=136.4 Gy, γ50=0.9 and n=0.011 for the Niemierko model and BEUD3(50)=132 Gy, m=0.35 and n=0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates. This large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter 'n' does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

46 CFR 25.30-20 - Fire extinguishing equipment required.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... Bait wells. 2. Glove compartments. 3. Buoyant flotation material. 4. Open slatted flooring. 5. Ice... approved semiportable fire extinguisher has wheels and is not required by this section, it must be securely...

46 CFR 25.30-20 - Fire extinguishing equipment required.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... Bait wells. 2. Glove compartments. 3. Buoyant flotation material. 4. Open slatted flooring. 5. Ice... approved semiportable fire extinguisher has wheels and is not required by this section, it must be securely...

Definition of compartment-based radical surgery in uterine cancer: radical hysterectomy in cervical cancer as 'total mesometrial resection (TMMR)' by M Höckel translated to robotic surgery (rTMMR).

PubMed

Kimmig, Rainer; Wimberger, Pauline; Buderath, Paul; Aktas, Bahriye; Iannaccone, Antonella; Heubner, Martin

2013-08-26

Radical hysterectomy has been developed as a standard treatment in Stage I and II cervical cancers with and without adjuvant therapy. However, there have been several attempts to standardize the technique of radical hysterectomy required for different tumor extension with variable success. Total mesometrial resection as ontogenetic compartment-based oncologic surgery - developed by open surgery - can be standardized identically for all patients with locally defined tumors. It appears to be promising for patients in terms of radicalness as well as complication rates. Robotic surgery may additionally reduce morbidity compared to open surgery. We describe robotically assisted total mesometrial resection (rTMMR) step by step in cervical cancer and present feasibility data from 26 patients. Patients (n = 26) with the diagnosis of cervical cancer were included. Patients were treated by robotic total mesometrial resection (rTMMR) and pelvic or pelvic/periaortic robotic therapeutic lymphadenectomy (rtLNE) for FIGO stage IA-IIB cervical cancer. No transition to open surgery was necessary. No intraoperative complications were noted. The postoperative complication rate was 23%. Within follow-up time (mean: 18 months) we noted one distant but no locoregional recurrence of cervical cancer. There were no deaths from cervical cancer during the observation period. We conclude that rTMMR and rtLNE is a feasible and safe technique for the treatment of compartment-defined cervical cancer.

Sintering-Resistant Nanoparticles in Wide-Mouthed Compartments for Sustained Catalytic Performance

NASA Astrophysics Data System (ADS)

Liu, Jia; Ji, Qingmin; Imai, Tsubasa; Ariga, Katsuhiko; Abe, Hideki

2017-02-01

Particle sintering is one of the most significant impediments to functional nanoparticles in many valuable applications especially catalysis. Herein, we report that sintering-resistant nanoparticle systems can be realized through a simple materials-design which maximizes the particle-to-particle traveling distance of neighbouring nanoparticles. As a demonstration, Pt nanoparticles were placed apart from each other in wide-mouthed compartments tailored on the surface of self-assembled silica nanosheets. These Pt nanoparticles retained their particle size after calcination at elevated temperatures because the compartment wall elongates the particle-to-particle traveling distance to preclude the possibility of sintering. Moreover, these Pt nanoparticles in wide-mouthed compartments were fully accessible to the environment and exhibited much higher catalytic activity for CO oxidation than the nanoparticles confined in the nanochannels of mesoporous silica. The proposed materials-design strategy is applicable not only to industrial catalysts operating in harsh conditions, but also opens up possibilities in developing advanced nanoparticle-based materials with sustained performance.

Estimating and mapping forest biomass using regression models and Spot-6 images (case study: Hyrcanian forests of north of Iran).

PubMed

Motlagh, Mohadeseh Ghanbari; Kafaky, Sasan Babaie; Mataji, Asadollah; Akhavan, Reza

2018-05-21

Hyrcanian forests of North of Iran are of great importance in terms of various economic and environmental aspects. In this study, Spot-6 satellite images and regression models were applied to estimate above-ground biomass in these forests. This research was carried out in six compartments in three climatic (semi-arid to humid) types and two altitude classes. In the first step, ground sampling methods at the compartment level were used to estimate aboveground biomass (Mg/ha). Then, by reviewing the results of other studies, the most appropriate vegetation indices were selected. In this study, three indices of NDVI, RVI, and TVI were calculated. We investigated the relationship between the vegetation indices and aboveground biomass measured at sample-plot level. Based on the results, the relationship between aboveground biomass values and vegetation indices was a linear regression with the highest level of significance for NDVI in all compartments. Since at the compartment level the correlation coefficient between NDVI and aboveground biomass was the highest, NDVI was used for mapping aboveground biomass. According to the results of this study, biomass values were highly different in various climatic and altitudinal classes with the highest biomass value observed in humid climate and high-altitude class.

Hydrophilic structures for condensation management in refrigerator appliances

DOEpatents

Kuehl, Steven John; Vonderhaar, John J; Wu, Guolian; Wu, Mianxue

2014-10-21

A refrigerator appliance that includes a freezer compartment having a freezer compartment door, and a refrigeration compartment having at least one refrigeration compartment door. The appliance further includes a mullion with an exterior surface. The mullion divides the compartments and the exterior surface directs condensation toward a transfer point. The appliance may also include a cabinet that houses the compartments and has two sides, each with an exterior surface. Further, at least one exterior surface directs condensation toward a transfer point.

The pacemaker role of thalamic reticular nucleus in controlling spike-wave discharges and spindles.

PubMed

Fan, Denggui; Liao, Fucheng; Wang, Qingyun

2017-07-01

Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles. Based on the proposed single-compartment thalamocortical neural field model, we firstly investigate the stimulation effect of RE on the initiations, terminations, and transitions of SWDs. It is shown that the activations and deactivations of RE triggered by single-pulse stimuli can drive the cortical subsystem to behave as the experimentally observed onsets and self-abatements of SWDs, as well as the transitions from 2-spike and wave discharges (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the specific relay nucleus (TC), rich transition behaviors in cortex can be obtained through the upstream projection path, RE→TC→Cortex. Although some of the complex dynamical patterns can be expected from the earlier single compartment thalamocortical model, the effect of brain network topology on the emergence of SWDs and spindles, as well as the transitions between them, has not been fully investigated. We thereby develop a spatially extended 3-compartment coupled network model with open-/closed-end connective configurations, to investigate the spatiotemporal effect of RE on the SWDs and spindles. Results show that the degrees of activations of RE 1 can induce the rich spatiotemporal evolution properties including the propagations from SWDs to spindles within different compartments and the transitions between them, through the RE 1 →TC 1 →Cortex 1 and Cortex 1 →Cortex 2 →Cortex 3 projecting paths, respectively. Overall, those results imply that RE possesses the pacemaker function in controlling SWDs and spindling oscillations, which computationally provide causal support for the involvement of RE in absence seizures and sleep spindles.

The pacemaker role of thalamic reticular nucleus in controlling spike-wave discharges and spindles

NASA Astrophysics Data System (ADS)

Fan, Denggui; Liao, Fucheng; Wang, Qingyun

2017-07-01

Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles. Based on the proposed single-compartment thalamocortical neural field model, we firstly investigate the stimulation effect of RE on the initiations, terminations, and transitions of SWDs. It is shown that the activations and deactivations of RE triggered by single-pulse stimuli can drive the cortical subsystem to behave as the experimentally observed onsets and self-abatements of SWDs, as well as the transitions from 2-spike and wave discharges (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the specific relay nucleus (TC), rich transition behaviors in cortex can be obtained through the upstream projection path, RE → TC → Cortex . Although some of the complex dynamical patterns can be expected from the earlier single compartment thalamocortical model, the effect of brain network topology on the emergence of SWDs and spindles, as well as the transitions between them, has not been fully investigated. We thereby develop a spatially extended 3-compartment coupled network model with open-/closed-end connective configurations, to investigate the spatiotemporal effect of RE on the SWDs and spindles. Results show that the degrees of activations of RE 1 can induce the rich spatiotemporal evolution properties including the propagations from SWDs to spindles within different compartments and the transitions between them, through the RE 1 → TC 1 → Cortex 1 and Cortex 1 → Cortex 2 → Cortex 3 projecting paths, respectively. Overall, those results imply that RE possesses the pacemaker function in controlling SWDs and spindling oscillations, which computationally provide causal support for the involvement of RE in absence seizures and sleep spindles.

Dermal, oral, and inhalation pharmacokinetics of methyl tertiary butyl ether (MTBE) in human volunteers.

PubMed

Prah, James; Ashley, David; Blount, Benjamin; Case, Martin; Leavens, Teresa; Pleil, Joachim; Cardinali, Frederick

2004-02-01

Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation kinetics, 14 volunteers were exposed to 51.3 microg/ml MTBE dermally in tap water for 1 h, drank 2.8 mg MTBE in 250 ml Gatorade(R), and inhaled 3.1 ppm. MTBE for 1 h. Blood and exhaled breath samples were then obtained. Blood MTBE peaked between 15 and 30 min following oral exposure, at the end of inhalation exposure, and ~5 min after dermal exposure. Elimination by each route was described well by a three-compartment model (Rsq >0.9). The Akaike Information Criterion for the three-compartment model was smaller than the two-compartment model, supporting it over the two-compartment model. One metabolite, tertiary butyl alcohol (TBA), measured in blood slowly increased and plateaued, but it did not return to the pre-exposure baseline at the 24-h follow-up. TBA is very water-soluble and has a blood:air partition ratio of 462, reducing elimination by exhalation. Oral exposure resulted in a significantly greater MTBE metabolism into TBA than by other routes based on a greater blood TBA:MTBE AUC ratio, implying significant first-pass metabolism. The slower TBA elimination may make it a better biomarker of MTBE exposure, though one must consider the exposure route when estimating MTBE exposure from TBA because of first-pass metabolism. Most subjects had a baseline blood TBA of 1-3 ppb. Because TBA is found in consumer products and can be used as a fuel additive, it is not a definitive marker of MTBE exposure. These data provide the risk assessment process of pharmacokinetic information relevant to the media through which most exposures occur-air and drinking water.

Optimizing homeostatic cell renewal in hierarchical tissues

PubMed Central

Fider, Nicole A.

2018-01-01

In order to maintain homeostasis, mature cells removed from the top compartment of hierarchical tissues have to be replenished by means of differentiation and self-renewal events happening in the more primitive compartments. As each cell division is associated with a risk of mutation, cell division patterns have to be optimized, in order to minimize or delay the risk of malignancy generation. Here we study this optimization problem, focusing on the role of division tree length, that is, the number of layers of cells activated in response to the loss of terminally differentiated cells, which is related to the balance between differentiation and self-renewal events in the compartments. Using both analytical methods and stochastic simulations in a metapopulation-style model, we find that shorter division trees are advantageous if the objective is to minimize the total number of one-hit mutants in the cell population. Longer division trees on the other hand minimize the accumulation of two-hit mutants, which is a more likely evolutionary goal given the key role played by tumor suppressor genes in cancer initiation. While division tree length is the most important property determining mutant accumulation, we also find that increasing the size of primitive compartments helps to delay two-hit mutant generation. PMID:29447149

Two distinct populations of Chiari I malformation based on presence or absence of posterior fossa crowdedness on magnetic resonance imaging.

PubMed

Taylor, Davis G; Mastorakos, Panagiotis; Jane, John A; Oldfield, Edward H

2017-06-01

OBJECTIVE A subset of patients with Chiari I malformation demonstrate patent subarachnoid spaces around the cerebellum, indicating that reduced posterior fossa volume alone does not account for tonsillar descent. The authors distinguish two subsets of Chiari I malformation patients based on the degree of "posterior fossa crowdedness" on MRI. METHODS Two of the coauthors independently reviewed the preoperative MR images of 49 patients with Chiari I malformation and categorized the posterior fossa as "spacious" or "crowded." Volumetric analysis of posterior fossa structures was then performed using open-source DICOM software. The preoperative clinical and imaging features of the two groups were compared. RESULTS The posterior fossae of 25 patients were classified as spacious and 20 as crowded by both readers; 4 were incongruent. The volumes of the posterior fossa compartment, posterior fossa tissue, and hindbrain (posterior fossa tissue including herniated tonsils) were statistically similar between the patients with spacious and crowed subtypes (p = 0.33, p = 0.17, p = 0.20, respectively). However, patients in the spacious and crowded subtypes demonstrated significant differences in the ratios of posterior fossa tissue to compartment volumes as well as hindbrain to compartment volumes (p = 0.001 and p = 0.0004, respectively). The average age at surgery was 29.2 ± 19.3 years (mean ± SD) and 21.9 ± 14.9 years for spacious and crowded subtypes, respectively (p = 0.08). Syringomyelia was more prevalent in the crowded subtype (50% vs 28%, p = 0.11). CONCLUSIONS The authors' study identifies two subtypes of Chiari I malformation, crowded and spacious, that can be distinguished by MRI appearance without volumetric analysis. Earlier age at surgery and presence of syringomyelia are more common in the crowded subtype. The presence of the spacious subtype suggests that crowdedness alone cannot explain the pathogenesis of Chiari I malformation in many patients, supporting the need for further investigation.

Chylomicron metabolism in rats: kinetic modeling indicates that the particles remain at endothelial sites for minutes[S

PubMed Central

Hultin, Magnus; Savonen, Roger; Chevreuil, Olivier; Olivecrona, Thomas

2013-01-01

Chylomicrons labeled in vivo with 14C-oleic acid (primarily in triglycerides, providing a tracer for lipolysis) and 3H-retinol (primarily in ester form, providing a tracer for the core lipids) were injected into rats. Radioactivity in tissues was followed at a series of times up to 40 min and the data were analyzed by compartmental modeling. For heart-like tissues it was necessary to allow the chylomicrons to enter into a compartment where lipolysis is rapid and then transfer to a second compartment where lipolysis is slower. The particles remained in these compartments for minutes and when they returned to blood they had reduced affinity for binding in the tissue. In contrast, the data for liver could readily be fitted with a single compartment for native and lipolyzed chylomicrons in blood, and there was no need for a pathway back to blood. A composite model was built from the individual tissue models. This whole-body model could simultaneously fit all data for both fed and fasted rats and allowed estimation of fluxes and residence times in the four compartments; native and lipolyzed chylomicrons (“remnants”) in blood, and particles in the tissue compartments where lipolysis is rapid and slow, respectively. PMID:23922383

Pharmacokinetics of oral hydrocortisone - Results and implications from a randomized controlled trial.

PubMed

Werumeus Buning, Jorien; Touw, Daan J; Brummelman, Pauline; Dullaart, Robin P F; van den Berg, Gerrit; van der Klauw, Melanie M; Kamp, Jasper; Wolffenbuttel, Bruce H R; van Beek, André P

2017-06-01

This study aimed at comparing pharmacokinetics of two different doses of hydrocortisone (HC) in patients with secondary adrenal insufficiency (SAI). Forty-six patients with SAI participated in this randomized double-blind crossover study. Patients received two different doses of HC (0.2-0.3mg HC/kg body weight/day and 0.4-0.6mg HC/kg body weight/day). One- and two-compartment population models for plasma free cortisol, plasma total cortisol and salivary cortisol were parameterized. The individual pharmacokinetic parameters clearance (CL), volume of distribution (V d ), elimination half-life (t 1/2 ), maximum concentration (C max ), and area under the curve (AUC) were calculated. The one-compartment models gave a better description of the data compared to the two-compartment models. Weight-adjusted dosing reduced variability in cortisol exposure with comparable AUCs between weight groups. However, there was large inter-individual variation in CL and V d of plasma free cortisol, plasma total cortisol and salivary cortisol. As a consequence, AUC 24h varied more than 10 fold. Cortisol exposure was increased with the higher dose, but this was dose proportional only for free cortisol concentrations and not for total cortisol. Cortisol concentrations after a doubling of the dose were only dose proportional for free cortisol. HC pharmacokinetics can differ up to 10-fold inter-individually and individual adjustment of treatment doses may be necessary. Doubling of the HC dose in fast metabolizers (patients that showed relative low AUC and thus high clearance compared to other patients), does not result in significantly enhanced exposure during large parts of the day and these patients may need other management strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

Topologically associating domains are stable units of replication-timing regulation.

PubMed

Pope, Benjamin D; Ryba, Tyrone; Dileep, Vishnu; Yue, Feng; Wu, Weisheng; Denas, Olgert; Vera, Daniel L; Wang, Yanli; Hansen, R Scott; Canfield, Theresa K; Thurman, Robert E; Cheng, Yong; Gülsoy, Günhan; Dennis, Jonathan H; Snyder, Michael P; Stamatoyannopoulos, John A; Taylor, James; Hardison, Ross C; Kahveci, Tamer; Ren, Bing; Gilbert, David M

2014-11-20

Eukaryotic chromosomes replicate in a temporal order known as the replication-timing program. In mammals, replication timing is cell-type-specific with at least half the genome switching replication timing during development, primarily in units of 400-800 kilobases ('replication domains'), whose positions are preserved in different cell types, conserved between species, and appear to confine long-range effects of chromosome rearrangements. Early and late replication correlate, respectively, with open and closed three-dimensional chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, late replication correlates with lamina-associated domains (LADs). Recent Hi-C mapping has unveiled substructure within chromatin compartments called topologically associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to replication domains. However, TADs can be further sub-stratified into smaller domains, challenging the significance of structures at any particular scale. Moreover, attempts to reconcile TADs and LADs to replication-timing data have not revealed a common, underlying domain structure. Here we localize boundaries of replication domains to the early-replicating border of replication-timing transitions and map their positions in 18 human and 13 mouse cell types. We demonstrate that, collectively, replication domain boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure replication domain boundaries, largely accounting for the previously reported lack of alignment. Moreover, cell-type-specific replication timing of TADs partitions the genome into two large-scale sub-nuclear compartments revealing that replication-timing transitions are indistinguishable from late-replicating regions in chromatin composition and lamina association and accounting for the reduced correlation of replication timing to LADs and heterochromatin. Our results reconcile cell-type-specific sub-nuclear compartmentalization and replication timing with developmentally stable structural domains and offer a unified model for large-scale chromosome structure and function.

SNARE-mediated Fusion of Single Proteoliposomes with Tethered Supported Bilayers in a Microfluidic Flow Cell Monitored by Polarized TIRF Microscopy

PubMed Central

Nikolaus, Joerg; Karatekin, Erdem

2016-01-01

In the ubiquitous process of membrane fusion the opening of a fusion pore establishes the first connection between two formerly separate compartments. During neurotransmitter or hormone release via exocytosis, the fusion pore can transiently open and close repeatedly, regulating cargo release kinetics. Pore dynamics also determine the mode of vesicle recycling; irreversible resealing results in transient, "kiss-and-run" fusion, whereas dilation leads to full fusion. To better understand what factors govern pore dynamics, we developed an assay to monitor membrane fusion using polarized total internal reflection fluorescence (TIRF) microscopy with single molecule sensitivity and ~15 msec time resolution in a biochemically well-defined in vitro system. Fusion of fluorescently labeled small unilamellar vesicles containing v-SNARE proteins (v-SUVs) with a planar bilayer bearing t-SNAREs, supported on a soft polymer cushion (t-SBL, t-supported bilayer), is monitored. The assay uses microfluidic flow channels that ensure minimal sample consumption while supplying a constant density of SUVs. Exploiting the rapid signal enhancement upon transfer of lipid labels from the SUV to the SBL during fusion, kinetics of lipid dye transfer is monitored. The sensitivity of TIRF microscopy allows tracking single fluorescent lipid labels, from which lipid diffusivity and SUV size can be deduced for every fusion event. Lipid dye release times can be much longer than expected for unimpeded passage through permanently open pores. Using a model that assumes retardation of lipid release is due to pore flickering, a pore "openness", the fraction of time the pore remains open during fusion, can be estimated. A soluble marker can be encapsulated in the SUVs for simultaneous monitoring of lipid and soluble cargo release. Such measurements indicate some pores may reseal after losing a fraction of the soluble cargo. PMID:27585113

Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

PubMed Central

Niu, Jing; Venkatasubramanian, Raja; Vinks, Alexander A.; Sadhasivam, Senthilkumar

2016-01-01

Background Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model. Methods Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check. Results A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated. Conclusions For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms that maternal heart rate has an important influence on the pharmacokinetics of propofol during pregnancy. Much lower propofol concentration in the fetus compared to maternal concentrations explain limited placental transfer in in-vivo paired model, and less direct fetal cardiac depression we observed earlier with propofol supplemented inhalational anesthesia compared to higher dose inhalational anesthesia in humans and sheep. PMID:26752560

Open abdomen management: A review of its history and a proposed management algorithm

PubMed Central

Kreis, Barbara Elize; de Mol van Otterloo, Johan Coenraad Alexander; Kreis, Robert Walter

2013-01-01

In this review we look into the historical development of open abdomen management. Its indication has spread in 70 years from intra-abdominal sepsis to damage control surgery and abdominal compartment syndrome. Different temporary abdominal closure techniques are essential to benefit the potential advantages of open abdomen management. Here, we discuss the different techniques and provide a new treatment strategy, based on available evidence, to facilitate more consistent decision making and further research on this complicated surgical topic. PMID:23823991

Population pharmacokinetics of a three-day chloroquine treatment in patients with Plasmodium vivax infection on the Thai-Myanmar border.

PubMed

Höglund, Richard; Moussavi, Younis; Ruengweerayut, Ronnatrai; Cheomung, Anurak; Äbelö, Angela; Na-Bangchang, Kesara

2016-02-29

A three-day course of chloroquine remains a standard treatment of Plasmodium vivax infection in Thailand with satisfactory clinical efficacy and tolerability although a continuous decline in in vitro parasite sensitivity has been reported. Information on the pharmacokinetics of chloroquine and its active metabolite desethylchloroquine are required for optimization of treatment to attain therapeutic exposure and thus prevent drug resistance development. The study was conducted at Mae Tao Clinic for migrant worker, Tak province, Thailand. Blood samples were collected from a total of 75 (8 Thais and 67 Burmeses; 36 males and 39 females; aged 17-52 years) patients with mono-infection with P. vivax malaria [median (95 % CI) admission parasitaemia 4898 (1206-29,480)/µL] following treatment with a three-day course of chloroquine (25 mg/kg body weight chloroquine phosphate over 3 days). Whole blood concentrations of chloroquine and desethylchloroquine were measured using high performance liquid chromatography with UV detection. Concentration-time profiles of both compounds were analysed using a population-based pharmacokinetic approach. All patients showed satisfactory response to standard treatment with a three-day course of chloroquine with 100 % cure rate within the follow-up period of 42 days. Neither recurrence of P. vivax parasitaemia nor appearance of P. falciparum occurred. A total of 1045 observations from 75 participants were included in the pharmacokinetic analysis. Chloroquine disposition was most adequately described by the two-compartment model with one transit compartment absorption model into the central compartment and a first-order transformation of chloroquine into desethylchloroquine with an additional peripheral compartment added to desethylchloroquine. First-order elimination from the central compartment of chloroquine and desethylchloroquine was assumed. The model exhibited a strong predictive ability and the pharmacokinetic parameters were estimated with adequate precision. The developed population-based pharmacokinetic model could be applied for future prediction of optimal dosage regimen of chloroquine in patients with P. vivax infection.

Fractal pharmacokinetics.

PubMed

Pereira, Luis M

2010-06-01

Pharmacokinetics (PK) has been traditionally dealt with under the homogeneity assumption. However, biological systems are nowadays comprehensively understood as being inherently fractal. Specifically, the microenvironments where drug molecules interact with membrane interfaces, metabolic enzymes or pharmacological receptors, are unanimously recognized as unstirred, space-restricted, heterogeneous and geometrically fractal. Therefore, classical Fickean diffusion and the notion of the compartment as a homogeneous kinetic space must be revisited. Diffusion in fractal spaces has been studied for a long time making use of fractional calculus and expanding on the notion of dimension. Combining this new paradigm with the need to describe and explain experimental data results in defining time-dependent rate constants with a characteristic fractal exponent. Under the one-compartment simplification this strategy is straightforward. However, precisely due to the heterogeneity of the underlying biology, often at least a two-compartment model is required to address macroscopic data such as drug concentrations. This simple modelling step-up implies significant analytical and numerical complications. However, a few methods are available that make possible the original desideratum. In fact, exploring the full range of parametric possibilities and looking at different drugs and respective biological concentrations, it may be concluded that all PK modelling approaches are indeed particular cases of the fractal PK theory.

[Distal femoral osteotomy using a lateral opening wedge technique].

PubMed

Feucht, M J; Mehl, J; Forkel, P; Imhoff, A B; Hinterwimmer, S

2017-08-01

To shift the weight-bearing axis of the lower limb medially by opening a lateral-based metaphyseal osteotomy at the distal femur. Femoral-based valgus malalignment and symptomatic lateral unicompartimental osteoarthritis, lateral hyperpression syndrome, cartilage therapy of the lateral compartment, lateral meniscal replacement/transplantation, medial instability with valgus thrust, reconstruction of the medial collateral ligament, patellar instability and/or maltracking. Advanced cartilage damage (>grade 2) or subtotal meniscal loss of the medial compartment, age >65 years (relative), nicotine abuse, body mass index >30, flexion contracture >25°, corrections with a wedge base >10 mm in case of congenital deformities, inflammatory or septic arthritis, severe osteoporosis. Lateral approach to the distal femur; biplanar osteotomy (frontal + axial osteotomy), gradual opening of the osteotomy, osteotomy fixation with a locking plate. Free range of motion. Partial weight bearing with 20 kg for 2 weeks, followed by progressive weight bearing thereafter. Mean improvement of knee scores from 20-30 points and mean 10-year survival rate of 80% in patients with lateral unicompartimental osteoarthritis. Mean complication rate of 9%.

[Water provisions for Muscovy ducks--behaviour at duck showers and modified plasson drinkers].

PubMed

Briese, Andreas; Hänsch, Friederike; Hartung, Jörg

2009-01-01

Feather pecking and cannibalism are serious problems in keeping Moscovy ducks. Prevention of feather pecking by regularly applied beak and claw trimming are increasingly criticised by the public. The recommendation of the Council of Europe (COE) for the keeping of Muscovy ducks in farming systems calls for environmental enrichment including water for preening and bathing after December 31,2010. A total of 126 female Muscovy ducks (not beak nor claw trimmed) from commercial breeding lines were kept for 63 resp. 70 days in four compartments with 15-16 ducks each during two production cycles. Two pens where equipped either with duck showers or open water facility (modified Plasson drinker). Water provisions were made available for the ducks four hours daily at working days from their fifth week of life until slaughter. Behaviour at the water provision was registered and analysed for the number of ducks being engaged with water (944 hours recordings over 59 days from four pens analysed in five-minute-intervals (11,540 observations). Additionally 858 feather preening bouts (five a day for each compartment) were analysed for the duration of feather preening behaviour at the water provision. From the fifth to the tenth week of life the mean percentage of animals of a pen was significantly higher at the open trough (trough: 8,3% (+/-5,37); shower: 4.9% (+/-6.1), Mann-Whitney p <0,01) and feather preening took significantly longer (trough: 134.4 sec (+/-154.8); shower: 111.2 sec (+/-152.0), Mann-Whitney p <0.01) than at the showers. Bout duration and percentage of animals observed at both water provisions increased with age. Nonetheless only ten percent of the feather preening behaviour exceeded five minutes. Most animals made use of water in the first hour of the time period when water was provided. In the first weeks of water provision open water troughs were used more often and preening behaviour was longer. When given the choice, younger ducks preferred open drinkers to showers while older ducks showed a higher preference for the duck showers. In future it may be useful to elaborate whether a combination of open water troughs in the first few weeks of the fattening period followed by the provision of showers when the birds have completed their feather coverage can help to reduce the frequency of feather pecking and cannibalism.

Pharmacokinetics of topically applied pilocarpine in the albino rabbit eye.

PubMed

Makoid, M C; Robinson, J R

1979-04-01

The temporal and spatial pattern of [3H]-pilocarpine nitrate distribution in the albino rabbit eye following topical administration was determined. A four-compartment caternary chain model describing this disposition corresponds to the precorneal area, the cornea, the aqueous humor, and the lens and vitreous. Simultaneous computer fitting of data from tissue corresponding to some compartments in the model supported the proposed model. Additional support was provided by the excellent correlation between predicted and observed values in multiple-dosing studies. Several important aspects of ocular drug disposition are evident from the model. The extensive parallel elimination at the absorption site gives rise to an apparent absorption rate constant that is one to two orders of magnitude larger than the true absorption rate constant. In addition, aqueous flow accounts for most of the drug removal. Thus, major effects on absorption and elimination, independent of the drug structure, suggest the possibility of similar pharmacokinetics for vastly different drugs.

Developing a physiologically based approach for modeling plutonium decorporation therapy with DTPA.

PubMed

Kastl, Manuel; Giussani, Augusto; Blanchardon, Eric; Breustedt, Bastian; Fritsch, Paul; Hoeschen, Christoph; Lopez, Maria Antonia

2014-11-01

To develop a physiologically based compartmental approach for modeling plutonium decorporation therapy with the chelating agent Diethylenetriaminepentaacetic acid (Ca-DTPA/Zn-DTPA). Model calculations were performed using the software package SAAM II (©The Epsilon Group, Charlottesville, Virginia, USA). The Luciani/Polig compartmental model with age-dependent description of the bone recycling processes was used for the biokinetics of plutonium. The Luciani/Polig model was slightly modified in order to account for the speciation of plutonium in blood and for the different affinities for DTPA of the present chemical species. The introduction of two separate blood compartments, describing low-molecular-weight complexes of plutonium (Pu-LW) and transferrin-bound plutonium (Pu-Tf), respectively, and one additional compartment describing plutonium in the interstitial fluids was performed successfully. The next step of the work is the modeling of the chelation process, coupling the physiologically modified structure with the biokinetic model for DTPA. RESULTS of animal studies performed under controlled conditions will enable to better understand the principles of the involved mechanisms.

Lung inhomogeneities, inflation and [18F]2-fluoro-2-deoxy-D-glucose uptake rate in acute respiratory distress syndrome.

PubMed

Cressoni, Massimo; Chiumello, Davide; Chiurazzi, Chiara; Brioni, Matteo; Algieri, Ilaria; Gotti, Miriam; Nikolla, Klodiana; Massari, Dario; Cammaroto, Antonio; Colombo, Andrea; Cadringher, Paolo; Carlesso, Eleonora; Benti, Riccardo; Casati, Rosangela; Zito, Felicia; Gattinoni, Luciano

2016-01-01

The aim of the study was to determine the size and location of homogeneous inflamed/noninflamed and inhomogeneous inflamed/noninflamed lung compartments and their association with acute respiratory distress syndrome (ARDS) severity.In total, 20 ARDS patients underwent 5 and 45 cmH2O computed tomography (CT) scans to measure lung recruitability. [(18)F]2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) uptake and lung inhomogeneities were quantified with a positron emission tomography-CT scan at 10 cmH2O. We defined four compartments with normal/abnormal [(18)F]FDG uptake and lung homogeneity.The homogeneous compartment with normal [(18)F]FDG uptake was primarily composed of well-inflated tissue (80±16%), double-sized in nondependent lung (32±27% versus 16±17%, p<0.0001) and decreased in size from mild, moderate to severe ARDS (33±14%, 26±20% and 5±9% of the total lung volume, respectively, p=0.05). The homogeneous compartment with high [(18)F]FDG uptake was similarly distributed between the dependent and nondependent lung. The inhomogeneous compartment with normal [(18)F]FDG uptake represented 4% of the lung volume. The inhomogeneous compartment with high [(18)F]FDG uptake was preferentially located in the dependent lung (21±10% versus 12±10%, p<0.0001), mostly at the open/closed interfaces and related to recruitability (r(2)=0.53, p<0.001).The homogeneous lung compartment with normal inflation and [(18)F]FDG uptake decreases with ARDS severity, while the inhomogeneous poorly/not inflated compartment increases. Most of the lung inhomogeneities are inflamed. A minor fraction of healthy tissue remains in severe ARDS. Copyright ©ERS 2016.

The FieldTrip-SimBio pipeline for EEG forward solutions.

PubMed

Vorwerk, Johannes; Oostenveld, Robert; Piastra, Maria Carla; Magyari, Lilla; Wolters, Carsten H

2018-03-27

Accurately solving the electroencephalography (EEG) forward problem is crucial for precise EEG source analysis. Previous studies have shown that the use of multicompartment head models in combination with the finite element method (FEM) can yield high accuracies both numerically and with regard to the geometrical approximation of the human head. However, the workload for the generation of multicompartment head models has often been too high and the use of publicly available FEM implementations too complicated for a wider application of FEM in research studies. In this paper, we present a MATLAB-based pipeline that aims to resolve this lack of easy-to-use integrated software solutions. The presented pipeline allows for the easy application of five-compartment head models with the FEM within the FieldTrip toolbox for EEG source analysis. The FEM from the SimBio toolbox, more specifically the St. Venant approach, was integrated into the FieldTrip toolbox. We give a short sketch of the implementation and its application, and we perform a source localization of somatosensory evoked potentials (SEPs) using this pipeline. We then evaluate the accuracy that can be achieved using the automatically generated five-compartment hexahedral head model [skin, skull, cerebrospinal fluid (CSF), gray matter, white matter] in comparison to a highly accurate tetrahedral head model that was generated on the basis of a semiautomatic segmentation with very careful and time-consuming manual corrections. The source analysis of the SEP data correctly localizes the P20 component and achieves a high goodness of fit. The subsequent comparison to the highly detailed tetrahedral head model shows that the automatically generated five-compartment head model performs about as well as a highly detailed four-compartment head model (skin, skull, CSF, brain). This is a significant improvement in comparison to a three-compartment head model, which is frequently used in praxis, since the importance of modeling the CSF compartment has been shown in a variety of studies. The presented pipeline facilitates the use of five-compartment head models with the FEM for EEG source analysis. The accuracy with which the EEG forward problem can thereby be solved is increased compared to the commonly used three-compartment head models, and more reliable EEG source reconstruction results can be obtained.

Transit and lifespan in neutrophil production: implications for drug intervention.

PubMed

Câmara De Souza, Daniel; Craig, Morgan; Cassidy, Tyler; Li, Jun; Nekka, Fahima; Bélair, Jacques; Humphries, Antony R

2018-02-01

A comparison of the transit compartment ordinary differential equation modelling approach to distributed and discrete delay differential equation models is studied by focusing on Quartino's extension to the Friberg transit compartment model of myelosuppression, widely relied upon in the pharmaceutical sciences to predict the neutrophil response after chemotherapy, and on a QSP delay differential equation model of granulopoiesis. An extension to the Quartino model is provided by considering a general number of transit compartments and introducing an extra parameter that allows for the decoupling of the maturation time from the production rate of cells. An overview of the well established linear chain technique, used to reformulate transit compartment models with constant transit rates as distributed delay differential equations (DDEs), is then given. A state-dependent time rescaling of the Quartino model is performed to apply the linear chain technique and rewrite the Quartino model as a distributed DDE, yielding a discrete DDE model in a certain parameter limit. Next, stability and bifurcation analyses are undertaken in an effort to situate such studies in a mathematical pharmacology context. We show that both the original Friberg and the Quartino extension models incorrectly define the mean maturation time, essentially treating the proliferative pool as an additional maturation compartment. This misspecification can have far reaching consequences on the development of future models of myelosuppression in PK/PD.

Complex Geometric Models of Diffusion and Relaxation in Healthy and Damaged White Matter

PubMed Central

Farrell, Jonathan A.D.; Smith, Seth A.; Reich, Daniel S.; Calabresi, Peter A.; van Zijl, Peter C.M.

2010-01-01

Which aspects of tissue microstructure affect diffusion weighted MRI signals? Prior models, many of which use Monte-Carlo simulations, have focused on relatively simple models of the cellular microenvironment and have not considered important anatomic details. With the advent of higher-order analysis models for diffusion imaging, such as high-angular-resolution diffusion imaging (HARDI), more realistic models are necessary. This paper presents and evaluates the reproducibility of simulations of diffusion in complex geometries. Our framework is quantitative, does not require specialized hardware, is easily implemented with little programming experience, and is freely available as open-source software. Models may include compartments with different diffusivities, permeabilities, and T2 time constants using both parametric (e.g., spheres and cylinders) and arbitrary (e.g., mesh-based) geometries. Three-dimensional diffusion displacement-probability functions are mapped with high reproducibility, and thus can be readily used to assess reproducibility of diffusion-derived contrasts. PMID:19739233

2010 Award for Outstanding Doctoral Thesis Research in Biological Physics Talk: How the Genome Folds

NASA Astrophysics Data System (ADS)

Lieberman-Aiden, Erez

2011-03-01

I describe Hi-C, a novel technology for probing the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. Working with collaborators at the Broad Institute and UMass Medical School, we used Hi-C to construct spatial proximity maps of the human genome at a resolution of 1Mb. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.

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

PubMed

Genestie, I; Morin, J P; Vannier, B; Lorenzon, G

1995-07-01

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.

Probabilistic pharmacokinetic models of decompression sickness in humans, part 1: Coupled perfusion-limited compartments.

PubMed

Murphy, F Gregory; Hada, Ethan A; Doolette, David J; Howle, Laurens E

2017-07-01

Decompression sickness (DCS) is a disease caused by gas bubbles forming in body tissues following a reduction in ambient pressure, such as occurs in scuba diving. Probabilistic models for quantifying the risk of DCS are typically composed of a collection of independent, perfusion-limited theoretical tissue compartments which describe gas content or bubble volume within these compartments. It has been previously shown that 'pharmacokinetic' gas content models, with compartments coupled in series, show promise as predictors of the incidence of DCS. The mechanism of coupling can be through perfusion or diffusion. This work examines the application of five novel pharmacokinetic structures with compartments coupled by perfusion to the prediction of the probability and time of onset of DCS in humans. We optimize these models against a training set of human dive trial data consisting of 4335 exposures with 223 DCS cases. Further, we examine the extrapolation quality of the models on an additional set of human dive trial data consisting of 3140 exposures with 147 DCS cases. We find that pharmacokinetic models describe the incidence of DCS for single air bounce dives better than a single-compartment, perfusion-limited model. We further find the U.S. Navy LEM-NMRI98 is a better predictor of DCS risk for the entire training set than any of our pharmacokinetic models. However, one of the pharmacokinetic models we consider, the CS2T3 model, is a better predictor of DCS risk for single air bounce dives and oxygen decompression dives. Additionally, we find that LEM-NMRI98 outperforms CS2T3 on the extrapolation data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuromodulation impact on nonlinear firing behavior of a reduced model motoneuron with the active dendrite

PubMed Central

Kim, Hojeong; Heckman, C. J.

2014-01-01

Neuromodulatory inputs from brainstem systems modulate the normal function of spinal motoneurons by altering the activation properties of persistent inward currents (PICs) in their dendrites. However, the effect of the PIC on firing outputs also depends on its location in the dendritic tree. To investigate the interaction between PIC neuromodulation and PIC location dependence, we used a two-compartment model that was biologically realistic in that it retains directional and frequency-dependent electrical coupling between the soma and the dendrites, as seen in multi-compartment models based on full anatomical reconstructions of motoneurons. Our two-compartment approach allowed us to systematically vary the coupling parameters between the soma and the dendrite to accurately reproduce the effect of location of the dendritic PIC on the generation of nonlinear (hysteretic) motoneuron firing patterns. Our results show that as a single parameter value for PIC activation was either increased or decreased by 20% from its default value, the solution space of the coupling parameter values for nonlinear firing outputs was drastically reduced by approximately 80%. As a result, the model tended to fire only in a linear mode at the majority of dendritic PIC sites. The same results were obtained when all parameters for the PIC activation simultaneously changed only by approximately ±10%. Our results suggest the democratization effect of neuromodulation: the neuromodulation by the brainstem systems may play a role in switching the motoneurons with PICs at different dendritic locations to a similar mode of firing by reducing the effect of the dendritic location of PICs on the firing behavior. PMID:25309410

Linking xylem water storage with anatomical parameters in five temperate tree species.

PubMed

Jupa, Radek; Plavcová, Lenka; Gloser, Vít; Jansen, Steven

2016-06-01

The release of water from storage compartments to the transpiration stream is an important functional mechanism that provides the buffering of sudden fluctuations in water potential. The ability of tissues to release water per change in water potential, referred to as hydraulic capacitance, is assumed to be associated with the anatomy of storage tissues. However, information about how specific anatomical parameters determine capacitance is limited. In this study, we measured sapwood capacitance (C) in terminal branches and roots of five temperate tree species (Fagus sylvatica L., Picea abies L., Quercus robur L., Robinia pseudoacacia L., Tilia cordata Mill.). Capacitance was calculated separately for water released mainly from capillary (CI; open vessels, tracheids, fibres, intercellular spaces and cracks) and elastic storage compartments (CII; living parenchyma cells), corresponding to two distinct phases of the moisture release curve. We found that C was generally higher in roots than branches, with CI being 3-11 times higher than CII Sapwood density and the ratio of dead to living xylem cells were most closely correlated with C In addition, the magnitude of CI was strongly correlated with fibre/tracheid lumen area, whereas CII was highly dependent on the thickness of axial parenchyma cell walls. Our results indicate that water released from capillary compartments predominates over water released from elastic storage in both branches and roots, suggesting the limited importance of parenchyma cells for water storage in juvenile xylem of temperate tree species. Contrary to intact organs, water released from open conduits in our small wood samples significantly increased CI at relatively high water potentials. Linking anatomical parameters with the hydraulic capacitance of a tissue contributes to a better understanding of water release mechanisms and their implications for plant hydraulics. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Distal Femoral Osteotomy for the Valgus Knee: Medial Closing Wedge Versus Lateral Opening Wedge: A Systematic Review.

PubMed

Wylie, James D; Jones, Daniel L; Hartley, Melissa K; Kapron, Ashley L; Krych, Aaron J; Aoki, Stephen K; Maak, Travis G

2016-10-01

(1) To determine the radiographic correction/healing rate, patient-reported outcomes, reoperation rate, and complication rate after distal femoral osteotomy (DFO) for the valgus knee with lateral compartment pathology. (2) To summarize the reported results of medial closing wedge and lateral opening wedge DFO. We conducted a systematic review of PubMed, MEDLINE, and CINAHL to identify studies reporting outcomes of DFOs for the valgus knee. Keywords included "distal femoral osteotomy," "chondral," "cartilage," "valgus," "joint restoration," "joint preservation," "arthritis," and "gonarthrosis." Two authors first reviewed the articles; our study exclusion criteria were then applied, and the articles were included on the basis relevance defined by the aforementioned criteria. The Methodological Index for Nonrandomized Studies scale judged the quality of the literature. Sixteen studies were relevant to the research questions out of 191 studies identified by the original search. Sixteen studies were identified reporting on 372 osteotomies with mean follow-up of 45 to 180 months. All studies reported mean radiographic correction to a near neutral mechanical axis, with 3.2% nonunion and 3.8% delayed union rates. There was a 9% complication rate and a 34% reoperation rate, of which 15% were converted to arthroplasty. There were similar results reported for medial closing wedge and lateral opening wedge techniques, with a higher conversion to arthroplasty in the medial closing wedge that was confounded by longer mean follow-up in this group (mean follow-up 100 v 58 months). DFOs for the valgus knee with lateral compartment disease provide improvements in patient-reported knee health-related quality of life at midterm follow-up but have high rates of reoperation. No evidence exists proving better results of either the lateral opening wedge or medial closing wedge techniques. Level IV, systematic review of Level IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

A new compartmental method for the analysis of liver FDG kinetics in small animal models.

PubMed

Garbarino, Sara; Vivaldi, Valentina; Delbary, Fabrice; Caviglia, Giacomo; Piana, Michele; Marini, Cecilia; Capitanio, Selene; Calamia, Iolanda; Buschiazzo, Ambra; Sambuceti, Gianmario

2015-12-01

Compartmental analysis is a standard method to quantify metabolic processes using fluorodeoxyglucose-positron emission tomography (FDG-PET). For liver studies, this analysis is complex due to the hepatocyte capability to dephosphorylate and release glucose and FDG into the blood. Moreover, a tracer is supplied to the liver by both the hepatic artery and the portal vein, which is not visible in PET images. This study developed an innovative computational approach accounting for the reversible nature of FDG in the liver and directly computing the portal vein tracer concentration by means of gut radioactivity measurements. Twenty-one mice were subdivided into three groups: the control group 'CTR' (n = 7) received no treatment, the short-term starvation group 'STS' (n = 7) was submitted to food deprivation with free access to water within 48 h before imaging, and the metformin group 'MTF' (n = 7) was treated with metformin (750 mg/Kg per day) for 1 month. All mice underwent a dynamic micro-PET study for 50 min after an (18)F-FDG injection. The compartmental analysis considered two FDG pools (phosphorylated and free) in both the gut and liver. A tracer was carried into the liver by the hepatic artery and the portal vein, and tracer delivery from the gut was considered as the sole input for portal vein tracer concentration. Accordingly, both the liver and gut were characterized by two compartments and two exchange coefficients. Each one of the two two-compartment models was mathematically described by a system of differential equations, and data optimization was performed by applying a Newton algorithm to the inverse problems associated to these differential systems. All rate constants were stable in each group. The tracer coefficient from the free to the metabolized compartment in the liver was increased by STS, while it was unaltered by MTF. By contrast, the tracer coefficient from the metabolized to the free compartment was reduced by MTF and increased by STS. Data demonstrated that our method was able to analyze FDG kinetics under pharmacological or pathophysiological stimulation, quantifying the fraction of the tracer trapped in the liver or dephosphorylated and released into the bloodstream.

Spectroscopic Biomarkers for Monitoring Wound Healing and Infection in Wounds

DTIC Science & Technology

2014-06-01

injuries, burns, acute vascular disruption, blastwave-associated pressure injuries, air, thrombotic, and fat embolism , and compartment syndrome. In...damage and compromised local circulation often associated with overt vascular injury. These injuries include traumatic amputations, open fractures , crush

PET Pharmacokinetic Modelling

NASA Astrophysics Data System (ADS)

Müller-Schauenburg, Wolfgang; Reimold, Matthias

Positron Emission Tomography is a well-established technique that allows imaging and quantification of tissue properties in-vivo. The goal of pharmacokinetic modelling is to estimate physiological parameters, e.g. perfusion or receptor density from the measured time course of a radiotracer. After a brief overview of clinical application of PET, we summarize the fundamentals of modelling: distribution volume, Fick's principle of local balancing, extraction and perfusion, and how to calculate equilibrium data from measurements after bolus injection. Three fundamental models are considered: (i) the 1-tissue compartment model, e.g. for regional cerebral blood flow (rCBF) with the short-lived tracer [15O]water, (ii) the 2-tissue compartment model accounting for trapping (one exponential + constant), e.g. for glucose metabolism with [18F]FDG, (iii) the reversible 2-tissue compartment model (two exponentials), e.g. for receptor binding. Arterial blood sampling is required for classical PET modelling, but can often be avoided by comparing regions with specific binding with so called reference regions with negligible specific uptake, e.g. in receptor imaging. To estimate the model parameters, non-linear least square fits are the standard. Various linearizations have been proposed for rapid parameter estimation, e.g. on a pixel-by-pixel basis, for the prize of a bias. Such linear approaches exist for all three models; e.g. the PATLAK-plot for trapping substances like FDG, and the LOGAN-plot to obtain distribution volumes for reversibly binding tracers. The description of receptor modelling is dedicated to the approaches of the subsequent lecture (chapter) of Millet, who works in the tradition of Delforge with multiple-injection investigations.

Emergent Chemical Behavior in Variable-Volume Protocells

PubMed Central

Shirt-Ediss, Ben; Solé, Ricard V.; Ruiz-Mirazo, Kepa

2015-01-01

Artificial protocellular compartments and lipid vesicles have been used as model systems to understand the origins and requirements for early cells, as well as to design encapsulated reactors for biotechnology. One prominent feature of vesicles is the semi-permeable nature of their membranes, able to support passive diffusion of individual solute species into/out of the compartment, in addition to an osmotic water flow in the opposite direction to the net solute concentration gradient. Crucially, this water flow affects the internal aqueous volume of the vesicle in response to osmotic imbalances, in particular those created by ongoing reactions within the system. In this theoretical study, we pay attention to this often overlooked aspect and show, via the use of a simple semi-spatial vesicle reactor model, that a changing solvent volume introduces interesting non-linearities into an encapsulated chemistry. Focusing on bistability, we demonstrate how a changing volume compartment can degenerate existing bistable reactions, but also promote emergent bistability from very simple reactions, which are not bistable in bulk conditions. One particularly remarkable effect is that two or more chemically-independent reactions, with mutually exclusive reaction kinetics, are able to couple their dynamics through the variation of solvent volume inside the vesicle. Our results suggest that other chemical innovations should be expected when more realistic and active properties of protocellular compartments are taken into account. PMID:25590570

[Application of three compartment model and response surface model to clinical anesthesia using Microsoft Excel].

PubMed

Abe, Eiji; Abe, Mari

2011-08-01

With the spread of total intravenous anesthesia, clinical pharmacology has become more important. We report Microsoft Excel file applying three compartment model and response surface model to clinical anesthesia. On the Microsoft Excel sheet, propofol, remifentanil and fentanyl effect-site concentrations are predicted (three compartment model), and probabilities of no response to prodding, shaking, surrogates of painful stimuli and laryngoscopy are calculated using predicted effect-site drug concentration. Time-dependent changes in these calculated values are shown graphically. Recent development in anesthetic drug interaction studies are remarkable, and its application to clinical anesthesia with this Excel file is simple and helpful for clinical anesthesia.

Estimating the magnitude of near-membrane PDE4 activity in living cells.

PubMed

Xin, Wenkuan; Feinstein, Wei P; Britain, Andrea L; Ochoa, Cristhiaan D; Zhu, Bing; Richter, Wito; Leavesley, Silas J; Rich, Thomas C

2015-09-15

Recent studies have demonstrated that functionally discrete pools of phosphodiesterase (PDE) activity regulate distinct cellular functions. While the importance of localized pools of enzyme activity has become apparent, few studies have estimated enzyme activity within discrete subcellular compartments. Here we present an approach to estimate near-membrane PDE activity. First, total PDE activity is measured using traditional PDE activity assays. Second, known cAMP concentrations are dialyzed into single cells and the spatial spread of cAMP is monitored using cyclic nucleotide-gated channels. Third, mathematical models are used to estimate the spatial distribution of PDE activity within cells. Using this three-tiered approach, we observed two pharmacologically distinct pools of PDE activity, a rolipram-sensitive pool and an 8-methoxymethyl IBMX (8MM-IBMX)-sensitive pool. We observed that the rolipram-sensitive PDE (PDE4) was primarily responsible for cAMP hydrolysis near the plasma membrane. Finally, we observed that PDE4 was capable of blunting cAMP levels near the plasma membrane even when 100 μM cAMP were introduced into the cell via a patch pipette. Two compartment models predict that PDE activity near the plasma membrane, near cyclic nucleotide-gated channels, was significantly lower than total cellular PDE activity and that a slow spatial spread of cAMP allowed PDE activity to effectively hydrolyze near-membrane cAMP. These results imply that cAMP levels near the plasma membrane are distinct from those in other subcellular compartments; PDE activity is not uniform within cells; and localized pools of AC and PDE activities are responsible for controlling cAMP levels within distinct subcellular compartments. Copyright © 2015 the American Physiological Society.

Estimating the magnitude of near-membrane PDE4 activity in living cells

PubMed Central

Xin, Wenkuan; Feinstein, Wei P.; Britain, Andrea L.; Ochoa, Cristhiaan D.; Zhu, Bing; Richter, Wito; Leavesley, Silas J.

2015-01-01

Recent studies have demonstrated that functionally discrete pools of phosphodiesterase (PDE) activity regulate distinct cellular functions. While the importance of localized pools of enzyme activity has become apparent, few studies have estimated enzyme activity within discrete subcellular compartments. Here we present an approach to estimate near-membrane PDE activity. First, total PDE activity is measured using traditional PDE activity assays. Second, known cAMP concentrations are dialyzed into single cells and the spatial spread of cAMP is monitored using cyclic nucleotide-gated channels. Third, mathematical models are used to estimate the spatial distribution of PDE activity within cells. Using this three-tiered approach, we observed two pharmacologically distinct pools of PDE activity, a rolipram-sensitive pool and an 8-methoxymethyl IBMX (8MM-IBMX)-sensitive pool. We observed that the rolipram-sensitive PDE (PDE4) was primarily responsible for cAMP hydrolysis near the plasma membrane. Finally, we observed that PDE4 was capable of blunting cAMP levels near the plasma membrane even when 100 μM cAMP were introduced into the cell via a patch pipette. Two compartment models predict that PDE activity near the plasma membrane, near cyclic nucleotide-gated channels, was significantly lower than total cellular PDE activity and that a slow spatial spread of cAMP allowed PDE activity to effectively hydrolyze near-membrane cAMP. These results imply that cAMP levels near the plasma membrane are distinct from those in other subcellular compartments; PDE activity is not uniform within cells; and localized pools of AC and PDE activities are responsible for controlling cAMP levels within distinct subcellular compartments. PMID:26201952

The fate of epithelial cells in the human large intestine.

PubMed

Barkla, D H; Gibson, P R

1999-08-01

One hundred and forty biopsies of the colon and rectum, collected during routine colonoscopies of 51 patients aged 19 to 74 years, were examined using light microscopy and transmission and scanning electron microscopy. The results indicated that surface epithelial cells undergo apoptosis, passing through fenestrations in the basement membrane to where they enter the lamina propria and are taken up by macrophages; and it is hypothesized that apoptotic cells are carried through the fenestrations on a current of fluid. The study also found that epithelial cells positioned over the crypts are better attached and more robust than those more distant from the crypt opening; and it is further hypothesized that, after reaching the top of the crypts, some goblet cells cease secreting mucus and pass onto the surface compartment of absorptive cells. An unexpected finding was that the lower regions of the crypts commonly contain isolated necrotic colonocytes. Apoptotic cells were rarely observed in the crypt epithelium. The findings of this study support the "recycling" model of epithelial cell death in the surface compartment of the human colon.

Multicompartmental model for iodide, thyroxine, and triiodothyronine metabolism in normal and spontaneously hyperthyroid cats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hays, M.T.; Broome, M.R.; Turrel, J.M.

A comprehensive multicompartmental kinetic model was developed to account for the distribution and metabolism of simultaneously injected radioactive iodide (iodide*), T3 (T3*), and T4 (T4*) in six normal and seven spontaneously hyperthyroid cats. Data from plasma samples (analyzed by HPLC), urine, feces, and thyroid accumulation were incorporated into the model. The submodels for iodide*, T3*, and T4* all included both a fast and a slow exchange compartment connecting with the plasma compartment. The best-fit iodide* model also included a delay compartment, presumed to be pooling of gastrosalivary secretions. This delay was 62% longer in the hyperthyroid cats than in themore » euthyroid cats. Unexpectedly, all of the exchange parameters for both T4 and T3 were significantly slowed in hyperthyroidism, possibly because the hyperthyroid cats were older. None of the plasma equivalent volumes of the exchange compartments of iodide*, T3*, or T4* was significantly different in the hyperthyroid cats, although the plasma equivalent volume of the fast T4 exchange compartments were reduced. Secretion of recycled T4* from the thyroid into the plasma T4* compartment was essential to model fit, but its quantity could not be uniquely identified in the absence of multiple thyroid data points. Thyroid secretion of T3* was not detectable. Comparing the fast and slow compartments, there was a shift of T4* deiodination into the fast exchange compartment in hyperthyroidism. Total body mean residence times (MRTs) of iodide* and T3* were not affected by hyperthyroidism, but mean T4* MRT was decreased 23%. Total fractional T4 to T3 conversion was unchanged in hyperthyroidism, although the amount of T3 produced by this route was increased nearly 5-fold because of higher concentrations of donor stable T4.« less

Synchronous temperature rate control for refrigeration with reduced energy consumption

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomes, Alberto Regio; Keres, Stephen L.; Kuehl, Steven J.

Methods of operation for refrigerator appliance configurations with a controller, a condenser, at least one evaporator, a compressor, and two refrigeration compartments. The configuration may be equipped with a variable-speed or variable-capacity compressor, variable speed evaporator or compartment fans, a damper, and/or a dual-temperature evaporator with a valve system to control flow of refrigerant through one or more pressure reduction devices. The methods may include synchronizing alternating cycles of cooling each compartment to a temperature approximately equal to the compartment set point temperature by operation of the compressor, fans, damper and/or valve system. The methods may also include controlling themore » cooling rate in one or both compartments. Refrigeration compartment cooling may begin at an interval before or after when the freezer compartment reaches its lower threshold temperature. Freezer compartment cooling may begin at an interval before or after when the freezer compartment reaches its upper threshold temperature.« less

Synchronous temperature rate control for refrigeration with reduced energy consumption

DOEpatents

Gomes, Alberto Regio; Keres, Stephen L.; Kuehl, Steven J.; Litch, Andrew D.; Richmond, Peter J.; Wu, Guolian

2015-09-22

Methods of operation for refrigerator appliance configurations with a controller, a condenser, at least one evaporator, a compressor, and two refrigeration compartments. The configuration may be equipped with a variable-speed or variable-capacity compressor, variable speed evaporator or compartment fans, a damper, and/or a dual-temperature evaporator with a valve system to control flow of refrigerant through one or more pressure reduction devices. The methods may include synchronizing alternating cycles of cooling each compartment to a temperature approximately equal to the compartment set point temperature by operation of the compressor, fans, damper and/or valve system. The methods may also include controlling the cooling rate in one or both compartments. Refrigeration compartment cooling may begin at an interval before or after when the freezer compartment reaches its lower threshold temperature. Freezer compartment cooling may begin at an interval before or after when the freezer compartment reaches its upper threshold temperature.

Physiologic volume of phosphorus during hemodialysis: predictions from a pseudo one-compartment model.

PubMed

Leypoldt, John K; Akonur, Alp; Agar, Baris U; Culleton, Bruce F

2012-10-01

The kinetics of plasma phosphorus concentrations during hemodialysis (HD) are complex and cannot be described by conventional one- or two-compartment kinetic models. It has recently been shown by others that the physiologic (or apparent distribution) volume for phosphorus (Vr-P) increases with increasing treatment time and shows a large variation among patients treated by thrice weekly and daily HD. Here, we describe the dependence of Vr-P on treatment time and predialysis plasma phosphorus concentration as predicted by a novel pseudo one-compartment model. The kinetics of plasma phosphorus during conventional and six times per week daily HD were simulated as a function of treatment time per session for various dialyzer phosphate clearances and patient-specific phosphorus mobilization clearances (K(M)). Vr-P normalized to extracellular volume from these simulations were reported and compared with previously published empirical findings. Simulated results were relatively independent of dialyzer phosphate clearance and treatment frequency. In contrast, Vr-P was strongly dependent on treatment time per session; the increase in Vr-P with treatment time was larger for higher values of K(M). Vr-P was inversely dependent on predialysis plasma phosphorus concentration. There was significant variation among predicted Vr-P values, depending largely on the value of K(M). We conclude that a pseudo one-compartment model can describe the empirical dependence of the physiologic volume of phosphorus on treatment time and predialysis plasma phosphorus concentration. Further, the variation in physiologic volume of phosphorus among HD patients is largely due to differences in patient-specific phosphorus mobilization clearance. © 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.

Respiratory mechanics during sevoflurane anesthesia in children with and without asthma.

PubMed

Habre, W; Scalfaro, P; Sims, C; Tiller, K; Sly, P D

1999-11-01

We studied lung function in children with and without asthma receiving anesthesia with sevoflurane. Fifty-two children had anesthesia induced with sevoflurane (up to 8%) in a mixture of 50% nitrous oxide in oxygen and then maintained at 3% with children breathing spontaneously via face mask and Jackson-Rees modification of the T-piece. Airway opening pressure and flow were then measured. After insertion of an oral endotracheal tube under 5% sevoflurane, measurements were repeated at 3%, as well as after increasing to 4.2%. Respiratory system resistance (Rrs) and compliance during expiration were calculated using multilinear regression analysis of airway opening pressure and flow, assuming a single-compartment model. Data from 44 children were analyzed (22 asthmatics and 22 normal children). The two groups were comparable with respect to age, weight, ventilation variables, and baseline respiratory mechanics. Intubation was associated with a significant increase in Rrs in asthmatics (17% +/- 49%), whereas in normal children, Rrs slightly decreased (-4% +/- 39%). At 4.2%, Rrs decreased slightly in both groups with almost no change in compliance system resistance. We concluded that in children with mild to moderate asthma, endotracheal intubation during sevoflurane anesthesia was associated with increase in Rrs that was not seen in nonasthmatic children. Tracheal intubation using sevoflurane as sole anesthetic is possible and its frequency is increasing. When comparing children with and without asthma, tracheal intubation under sevoflurane was associated with an increase in respiratory system resistance in asthmatic children. However, no apparent clinical adverse event was observed.

76 FR 18031 - Airworthiness Directives; Dassault Aviation Model Mystere-Falcon 50 Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-01

... system line to engine 2, and engine 2 Low Pressure (LP) bleed line. If the swapping of these two lines is... line to engine 2, and engine 2 Low Pressure (LP) bleed line. If the swapping of these two lines is not... the connection of the two lines (extinguishing and LP bleed lines) at frame 42 in the rear compartment...

Understanding the drug release mechanism from a montmorillonite matrix and its binary mixture with a hydrophilic polymer using a compartmental modelling approach

NASA Astrophysics Data System (ADS)

Choiri, S.; Ainurofiq, A.

2018-03-01

Drug release from a montmorillonite (MMT) matrix is a complex mechanism controlled by swelling mechanism of MMT and an interaction of drug and MMT. The aim of this research was to explain a suitable model of the drug release mechanism from MMT and its binary mixture with a hydrophilic polymer in the controlled release formulation based on a compartmental modelling approach. Theophylline was used as a drug model and incorporated into MMT and a binary mixture with hydroxyl propyl methyl cellulose (HPMC) as a hydrophilic polymer, by a kneading method. The dissolution test was performed and the modelling of drug release was assisted by a WinSAAM software. A 2 model was purposed based on the swelling capability and basal spacing of MMT compartments. The model evaluation was carried out to goodness of fit and statistical parameters and models were validated by a cross-validation technique. The drug release from MMT matrix regulated by a burst release mechanism of unloaded drug, swelling ability, basal spacing of MMT compartment, and equilibrium between basal spacing and swelling compartments. Furthermore, the addition of HPMC in MMT system altered the presence of swelling compartment and equilibrium between swelling and basal spacing compartment systems. In addition, a hydrophilic polymer reduced the burst release mechanism of unloaded drug.

Fabrication and characterization of anisotropic nanofiber scaffolds for advanced drug delivery systems

PubMed Central

Jalani, Ghulam; Jung, Chan Woo; Lee, Jae Sang; Lim, Dong Woo

2014-01-01

Stimuli-responsive, polymer-based nanostructures with anisotropic compartments are of great interest as advanced materials because they are capable of switching their shape via environmentally-triggered conformational changes, while maintaining discrete compartments. In this study, a new class of stimuli-responsive, anisotropic nanofiber scaffolds with physically and chemically distinct compartments was prepared via electrohydrodynamic cojetting with side-by-side needle geometry. These nanofibers have a thermally responsive, physically-crosslinked compartment, and a chemically-crosslinked compartment at the nanoscale. The thermally responsive compartment is composed of physically crosslinkable poly(N-isopropylacrylamide) poly(NIPAM) copolymers, and poly(NIPAM-co-stearyl acrylate) poly(NIPAM-co-SA), while the thermally-unresponsive compartment is composed of polyethylene glycol dimethacrylates. The two distinct compartments were physically crosslinked by the hydrophobic interaction of the stearyl chains of poly(NIPAM-co-SA) or chemically stabilized via ultraviolet irradiation, and were swollen in physiologically relevant buffers due to their hydrophilic polymer networks. Bicompartmental nanofibers with the physically-crosslinked network of the poly(NIPAM-co-SA) compartment showed a thermally-triggered shape change due to thermally-induced aggregation of poly(NIPAM-co-SA). Furthermore, when bovine serum albumin and dexamethasone phosphate were separately loaded into each compartment, the bicompartmental nanofibers with anisotropic actuation exhibited decoupled, controlled release profiles of both drugs in response to a temperature. A new class of multicompartmental nanofibers could be useful for advanced nanofiber scaffolds with two or more drugs released with different kinetics in response to environmental stimuli. PMID:24872702

A nonlinear model for myogenic regulation of blood flow to bone: equilibrium states and stability characteristics.

PubMed

Harrigan, T P

1996-01-01

A simple compartmental model for myogenic regulation of interstitial pressure in bone is developed, and the interaction between changes in interstitial pressure and changes in arterial and venous resistance is studied. The arterial resistance is modeled by a myogenic model that depends on transmural pressure, and the venous resistance is modeled by using a vascular waterfall. Two series capacitances model blood storage in the vascular system and interstitial fluid storage in the extravascular space. The static results mimic the observed effect that vasodilators work less well in bone than do vasoconstrictors. The static results also show that the model gives constant flow rates over a limited range of arterial pressure. The dynamic model shows unstable behavior at small values of bony capacitance and at high enough myogenic gain. At low myogenic gain, only a single equilibrium state is present, but a high enough myogenic gain, two new equilibrium states appear. At additional increases in gain, one of the two new states merges with and then separates from the original state, and the original state becomes a saddle point. The appearance of the new states and the transition of the original state to a saddle point do not depend on the bony capacitance, and these results are relevant to general fluid compartments. Numerical integration of the rate equations confirms the stability calculations and shows limit cycling behavior in several situations. The relevance of this model to circulation in bone and to other compartments is discussed.

High-energy roller injuries to the upper extremity.

PubMed

Askins, G; Finley, R; Parenti, J; Bush, D; Brotman, S

1986-12-01

Eleven cases of high-energy industrial roller injuries treated between 1980 and 1984 were retrospectively reviewed. The dominant extremity was affected in nine. Six patients sustained fractures and/or dislocations, and three of these patients required fasciotomies for clinical signs of impending compartment syndromes. All fracture/dislocations, with the exception of a scapula fracture, anterior dislocation of a thumb interphalangeal joint, and a fractured coronoid process of the ulna, required open reduction with internal fixation. Three patients required split-thickness skin grafting for extensive skin degloving. Two patients required immediate amputation. Late sequelae included prolonged edema, nutritional depletion, neuroma formation of the superficial branch of the radial nerve, late carpal tunnel syndrome, and partial brachial plexus palsy. Industrial roller injuries continue to be an occupational hazard associated with more severe crushing trauma than the low-energy wringer washer injuries first described by MacCollum (11). Attention must be paid to the treatment of crushed skin, muscle, and nerves, fracture stabilization, nutritional support, and occupational therapy. Concurrent monitoring for signs of a developing compartment syndrome and complications of rhabdomyolysis is essential.

An earthquake instability model based on faults containing high fluid-pressure compartments

USGS Publications Warehouse

Lockner, D.A.; Byerlee, J.D.

1995-01-01

It has been proposed that large strike-slip faults such as the San Andreas contain water in seal-bounded compartments. Arguments based on heat flow and stress orientation suggest that in most of the compartments, the water pressure is so high that the average shear strength of the fault is less than 20 MPa. We propose a variation of this basic model in which most of the shear stress on the fault is supported by a small number of compartments where the pore pressure is relatively low. As a result, the fault gouge in these compartments is compacted and lithified and has a high undisturbed strength. When one of these locked regions fails, the system made up of the neighboring high and low pressure compartments can become unstable. Material in the high fluid pressure compartments is initially underconsolidated since the low effective confining pressure has retarded compaction. As these compartments are deformed, fluid pressure remains nearly unchanged so that they offer little resistance to shear. The low pore pressure compartments, however, are overconsolidated and dilate as they are sheared. Decompression of the pore fluid in these compartments lowers fluid pressure, increasing effective normal stress and shear strength. While this effect tends to stabilize the fault, it can be shown that this dilatancy hardening can be more than offset by displacement weakening of the fault (i.e., the drop from peak to residual strength). If the surrounding rock mass is sufficiently compliant to produce an instability, slip will propagate along the fault until the shear fracture runs into a low-stress region. Frictional heating and the accompanying increase in fluid pressure that are suggested to occur during shearing of the fault zone will act as additional destabilizers. However, significant heating occurs only after a finite amount of slip and therefore is more likely to contribute to the energetics of rupture propagation than to the initiation of the instability. We present results of a one-dimensional dynamic Burridge-Knopoff-type model to demonstrate various aspects of the fluid-assisted fault instability described above. In the numerical model, the fault is represented by a series of blocks and springs, with fault rheology expressed by static and dynamic friction. In addition, the fault surface of each block has associated with it pore pressure, porosity and permeability. All of these variables are allowed to evolve with time, resulting in a wide range of phenomena related to fluid diffusion, dilatancy, compaction and heating. These phenomena include creep events, diffusion-controlled precursors, triggered earthquakes, foreshocks, aftershocks, and multiple earthquakes. While the simulations have limitations inherent to 1-D fault models, they demonstrate that the fluid compartment model can, in principle, provide the rich assortment of phenomena that have been associated with earthquakes. ?? 1995 Birkha??user Verlag.

14 CFR 23.901 - Installation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS... maintenance. (c) Engine cowls and nacelles must be easily removable or openable by the pilot to provide adequate access to and exposure of the engine compartment for preflight checks. (d) Each turbine engine...

14 CFR 23.901 - Installation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS... maintenance. (c) Engine cowls and nacelles must be easily removable or openable by the pilot to provide adequate access to and exposure of the engine compartment for preflight checks. (d) Each turbine engine...

14 CFR 23.901 - Installation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS... maintenance. (c) Engine cowls and nacelles must be easily removable or openable by the pilot to provide adequate access to and exposure of the engine compartment for preflight checks. (d) Each turbine engine...

14 CFR 23.901 - Installation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS... maintenance. (c) Engine cowls and nacelles must be easily removable or openable by the pilot to provide adequate access to and exposure of the engine compartment for preflight checks. (d) Each turbine engine...

14 CFR 23.901 - Installation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS... maintenance. (c) Engine cowls and nacelles must be easily removable or openable by the pilot to provide adequate access to and exposure of the engine compartment for preflight checks. (d) Each turbine engine...

The novel substituted acylproline-containing dipeptide, GVS-111, promotes the restoration of learning and memory impaired by bilateral frontal lobectomy in rats.

PubMed

Ostrovskaya, R U; Romanova, G A; Trofimov, S S; Gudasheva, T A; Voronina, T A; Halikas, J A; Seredenin, S B

1997-06-01

The present study investigated the potential benefit of the ethyl ester of N-phenylacetylprolylglycine (GVS-111) on the model of bilateral frontal lobectomy (BFL) in rats. The animals in Experiment 1 were trained in an active avoidance task and subsequently underwent BFL. The animals in Experiment 2 were first assessed in an open field and in a passive avoidance test before the BFL was performed. BFL dramatically decreased performance in the active avoidance test, disturbed habituation of horizontal activity in the open field and diminished the latency to enter the dark compartment in the passive avoidance test. GVS-111, administered in a dose of 0.5 mg/kg/day i.p. for 9 days following the operation, was found to improve performance in both active avoidance and passive avoidance and restored habituation of horizontal activity in the lobectomized animals.

Multiscale Analysis of Open-Cell Aluminum Foam for Impact Energy Absorption

NASA Astrophysics Data System (ADS)

Kim, Ji Hoon; Kim, Daeyong; Lee, Myoung-Gyu; Lee, Jong Kook

2016-09-01

The energy-absorbing characteristics of crash members in automotive collision play an important role in controlling the amount of damage to the passenger compartment. Aluminum foams have high strength-to-weight ratio and high deformability, thus good crashworthiness is expected while maintaining or even saving weights when foams are implemented in crash members. In order to investigate the effect of the open-cell aluminum foam fillers on impact performance and weight saving, a multiscale framework for evaluating the crashworthiness of aluminum foam-filled members is used. To circumvent the difficulties of mechanical tests on foams, a micromechanical model of the aluminum foam is constructed using the x-ray micro tomography and virtual tests are conducted for the micromechanical model to characterize the behavior of the foam. In the macroscale, the aluminum foam is represented by the crushable foam constitutive model, which is then incorporated into the impact test simulation of the foam-filled crash member. The multiscale foam-filled crash member model was validated for the high-speed impact test, which confirms that the material model characterized by the micromechanical approach represents the behavior of the open-cell foam under impact loading well. Finally, the crash member design for maximizing the energy absorption is discussed by investigating various designs from the foam-only structure to the hollow tube structure. It was found that the foam structure absorbs more energy than the hollow tube or foam-filled structure with the same weight.

The Ubiquitous Distribution of Late Embryogenesis Abundant Proteins across Cell Compartments in Arabidopsis Offers Tailored Protection against Abiotic Stress[C][W][OPEN

PubMed Central

Candat, Adrien; Paszkiewicz, Gaël; Neveu, Martine; Gautier, Romain; Logan, David C.; Avelange-Macherel, Marie-Hélène; Macherel, David

2014-01-01

Late embryogenesis abundant (LEA) proteins are hydrophilic, mostly intrinsically disordered proteins, which play major roles in desiccation tolerance. In Arabidopsis thaliana, 51 genes encoding LEA proteins clustered into nine families have been inventoried. To increase our understanding of the yet enigmatic functions of these gene families, we report the subcellular location of each protein. Experimental data highlight the limits of in silico predictions for analysis of subcellular localization. Thirty-six LEA proteins localized to the cytosol, with most being able to diffuse into the nucleus. Three proteins were exclusively localized in plastids or mitochondria, while two others were found dually targeted to these organelles. Targeting cleavage sites could be determined for five of these proteins. Three proteins were found to be endoplasmic reticulum (ER) residents, two were vacuolar, and two were secreted. A single protein was identified in pexophagosomes. While most LEA protein families have a unique subcellular localization, members of the LEA_4 family are widely distributed (cytosol, mitochondria, plastid, ER, and pexophagosome) but share the presence of the class A α-helix motif. They are thus expected to establish interactions with various cellular membranes under stress conditions. The broad subcellular distribution of LEA proteins highlights the requirement for each cellular compartment to be provided with protective mechanisms to cope with desiccation or cold stress. PMID:25005920

Modelling cell population growth with applications to cancer therapy in human tumour cell lines.

PubMed

Basse, Britta; Baguley, Bruce C; Marshall, Elaine S; Wake, Graeme C; Wall, David J N

2004-01-01

In this paper we present an overview of the work undertaken to model a population of cells and the effects of cancer therapy. We began with a theoretical one compartment size structured cell population model and investigated its asymptotic steady size distributions (SSDs) (On a cell growth model for plankton, MMB JIMA 21 (2004) 49). However these size distributions are not similar to the DNA (size) distributions obtained experimentally via the flow cytometric analysis of human tumour cell lines (data obtained from the Auckland Cancer Society Research Centre, New Zealand). In our one compartment model, size was a generic term, but in order to obtain realistic steady size distributions we chose size to be DNA content and devised a multi-compartment mathematical model for the cell division cycle where each compartment corresponds to a distinct phase of the cell cycle (J. Math. Biol. 47 (2003) 295). We then incorporated another compartment describing the possible induction of apoptosis (cell death) from mitosis phase (Modelling cell death in human tumour cell lines exposed to anticancer drug paclitaxel, J. Math. Biol. 2004, in press). This enabled us to compare our model to flow cytometric data of a melanoma cell line where the anticancer drug, paclitaxel, had been added. The model gives a dynamic picture of the effects of paclitaxel on the cell cycle. We hope to use the model to describe the effects of other cancer therapies on a number of different cell lines. Copyright 2004 Elsevier Ltd.

The Role of Water Compartments in the Material Properties of Cortical Bone

PubMed Central

Granke, Mathilde; Does, Mark D.; Nyman, Jeffry S.

2015-01-01

Comprising ~20% of the volume, water is a key determinant of the mechanical behavior of cortical bone. It essentially exists in 2 general compartments: within pores and bound to the matrix. The amount of pore water – residing in vascular-lacunar-canalicular space – primarily reflects intracortical porosity (i.e., open spaces within the matrix largely due to Haversian canals and resorption sites), and as such, is inversely proportional to most mechanical properties of bone. Movement of water according to pressure gradients generated during dynamic loading likely confers hydraulic stiffening to the bone as well. Nonetheless, bound water is a primary contributor to mechanical behavior of bone in that it is responsible for giving collagen the ability to confer ductility or plasticity to bone (i.e., allows deformation to continue once permanent damage begins to form in the matrix) and decreases with age along with fracture resistance. Thus, dehydration by air-drying or by solvents with less hydrogen bonding capacity causes bone to become brittle, but interestingly, it also increases stiffness and strength across the hierarchical levels of organization. Despite the importance of matrix hydration to fracture resistance, little is known about why bound water decreases with age in hydrated human bone. Using 1H nuclear magnetic resonance (NMR), both bound and pore water concentrations in bone can be measured ex vivo because the proton relaxation times differ between the two water compartments giving rise to two distinct signals. There are also emerging techniques to measure bound and pore water in vivo with magnetic resonance imaging (MRI). NMR/MRI-derived bound water concentration is positively correlated with both strength and toughness of hydrated bone, and may become a useful clinical marker of fracture risk. PMID:25783011

Effect of open wedge high tibial osteotomy on the lateral tibiofemoral compartment in sheep. Part III: analysis of the microstructure of the subchondral bone and correlations with the articular cartilage and meniscus.

PubMed

Ziegler, Raphaela; Goebel, Lars; Seidel, Roland; Cucchiarini, Magali; Pape, Dietrich; Madry, Henning

2015-09-01

First, to evaluate whether medial open wedge high tibial osteotomy (HTO) induces alterations of the microstructure of the lateral tibial subchondral bone plate of sheep. Second, to test the hypothesis that specific correlations exist between topographical structural alterations of the subchondral bone, the cartilage and the lateral meniscus. Three experimental groups received biplanar osteotomies of the right proximal tibiae: (a) closing wedge HTO (4.5° of tibial varus), (b) opening wedge HTO (4.5° tibial valgus; standard correction) and (c) opening wedge HTO (9.5° of valgus; overcorrection), each of which was compared to the non-osteotomised contralateral proximal tibiae. After 6 months, subchondral bone structure indices were measured by computed tomography. Correlations between the subchondral bone, the articular cartilage and the lateral meniscus were determined. Increased loading by valgus overcorrection led to an enlarged specific bone surface (BS/BV) in the subarticular spongiosa compared with unloading by varisation. The subchondral bone plate was 3.9-fold thicker in the central region of the lateral tibial plateau than in the submeniscal periphery. Its thickness in the central region significantly correlated with the thickness of the articular cartilage. In the submeniscal region, such correlation did not exist. In general, a higher degree of osteoarthritis (OA) correlated with alterations of the subchondral bone plate microstructure. OA of the submeniscal articular cartilage also correlated with worse matrix staining of the lateral meniscus. Osteoarthritis changes are associated with alterations of the subchondral bone plate microstructure. Specific topographical relationships exist in the central region between the articular cartilage and subchondral bone plate thickness, and in the submeniscal periphery between and the articular cartilage and lateral meniscus. From a clinical perspective, the combined follow-up data from this and the previous two investigations suggest that open wedge valgus HTO is a safe procedure for the lateral compartment to manage medial osteoarthritis of the knee with varus malalignment in the short term.

Oscillation mechanics of the respiratory system.

PubMed

Bates, Jason H T; Irvin, Charles G; Farré, Ramon; Hantos, Zoltán

2011-07-01

The mechanical impedance of the respiratory system defines the pressure profile required to drive a unit of oscillatory flow into the lungs. Impedance is a function of oscillation frequency, and is measured using the forced oscillation technique. Digital signal processing methods, most notably the Fourier transform, are used to calculate impedance from measured oscillatory pressures and flows. Impedance is a complex function of frequency, having both real and imaginary parts that vary with frequency in ways that can be used empirically to distinguish normal lung function from a variety of different pathologies. The most useful diagnostic information is gained when anatomically based mathematical models are fit to measurements of impedance. The simplest such model consists of a single flow-resistive conduit connecting to a single elastic compartment. Models of greater complexity may have two or more compartments, and provide more accurate fits to impedance measurements over a variety of different frequency ranges. The model that currently enjoys the widest application in studies of animal models of lung disease consists of a single airway serving an alveolar compartment comprising tissue with a constant-phase impedance. This model has been shown to fit very accurately to a wide range of impedance data, yet contains only four free parameters, and as such is highly parsimonious. The measurement of impedance in human patients is also now rapidly gaining acceptance, and promises to provide a more comprehensible assessment of lung function than parameters derived from conventional spirometry. © 2011 American Physiological Society.

Modeling the effects of exercise during 100% oxygen prebreathe on the risk of hypobaric decompression sickness

NASA Technical Reports Server (NTRS)

Loftin, K. C.; Conkin, J.; Powell, M. R.

1997-01-01

BACKGROUND: Several previous studies indicated that exercise during prebreathe with 100% O2 decreased the incidence of hypobaric decompression sickness (DCS). We report a meta-analysis of these investigations combined with a new study in our laboratory to develop a statistical model as a predictive tool for DCS. HYPOTHESIS: Exercise during prebreathe increases N2 elimination in a theoretical 360-min half-time compartment decreasing the incidence of DCS. METHODS: A dose-response probability tissue ratio (TR) model with 95% confidence limits was created for two groups, prebreathe with exercise (n = 113) and resting prebreathe (n = 113), using nonlinear regression analysis with maximum likelihood optimization. RESULTS: The model predicted that prebreathe exercise would reduce the residual N2 in a 360-min half-time compartment to a level analogous to that in a 180-min compartment. This finding supported the hypothesis. The incidence of DCS for the exercise prebreathe group was significantly decreased (Chi-Square = 17.1, p < 0.0001) from the resting prebreathe group. CONCLUSIONS: The results suggested that exercise during prebreathe increases tissue perfusion and N2 elimination approximately 2-fold and markedly lowers the risk of DCS. Based on the model, the prebreathe duration may be reduced from 240 min to a predicted 91 min for the protocol in our study, but this remains to be verified. The model provides a useful planning tool to develop and test appropriate prebreathe exercise protocols and to predict DCS risks for astronauts.

Spontaneous action potentials and neural coding in unmyelinated axons.

PubMed

O'Donnell, Cian; van Rossum, Mark C W

2015-04-01

The voltage-gated Na and K channels in neurons are responsible for action potential generation. Because ion channels open and close in a stochastic fashion, spontaneous (ectopic) action potentials can result even in the absence of stimulation. While spontaneous action potentials have been studied in detail in single-compartment models, studies on spatially extended processes have been limited. The simulations and analysis presented here show that spontaneous rate in unmyelinated axon depends nonmonotonically on the length of the axon, that the spontaneous activity has sub-Poisson statistics, and that neural coding can be hampered by the spontaneous spikes by reducing the probability of transmitting the first spike in a train.

3-compartment talaporfin sodium pharmacokinetic model by optimization using fluorescence measurement data from canine skin to estimate the concentration in interstitial space

NASA Astrophysics Data System (ADS)

Uno, Yuko; Ogawa, Emiyu; Aiyoshi, Eitaro; Arai, Tsunenori

2018-02-01

We constructed the 3-compartment talaporfin sodium pharmacokinetic model for canine by an optimization using the fluorescence measurement data from canine skin to estimate the concentration in the interstitial space. It is difficult to construct the 3-compartment model consisted of plasma, interstitial space, and cell because there is a lack of the dynamic information. Therefore, we proposed the methodology to construct the 3-compartment model using the measured talaporfin sodium skin fluorescence change considering originated tissue part by a histological observation. In a canine animal experiment, the talaporfin sodium concentration time history in plasma was measured by a spectrophotometer with a prepared calibration curve. The time history of talaporfin sodium Q-band fluorescence on left femoral skin of a beagle dog excited by talaporfin sodium Soret-band of 409 nm was measured in vivo by our previously constructed measurement system. The measured skin fluorescence was classified to its source, that is, specific ratio of plasma, interstitial space, and cell. We represented differential rate equations of the talaporfin sodium concentration in plasma, interstitial space, cell. The specific ratios and a converting constant to obtain absolute value of skin concentration were arranged. Minimizing the squared error of the difference between the measured fluorescence data and calculated concentration by the conjugate gradient method in MATLAB, the rate constants in the 3-compartment model were determined. The accuracy of the fitting operation was confirmed with determination coefficient of 0.98. We could construct the 3-compartment pharmacokinetic model for canine using the measured talaporfin sodium fluorescence change from canine skin.

Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon).

PubMed

Scala, Christopher; Marsot, Amélie; Limoges, Marie-Josée; Locatelli, Yann; Simon, Nicolas; Alvarez, Jean-Claude

2015-03-01

To assess the population pharmacokinetics of methadone in deer. Prospective non-randomized experimental trial. Twelve healthy adult sika deer (nine males and three females). Deer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg(-1) or 1 mg kg(-1) . Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM). A two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour(-1) ), metabolic clearance (34.6 L hour(-1) ), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour(-1) ), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour(-1) , 121.0 L hour (-1) , 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration. Following intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Environmental behaviors and potential ecological risks of heavy metals (Cd, Cr, Cu, Pb, and Zn) in multimedia in an oilfield in China.

PubMed

Hu, Yan; Wang, Dazhou; Li, Yu

2016-07-01

The environmental behaviors of five heavy metals (Cd, Cr, Cu, Pb, and Zn) in a Chinese oilfield were investigated using a steady-state multimedia aquivalence (SMA) model. The modeling results showed good agreement with the actual measured values, with average residual errors of 0.69, 0.83, 0.35, 0.16, and 0.54 logarithmic units for air, water, soil, sediment, and vegetation compartments, respectively. Model results indicated that most heavy metals were buried in sediment, and that transfers between adjacent compartments were mainly deposition from the water to the sediment compartment (48.59 %) and from the air to the soil compartment (47.74 %) via atmospheric dry/wet deposition. Sediment and soil were the dominant sinks, accounting for 68.80 and 25.26 % of all the heavy metals in the multimedia system, respectively. The potential ecological risks from the five heavy metals in the sediment and soil compartments were assessed by the potential ecological risk index (PERI). The assessment results demonstrate that the heavy metals presented low levels of ecological risk in the sediment compartment, and that Cd was the most significant contributor to the integrated potential ecological risk in the oilfield. The SMA model provided useful simulations of the transport and fate of heavy metals and is a useful tool for ecological risk assessment and contaminated site management.

Extended phase graph formalism for systems with magnetization transfer and exchange

PubMed Central

Teixeira, Rui Pedro A.G.; Hajnal, Joseph V.

2017-01-01

Purpose An extended phase graph framework (EPG‐X) for modeling systems with exchange or magnetization transfer (MT) is proposed. Theory EPG‐X models coupled two‐compartment systems by describing each compartment with separate phase graphs that exchange during evolution periods. There are two variants: EPG‐X(BM) for systems governed by the Bloch‐McConnell equations, and EPG‐X(MT) for the pulsed MT formalism. For the MT case, the “bound” protons have no transverse components, so their phase graph consists of only longitudinal states. Methods The EPG‐X model was validated against steady‐state solutions and isochromat‐based simulation of gradient‐echo sequences. Three additional test cases were investigated: (i) MT effects in multislice turbo spin‐echo; (ii) variable flip angle gradient‐echo imaging of the type used for MR fingerprinting; and (iii) water exchange in multi‐echo spin‐echo T2 relaxometry. Results EPG‐X was validated successfully against isochromat based transient simulations and known steady‐state solutions. EPG‐X(MT) simulations matched in‐vivo measurements of signal attenuation in white matter in multislice turbo spin‐echo images. Magnetic resonance fingerprinting–style experiments with a bovine serum albumin (MT) phantom showed that the data were not consistent with a single‐pool model, but EPG‐X(MT) could be used to fit the data well. The EPG‐X(BM) simulations of multi‐echo spin‐echo T2 relaxometry suggest that exchange could lead to an underestimation of the myelin‐water fraction. Conclusions The EPG‐X framework can be used for modeling both steady‐state and transient signal response of systems exhibiting exchange or MT. This may be particularly beneficial for relaxometry approaches that rely on characterizing transient rather than steady‐state sequences. Magn Reson Med 80:767–779, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:29243295

Feasibility of Rapid Multitracer PET Tumor Imaging

NASA Astrophysics Data System (ADS)

Kadrmas, D. J.; Rust, T. C.

2005-10-01

Positron emission tomography (PET) can characterize different aspects of tumor physiology using various tracers. PET scans are usually performed using only one tracer since there is no explicit signal for distinguishing multiple tracers. We tested the feasibility of rapidly imaging multiple PET tracers using dynamic imaging techniques, where the signals from each tracer are separated based upon differences in tracer half-life, kinetics, and distribution. Time-activity curve populations for FDG, acetate, ATSM, and PTSM were simulated using appropriate compartment models, and noisy dual-tracer curves were computed by shifting and adding the single-tracer curves. Single-tracer components were then estimated from dual-tracer data using two methods: principal component analysis (PCA)-based fits of single-tracer components to multitracer data, and parallel multitracer compartment models estimating single-tracer rate parameters from multitracer time-activity curves. The PCA analysis found that there is information content present for separating multitracer data, and that tracer separability depends upon tracer kinetics, injection order and timing. Multitracer compartment modeling recovered rate parameters for individual tracers with good accuracy but somewhat higher statistical uncertainty than single-tracer results when the injection delay was >10 min. These approaches to processing rapid multitracer PET data may potentially provide a new tool for characterizing multiple aspects of tumor physiology in vivo.

Compartmental hollow fiber capillary membrane-based bioreactor technology for in vitro studies on red blood cell lineage direction of hematopoietic stem cells.

PubMed

Housler, Greggory J; Miki, Toshio; Schmelzer, Eva; Pekor, Christopher; Zhang, Xiaokui; Kang, Lin; Voskinarian-Berse, Vanessa; Abbot, Stewart; Zeilinger, Katrin; Gerlach, Jörg C

2012-02-01

Continuous production of red blood cells (RBCs) in an automated closed culture system using hematopoietic stem cell (HSC) progenitor cell populations is of interest for clinical application because of the high demand for blood transfusions. Previously, we introduced a four-compartment bioreactor that consisted of two bundles of hollow fiber microfiltration membranes for transport of culture medium (forming two medium compartments), interwoven with one bundle of hollow fiber membranes for transport of oxygen (O(2)), carbon dioxide (CO(2)), and other gases (forming one gas compartment). Small-scale prototypes were developed of the three-dimensional (3D) perfusion cell culture systems, which enable convection-based mass transfer and integral oxygenation in the cell compartment. CD34(+) HSC were isolated from human cord blood units using a magnetic separation procedure. Cells were inoculated into 2- or 8-mL scaled-down versions of the previously designed 800-mL cell compartment devices and perfused with erythrocyte proliferation and differentiation medium. First, using the small-scale 2-mL analytical scale bioreactor, with an initial seeding density of 800,000 cells/mL, we demonstrated approximately 100-fold cell expansion and differentiation after 7 days of culture. An 8-mL laboratory-scale bioreactor was then used to show pseudocontinuous production by intermediately harvesting cells. Subsequently, we were able to use a model to demonstrate semicontinuous production with up to 14,288-fold expansion using seeding densities of 800,000 cells/mL. The down-scaled culture technology allows for expansion of CD34(+) cells and stimulating these progenitors towards RBC lineage, expressing approximately 40% CD235(+) and enucleation. The 3D perfusion technology provides an innovative tool for studies on RBC production, which is scalable.

Estimation of the Basic Reproductive Ratio for Dengue Fever at the Take-Off Period of Dengue Infection.

PubMed

Jafaruddin; Indratno, Sapto W; Nuraini, Nuning; Supriatna, Asep K; Soewono, Edy

2015-01-01

Estimating the basic reproductive ratio ℛ 0 of dengue fever has continued to be an ever-increasing challenge among epidemiologists. In this paper we propose two different constructions to estimate ℛ 0 which is derived from a dynamical system of host-vector dengue transmission model. The construction is based on the original assumption that in the early states of an epidemic the infected human compartment increases exponentially at the same rate as the infected mosquito compartment (previous work). In the first proposed construction, we modify previous works by assuming that the rates of infection for mosquito and human compartments might be different. In the second construction, we add an improvement by including more realistic conditions in which the dynamics of an infected human compartments are intervened by the dynamics of an infected mosquito compartment, and vice versa. We apply our construction to the real dengue epidemic data from SB Hospital, Bandung, Indonesia, during the period of outbreak Nov. 25, 2008-Dec. 2012. We also propose two scenarios to determine the take-off rate of infection at the beginning of a dengue epidemic for construction of the estimates of ℛ 0: scenario I from equation of new cases of dengue with respect to time (daily) and scenario II from equation of new cases of dengue with respect to cumulative number of new cases of dengue. The results show that our first construction of ℛ 0 accommodates the take-off rate differences between mosquitoes and humans. Our second construction of the ℛ 0 estimation takes into account the presence of infective mosquitoes in the early growth rate of infective humans and vice versa. We conclude that the second approach is more realistic, compared with our first approach and the previous work.

Compartmental Hollow Fiber Capillary Membrane–Based Bioreactor Technology for In Vitro Studies on Red Blood Cell Lineage Direction of Hematopoietic Stem Cells

PubMed Central

Housler, Greggory J.; Miki, Toshio; Schmelzer, Eva; Pekor, Christopher; Zhang, Xiaokui; Kang, Lin; Voskinarian-Berse, Vanessa; Abbot, Stewart; Zeilinger, Katrin

2012-01-01

Continuous production of red blood cells (RBCs) in an automated closed culture system using hematopoietic stem cell (HSC) progenitor cell populations is of interest for clinical application because of the high demand for blood transfusions. Previously, we introduced a four-compartment bioreactor that consisted of two bundles of hollow fiber microfiltration membranes for transport of culture medium (forming two medium compartments), interwoven with one bundle of hollow fiber membranes for transport of oxygen (O2), carbon dioxide (CO2), and other gases (forming one gas compartment). Small-scale prototypes were developed of the three-dimensional (3D) perfusion cell culture systems, which enable convection-based mass transfer and integral oxygenation in the cell compartment. CD34+ HSC were isolated from human cord blood units using a magnetic separation procedure. Cells were inoculated into 2- or 8-mL scaled-down versions of the previously designed 800-mL cell compartment devices and perfused with erythrocyte proliferation and differentiation medium. First, using the small-scale 2-mL analytical scale bioreactor, with an initial seeding density of 800,000 cells/mL, we demonstrated approximately 100-fold cell expansion and differentiation after 7 days of culture. An 8-mL laboratory-scale bioreactor was then used to show pseudocontinuous production by intermediately harvesting cells. Subsequently, we were able to use a model to demonstrate semicontinuous production with up to 14,288-fold expansion using seeding densities of 800,000 cells/mL. The down-scaled culture technology allows for expansion of CD34+ cells and stimulating these progenitors towards RBC lineage, expressing approximately 40% CD235+ and enucleation. The 3D perfusion technology provides an innovative tool for studies on RBC production, which is scalable. PMID:21933020

A mathematical model of a recombinant humanized anti-cocaine monoclonal antibody's effects on cocaine pharmacokinetics in mice.

PubMed

Wetzel, Hanna N; Zhang, Tongli; Norman, Andrew B

2017-09-01

A recombinant humanized anti-cocaine monoclonal antibody (mAb), h2E2, is at an advanced stage of pre-clinical development as an immunotherapy for cocaine abuse. It is hypothesized that h2E2 binds to and sequesters cocaine in the blood. A three-compartment model of the effects of h2E2 on cocaine's distribution was constructed. The model assumes that h2E2 binds to cocaine and that the h2E2-cocaine complex does not enter the brain but distributes between the central and peripheral compartments. Free cocaine is eliminated from both the central and peripheral compartments, and h2E2 and the h2E2-cocaine complex are eliminated from the central compartment only. This model was tested against a new dataset measuring cocaine concentrations in the brain and plasma over 1h in the presence and absence of h2E2. The mAb significantly increased plasma cocaine concentrations with a concomitant significant decrease in brain concentration. Plasma concentrations declined over the 1-hour sampling period in both groups. With a set of parameters within reasonable physiological ranges, the three-compartment model was able to qualitatively and quantitatively simulate the increased plasma concentration in the presence of the antibody and the decreased peak brain concentration in the presence of antibody. Importantly, the model explained the decline in plasma concentrations over time as distribution of the cocaine-h2E2 complex into a peripheral compartment. This model will facilitate the targeting of ideal mAb PK/PD properties thus accelerating the identification of lead candidate anti-drug mAbs. Copyright © 2017 Elsevier Inc. All rights reserved.

Transmission of infrasonic pressure waves from cerebrospinal to intralabyrinthine fluids through the human cochlear aqueduct: Non-invasive measurements with otoacoustic emissions.

PubMed

Traboulsi, Raghida; Avan, Paul

2007-11-01

The cochlear aqueduct connecting intralabyrinthine and cerebrospinal fluids (CSF) acts as a low-pass filter that should be able to transmit infrasonic pressure waves from CSF to cochlea. Recent experiments have shown that otoacoustic emissions generated at 1kHz respond to pressure-related stapes impedance changes with a change in phase relative to the generator tones, and provide a non-invasive means of assessing intracochlear pressure changes. In order to characterize the transmission to the cochlea of CSF pressure waves due to respiration, the distortion-product otoacoustic emissions (DPOAE) of 12 subjects were continuously monitored around 1kHz at a rate of 6.25epochs/s, and their phase relative to the stimulus tones was extracted. The subjects breathed normally, in different postures, while thoracic movements were recorded so as to monitor respiration. A correlate of respiration was found in the time variation of DPOAE phase, with an estimated mean amplitude of 10 degrees , i.e. 60mm water, suggesting little attenuation across the aqueduct. Its phase lag relative to thoracic movements varied between 0 degrees and -270 degrees . When fed into a two-compartment model of CSF and labyrinthine spaces, these results suggest that respiration rate at rest is just above the resonance frequency of the CSF compartment, and just below the corner frequency of the cochlear-aqueduct low-pass filter, in line with previous estimates from temporal bone and intracranial measurements. The fact that infrasonic CSF waves can be monitored through the cochlea opens diagnostic possibilities in neurology.

Quantification of Skeletal Blood Flow and Fluoride Metabolism in Rats using PET in a Pre-Clinical Stress Fracture Model

PubMed Central

Tomlinson, Ryan E.; Silva, Matthew J.; Shoghi, Kooresh I.

2013-01-01

Purpose Blood flow is an important factor in bone production and repair, but its role in osteogenesis induced by mechanical loading is unknown. Here, we present techniques for evaluating blood flow and fluoride metabolism in a pre-clinical stress fracture model of osteogenesis in rats. Procedures Bone formation was induced by forelimb compression in adult rats. 15O water and 18F fluoride PET imaging were used to evaluate blood flow and fluoride kinetics 7 days after loading. 15O water was modeled using a one-compartment, two-parameter model, while a two-compartment, three-parameter model was used to model 18F fluoride. Input functions were created from the heart, and a stochastic search algorithm was implemented to provide initial parameter values in conjunction with a Levenberg–Marquardt optimization algorithm. Results Loaded limbs are shown to have a 26% increase in blood flow rate, 113% increase in fluoride flow rate, 133% increase in fluoride flux, and 13% increase in fluoride incorporation into bone as compared to non-loaded limbs (p < 0.05 for all results). Conclusions The results shown here are consistent with previous studies, confirming this technique is suitable for evaluating the vascular response and mineral kinetics of osteogenic mechanical loading. PMID:21785919

Pharmacokinetics of ketamine and its metabolite norketamine administered at a sub-anesthetic dose together with xylazine to calves prior to castration.

PubMed

Gehring, R; Coetzee, J F; Tarus-Sang, J; Apley, M D

2009-04-01

The objective of this study was to evaluate the plasma pharmacokinetics of ketamine and its active metabolite norketamine administered intravenously at a dose of 0.1 mg/kg together with xylazine (0.05 mg/kg) to control the pain associated with castration in calves. A two-compartment model with an additional metabolite compartment linked to the central compartment was used to simultaneously describe the time-concentration profiles of both ketamine and its major metabolite norketamine. Parameter values estimated from the time-concentration profiles observed in this study were volume of the central compartment (V(c) = 132.82 +/- 68.23 mL/kg), distribution clearance (CL(D) = 15.49 +/- 2.56 mL/min/kg), volume of the peripheral compartment (V(T) = 257.05 +/- 41.65 mL/kg), ketamine clearance by the formation of the norketamine metabolite (CL(2M) = 8.56 +/- 7.37 mL/kg/min) and ketamine clearance by other routes (CL(o) = 16.41 +/- 3.42 mL/kg/min). Previously published data from rats suggest that the metabolite norketamine contributes to the analgesic effect of ketamine, with a potency that is one-third of the parent drug. An understanding of the time-concentration relationships and the disposition of the parent drug and its metabolite is therefore important for a better understanding of the analgesic potential of ketamine in cattle.

The vesosome-- a multicompartment drug delivery vehicle.

PubMed

Kisak, E T; Coldren, B; Evans, C A; Boyer, C; Zasadzinski, J A

2004-01-01

Assembling structures to divide space controllably and spontaneously into subunits at the nanometer scale is a significant challenge, although one that biology has solved in two distinct ways: prokaryotes and eukaryotes. Prokaryotes have a single compartment delimited by one or more lipid-protein membranes. Eukaryotes have nested-membrane structures that provide internal compartments--such as the cell nucleus and cell organelles in which specialized functions are carried out. We have developed a simple method of creating nested bilayer compartments in vitro via the "interdigitated" bilayer phase formed by adding ethanol to a variety of saturated phospholipids. At temperatures below the gel-liquid crystalline transition, T(m), the interdigitated lipid-ethanol sheets are rigid and flat; when the temperature is raised above T(m), the sheets become flexible and close on themselves and the surrounding solution to form closed compartments. During this closure, the sheets can entrap other vesicles, biological macromolecules, or colloidal particles. The result is efficient and spontaneous encapsulation without disruption of even fragile materials to form biomimetic nano-environments for possible use in drug delivery, colloidal stabilization, or as microreactors. The vesosome structure can take full advantage of the 40 years of progress in liposome development including steric stabilization, pH loading of drugs, and intrinsic biocompatibility. However, the multiple compartments of the vesosome give better protection to the interior contents in serum, leading to extended release of model compounds in comparison to unilamellar liposomes.

Carbon nanotubes exhibit fibrillar pharmacology in primates

DOE PAGES

Alidori, Simone; Thorek, Daniel L. J.; Beattie, Bradley J.; ...

2017-08-28

Nanomedicine rests at the nexus of medicine, bioengineering, and biology with great potential for improving health through innovation and development of new drugs and devices. Carbon nanotubes are an example of a fibrillar nanomaterial poised to translate into medical practice. The leading candidate material in this class is ammonium-functionalized carbon nanotubes (fCNT) that exhibits unexpected pharmacological behavior in vivo with important biotechnology applications. Here, we provide a multi-organ evaluation of the distribution, uptake and processing of fCNT in nonhuman primates using quantitative whole body positron emission tomography (PET), compartmental modeling of pharmacokinetic data, serum biomarkers and ex vivo pathology investigation.more » Kidney and liver are the two major organ systems that accumulate and excrete [ 86Y]fCNT in nonhuman primates and accumulation is cell specific as described by compartmental modeling analyses of the quantitative PET data. A serial two-compartment model explains renal processing of tracer-labeled fCNT; hepatic data fits a parallel two-compartment model. These modeling data also reveal significant elimination of the injected activity (>99.8%) from the primate within 3 days (t 1/2 = 11.9 hours). Thus, these favorable results in nonhuman primates provide important insight to the fate of fCNT in vivo and pave the way to further engineering design considerations for sophisticated nanomedicines to aid late stage development and clinical use in man.« less

Carbon nanotubes exhibit fibrillar pharmacology in primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alidori, Simone; Thorek, Daniel L. J.; Beattie, Bradley J.

Nanomedicine rests at the nexus of medicine, bioengineering, and biology with great potential for improving health through innovation and development of new drugs and devices. Carbon nanotubes are an example of a fibrillar nanomaterial poised to translate into medical practice. The leading candidate material in this class is ammonium-functionalized carbon nanotubes (fCNT) that exhibits unexpected pharmacological behavior in vivo with important biotechnology applications. Here, we provide a multi-organ evaluation of the distribution, uptake and processing of fCNT in nonhuman primates using quantitative whole body positron emission tomography (PET), compartmental modeling of pharmacokinetic data, serum biomarkers and ex vivo pathology investigation.more » Kidney and liver are the two major organ systems that accumulate and excrete [ 86Y]fCNT in nonhuman primates and accumulation is cell specific as described by compartmental modeling analyses of the quantitative PET data. A serial two-compartment model explains renal processing of tracer-labeled fCNT; hepatic data fits a parallel two-compartment model. These modeling data also reveal significant elimination of the injected activity (>99.8%) from the primate within 3 days (t 1/2 = 11.9 hours). Thus, these favorable results in nonhuman primates provide important insight to the fate of fCNT in vivo and pave the way to further engineering design considerations for sophisticated nanomedicines to aid late stage development and clinical use in man.« less

Electrode for electrochemical cell

DOEpatents

Kaun, T.D.; Nelson, P.A.; Miller, W.E.

1980-05-09

An electrode structure for a secondary electrochemical cell includes an outer enclosure defining a compartment containing electrochemical active material. The enclosure includes a rigid electrically conductive metal sheet with perforated openings over major side surfaces. The enclosure can be assembled as first and second trays each with a rigid sheet of perforated electrically conductive metal at major side surfaces and normally extending flanges at parametric margins. The trays can be pressed together with moldable active material between the two to form an expandable electrode. A plurality of positive and negative electrodes thus formed are arranged in an alternating array with porous frangible interelectrode separators within the housing of the secondary electrochemical cell.

Electrode for electrochemical cell

DOEpatents

Kaun, Thomas D.; Nelson, Paul A.; Miller, William E.

1981-01-01

An electrode structure for a secondary electrochemical cell includes an outer enclosure defining a compartment containing electrochemical active material. The enclosure includes a rigid electrically conductive metal sheet with perforated openings over major side surfaces. The enclosure can be assembled as first and second trays each with a rigid sheet of perforated electrically conductive metal at major side surfaces and normally extending flanges at parametric margins. The trays can be pressed together with moldable active material between the two to form an expandable electrode. A plurality of positive and negative electrodes thus formed are arranged in an alternating array with porous frangible interelectrode separators within the housing of the secondary electrochemical cell.

Construction of Matryoshka-type structures from supercharged protein nanocages.

PubMed

Beck, Tobias; Tetter, Stephan; Künzle, Matthias; Hilvert, Donald

2015-01-12

Designing nanoscaled hierarchical structures with increasing levels of complexity is challenging. Here we show that electrostatic interactions between two complementarily supercharged protein nanocages can be effectively utilized to create nested Matryoshka-type structures. Cage-within-cage complexes containing spatially ordered iron oxide nanoparticles spontaneously self-assemble upon mixing positively supercharged ferritin compartments with AaLS-13, a larger shell-forming protein with a negatively supercharged lumen. Exploiting engineered Coulombic interactions and protein dynamics in this way opens up new avenues for creating hierarchically organized supramolecular assemblies for application as delivery vehicles, reaction chambers, and artificial organelles. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An investigation of the role of metabolism in dapsone-induced methaemoglobinaemia using a two compartment in vitro test system.

PubMed Central

Tingle, M D; Coleman, M D; Park, B K

1990-01-01

1. We have utilized a two compartment system in which two teflon chambers are separated by a semi-permeable membrane in order to investigate the role of metabolism in dapsone-induced methaemoglobinaemia. Compartment A contained a drug metabolizing system (microsomes prepared from human liver +/- NADPH), whilst compartment B contained target cells (human red cells). 2. Incubation of dapsone (1-100 microM) with human liver microsomes (2 mg protein) and NADPH (1 mM) in compartment A (final volume 500 microliters) led to a concentration-dependent increase in the methaemoglobinaemia (15.4-18.9% at 100 microM) compared with control (2.3 +/- 0.4%) detected in the red cells within compartment B. In the absence of NADPH dapsone had no effect. 3. Of the putative dapsone metabolites investigated, only dapsone-hydroxylamine caused methaemoglobin formation in the absence of NADPH (40.6 +/- 6.3% with 100 microM). However, methaemoglobin was also detected when monoacetyl-dapsone, 4-amino-4'-nitro-diphenylsulphone and 4-aminoacetyl-4'-nitro-diphenylsulphone were incubated with human liver microsomes in the presence of NADPH. 4 Dapsone-dependent methaemoglobin formation was inhibited by addition of ketoconazole (1-1000 microM) to compartment A, with IC50 values of 285 and 806 microM for the two liver microsomal samples studied. In contrast, methaemoglobin formation was not inhibited by cimetidine or a number of drugs pharmacologically-related to dapsone. The presence of glutathione or ascorbate (500 microM) did not alter the level of methaemoglobin observed. PMID:2288829

Epidemic Spreading in a Multi-compartment System

NASA Astrophysics Data System (ADS)

Gao, Zong-Mao; Gu, Jiao; Li, Wei

2012-02-01

We introduce the variant rate and white noise into the susceptible-infected-removed (SIR) model for epidemics, discuss the epidemic dynamics of a multiple-compartment system, and describe this system by using master equations. For both the local epidemic spreading system and the whole multiple-compartment system, we find that a threshold could be useful in forecasting when the epidemic vanishes. Furthermore, numerical simulations show that a model with the variant infection rate and white noise can improve fitting with real SARS data.

Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ucciferri, Nadia; Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa; Sbrana, Tommaso

2014-12-17

Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell–cell or cell–tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting differentmore » cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.« less

Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism.

PubMed

Ucciferri, Nadia; Sbrana, Tommaso; Ahluwalia, Arti

2014-01-01

Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

Metabolic modeling of dynamic brain 13C NMR multiplet data: Concepts and simulations with a two-compartment neuronal-glial model

PubMed Central

Shestov, Alexander A.; Valette, Julien; Deelchand, Dinesh K.; Uğurbil, Kâmil; Henry, Pierre-Gilles

2016-01-01

Metabolic modeling of dynamic 13C labeling curves during infusion of 13C-labeled substrates allows quantitative measurements of metabolic rates in vivo. However metabolic modeling studies performed in the brain to date have only modeled time courses of total isotopic enrichment at individual carbon positions (positional enrichments), not taking advantage of the additional dynamic 13C isotopomer information available from fine-structure multiplets in 13C spectra. Here we introduce a new 13C metabolic modeling approach using the concept of bonded cumulative isotopomers, or bonded cumomers. The direct relationship between bonded cumomers and 13C multiplets enables fitting of the dynamic multiplet data. The potential of this new approach is demonstrated using Monte-Carlo simulations with a brain two-compartment neuronal-glial model. The precision of positional and cumomer approaches are compared for two different metabolic models (with and without glutamine dilution) and for different infusion protocols ([1,6-13C2]glucose, [1,2-13C2]acetate, and double infusion [1,6-13C2]glucose + [1,2-13C2]acetate). In all cases, the bonded cumomer approach gives better precision than the positional approach. In addition, of the three different infusion protocols considered here, the double infusion protocol combined with dynamic bonded cumomer modeling appears the most robust for precise determination of all fluxes in the model. The concepts and simulations introduced in the present study set the foundation for taking full advantage of the available dynamic 13C multiplet data in metabolic modeling. PMID:22528840

Redistribution of wastewater alkalinity with a microbial fuel cell to support nitrification of reject water.

PubMed

Modin, Oskar; Fukushi, Kensuke; Rabaey, Korneel; Rozendal, René A; Yamamoto, Kazuo

2011-04-01

In wastewater treatment plants, the reject water from the sludge treatment processes typically contains high ammonium concentrations, which constitute a significant internal nitrogen load in the plant. Often, a separate nitrification reactor is used to treat the reject water before it is fed back into the plant. The nitrification reaction consumes alkalinity, which has to be replenished by dosing e.g. NaOH or Ca(OH)(2). In this study, we investigated the use of a two-compartment microbial fuel cell (MFC) to redistribute alkalinity from influent wastewater to support nitrification of reject water. In an MFC, alkalinity is consumed in the anode compartment and produced in the cathode compartment. We use this phenomenon and the fact that the influent wastewater flow is many times larger than the reject water flow to transfer alkalinity from the influent wastewater to the reject water. In a laboratory-scale system, ammonium oxidation of synthetic reject water passed through the cathode chamber of an MFC, increased from 73.8 ± 8.9 mgN/L under open-circuit conditions to 160.1 ± 4.8 mgN/L when a current of 1.96 ± 0.37 mA (15.1 mA/L total MFC liquid volume) was flowing through the MFC. These results demonstrated the positive effect of an MFC on ammonium oxidation of alkalinity-limited reject water. Copyright © 2011 Elsevier Ltd. All rights reserved.

Lateral Transorbital Endoscopic Access to the Hippocampus, Amygdala, and Entorhinal Cortex: Initial Clinical Experience.

PubMed

Chen, H Isaac; Bohman, Leif-Erik; Emery, Lyndsey; Martinez-Lage, Maria; Richardson, Andrew G; Davis, Kathryn A; Pollard, John R; Litt, Brian; Gausas, Roberta E; Lucas, Timothy H

2015-01-01

Transorbital approaches traditionally have focused on skull base and cavernous sinus lesions medial to the globe. Lateral orbital approaches to the temporal lobe have not been widely explored despite several theoretical advantages compared to open craniotomy. Recently, we demonstrated the feasibility of the lateral transorbital technique in cadaveric specimens with endoscopic visualization. We describe our initial clinical experience with the endoscope-assisted lateral transorbital approach to lesions in the temporal lobe. Two patients with mesial temporal lobe pathology presenting with seizures underwent surgery. The use of a transpalpebral or Stallard-Wright eyebrow incision enabled access to the intraorbital compartment, and a lateral orbital wall 'keyhole' opening permitted visualization of the anterior temporal pole. This approach afforded adequate access to the surgical target and surrounding structures and was well tolerated by the patients. To the best of our knowledge, this report constitutes the first case series describing the endoscope-assisted lateral transorbital approach to the temporal lobe. We discuss the limits of exposure, the nuances of opening and closing, and comparisons to open craniotomy. Further prospective investigation of this approach is warranted for comparison to traditional approaches to the mesial temporal lobe. © 2015 S. Karger AG, Basel.

Influence of Bicompartmental Knee Replacement on Stand-to-Sit Movement

ERIC Educational Resources Information Center

Wang, He; Frame, Jeff; Rolston, Lindsey

2012-01-01

Knee osteoarthritis often occurs in medial and patellofemoral compartments. A bicompartmental knee replacement system replaces these two affected knee compartments and keeps the lateral compartment and cruciate ligaments intact. It is yet to be determined whether limbs with bicompartmental knee systems can demonstrate frontal-plane knee mechanics…

Chemical-Specific Representation of Air-Soil Exchange and Soil Penetration in Regional Multimedia Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

McKone, T.E.; Bennett, D.H.

2002-08-01

In multimedia mass-balance models, the soil compartment is an important sink as well as a conduit for transfers to vegetation and shallow groundwater. Here a novel approach for constructing soil transport algorithms for multimedia fate models is developed and evaluated. The resulting algorithms account for diffusion in gas and liquid components; advection in gas, liquid, or solid phases; and multiple transformation processes. They also provide an explicit quantification of the characteristic soil penetration depth. We construct a compartment model using three and four soil layers to replicate with high reliability the flux and mass distribution obtained from the exact analyticalmore » solution describing the transient dispersion, advection, and transformation of chemicals in soil with fixed properties and boundary conditions. Unlike the analytical solution, which requires fixed boundary conditions, the soil compartment algorithms can be dynamically linked to other compartments (air, vegetation, ground water, surface water) in multimedia fate models. We demonstrate and evaluate the performance of the algorithms in a model with applications to benzene, benzo(a)pyrene, MTBE, TCDD, and tritium.« less

A novel multi-coaxial hollow fiber bioreactor for adherent cell types. Part 1: hydrodynamic studies.

PubMed

Wolfe, Stephen P; Hsu, Edward; Reid, Lola M; Macdonald, Jeffrey M

2002-01-05

A novel multi-coaxial bioreactor for three-dimensional cultures of adherent cell types, such as liver, is described. It is composed of four tubes of increasing diameter placed one inside the other, creating four spatially isolated compartments. Liver acinar structure and physiological parameters are mimicked by sandwiching cells in the space between the two innermost semi-permeable tubes, or hollows fibers, and creating a radial flow of media from an outer compartment (ECC), through the cell mass compartment, and to an inner compartment (ICC). The outermost compartment is created by gas-permeable tubing, and the housing is used to oxygenate the perfusion media to periportal levels in the ECC. Experiments were performed using distilled water to correlate the radial flow rate (Q(r)) with (1) the pressure drop (DeltaP) between the media compartments that sandwich the cell compartment and (2) the pressure in the cell compartment (P(c)). These results were compared with the theoretical profile calculated based on the hydraulic permeability of the two innermost fibers. Phase-contrast velocity-encoded magnetic resonance imaging was used to visualize directly the axial velocities inside the bioreactor and confirm the assumptions of laminar flow and zero axial velocity at the boundaries of each compartment in the bioreactor. Axial flow rates were calculated from the magnetic resonance imaging results and were similar to the measured axial flow rates for the previously described experiments. Copyright 2002 John Wiley & Sons, Inc.

Outside-In Deep Medial Collateral Ligament Release During Arthroscopic Medial Meniscus Surgery.

PubMed

Todor, Adrian; Caterev, Sergiu; Nistor, Dan Viorel

2016-08-01

Arthroscopic partial medial meniscectomy is a very common orthopaedic procedure performed for symptomatic, irreparable meniscus tears. It is usually associated with a very good outcome and minimal complications. In some patients with tight medial compartment, the posterior horn of the medial meniscus can be difficult to visualize, and access in this area with instruments may be challenging. To increase the opening of the medial compartment, after valgus-extension stress position of the knee, different techniques of deep medial collateral ligament release have been described. The outside-in pie-crusting technique shown in this technical note has documented effectiveness and good outcomes with minimal or no morbidity.

Compartment syndrome of the thigh complicating surgical treatment of ipsilateral femur and ankle fractures

NASA Technical Reports Server (NTRS)

Moore, M. R.; Garfin, S. R.; Hargens, A. R.

1987-01-01

A 26-year-old man presented with ipsilateral femur and ankle fractures. The patient was treated with interlocking nail of his femur fracture, followed by open reduction and internal fixation of his ankle fracture under tourniquet control. Postoperatively, the patient developed compartment syndrome of his thigh with elevated pressures, requiring decompressive fasciotomies. This case illustrates the possible complication of treating a femur fracture with intramedullary nailing and then immediately applying a tourniquet to treat an ipsilateral extremity fracture. Because of the complication with this patient, we feel the procedure should be staged, or a tourniquet should be avoided if possible.

Comparison of PrestoBlue® and plating method to evaluate antimicrobial activity of ascorbic acid, boric acid and curcumin in an in vitro gastrointestinal model.

PubMed

Hernandez-Patlan, D; Solis-Cruz, B; Méndez-Albores, A; Latorre, J D; Hernandez-Velasco, X; Tellez, G; López-Arellano, R

2018-02-01

To compare the conventional plating method vs a fluorometric method using PrestoBlue ® as a dye by determining the antimicrobial activity of two organic acids and curcumin (CUR) against Salmonella Enteritidis in an avian in vitro digestion model that simulates the crop, proventriculus and intestine. A concentration of 10 8  CFU per ml of S. Enteritidis was exposed to groups with different rates of ascorbic acid (AA), boric acid (BA) and CUR. Significant differences were observed when the means of the treatments were compared with the controls in the compartments that simulate the crop and intestine (P < 0·05). Ascorbic acid alone and high rates of AA in the mixtures were the most efficient treatments in the crop compartment. However, in the intestinal compartment BA alone and at different rates in the mixture BA-CUR (1 : 1) were the best treatments to decrease the concentration of S. Enteritidis. The results of this study suggest that there could be an antagonistic bactericidal effect between AA and CUR and AA and BA as well as a synergistic bactericidal effect between BA and CUR. These findings may contribute to the development of a formulation with microencapsulated compounds to liberate them in different compartments to combat S. Enteritidis infections in broiler chickens. © 2017 The Society for Applied Microbiology.

33 CFR 183.620 - Natural ventilation system.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Natural ventilation system. 183... (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Ventilation § 183.620 Natural ventilation system. (a) Except for compartments open to the atmosphere, a natural ventilation system that meets the...

33 CFR 183.620 - Natural ventilation system.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Natural ventilation system. 183... (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Ventilation § 183.620 Natural ventilation system. (a) Except for compartments open to the atmosphere, a natural ventilation system that meets the...

Muscle contributions to medial tibiofemoral compartment contact loading following ACL reconstruction using semitendinosus and gracilis tendon grafts.

PubMed

Konrath, Jason M; Saxby, David J; Killen, Bryce A; Pizzolato, Claudio; Vertullo, Christopher J; Barrett, Rod S; Lloyd, David G

2017-01-01

The muscle-tendon properties of the semitendinosus (ST) and gracilis (GR) are substantially altered following tendon harvest for the purpose of anterior cruciate ligament reconstruction (ACLR). This study adopted a musculoskeletal modelling approach to determine how the changes to the ST and GR muscle-tendon properties alter their contribution to medial compartment contact loading within the tibiofemoral joint in post ACLR patients, and the extent to which other muscles compensate under the same external loading conditions during walking, running and sidestep cutting. Motion capture and electromyography (EMG) data from 16 lower extremity muscles were acquired during walking, running and cutting in 25 participants that had undergone an ACLR using a quadruple (ST+GR) hamstring auto-graft. An EMG-driven musculoskeletal model was used to estimate the medial compartment contact loads during the stance phase of each gait task. An adjusted model was then created by altering muscle-tendon properties for the ST and GR to reflect their reported changes following ACLR. Parameters for the other muscles in the model were calibrated to match the experimental joint moments. The medial compartment contact loads for the standard and adjusted models were similar. The combined contributions of ST and GR to medial compartment contact load in the adjusted model were reduced by 26%, 17% and 17% during walking, running and cutting, respectively. These deficits were balanced by increases in the contribution made by the semimembranosus muscle of 33% and 22% during running and cutting, respectively. Alterations to the ST and GR muscle-tendon properties in ACLR patients resulted in reduced contribution to medial compartment contact loads during gait tasks, for which the semimembranosus muscle can compensate.

Simulating wall and corner fire tests on wood products with the OSU room fire model

Treesearch

H. C. Tran

1994-01-01

This work demonstrates the complexity of modeling wall and corner fires in a compartment. The model chosen for this purpose is the Ohio State University (OSU) room fire model. This model was designed to simulate fire growth on walls in a compartment and therefore lends itself to direct comparison with standard room test results. The model input were bench-scale data...

Measurement of compartment elasticity using pressure related ultrasound: a method to identify patients with potential compartment syndrome.

PubMed

Sellei, R M; Hingmann, S J; Kobbe, P; Weber, C; Grice, J E; Zimmerman, F; Jeromin, S; Gansslen, A; Hildebrand, F; Pape, H C

2015-01-01

PURPOSE OF THE STUDY Decision-making in treatment of an acute compartment syndrome is based on clinical assessment, supported by invasive monitoring. Thus, evolving compartment syndrome may require repeated pressure measurements. In suspected cases of potential compartment syndromes clinical assessment alone seems to be unreliable. The objective of this study was to investigate the feasibility of a non-invasive application estimating whole compartmental elasticity by ultrasound, which may improve accuracy of diagnostics. MATERIAL AND METHODS In an in-vitro model, using an artificial container simulating dimensions of the human anterior tibial compartment, intracompartmental pressures (p) were raised subsequently up to 80 mm Hg by infusion of saline solution. The compartmental depth (mm) in the cross-section view was measured before and after manual probe compression (100 mm Hg) upon the surface resulting in a linear compartmental displacement (Δd). This was repeated at rising compartmental pressures. The resulting displacements were related to the corresponding intra-compartmental pressures simulated in our model. A hypothesized relationship between pressures related compartmental displacement and the elasticity at elevated compartment pressures was investigated. RESULTS With rising compartmental pressures, a non-linear, reciprocal proportional relation between the displacement (mm) and the intra-compartmental pressure (mm Hg) occurred. The Pearson's coefficient showed a high correlation (r2 = -0.960). The intraobserver reliability value kappa resulted in a statistically high reliability (κ = 0.840). The inter-observer value indicated a fair reliability (κ = 0.640). CONCLUSIONS Our model reveals that a strong correlation between compartmental strain displacements assessed by ultrasound and the intra-compartmental pressure changes occurs. Further studies are required to prove whether this assessment is transferable to human muscle tissue. Determining the complete compartmental elasticity by ultrasound enhancement, this application may improve detection of early signs of potential compartment syndrome. Key words: compartment syndrome, intra-compartmental pressure, non-invasive diagnostic, elasticity measurement, elastography.

Effect of open rhinoplasty on the smile line.

PubMed

Tabrizi, Reza; Mirmohamadsadeghi, Hoori; Daneshjoo, Danadokht; Zare, Samira

2012-05-01

Open rhinoplasty is an esthetic surgical technique that is becoming increasingly popular, and can affect the nose and upper lip compartments. The aim of this study was to evaluate the effect of open rhinoplasty on tooth show and the smile line. The study participants were 61 patients with a mean age of 24.3 years (range, 17.2 to 39.6 years). The surgical procedure consisted of an esthetic open rhinoplasty without alar resection. Analysis of tooth show was limited to pre- and postoperative (at 12 months) tooth show measurements at rest and the maximum smile with a ruler (when participants held their heads naturally). Statistical analyses were performed with SPSS 13.0, and paired-sample t tests were used to compare tooth show means before and after the operation. Analysis of the rest position showed no statistically significant change in tooth show (P = .15), but analysis of participants' maximum smile data showed a statistically significant increase in tooth show after surgery (P < .05). In contrast, Pearson correlation analysis showed a positive relation between rhinoplasty and tooth show increases in maximum smile, especially in subjects with high smile lines. This study shows that the nasolabial compartment is a single unit and any change in 1 part may influence the other parts. Further studies should be conducted to investigate these interactions. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Compartmental analysis of the disposition of benzo[a]pyrene in rats.

PubMed

Bevan, D R; Weyand, E H

1988-11-01

We have previously reported the disposition of benzo[a]pyrene (B[a]P) and its metabolites in male Sprague-Dawley rats following intratracheal instillation of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1986) Cancer Res., 46, 5655-5661]. In some experiments, cannulas were implanted in the bile duct of the animals prior to administration of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1987) Drug Metab. Disposition, 15, 442-448]. Based on these data, we have developed a compartmental model of the distribution of radioactivity to provide a quantitative description of the fate of B[a]P and its metabolites in rats. Modeling of the distribution of radioactivity was performed using the Simulation, Analysis and Modeling (SAAM) and conversational SAAM (CONSAM) computer programs. Compartments in the model included organs into which the largest amounts of radioactivity were distributed as well as pathways for excretion of radioactivity from the animals. Data from animals with and without cannulas implanted in the bile duct were considered simultaneously during modeling. Radioactivity was so rapidly absorbed from the lungs that an absorption phase into blood was not apparent at the earliest sampling times. Using the model of extrapolate to shorter times, it was predicted that the maximum amount of radioactivity was present in blood within 2 min after administration. In addition, considerable recycling of radioactivity back to lungs from blood was predicted by the model. Transfer of radioactivity from blood to liver and carcass (skin, muscle, bones, fat and associated blood) also was extensive. Carcass was modeled as the sum of two compartments to obtain agreement between the model and experimental data. The model accounted for enterohepatic circulation of B[a]P metabolites; data also required that intestinal secretion be included in the model. Quantitative data obtained from compartmental analysis included rate constants for transfer of radioactivity among compartments as well as statistical parameters indicating the identifiability of the rate constants. That the model is consistent with two sets of data, those obtained in animals with and without a biliary cannula, indicates its potential utility in predicting the disposition of B[a]P and its metabolites in vivo.

Optimization of Dissolution Compartments in a Biorelevant Dissolution Apparatus Golem v2, Supported by Multivariate Analysis.

PubMed

Stupák, Ivan; Pavloková, Sylvie; Vysloužil, Jakub; Dohnal, Jiří; Čulen, Martin

2017-11-23

Biorelevant dissolution instruments represent an important tool for pharmaceutical research and development. These instruments are designed to simulate the dissolution of drug formulations in conditions most closely mimicking the gastrointestinal tract. In this work, we focused on the optimization of dissolution compartments/vessels for an updated version of the biorelevant dissolution apparatus-Golem v2. We designed eight compartments of uniform size but different inner geometry. The dissolution performance of the compartments was tested using immediate release caffeine tablets and evaluated by standard statistical methods and principal component analysis. Based on two phases of dissolution testing (using 250 and 100 mL of dissolution medium), we selected two compartment types yielding the highest measurement reproducibility. We also confirmed a statistically ssignificant effect of agitation rate and dissolution volume on the extent of drug dissolved and measurement reproducibility.

Modeling the impact of biota on polychlorinated biphenyls (PCBs) fate and transport in Lake Ontario using a population-based multi-compartment fugacity approach.

PubMed

Sun, Xiangfei; Ng, Carla A; Small, Mitchell J

2018-06-12

Organisms have long been treated as receptors in exposure studies of polychlorinated biphenyls (PCBs) and other persistent organic pollutants (POPs). The influences of environmental pollution on organisms are well recognized. However, the impact of biota on PCB transport in an environmental system has not been considered in sufficient detail. In this study, a population-based multi-compartment fugacity model is developed by reconfiguring the organisms as populated compartments and reconstructing all the exchange processes between the organism compartments and environmental compartments, especially the previously ignored feedback routes from biota to the environment. We evaluate the model performance by simulating the PCB concentration distribution in Lake Ontario using published loading records. The lake system is divided into three environment compartments (air, water, and sediment) and several organism groups according to the dominant local biotic species. The comparison indicates that the simulated results are well-matched by a list of published field measurements from different years. We identify a new process, called Facilitated Biotic Intermedia Transport (FBIT), to describe the enhanced pollution transport that occurs between environmental media and organisms. As the hydrophobicity of PCB congener increases, the organism population exerts greater influence on PCB mass flows. In a high biomass scenario, the model simulation indicates significant FBIT effects and biotic storage effects with hydrophobic PCB congeners, which also lead to significant shifts in systemic contaminant exchange rates between organisms and the environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Correction for photobleaching in dynamic fluorescence microscopy: application in the assessment of pharmacokinetic parameters in ultrasound-mediated drug delivery

NASA Astrophysics Data System (ADS)

Derieppe, M.; Bos, C.; de Greef, M.; Moonen, C.; de Senneville, B. Denis

2016-01-01

We have previously demonstrated the feasibility of monitoring ultrasound-mediated uptake of a hydrophilic model drug in real time with dynamic confocal fluorescence microscopy. In this study, we evaluate and correct the impact of photobleaching to improve the accuracy of pharmacokinetic parameter estimates. To model photobleaching of the fluorescent model drug SYTOX Green, a photobleaching process was added to the current two-compartment model describing cell uptake. After collection of the uptake profile, a second acquisition was performed when SYTOX Green was equilibrated, to evaluate the photobleaching rate experimentally. Photobleaching rates up to 5.0 10-3 s-1 were measured when applying power densities up to 0.2 W.cm-2. By applying the three-compartment model, the model drug uptake rate of 6.0 10-3 s-1 was measured independent of the applied laser power. The impact of photobleaching on uptake rate estimates measured by dynamic fluorescence microscopy was evaluated. Subsequent compensation improved the accuracy of pharmacokinetic parameter estimates in the cell population subjected to sonopermeabilization.

Human factors model concerning the man-machine interface of mining crewstations

NASA Technical Reports Server (NTRS)

Rider, James P.; Unger, Richard L.

1989-01-01

The U.S. Bureau of Mines is developing a computer model to analyze the human factors aspect of mining machine operator compartments. The model will be used as a research tool and as a design aid. It will have the capability to perform the following: simulated anthropometric or reach assessment, visibility analysis, illumination analysis, structural analysis of the protective canopy, operator fatigue analysis, and computation of an ingress-egress rating. The model will make extensive use of graphics to simplify data input and output. Two dimensional orthographic projections of the machine and its operator compartment are digitized and the data rebuilt into a three dimensional representation of the mining machine. Anthropometric data from either an individual or any size population may be used. The model is intended for use by equipment manufacturers and mining companies during initial design work on new machines. In addition to its use in machine design, the model should prove helpful as an accident investigation tool and for determining the effects of machine modifications made in the field on the critical areas of visibility and control reach ability.

Surgical resection of skull-base chordomas: experience in case selection for surgical approach according to anatomical compartments and review of the literature.

PubMed

Shimony, Nir; Gonen, Lior; Shofty, Ben; Abergel, Avraham; Fliss, Dan M; Margalit, Nevo

2017-10-01

Chordoma is a rare bony malignancy known to have a high rate of local recurrence after surgery. The best treatment paradigm is still being evaluated. We report our experience and review the literature. We emphasize on the difference between endoscopic and open craniotomy in regard to the anatomical compartment harboring the tumor, the limitations of the approaches and the rate of surgical resection. We retrospectively collected all patients with skull-base chordomas operated on between 2004 and 2014. Detailed radiological description of the compartments being occupied by the tumor and the degree of surgical resection is discussed. Eighteen patients were operated on in our facility for skull-base chordoma. Seventeen endoscopic surgeries were done in 15 patients, and 7 craniotomies were done in 5 patients. The mean age was 48.9 years (±19.8 years). When reviewing the anatomical compartments, we found that the most common were the upper clivus (95.6%) and lower clivus (58.3%), left cavernous sinus (66.7%) and petrous apex (∼60%). Most of the patients had intradural tumor involvement (70.8%). In all craniotomy cases, there was residual tumor in multiple compartments. In the endoscopic cases, the most difficult compartments for total resection were the lower clivus, and lateral extensions to the petrous apex or cavernous sinus. Our experience shows that the endoscopic approach is a good option for midline tumors without significant lateral extension. In cases with very lateral or lower extensions, additional approaches should be added trying to achieve complete resection.

The STATFLUX code: a statistical method for calculation of flow and set of parameters, based on the Multiple-Compartment Biokinetical Model

NASA Astrophysics Data System (ADS)

Garcia, F.; Mesa, J.; Arruda-Neto, J. D. T.; Helene, O.; Vanin, V.; Milian, F.; Deppman, A.; Rodrigues, T. E.; Rodriguez, O.

2007-03-01

The code STATFLUX, implementing a new and simple statistical procedure for the calculation of transfer coefficients in radionuclide transport to animals and plants, is proposed. The method is based on the general multiple-compartment model, which uses a system of linear equations involving geometrical volume considerations. Flow parameters were estimated by employing two different least-squares procedures: Derivative and Gauss-Marquardt methods, with the available experimental data of radionuclide concentrations as the input functions of time. The solution of the inverse problem, which relates a given set of flow parameter with the time evolution of concentration functions, is achieved via a Monte Carlo simulation procedure. Program summaryTitle of program:STATFLUX Catalogue identifier:ADYS_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADYS_v1_0 Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Licensing provisions: none Computer for which the program is designed and others on which it has been tested:Micro-computer with Intel Pentium III, 3.0 GHz Installation:Laboratory of Linear Accelerator, Department of Experimental Physics, University of São Paulo, Brazil Operating system:Windows 2000 and Windows XP Programming language used:Fortran-77 as implemented in Microsoft Fortran 4.0. NOTE: Microsoft Fortran includes non-standard features which are used in this program. Standard Fortran compilers such as, g77, f77, ifort and NAG95, are not able to compile the code and therefore it has not been possible for the CPC Program Library to test the program. Memory required to execute with typical data:8 Mbytes of RAM memory and 100 MB of Hard disk memory No. of bits in a word:16 No. of lines in distributed program, including test data, etc.:6912 No. of bytes in distributed program, including test data, etc.:229 541 Distribution format:tar.gz Nature of the physical problem:The investigation of transport mechanisms for radioactive substances, through environmental pathways, is very important for radiological protection of populations. One such pathway, associated with the food chain, is the grass-animal-man sequence. The distribution of trace elements in humans and laboratory animals has been intensively studied over the past 60 years [R.C. Pendlenton, C.W. Mays, R.D. Lloyd, A.L. Brooks, Differential accumulation of iodine-131 from local fallout in people and milk, Health Phys. 9 (1963) 1253-1262]. In addition, investigations on the incidence of cancer in humans, and a possible causal relationship to radioactive fallout, have been undertaken [E.S. Weiss, M.L. Rallison, W.T. London, W.T. Carlyle Thompson, Thyroid nodularity in southwestern Utah school children exposed to fallout radiation, Amer. J. Public Health 61 (1971) 241-249; M.L. Rallison, B.M. Dobyns, F.R. Keating, J.E. Rall, F.H. Tyler, Thyroid diseases in children, Amer. J. Med. 56 (1974) 457-463; J.L. Lyon, M.R. Klauber, J.W. Gardner, K.S. Udall, Childhood leukemia associated with fallout from nuclear testing, N. Engl. J. Med. 300 (1979) 397-402]. From the pathways of entry of radionuclides in the human (or animal) body, ingestion is the most important because it is closely related to life-long alimentary (or dietary) habits. Those radionuclides which are able to enter the living cells by either metabolic or other processes give rise to localized doses which can be very high. The evaluation of these internally localized doses is of paramount importance for the assessment of radiobiological risks and radiological protection. The time behavior of trace concentration in organs is the principal input for prediction of internal doses after acute or chronic exposure. The General Multiple-Compartment Model (GMCM) is the powerful and more accepted method for biokinetical studies, which allows the calculation of concentration of trace elements in organs as a function of time, when the flow parameters of the model are known. However, few biokinetics data exist in the literature, and the determination of flow and transfer parameters by statistical fitting for each system is an open problem. Restriction on the complexity of the problem:This version of the code works with the constant volume approximation, which is valid for many situations where the biological half-live of a trace is lower than the volume rise time. Another restriction is related to the central flux model. The model considered in the code assumes that exist one central compartment (e.g., blood) that connect the flow with all compartments, and the flow between other compartments is not included. Typical running time:Depends on the choice for calculations. Using the Derivative Method the time is very short (a few minutes) for any number of compartments considered. When the Gauss-Marquardt iterative method is used the calculation time can be approximately 5-6 hours when ˜15 compartments are considered.

Whole transcriptome profiling of patient-derived xenograft models as a tool to identify both tumor and stromal specific biomarkers.

PubMed

Bradford, James R; Wappett, Mark; Beran, Garry; Logie, Armelle; Delpuech, Oona; Brown, Henry; Boros, Joanna; Camp, Nicola J; McEwen, Robert; Mazzola, Anne Marie; D'Cruz, Celina; Barry, Simon T

2016-04-12

The tumor microenvironment is emerging as a key regulator of cancer growth and progression, however the exact mechanisms of interaction with the tumor are poorly understood. Whilst the majority of genomic profiling efforts thus far have focused on the tumor, here we investigate RNA-Seq as a hypothesis-free tool to generate independent tumor and stromal biomarkers, and explore tumor-stroma interactions by exploiting the human-murine compartment specificity of patient-derived xenografts (PDX).Across a pan-cancer cohort of 79 PDX models, we determine that mouse stroma can be separated into distinct clusters, each corresponding to a specific stromal cell type. This implies heterogeneous recruitment of mouse stroma to the xenograft independent of tumor type. We then generate cross-species expression networks to recapitulate a known association between tumor epithelial cells and fibroblast activation, and propose a potentially novel relationship between two hypoxia-associated genes, human MIF and mouse Ddx6. Assessment of disease subtype also reveals MMP12 as a putative stromal marker of triple-negative breast cancer. Finally, we establish that our ability to dissect recruited stroma from trans-differentiated tumor cells is crucial to identifying stem-like poor-prognosis signatures in the tumor compartment.In conclusion, RNA-Seq is a powerful, cost-effective solution to global analysis of human tumor and mouse stroma simultaneously, providing new insights into mouse stromal heterogeneity and compartment-specific disease markers that are otherwise overlooked by alternative technologies. The study represents the first comprehensive analysis of its kind across multiple PDX models, and supports adoption of the approach in pre-clinical drug efficacy studies, and compartment-specific biomarker discovery.

An electrical description of the generation of slow waves in the antrum of the guinea-pig

PubMed Central

Edwards, FR; Hirst, GDS

2005-01-01

This paper provides an electrical description of the generation of slow waves in the guinea-pig gastric antrum. A short segment of a circular smooth muscle bundle with an attached network of myenteric interstitial cells of Cajal (ICC-MY) and longitudinal muscle sheet was modelled as three electrical compartments with resistive connexions between the ICC-MY compartment and each of the smooth muscle compartments. The circular smooth muscle layer contains a proportion of intramuscular interstitial cells of Cajal (ICC-IM), responsible for the regenerative component of the slow wave. Hence the equivalent cell representing the circular muscle layer incorporated a mechanism, modelled as a two stage reaction, which produces an intracellular messenger. The first stage of the reaction is proposed to be activated in a voltage-dependent manner as described by Hodgkin and Huxley. A similar mechanism was incorporated into the equivalent cell describing the ICC-MY network. Spontaneous discrete transient depolarizations, termed unitary potentials, are detected in records taken from either bundles of circular smooth muscle containing ICC-IM or from ICC-MY. In the simulation the mean rate of discharge of unitary potentials was allowed to vary with the concentration of messenger according to a conventional dose–effect relationship. Such a mechanism, which describes regenerative potentials generated by the circular muscle layer, also simulated the plateau component of the pacemaker potential in the ICC-MY network. A voltage-sensitive membrane conductance was included in the ICC-MY compartment; this was used to describe the primary component of the pacemaker potential. The model generates a range of membrane potential changes with properties similar to those generated by the three cell types present in the intact tissue. PMID:15613372

Modelling Transcapillary Transport of Fluid and Proteins in Hemodialysis Patients

PubMed Central

Pietribiasi, Mauro; Waniewski, Jacek; Załuska, Alicja; Załuska, Wojciech; Lindholm, Bengt

2016-01-01

Background The kinetics of protein transport to and from the vascular compartment play a major role in the determination of fluid balance and plasma refilling during hemodialysis (HD) sessions. In this study we propose a whole-body mathematical model describing water and protein shifts across the capillary membrane during HD and compare its output to clinical data while evaluating the impact of choosing specific values for selected parameters. Methods The model follows a two-compartment structure (vascular and interstitial space) and is based on balance equations of protein mass and water volume in each compartment. The capillary membrane was described according to the three-pore theory. Two transport parameters, the fractional contribution of large pores (αLP) and the total hydraulic conductivity (LpS) of the capillary membrane, were estimated from patient data. Changes in the intensity and direction of individual fluid and solute flows through each part of the transport system were analyzed in relation to the choice of different values of small pores radius and fractional conductivity, lymphatic sensitivity to hydraulic pressure, and steady-state interstitial-to-plasma protein concentration ratio. Results The estimated values of LpS and αLP were respectively 10.0 ± 8.4 mL/min/mmHg (mean ± standard deviation) and 0.062 ± 0.041. The model was able to predict with good accuracy the profiles of plasma volume and serum total protein concentration in most of the patients (average root-mean-square deviation < 2% of the measured value). Conclusions The applied model provides a mechanistic interpretation of fluid transport processes induced by ultrafiltration during HD, using a minimum of tuned parameters and assumptions. The simulated values of individual flows through each kind of pore and lymphatic absorption rate yielded by the model may suggest answers to unsolved questions on the relative impact of these not-measurable quantities on total vascular refilling and fluid balance. PMID:27483369

Evaluation of Subchondral Bone Marrow Lipids of Acute Anterior Cruciate Ligament (ACL)-Injured Patients at 3 T

PubMed Central

Wang, Ligong; Salibi, Nouha; Chang, Gregory; Bencardino, Jenny T.; Babb, James S.; Rokito, Andrew; Jazrawi, Laith; Sherman, Orrin; Regatte, Ravinder R.

2014-01-01

Rationale and Objectives The objectives of this study were to investigate the changes in compartment-specific subchondral bone marrow lipids of femoral–tibial bone in acute anterior cruciate ligament (ACL)-injured patients compared to that of healthy volunteers and patients with osteoarthritis (OA) (Kellgren–Lawrence [KL] grade 2–3). Materials and Methods A total of 55 subjects were recruited in the study and subdivided into three subgroups: 17 healthy controls (4 females, 13 males; mean age = 41 ± 16, age range 24–78 years), 17 patients with acute ACL injury (3 females, 14 males; mean age = 30 ± 11, age range 18–61 years), and 21 patients with KL2–3 OA (12 females, 9 males; mean age = 65 ± 12, age range 44–89 years). Routine clinical proton density–weighted fast spin echo images in sagittal (without fat saturation), axial, and coronal (fat saturation) planes were acquired on a 3 T clinical scanner for cartilage morphology using Whole-Organ Magnetic Resonance Imaging Score grading. A voxel of 10 × 10 × 10 mm3 was positioned in the medial and lateral compartments of the tibia and femur for proton magnetic resonance spectroscopy measurements using the single voxel stimulated echo acquisition mode pulse sequence. All proton magnetic resonance data were processed with Java-based magnetic resonance user interface. Wilcoxon rank sum test and mixed model two-way analysis of variance were performed to determine significant differences between different compartments and examine the effect of ACL injury, OA grade and compartment, and their interactions. Results The index of unsaturation in lateral tibial compartment in ACL-injured patients was significantly higher (P < .05) than all compartments except lateral femoral in patients with KL2–3 OA. Significantly lower values (P < .05) were also identified in saturated lipids at 2.03 ppm in all compartments in ACL-injured patients than those of all compartments in patients with KL2–3 OA. Conclusions The preliminary results suggest that the indices of unsaturation in the lateral tibial compartment and the peaks of saturated lipids at 1.3 and 2.03 ppm in medial tibial compartment may be clinically useful to characterize subchondral bone marrow among healthy controls, acute ACL-injured patients, and patients with OA. PMID:24717549

Evaluation of subchondral bone marrow lipids of acute anterior cruciate ligament (ACL)-injured patients at 3 T.

PubMed

Wang, Ligong; Salibi, Nouha; Chang, Gregory; Bencardino, Jenny T; Babb, James S; Rokito, Andrew; Jazrawi, Laith; Sherman, Orrin; Regatte, Ravinder R

2014-06-01

The objectives of this study were to investigate the changes in compartment-specific subchondral bone marrow lipids of femoral-tibial bone in acute anterior cruciate ligament (ACL)-injured patients compared to that of healthy volunteers and patients with osteoarthritis (OA) (Kellgren-Lawrence [KL] grade 2-3). A total of 55 subjects were recruited in the study and subdivided into three subgroups: 17 healthy controls (4 females, 13 males; mean age = 41 ± 16, age range 24-78 years), 17 patients with acute ACL injury (3 females, 14 males; mean age = 30 ± 11, age range 18-61 years), and 21 patients with KL2-3 OA (12 females, 9 males; mean age = 65 ± 12, age range 44-89 years). Routine clinical proton density-weighted fast spin echo images in sagittal (without fat saturation), axial, and coronal (fat saturation) planes were acquired on a 3 T clinical scanner for cartilage morphology using Whole-Organ Magnetic Resonance Imaging Score grading. A voxel of 10 × 10 × 10 mm(3) was positioned in the medial and lateral compartments of the tibia and femur for proton magnetic resonance spectroscopy measurements using the single voxel stimulated echo acquisition mode pulse sequence. All proton magnetic resonance data were processed with Java-based magnetic resonance user interface. Wilcoxon rank sum test and mixed model two-way analysis of variance were performed to determine significant differences between different compartments and examine the effect of ACL injury, OA grade and compartment, and their interactions. The index of unsaturation in lateral tibial compartment in ACL-injured patients was significantly higher (P < .05) than all compartments except lateral femoral in patients with KL2-3 OA. Significantly lower values (P < .05) were also identified in saturated lipids at 2.03 ppm in all compartments in ACL-injured patients than those of all compartments in patients with KL2-3 OA. The preliminary results suggest that the indices of unsaturation in the lateral tibial compartment and the peaks of saturated lipids at 1.3 and 2.03 ppm in medial tibial compartment may be clinically useful to characterize subchondral bone marrow among healthy controls, acute ACL-injured patients, and patients with OA. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

NMR studies of cation transport across membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shochet, N.R.

1985-01-01

/sup 23/Na NMR Studies of cation transport across membranes were conducted both on model and biological membranes. Two ionophores, the carrier monensin and the channel-former gramicidin, were chosen to induce cation transport in large unilamellar phosphatidylcholine vesicles. The distinction between the NMR signals arising from the two sides of the membrane was achieved by the addition of an anionic paramagnetic shift reagent to the outer solution. The kinetics of the cation transport across the membrane was observed simultaneously monitoring the changes in the /sup 23/Na NMR signals of both compartments. Two mathematical models were developed for the estimation of themore » transport parameters of the monensin- and gramicidin-induced cation transport. The models were able to fit the experimental data very well. A new method for the estimation of the volume trapped inside the vesicles was developed. The method uses the relative areas of the intra- and extravesicular NMR signals arising from a suspension of vesicles bathed in the same medium they contain, as a measure for the relative volumes of these compartments. Sodium transport across biological membranes was studied by /sup 23/ NMR, using suspensions of cultured nerve cells. The sodium influx through voltage-gated channels was studied using the channel modifier batrachotoxin in combination with scorpion toxin.« less

Population Pharmacokinetics to Model the Time-Varying Clearance of the PEGylated Asparaginase Oncaspar® in Children with Acute Lymphoblastic Leukemia.

PubMed

Würthwein, Gudrun; Lanvers-Kaminsky, Claudia; Hempel, Georg; Gastine, Silke; Möricke, Anja; Schrappe, Martin; Karlsson, Mats O; Boos, Joachim

2017-12-01

The pharmacokinetics of the polyethylene glycol (PEG)-conjugated asparaginase Oncaspar ® are characterized by an increase in elimination over time. The focus of our analysis is the better understanding of this time-dependency. In paediatric acute lymphoblastic leukemia therapy (AIEOP-BFM ALL 2009), two administrations of Oncaspar ® (2500 U/m 2 intravenously) in induction phase (14-day interval) and one single administration in reinduction were followed by weekly monitoring of asparaginase activity. Non-linear mixed-effects modeling techniques (NONMEM) were used. Samples indicating immunological inactivation were excluded to describe the pharmacokinetics under standard conditions. Models with time-constant or time-varying clearance (CL) as well as transit compartment models with an increase in CL over a chain of compartments were investigated. Models with time-constant elimination could not adequately describe 6107 asparaginase activities from 1342 patients. Implementing a time-varying CL improved the fit. Modeling an increase of CL over time after dose (E max - and Weibull-functions) were superior to models with an increase of CL over time after the first administration. However, a transit compartment model came out to be the best structural model. The increase in elimination of PEGylated asparaginase appears to be driven by physicochemical processes that are drug-related. The observed hydrolytically in vitro instability of the drug leads to the hypothesis that this increase in CL might be due to an in vivo hydrolysis of the instable ester bond between PEG and the enzyme combined with an increased elimination of the partly de-PEGylated enzyme (Trial registered at www.clinicaltrials.gov , NCT0111744).

Prediction of medial and lateral contact force of the knee joint during normal and turning gait after total knee replacement.

PubMed

Purevsuren, Tserenchimed; Dorj, Ariunzaya; Kim, Kyungsoo; Kim, Yoon Hyuk

2016-04-01

The computational modeling approach has commonly been used to predict knee joint contact forces, muscle forces, and ligament loads during activities of daily living. Knowledge of these forces has several potential applications, for example, within design of equipment to protect the knee joint from injury and to plan adequate rehabilitation protocols, although clinical applications of computational models are still evolving and one of the limiting factors is model validation. The objective of this study was to extend previous modeling technique and to improve the validity of the model prediction using publicly available data set of the fifth "Grand Challenge Competition to Predict In Vivo Knee Loads." A two-stage modeling approach, which combines conventional inverse dynamic analysis (the first stage) with a multi-body subject-specific lower limb model (the second stage), was used to calculate medial and lateral compartment contact forces. The validation was performed by direct comparison of model predictions and experimental measurement of medial and lateral compartment contact forces during normal and turning gait. The model predictions of both medial and lateral contact forces showed strong correlations with experimental measurements in normal gait (r = 0.75 and 0.71) and in turning gait trials (r = 0.86 and 0.72), even though the current technique over-estimated medial compartment contact forces in swing phase. The correlation coefficient, Sprague and Geers metrics, and root mean squared error indicated that the lateral contact forces were predicted better than medial contact forces in comparison with the experimental measurements during both normal and turning gait trials. © IMechE 2016.

77 FR 17422 - Notice of Final Determination of Sales at Less Than Fair Value and Affirmative Critical...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-26

... listings to reflect certain verification findings. Also, in February 2012, the petitioner and the... two interior storage compartments accessible through one or more separate external doors or drawers or... external door or drawer is either a refrigerator compartment or convertible compartment, but is not a...

76 FR 23281 - Bottom Mount Combination Refrigerator-Freezers From the Republic of Korea and Mexico: Initiation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... feel are relevant to the development of an accurate listing of physical characteristics. Specifically... two interior storage compartments accessible through one or more separate external doors or drawers or... external door or drawer is either a refrigerator compartment or convertible compartment, but is not a...

A Latent Cue Preference Based on Sodium Depletion in Rats

ERIC Educational Resources Information Center

Stouffer, Eric M.; White, Norman M.

2005-01-01

Three experiments show latent (or incidental) learning of salt-cue relationships using a conditioned cue-preference paradigm. Rats drank a salt solution while confined in one compartment and water in an adjacent, distinct compartment on alternate days. When given access to the two compartments with no solutions present, sodium-deprived rats…

16 CFR 305.3 - Description of covered products.

Code of Federal Regulations, 2014 CFR

2014-01-01

...-freezers. (1) Electric refrigerator means a cabinet designed for the refrigerated storage of food, designed... temperatures below 32 °F (0 °C), but does not provide a separate low temperature compartment designed for the... a cabinet which consists of two or more compartments with at least one of the compartments designed...

Validation of Perfusion Quantification with 3D Gradient Echo Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using a Blood Pool Contrast Agent in Skeletal Swine Muscle

PubMed Central

Hindel, Stefan; Sauerbrey, Anika; Maaß, Marc; Maderwald, Stefan; Schlamann, Marc; Lüdemann, Lutz

2015-01-01

The purpose of our study was to validate perfusion quantification in a low-perfused tissue by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with shared k-space sampling using a blood pool contrast agent. Perfusion measurements were performed in a total of seven female pigs. An ultrasonic Doppler probe was attached to the right femoral artery to determine total flow in the hind leg musculature. The femoral artery was catheterized for continuous local administration of adenosine to increase blood flow up to four times the baseline level. Three different stable perfusion levels were induced. The MR protocol included a 3D gradient-echo sequence with a temporal resolution of approximately 1.5 seconds. Before each dynamic sequence, static MR images were acquired with flip angles of 5°, 10°, 20°, and 30°. Both static and dynamic images were used to generate relaxation rate and baseline magnetization maps with a flip angle method. 0.1 mL/kg body weight of blood pool contrast medium was injected via a central venous catheter at a flow rate of 5 mL/s. The right hind leg was segmented in 3D into medial, cranial, lateral, and pelvic thigh muscles, lower leg, bones, skin, and fat. The arterial input function (AIF) was measured in the aorta. Perfusion of the different anatomic regions was calculated using a one- and a two-compartment model with delay- and dispersion-corrected AIFs. The F-test for model comparison was used to decide whether to use the results of the one- or two-compartment model fit. Total flow was calculated by integrating volume-weighted perfusion values over the whole measured region. The resulting values of delay, dispersion, blood volume, mean transit time, and flow were all in physiologically and physically reasonable ranges. In 107 of 160 ROIs, the blood signal was separated, using a two-compartment model, into a capillary and an arteriolar signal contribution, decided by the F-test. Overall flow in hind leg muscles, as measured by the ultrasound probe, highly correlated with total flow determined by MRI, R = 0.89 and P = 10−7. Linear regression yielded a slope of 1.2 and a y-axis intercept of 259 mL/min. The mean total volume of the investigated muscle tissue corresponds to an offset perfusion of 4.7mL/(min ⋅ 100cm3). The DCE-MRI technique presented here uses a blood pool contrast medium in combination with a two-compartment tracer kinetic model and allows absolute quantification of low-perfused non-cerebral organs such as muscles. PMID:26061498

External versus internal fixation for bicondylar tibial plateau fractures: systematic review and meta-analysis.

PubMed

Metcalfe, David; Hickson, Craig J; McKee, Lesley; Griffin, Xavier L

2015-12-01

It is uncertain whether external fixation or open reduction internal fixation (ORIF) is optimal for patients with bicondylar tibial plateau fractures. A systematic review using Ovid MEDLINE, Embase Classic, Embase, AMED, the Cochrane Library, Open Grey, Orthopaedic Proceedings, WHO International Clinical Trials Registry Platform, Current Controlled Trials, US National Institute for Health Trials Registry, and the Cochrane Central Register of Controlled Trials. The search was conducted on 3rd October 2014 and no language limits were applied. Inclusion criteria were all clinical study designs comparing external fixation with open reduction internal fixation of bicondylar tibial plateau fractures. Studies of only one treatment modality were excluded, as were those that included unicondylar tibial plateau fractures. Treatment effects from studies reporting dichotomous outcomes were summarised using odds ratios. Continuous outcomes were converted to standardized mean differences to assess the treatment effect, and inverse variance methods used to combine data. A fixed effect model was used for meta-analyses. Patients undergoing external fixation were more likely to have returned to preinjury activities by six and twelve months (P = 0.030) but not at 24 months follow-up. However, external fixation was complicated by a greater number of infections (OR 2.59, 95 % CI 1.25-5.36, P = 0.01). There were no statistically significant differences in the rates of deep infection, venous thromboembolism, compartment syndrome, or need for re-operation between the two groups. Although external fixation and ORIF are associated with different complication profiles, both are acceptable strategies for managing bicondylar tibial plateau fractures.

EFFECTS OF FOREFOOT RUNNING ON CHRONIC EXERTIONAL COMPARTMENT SYNDROME: A CASE SERIES

PubMed Central

Gregory, Robert; Alitz, Curtis; Gerber, J. Parry

2011-01-01

Introduction: Chronic exertional compartment syndrome (CECS) is a condition that occurs almost exclusively with running whereby exercise increases intramuscular pressure compromising circulation, prohibiting muscular function, and causing pain in the lower leg. Currently, a lack of evidence exists for the effective conservative management of CECS. Altering running mechanics by adopting forefoot running as opposed to heel striking may assist in the treatment of CECS, specifically with anterior compartment symptoms. Case Description: The purpose of this case series is to describe the outcomes for subjects with CECS through a systematic conservative treatment model focused on forefoot running. Subject one was a 21 y/o female with a 4 year history of CECS and subject two was a 21 y/o male, 7 months status-post two-compartment right leg fasciotomy with a return of symptoms and a new onset of symptoms on the contralateral side. Outcome: Both subjects modified their running technique over a period of six weeks. Kinematic and kinetic analysis revealed increased step rate while step length, impulse, and peak vertical ground reaction forces decreased. In addition, leg intracompartmental pressures decreased from pre-training to post-training. Within 6 weeks of intervention subjects increased their running distance and speed absent of symptoms of CECS. Follow-up questionnaires were completed by the subjects at 7 months following intervention; subject one reported running distances up to 12.87 km pain-free and subject two reported running 6.44 km pain-free consistently 3 times a week. Discussion: This case series describes a potentially beneficial conservative management approach to CECS in the form of forefoot running instruction. Further research in this area is warranted to further explore the benefits of adopting a forefoot running technique for CECS as well as other musculoskeletal overuse complaints. PMID:22163093

Effects of forefoot running on chronic exertional compartment syndrome: a case series.

PubMed

Diebal, Angela R; Gregory, Robert; Alitz, Curtis; Gerber, J Parry

2011-12-01

Chronic exertional compartment syndrome (CECS) is a condition that occurs almost exclusively with running whereby exercise increases intramuscular pressure compromising circulation, prohibiting muscular function, and causing pain in the lower leg. Currently, a lack of evidence exists for the effective conservative management of CECS. Altering running mechanics by adopting forefoot running as opposed to heel striking may assist in the treatment of CECS, specifically with anterior compartment symptoms. The purpose of this case series is to describe the outcomes for subjects with CECS through a systematic conservative treatment model focused on forefoot running. Subject one was a 21 y/o female with a 4 year history of CECS and subject two was a 21 y/o male, 7 months status-post two-compartment right leg fasciotomy with a return of symptoms and a new onset of symptoms on the contralateral side. Both subjects modified their running technique over a period of six weeks. Kinematic and kinetic analysis revealed increased step rate while step length, impulse, and peak vertical ground reaction forces decreased. In addition, leg intracompartmental pressures decreased from pre-training to post-training. Within 6 weeks of intervention subjects increased their running distance and speed absent of symptoms of CECS. Follow-up questionnaires were completed by the subjects at 7 months following intervention; subject one reported running distances up to 12.87 km pain-free and subject two reported running 6.44 km pain-free consistently 3 times a week. This case series describes a potentially beneficial conservative management approach to CECS in the form of forefoot running instruction. Further research in this area is warranted to further explore the benefits of adopting a forefoot running technique for CECS as well as other musculoskeletal overuse complaints.

STS-100 crew in docking compartment after docking with ISS

NASA Image and Video Library

2001-04-21

ISS002-311-032 (23 April 2001) --- The six astronauts and one cosmonaut comprising the STS-100 crew assemble in the Pressurized Mating Adapter (PMA-2) while waiting to visit the Expedition Two crew and the International Space Station (ISS). With his arm extended to left foreground is astronaut Kent V. Rominger, STS-100 mission commander. In the circular arrangement of crewmembers, clockwise from Rominger's position, are astronauts Umberto Guidoni, Scott E. Parazynski, Chris A. Hadfield, Jeffrey S. Ashby and John L. Phillips. Cosmonaut Yuri V. Lonchakov's head emerges at bottom center. On the other side of the glass were the Expedition Two crewmembers--cosmonaut Yury V. Usachev and astronauts James S. Voss and Susan J. Helms. Lonchakov and Usachev represent Rosaviakosmos; Hadfield is with the Canadian Space Agency (CSA) and Guidoni is associated with the European Space Agency (ESA). The ten were beginning a day that went on to see the first opening of hatches linking the two spacecraft, an impressive first step by the station's new Canadarm2 and the berthing to the station of Raffaello, the Italian-built logistics module. Hatch opening was set for 4 a.m. (CDT), April 23.

Chromosomal Organization by an Interplay of Loop Extrusion and Compartment Interaction

NASA Astrophysics Data System (ADS)

Nuebler, Johannes; Fudenberg, Geoffrey; Imakaev, Maxim; Lu, Carolyn; Goloborodko, Anton; Abdennur, Nezar; Mirny, Leonid

The chromatin fiber in eukaryotic nuclei is far from being simply a confined but otherwise randomly arranged polymer. Rather, it shows a high degree of spatial organization on all length scales, from individual nucleosomes up to well-segregated chromosome territories. On intermediate scales, chromosome conformation capture techniques have revealed two ubiquitous modes of organization: an alternating structure of A/B compartments, where each type preferentially associates with other base pairs of its type, and, typically on a smaller scale, the formation of topologically associating domains (TADs) with increased association within each domain but not across boundaries. The mechanisms behind this organization are only beginning to emerge. We review how the model of active loop extrusion can explain in a unified way such diverse phenomena as TAD formation and mitotic compaction and segregation, and we address in particular to what extent the interplay of active loop extrusion and compartment structure is compatible with recent experiments that interfere with the loading of the proposed loop extrusion factor cohesin. 4D Nucleome.

Fluid and Electrolyte Balance model (FEB)

NASA Technical Reports Server (NTRS)

Fitzjerrell, D. G.

1973-01-01

The effects of various oral input water loads on solute and water distribution throughout the body are presented in the form of a model. The model was a three compartment model; the three compartments being plasma, interstitial fluid and cellular fluid. Sodium, potassium, chloride and urea were the only major solutes considered explicitly. The control of body water and electrolyte distribution was affected via drinking and hormone levels.

Experimental and statistical analyses to characterize in-vehicle fine particulate matter behavior inside public transit buses operating on B20-grade biodiesel fuel

NASA Astrophysics Data System (ADS)

Vijayan, Abhilash; Kumar, Ashok

2010-11-01

This paper presents results from an in-vehicle air quality study of public transit buses in Toledo, Ohio, involving continuous monitoring, and experimental and statistical analyses to understand in-vehicle particulate matter (PM) behavior inside buses operating on B20-grade biodiesel fuel. The study also focused on evaluating the effects of vehicle's fuel type, operating periods, operation status, passenger counts, traffic conditions, and the seasonal and meteorological variation on particulates with aerodynamic diameter less than 1 micron (PM 1.0). The study found that the average PM 1.0 mass concentrations in B20-grade biodiesel-fueled bus compartments were approximately 15 μg m -3, while PM 2.5 and PM 10 concentration averages were approximately 19 μg m -3 and 37 μg m -3, respectively. It was also observed that average hourly concentration trends of PM 1.0 and PM 2.5 followed a "μ-shaped" pattern during transit hours. Experimental analyses revealed that the in-vehicle PM 1.0 mass concentrations were higher inside diesel-fueled buses (10.0-71.0 μg m -3 with a mean of 31.8 μg m -3) as compared to biodiesel buses (3.3-33.5 μg m -3 with a mean of 15.3 μg m -3) when the windows were kept open. Vehicle idling conditions and open door status were found to facilitate smaller particle concentrations inside the cabin, while closed door facilitated larger particle concentrations suggesting that smaller particles were originating outside the vehicle and larger particles were formed within the cabin, potentially from passenger activity. The study also found that PM 1.0 mass concentrations at the back of bus compartment (5.7-39.1 μg m -3 with a mean of 28.3 μg m -3) were higher than the concentrations in the front (5.7-25.9 μg m -3 with a mean of 21.9 μg m -3), and the mass concentrations inside the bus compartment were generally 30-70% lower than the just-outside concentrations. Further, bus route, window position, and time of day were found to affect the in-vehicle PM concentrations significantly. Overall, the in-vehicle PM 1.0 concentrations inside the buses operating on B20-grade biodiesel ranged from 0.7 μg m -3 to 243 μg m -3, with a median of 11.6 μg m -3. Statistical models developed to study the effects of vehicle operation and ambient conditions on in-vehicle PM concentrations suggested that while open door status was the most important influencing variable for finer particles and higher passenger activity resulted in higher coarse particles concentrations inside the vehicle compartments, ambient PM concentrations contributed to all PM fractions inside the bus irrespective of particle size.

Unconventional mechanisms control cyclic respiratory gas release in flying Drosophila.

PubMed

Lehmann, Fritz-Olaf; Heymann, Nicole

2005-10-01

The high power output of flight muscles places special demands on the respiratory gas exchange system in insects. In small insects, respiration relies on diffusion, and for elevated locomotor performance such as flight, instantaneous gas exchange rates typically co-vary with the animal's metabolic activity. By contrast, under certain conditions, instantaneous release rate of carbon dioxide from the fruit fly Drosophila flying in a virtual-reality flight arena may oscillate distinctly at low frequency (0.37+/-0.055 Hz), even though flight muscle mechanical power output requires constant metabolic activity. Cross-correlation analysis suggests that this uncoupling between respiratory and metabolic rate is not driven by conventional types of convective flow reinforcement such as abdominal pumping, but might result from two unusual mechanisms for tracheal breathing. Simplified analytical modeling of diffusive tracheal gas exchange suggests that cyclic release patterns in the insect occur as a consequence of the stochastically synchronized control of spiracle opening area by the four large thoracic spiracles. Alternatively, in-flight motion analysis of the abdomen and proboscis using infra-red video imaging suggests utilization of the proboscis extension reflex (PER) for tracheal convection. Although the respiratory benefit of synchronized spiracle opening activity in the fruit fly is unclear, proboscis-induced tracheal convection might potentially help to balance the local oxygen supply between different body compartments of the flying animal.

Delivery of Chemotherapeutics Across the Blood–Brain Barrier: Challenges and Advances

PubMed Central

Doolittle, Nancy D.; Muldoon, Leslie L.; Culp, Aliana Y.; Neuwelt, Edward A.

2017-01-01

The blood–brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2–26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD. PMID:25307218

Method and apparatus for rebalancing a redox flow cell system

NASA Technical Reports Server (NTRS)

Gahn, Randall F. (Inventor)

1986-01-01

A rebalance cell is provided for a REDOX electrochemical system of the type having anode and cathode fluids which are aqueous HCl solutions with two metal species in each. The rebalance cell has a cathode compartment and a chlorine compartment separated by an ion permeable membrane. By applying an electrical potential to the rebalance cell while circulating cathode fluid through the cathode compartment and while circulating an identical fluid through the chlorine compartment, any significant imbalance of the REDOX system is prevented.

Method and apparatus for rebalancing a REDOX flow cell system

NASA Technical Reports Server (NTRS)

Gahn, R. F. (Inventor)

1985-01-01

A rebalance cell is provided for a REDOX electrochemical system of the type with anode and cathode fluids which are aqueous HC1 solutions with two metal species in each. The rebalance cell has a cathode compartment and a chlorine compartment separated by an ion permeable membrane. By applying an electrical potential to the rebalance cell while circulating cathode fluid through the cathode compartment and while circulating an identical fluid through the chlorine compartment, any significant imbalance of the REDOX system is prevented.

A Comparative Data-Based Modeling Study on Respiratory CO2 Gas Exchange during Mechanical Ventilation

PubMed Central

Kim, Chang-Sei; Ansermino, J. Mark; Hahn, Jin-Oh

2016-01-01

The goal of this study is to derive a minimally complex but credible model of respiratory CO2 gas exchange that may be used in systematic design and pilot testing of closed-loop end-tidal CO2 controllers in mechanical ventilation. We first derived a candidate model that captures the essential mechanisms involved in the respiratory CO2 gas exchange process. Then, we simplified the candidate model to derive two lower-order candidate models. We compared these candidate models for predictive capability and reliability using experimental data collected from 25 pediatric subjects undergoing dynamically varying mechanical ventilation during surgical procedures. A two-compartment model equipped with transport delay to account for CO2 delivery between the lungs and the tissues showed modest but statistically significant improvement in predictive capability over the same model without transport delay. Aggregating the lungs and the tissues into a single compartment further degraded the predictive fidelity of the model. In addition, the model equipped with transport delay demonstrated superior reliability to the one without transport delay. Further, the respiratory parameters derived from the model equipped with transport delay, but not the one without transport delay, were physiologically plausible. The results suggest that gas transport between the lungs and the tissues must be taken into account to accurately reproduce the respiratory CO2 gas exchange process under conditions of wide-ranging and dynamically varying mechanical ventilation conditions. PMID:26870728

Patterns of diffusibility of lignin and carbohydrate degrading systems in wood-rotting fungi

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenberg, S.L.

1979-09-01

In an attempt to identify organisms that produce diffusible lignin-degrading systems, a culturing apparatus was constructed which contained two compartments separated by a bacteriological membrane filter. Lignin-degrading fungi were grown with lignocellulose in one compartment, and diffusion channels were maintained through the membrane to sterile lignocellulose in the adjoining compartment. For the fungi tested, both lignin and carbohydrate were degraded when the mycelium and the substrate were in physical contact, but only carbohydrate was degraded significantly in the adjoining compartment containing sterile lignocellulose. Two organisms, Coriolus versicolor and Trichoderma reesii QM 9414 displayed slight diffusible lignin-degrading activity. Some fungi producedmore » more diffusible carbohydrate-degrading activity than others.« less

Fire safety evaluation of aircraft lavatory and cargo compartments

NASA Technical Reports Server (NTRS)

Kourtides, D. A.; Parker, J. A.; Hilado, C. J.; Anderson, R. A.; Tustin, E.; Arnold, D. E.; Gaume, J. G.; Binding, A. T.; Mikeska, J. L.

1975-01-01

Large-scale aircraft lavatory and cargo compartment fire tests are described. Tests were conducted to evaluate the effectiveness of these compartments to contain fire and smoke. Two tests were conducted and are detailed. Test 1 involved a production Boeing 747 lavatory of the latest design installed in an enclosure outside the aircraft, to collect gases and expose animals to these gases. Results indicate that the interior of the lavatory was completely burned, evolving smoke and combustion products in the enclosure. Test 2 involved a simulated Douglas DC-10 cargo compartment retro-fitted with standard fiberglass liner. The fire caused excessive damage to the liner and burned through the ceiling in two areas. Test objectives, methods, materials, and results are presented and discussed.

Simple Kinematic Pathway Approach (KPA) to Catchment-scale Travel Time and Water Age Distributions

NASA Astrophysics Data System (ADS)

Soltani, S. S.; Cvetkovic, V.; Destouni, G.

2017-12-01

The distribution of catchment-scale water travel times is strongly influenced by morphological dispersion and is partitioned between hillslope and larger, regional scales. We explore whether hillslope travel times are predictable using a simple semi-analytical "kinematic pathway approach" (KPA) that accounts for dispersion on two levels of morphological and macro-dispersion. The study gives new insights to shallow (hillslope) and deep (regional) groundwater travel times by comparing numerical simulations of travel time distributions, referred to as "dynamic model", with corresponding KPA computations for three different real catchment case studies in Sweden. KPA uses basic structural and hydrological data to compute transient water travel time (forward mode) and age (backward mode) distributions at the catchment outlet. Longitudinal and morphological dispersion components are reflected in KPA computations by assuming an effective Peclet number and topographically driven pathway length distributions, respectively. Numerical simulations of advective travel times are obtained by means of particle tracking using the fully-integrated flow model MIKE SHE. The comparison of computed cumulative distribution functions of travel times shows significant influence of morphological dispersion and groundwater recharge rate on the compatibility of the "kinematic pathway" and "dynamic" models. Zones of high recharge rate in "dynamic" models are associated with topographically driven groundwater flow paths to adjacent discharge zones, e.g. rivers and lakes, through relatively shallow pathway compartments. These zones exhibit more compatible behavior between "dynamic" and "kinematic pathway" models than the zones of low recharge rate. Interestingly, the travel time distributions of hillslope compartments remain almost unchanged with increasing recharge rates in the "dynamic" models. This robust "dynamic" model behavior suggests that flow path lengths and travel times in shallow hillslope compartments are controlled by topography, and therefore application and further development of the simple "kinematic pathway" approach is promising for their modeling.

Gas Exchange Models for a Flexible Insect Tracheal System.

PubMed

Simelane, S M; Abelman, S; Duncan, F D

2016-06-01

In this paper two models for movement of respiratory gases in the insect trachea are presented. One model considers the tracheal system as a single flexible compartment while the other model considers the trachea as a single flexible compartment with gas exchange. This work represents an extension of Ben-Tal's work on compartmental gas exchange in human lungs and is applied to the insect tracheal system. The purpose of the work is to study nonlinear phenomena seen in the insect respiratory system. It is assumed that the flow inside the trachea is laminar, and that the air inside the chamber behaves as an ideal gas. Further, with the isothermal assumption, the expressions for the tracheal partial pressures of oxygen and carbon dioxide, rate of volume change, and the rates of change of oxygen concentration and carbon dioxide concentration are derived. The effects of some flow parameters such as diffusion capacities, reaction rates and air concentrations on net flow are studied. Numerical simulations of the tracheal flow characteristics are performed. The models developed provide a mathematical framework to further investigate gas exchange in insects.

Cytoplasmic rearrangements associated with amphibian egg symmetrization

NASA Technical Reports Server (NTRS)

Malacinski, G. M.

1984-01-01

Cytoplasmic rearrangements which follow fertilization were mentioned in normal and inverted eggs. A set of yolk compartments was resolved by cytological analyses of both normally oriented and inverted eggs. Those compartments were characterized by their yolk platelet compositions and movement during egg inversion. It is found that during egg inversion the yolk compartments shift minor cytoplasmic compartments which line the egg cortex. Those yolk mass shifts occurred only after the inverted egg was activated. The direction of shift of the major yolk components, rather than the sperm entrance site, determines the dorsal/ventral polarity of the inverted egg. Among different spawnings the rate of shift varied. Eggs that displayed the fastest rate of shift exhibited the highest frequency of developmental abnormalities during organogenesis. Interpretation of novel observations on cytoplasmic organization provide criticism of some earlier models. A new density compartment model is presented as a coherent way to view the organization of the egg cytoplasm and the development of bilateral symmetry.

Application of China's National Forest Continuous Inventory database.

PubMed

Xie, Xiaokui; Wang, Qingli; Dai, Limin; Su, Dongkai; Wang, Xinchuang; Qi, Guang; Ye, Yujing

2011-12-01

The maintenance of a timely, reliable and accurate spatial database on current forest ecosystem conditions and changes is essential to characterize and assess forest resources and support sustainable forest management. Information for such a database can be obtained only through a continuous forest inventory. The National Forest Continuous Inventory (NFCI) is the first level of China's three-tiered inventory system. The NFCI is administered by the State Forestry Administration; data are acquired by five inventory institutions around the country. Several important components of the database include land type, forest classification and ageclass/ age-group. The NFCI database in China is constructed based on 5-year inventory periods, resulting in some of the data not being timely when reports are issued. To address this problem, a forest growth simulation model has been developed to update the database for years between the periodic inventories. In order to aid in forest plan design and management, a three-dimensional virtual reality system of forest landscapes for selected units in the database (compartment or sub-compartment) has also been developed based on Virtual Reality Modeling Language. In addition, a transparent internet publishing system for a spatial database based on open source WebGIS (UMN Map Server) has been designed and utilized to enhance public understanding and encourage free participation of interested parties in the development, implementation, and planning of sustainable forest management.

Simultaneous Characterization of Intravenous and Oral Pharmacokinetics of Lychnopholide in Rats by Transit Compartment Model.

PubMed

Lachi-Silva, Larissa; Sy, Sherwin K B; Voelkner, Alexander; de Sousa, João Paulo Barreto; Lopes, João Luis C; Silva, Denise B; Lopes, Norberto P; Kimura, Elza; Derendorf, Hartmut; Diniz, Andrea

2015-08-01

The pharmacokinetic properties of a new molecular entity are important aspects in evaluating the viability of the compound as a pharmacological agent. The sesquiterpene lactone lychnopholide exhibits important biological activities. The objective of this study was to characterize the pharmacokinetics of lychnopholide after intravenous administration of 1.65 mg/kg (n = 5) and oral administration of 3.3 mg/kg (n = 3) lychnopholide in rats (0.2 ± 0.02 kg in weight) through nonlinear mixed effects modeling and non-compartmental pharmacokinetic analysis. A highly sensitive analytical method was used to quantify the plasma lychnopholide concentrations in rats. Plasma protein binding of this compound was over 99 % as determined by a filtration method. A two-compartment body model plus three transit compartments to characterize the absorption process best described the disposition of lychnopholide after both routes of administration. The oral bioavailability was approximately 68 %. The clearance was 0.131 l/min and intercompartmental clearance was 0.171 l/min; steady-state volume of distribution was 4.83 l. The mean transit time for the absorption process was 9.15 minutes. No flip-flop phenomenon was observed after oral administration. The pharmacokinetic properties are favorable for further development of lychnopholide as a potential oral pharmacological agent. Georg Thieme Verlag KG Stuttgart · New York.

Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data

PubMed Central

Wojciechowski, Jessica; Mudge, Stuart; Upton, Richard N.; Foster, David J. R.

2017-01-01

ABSTRACT The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions. A population pharmacokinetic model was developed in a stepwise manner using NONMEM, version 7.3. The final covariate model was developed according to a forward inclusion (P < 0.01) and then backward deletion (P < 0.001) procedure. The final model was a two-compartment model with two-transit absorption compartments. Structural covariates in the base model included formulation effects on relative bioavailability (F), absorption lag (ALAG), and the transit absorption rate (KTR) under the fed status. An absorption delay (lag) for the fed status (FTLAG2 = 0.203 h) was also included in the model as a structural covariate. The fed status was observed to decrease F by 10.5%, and the effect of female sex was a 14.4% increase in clearance. The manuscript presents the first population pharmacokinetic model of doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC, and it could potentially be used to critically examine and optimize doxycycline dose regimens. PMID:28052851

Population Pharmacokinetic Model of Doxycycline Plasma Concentrations Using Pooled Study Data.

PubMed

Hopkins, Ashley M; Wojciechowski, Jessica; Abuhelwa, Ahmad Y; Mudge, Stuart; Upton, Richard N; Foster, David J R

2017-03-01

The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions. A population pharmacokinetic model was developed in a stepwise manner using NONMEM, version 7.3. The final covariate model was developed according to a forward inclusion ( P < 0.01) and then backward deletion ( P < 0.001) procedure. The final model was a two-compartment model with two-transit absorption compartments. Structural covariates in the base model included formulation effects on relative bioavailability ( F ), absorption lag (ALAG), and the transit absorption rate (KTR) under the fed status. An absorption delay (lag) for the fed status (FTLAG2 = 0.203 h) was also included in the model as a structural covariate. The fed status was observed to decrease F by 10.5%, and the effect of female sex was a 14.4% increase in clearance. The manuscript presents the first population pharmacokinetic model of doxycycline plasma concentrations following oral doxycycline administration. The model was used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC, and it could potentially be used to critically examine and optimize doxycycline dose regimens. Copyright © 2017 American Society for Microbiology.

The renal compartment: a hydraulic view.

PubMed

Cruces, Pablo; Salas, Camila; Lillo, Pablo; Salomon, Tatiana; Lillo, Felipe; Hurtado, Daniel E

2014-12-01

The hydraulic behavior of the renal compartment is poorly understood. In particular, the role of the renal capsule on the intrarenal pressure has not been thoroughly addressed to date. We hypothesized that pressure and volume in the renal compartment are not linearly related, similar to other body compartments. The pressure-volume curve of the renal compartment was obtained by injecting fluid into the renal pelvis and recording the rise in intrarenal pressure in six anesthetized and mechanically ventilated piglets, using a catheter Camino 4B® inserted into the renal parenchyma. In healthy kidneys, pressure has a highly nonlinear dependence on the injected volume, as revealed by an exponential fit to the data (R (2) = 0.92). On the contrary, a linear relation between pressure and volume is observed in decapsulated kidneys. We propose a biomechanical model for the renal capsule that is able to explain the nonlinear pressure-volume dependence for moderate volume increases. We have presented experimental evidence and a theoretical model that supports the existence of a renal compartment. The mechanical role of the renal capsule investigated in this work may have important implications in elucidating the role of decompressive capsulotomy in reducing the intrarenal pressure in acutely injured kidneys.

14 CFR 29.1187 - Drainage and ventilation of fire zones.

Code of Federal Regulations, 2012 CFR

2012-01-01

... component containing flammable fluids. The drainage means must be— (1) Effective under conditions expected... flammable vapors. (c) No ventilation opening may be where it would allow the entry of flammable fluids... section of the powerplant compartment) unless the amount of extinguishing agent and the rate of discharge...

14 CFR 29.1187 - Drainage and ventilation of fire zones.

Code of Federal Regulations, 2010 CFR

2010-01-01

... component containing flammable fluids. The drainage means must be— (1) Effective under conditions expected... flammable vapors. (c) No ventilation opening may be where it would allow the entry of flammable fluids... section of the powerplant compartment) unless the amount of extinguishing agent and the rate of discharge...

14 CFR 29.1187 - Drainage and ventilation of fire zones.

Code of Federal Regulations, 2011 CFR

2011-01-01

... component containing flammable fluids. The drainage means must be— (1) Effective under conditions expected... flammable vapors. (c) No ventilation opening may be where it would allow the entry of flammable fluids... section of the powerplant compartment) unless the amount of extinguishing agent and the rate of discharge...

14 CFR 29.1187 - Drainage and ventilation of fire zones.

Code of Federal Regulations, 2013 CFR

2013-01-01

... component containing flammable fluids. The drainage means must be— (1) Effective under conditions expected... flammable vapors. (c) No ventilation opening may be where it would allow the entry of flammable fluids... section of the powerplant compartment) unless the amount of extinguishing agent and the rate of discharge...

14 CFR 29.1187 - Drainage and ventilation of fire zones.

Code of Federal Regulations, 2014 CFR

2014-01-01

... component containing flammable fluids. The drainage means must be— (1) Effective under conditions expected... flammable vapors. (c) No ventilation opening may be where it would allow the entry of flammable fluids... section of the powerplant compartment) unless the amount of extinguishing agent and the rate of discharge...

14 CFR 23.365 - Pressurized cabin loads.

Code of Federal Regulations, 2010 CFR

2010-01-01

... stress concentrations, must be accounted for. (c) If landings may be made with the cabin pressurized... be designed for the effects of sudden release of pressure in any compartment with external doors or windows. This condition must be investigated for the effects of failure of the largest opening in the...

Identifiability Results for Several Classes of Linear Compartment Models.

PubMed

Meshkat, Nicolette; Sullivant, Seth; Eisenberg, Marisa

2015-08-01

Identifiability concerns finding which unknown parameters of a model can be estimated, uniquely or otherwise, from given input-output data. If some subset of the parameters of a model cannot be determined given input-output data, then we say the model is unidentifiable. In this work, we study linear compartment models, which are a class of biological models commonly used in pharmacokinetics, physiology, and ecology. In past work, we used commutative algebra and graph theory to identify a class of linear compartment models that we call identifiable cycle models, which are unidentifiable but have the simplest possible identifiable functions (so-called monomial cycles). Here we show how to modify identifiable cycle models by adding inputs, adding outputs, or removing leaks, in such a way that we obtain an identifiable model. We also prove a constructive result on how to combine identifiable models, each corresponding to strongly connected graphs, into a larger identifiable model. We apply these theoretical results to several real-world biological models from physiology, cell biology, and ecology.

A simple model of fluid flow and electrolyte balance in the body

NASA Technical Reports Server (NTRS)

White, R. J.; Neal, L.

1973-01-01

The model is basically a three-compartment model, the three compartments being the plasma, interstitial fluid and cellular fluid. Sodium, potassium, chloride and urea are the only major solutes considered explicitly. The control of body water and electrolyte distribution is affected via drinking and hormone levels. Basically, the model follows the effect of various oral input water loads on solute and water distribution throughout the body.

Population pharmacokinetics of bupivacaine in combined lumbar and sciatic nerve block

PubMed Central

Eljebari, Hanene; Jebabli, Nadia; Salouage, Issam; Gaies, Emna; Lakhal, Mohamed; Boussofara, Mehdi; Klouz, Anis

2014-01-01

Objectives: The primary aim of this study was to establish the population pharmacokinetic (PPK) model of bupivacaine after combined lumbar plexus and sciatic nerve blocks and secondary aim is to assess the effect of patient's characteristics including age, body weight and sex on pharmacokinetic parameters. Materials and Methods: A total of 31 patients scheduled for elective lower extremity surgery with combined lumbar and sciatic nerve block using plain bupivacaine 0.5% were included. The total bupivacaine plasma concentrations were measured before injection and after two blocks placement and at selected time points. Monitoring of bupivacaine was made by high performance liquid chromatography (HPLC) with ultraviolet detection. Non-linear mixed effects modeling was used to analyze the PPK of bupivacaine. Results: One compartment model with first order absorption, two input compartments and a central elimination was selected. The Shapiro-Wilks test of normality for normalized prediction distribution errors for this model (P = 0.156) showed this as a valid model. The selected model predicts a population clearance of 930 ml/min (residual standard error [RSE] = 15.48%, IC 95% = 930 ± 282.24) with inter individual variability of 75.29%. The central volume of distribution was 134 l (RSE = 12.76%, IC = 134 ± 33.51 L) with inter individual variability of 63.40%. The absorption of bupivacaine in two sites Ka1 and Ka2 were 0.00462/min for the lumbar site and 0.292/min for the sciatic site. Age, body weight and sex have no effect on the bupivacaine pharmacokinetics in this studied population. Conclusion: The developed model helps us to assess the systemic absorption of bupivacaine at two injections sites. PMID:24741194

Scopadulcic acid B, a new tetracyclic diterpenoid from Scoparia dulcis L. Its structure, H+, K(+)-adenosine triphosphatase inhibitory activity and pharmacokinetic behaviour in rats.

PubMed

Hayashi, T; Okamura, K; Kakemi, M; Asano, S; Mizutani, M; Takeguchi, N; Kawasaki, M; Tezuka, Y; Kikuchi, T; Morita, N

1990-10-01

The structure of scopadulcic acid B (2, SDB), a major ingredient of the Paraguayan herb "Typychá kuratũ" (Scoparia dulcis L.), was elucidated mainly by comparison of its spectral data with that of scopadulcic acid A (1). SDB inhibited both the K(+)-dependent adenosine triphosphatase (ATPase) activity of a hog gastric proton pump (H+, K(+)-ATPase) with a value of 20-30 microM for IC50 and proton transport into gastric vesicles. Pharmacokinetic studies of SDB in rats indicated that plasma SDB concentrations after i.v. injection of the sodium salt of SDB (SDB-Na) were described reasonably well by a two-compartment open model with Michaelis-Menten elimination kinetics. Plasma concentrations after oral administration of SDB-Na or SDB showed a much slower decline than what was expected following the i. v. study. It was suggested that the sustained plasma level of SDB after oral administration of SDB-Na or SDB was accounted for by relatively slow but efficient gastro-intestinal absorption in rats.

Comparative Pharmacokinetics of Cefquinome (Cobactan 2.5%) following Repeated Intramuscular Administrations in Sheep and Goats

PubMed Central

El-Hewaity, Mohamed; Abd El Latif, Amera

2014-01-01

The comparative pharmacokinetic profile of cefquinome was studied in sheep and goats following repeated intramuscular (IM) administrations of 2 mg/kg body weight. Cefquinome concentrations in serum were determined by microbiological assay technique using Micrococcus luteus (ATCC 9341) as test organism. Following intramuscular injection of cefquinome in sheep and goats, the disposition curves were best described by two-compartment open model in both sheep and goats. The pharmacokinetics of cefquinome did not differ significantly between sheep and goats; similar intramuscular dose rate of cefquinome should therefore be applicable to both species. On comparing the data of serum levels of repeated intramuscular injections with first intramuscular injection, it was revealed that repeated intramuscular injections of cefquinome have cumulative effect in both species sheep and goats. The in vitro serum protein-binding tendency was 15.65% in sheep and 14.42% in goats. The serum concentrations of cefquinome along 24 h after injection in this study were exceeding the MICs of different susceptible microorganisms responsible for serious disease problems. These findings indicate successful use of cefquinome in sheep and goats. PMID:26464946

Spatial separation of two different pathways accounting for the generation of calcium signals in astrocytes.

PubMed

Oschmann, Franziska; Mergenthaler, Konstantin; Jungnickel, Evelyn; Obermayer, Klaus

2017-02-01

Astrocytes integrate and process synaptic information and exhibit calcium (Ca2+) signals in response to incoming information from neighboring synapses. The generation of Ca2+ signals is mostly attributed to Ca2+ release from internal Ca2+ stores evoked by an elevated metabotropic glutamate receptor (mGluR) activity. Different experimental results associated the generation of Ca2+ signals to the activity of the glutamate transporter (GluT). The GluT itself does not influence the intracellular Ca2+ concentration, but it indirectly activates Ca2+ entry over the membrane. A closer look into Ca2+ signaling in different astrocytic compartments revealed a spatial separation of those two pathways. Ca2+ signals in the soma are mainly generated by Ca2+ release from internal Ca2+ stores (mGluR-dependent pathway). In astrocytic compartments close to the synapse most Ca2+ signals are evoked by Ca2+ entry over the plasma membrane (GluT-dependent pathway). This assumption is supported by the finding, that the volume ratio between the internal Ca2+ store and the intracellular space decreases from the soma towards the synapse. We extended a model for mGluR-dependent Ca2+ signals in astrocytes with the GluT-dependent pathway. Additionally, we included the volume ratio between the internal Ca2+ store and the intracellular compartment into the model in order to analyze Ca2+ signals either in the soma or close to the synapse. Our model results confirm the spatial separation of the mGluR- and GluT-dependent pathways along the astrocytic process. The model allows to study the binary Ca2+ response during a block of either of both pathways. Moreover, the model contributes to a better understanding of the impact of channel densities on the interaction of both pathways and on the Ca2+ signal.

Two-Compartment Model as a Teaching Tool for Cholesterol Homeostasis

ERIC Educational Resources Information Center

Wrona, Artur; Balbus, Joanna; Hrydziuszko, Olga; Kubica, Krystian

2015-01-01

Cholesterol is a vital structural and functional molecule in the human body that is only slightly soluble in water and therefore does not easily travels by itself in the bloodstream. To enable cholesterol's targeted delivery to cells and tissues, it is encapsulated by different fractions of lipoproteins, complex particles containing both proteins…

Population pharmacokinetic analysis of blood and joint synovial fluid concentrations of robenacoxib from healthy dogs and dogs with osteoarthritis.

PubMed

Silber, Hanna E; Burgener, Claudia; Letellier, Ingrid M; Peyrou, Mathieu; Jung, Martin; King, Jonathan N; Gruet, Philippe; Giraudel, Jerome M

2010-12-01

The purpose of this population analysis was to characterize the pharmacokinetic properties of robenacoxib in blood and stifle joint synovial fluid of dogs. Data were obtained from two studies: 1) 8 healthy Beagle dogs in which an acute inflammation was induced by injection of urate crystals into one joint; 2) 95 dogs from various breeds diagnosed with osteoarthritis (OA). Robenacoxib concentrations in blood and synovial fluid were measured using a validated HPLC-UV and LC-MS method. Non-linear mixed effects modeling was performed using NONMEM6. A two-compartment pharmacokinetic model with linear elimination was developed to describe blood concentrations of robenacoxib. Blood clearance in healthy animals was found to be 75% higher than in OA dogs. Synovial fluid concentrations were modeled using an effect-compartment-type model predicting longer residence times in OA dogs compared to healthy Beagles (e.g. concentrations above the IC(50) for COX-2, respectively, 16 h vs. 10 h at 1.5 mg/kg). Robenacoxib was found to reside longer at the effect site (inflamed joint) compared to blood in both healthy and OA dogs. These results may explain the good efficacy observed with once-daily dosing in clinical trials and the high safety index of robenacoxib in dogs.

Kinetic analysis of the translocator protein positron emission tomography ligand [18F]GE-180 in the human brain.

PubMed

Feeney, Claire; Scott, Gregory; Raffel, Joel; Roberts, S; Coello, Christopher; Jolly, Amy; Searle, Graham; Goldstone, A P; Brooks, David J; Nicholas, Richard S; Trigg, William; Gunn, Roger N; Sharp, David J

2016-11-01

PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand [ 11 C]PK-11195 limits accurate quantification. [ 18 F]GE-180, a novel TSPO ligand, displays superior binding to [ 11 C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [ 18 F]GE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures. Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of [ 18 F]GE-180. Kinetic modelling of time-activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution (V T ) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region. The two-tissue compartment model was the best model. The average regional delivery rate constant (K 1 ) was 0.01 mL cm -3  min -1 indicating low extraction across the blood-brain barrier (1 %). The estimated median V T across all ROIs was also low, ranging from 0.16 mL cm -3 in the striatum to 0.38 mL cm -3 in the thalamus. There were no significant differences in V T between HABs and MABs across all ROIs. A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low V T estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of [ 18 F]GE-180 in populations with neuroinflammatory disease is needed to determine its suitability for quantitative assessment of TSPO expression.

Dimensional reduction for a SIR type model

NASA Astrophysics Data System (ADS)

Cahyono, Edi; Soeharyadi, Yudi; Mukhsar

2018-03-01

Epidemic phenomena are often modeled in the form of dynamical systems. Such model has also been used to model spread of rumor, spread of extreme ideology, and dissemination of knowledge. Among the simplest is SIR (susceptible, infected and recovered) model, a model that consists of three compartments, and hence three variables. The variables are functions of time which represent the number of subpopulations, namely suspect, infected and recovery. The sum of the three is assumed to be constant. Hence, the model is actually two dimensional which sits in three-dimensional ambient space. This paper deals with the reduction of a SIR type model into two variables in two-dimensional ambient space to understand the geometry and dynamics better. The dynamics is studied, and the phase portrait is presented. The two dimensional model preserves the equilibrium and the stability. The model has been applied for knowledge dissemination, which has been the interest of knowledge management.

MATHEMATICAL ANALYSIS OF STEADY-STATE SOLUTIONS IN COMPARTMENT AND CONTINUUM MODELS OF CELL POLARIZATION

PubMed Central

ZHENG, ZHENZHEN; CHOU, CHING-SHAN; YI, TAU-MU; NIE, QING

2013-01-01

Cell polarization, in which substances previously uniformly distributed become asymmetric due to external or/and internal stimulation, is a fundamental process underlying cell mobility, cell division, and other polarized functions. The yeast cell S. cerevisiae has been a model system to study cell polarization. During mating, yeast cells sense shallow external spatial gradients and respond by creating steeper internal gradients of protein aligned with the external cue. The complex spatial dynamics during yeast mating polarization consists of positive feedback, degradation, global negative feedback control, and cooperative effects in protein synthesis. Understanding such complex regulations and interactions is critical to studying many important characteristics in cell polarization including signal amplification, tracking dynamic signals, and potential trade-off between achieving both objectives in a robust fashion. In this paper, we study some of these questions by analyzing several models with different spatial complexity: two compartments, three compartments, and continuum in space. The step-wise approach allows detailed characterization of properties of the steady state of the system, providing more insights for biological regulations during cell polarization. For cases without membrane diffusion, our study reveals that increasing the number of spatial compartments results in an increase in the number of steady-state solutions, in particular, the number of stable steady-state solutions, with the continuum models possessing infinitely many steady-state solutions. Through both analysis and simulations, we find that stronger positive feedback, reduced diffusion, and a shallower ligand gradient all result in more steady-state solutions, although most of these are not optimally aligned with the gradient. We explore in the different settings the relationship between the number of steady-state solutions and the extent and accuracy of the polarization. Taken together these results furnish a detailed description of the factors that influence the tradeoff between a single correctly aligned but poorly polarized stable steady-state solution versus multiple more highly polarized stable steady-state solutions that may be incorrectly aligned with the external gradient. PMID:21936604

Dynamics of hydrophobic organic contaminants in the Baltic proper pelagial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Axelman, J.; Broman, D.; Naef, C.

Hydrophobic organic contaminants occur in different forms in natural water. Apart from being truly dissolved in water they partition into dissolved organic carbon (DOC) and particles of different sizes including pelagic bacteria, phytoplankton and zooplankton. The distribution between the different forms is dependent on carbon turnover rates in and transport between the different compartments and on the physical and chemical properties of the compound in focus. The water phase, the DOC-phase and two particle size fractions, 0.2--2pm and 2--20 pm representing the base of the pelagic food web, were analyzed for their content of PCBs and PAHs during summer andmore » winter conditions in the open sea in the Baltic proper. New methods for separating truly dissolved from DOC-bound compounds have been developed using a high capacity perfusion adsorbent and large scale gas sparging. The small particle size fraction was sampled using high volume tangential flow filtration. The possibility to separate between these four different compartments has given a more detailed picture of the short term dynamics of hydrophobic organic compounds in the important base of the pelagial food web.« less

Animal exposure during burn tests

NASA Technical Reports Server (NTRS)

Gaume, J. G.

1976-01-01

An animal exposure test system has been designed and fabricated for the purpose of collecting physiological and environmental (temperature) data from animal subjects exposed to combustion gases in large scale fire tests. The AETS consists of an open wire mesh, two-compartment cage, one containing an exercise wheel for small rodents, and the other containing one rat instrumented externally for electrocardiogram and respiration. The ECG and respiration sensors are located in a belt placed around the torso of the subject, electrode wires forming an umbilical to a connector in the top of the compartment. A cable extends from the connector to the power supply and signal conditioning electronics. These are connected to a dual-beam oscilloscope for real time monitoring and a magnetic tape recorder having three or more channels. Endpoints observed are bradycardia, cardiac arrhythmias, changes in respiratory pattern, respiratory arrest and cardiac arrest. The ECG record also appears to be a good method of monitoring animal activity as indicated by an increase in EMG noise superimposed on the record during increased activity of the torso musculature. Examples of the recordings are presented and discussed as to their significance regarding toxicity of fire gases.

Effect of ischemic cerebral volume changes on behavior.

PubMed

Lyden, P D; Lonzo, L M; Nunez, S Y; Dockstader, T; Mathieu-Costello, O; Zivin, J A

1997-08-01

Ischemia causes long-term effects on brain volume and neurologic function but the relationship between the two is poorly characterized. We studied the relationships between brain volume and three measures of rodent behavior after cerebral ischemia was induced by injecting several thousand microspheres into the internal carotid arteries of rats. Forty eight hours later, each subject was rated using a global neurologic rating scale. Several weeks later, the subjects were tested for open field activity and visual spatial learning. Post-mortem we measured the volume of the cerebral hemispheres and estimated the volume densities of cortex, white matter, hippocampus, basal ganglia, thalamus, ventricle, and visible infarction. Ischemia caused significant impairment, as measured by the global rating scale; the probability of an abnormal rating was correlated with the number of microspheres trapped in the brains. Visual spatial learning was significantly impaired by ischemia, but this deficit was independent of the count of microspheres, whether the subject was abnormal at 48 h, and whether the left or right hemisphere was embolized. Cerebral hemisphere volume was reduced from 430 mm3 to 376 mm3 (P < 0.05). The cortex was reduced from 22 to 19% of cerebrum (P < 0.05) and the white matter compartment was reduced to similar degree. The lesion volume was 6% of cerebrum, comparable to that seen with other ischemia methods. The global outcome rating was significantly related to total cerebral volume, but not to volume changes in any single compartment. On the other hand, visual spatial learning was significantly influenced by volume changes in the cortex and white matter, but not by the topography of the visible infarctions. Open field activity was not altered by infarction. Our data suggests that the total volume of brain tissue lost to infarction may partially determine global neurological rating independently of the topography of the volume loss. Integrative functions such as learning may depend more on the integrity of specific compartments and less on the total volume of intact brain. The volume of visible cystic infarction was not related to long term behavioral outcome. These results should be confirmed using another method of inducing ischemia.

Method for preparing dosimeter for measuring skin dose

DOEpatents

Jones, Donald E.; Parker, DeRay; Boren, Paul R.

1982-01-01

A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with neutron-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

Dosimeter for measuring skin dose and more deeply penetrating radiation

DOEpatents

Jones, Donald E.; Parker, DeRay; Boren, Paul R.

1981-01-01

A personnel dosimeter includes a plurality of compartments containing thermoluminescent dosimeter phosphors for registering radiation dose absorbed in the wearer's sensitive skin layer and for registering more deeply penetrating radiation. Two of the phosphor compartments communicate with thin windows of different thicknesses to obtain a ratio of shallowly penetrating radiation, e.g. beta. A third phosphor is disposed within a compartment communicating with a window of substantially greater thickness than the windows of the first two compartments for estimating the more deeply penetrating radiation dose. By selecting certain phosphors that are insensitive to neutrons and by loading the holder material with netruon-absorbing elements, energetic neutron dose can be estimated separately from other radiation dose. This invention also involves a method of injection molding of dosimeter holders with thin windows of consistent thickness at the corresponding compartments of different holders. This is achieved through use of a die insert having the thin window of precision thickness in place prior to the injection molding step.

Bioavailability of a Lipidic Formulation of Curcumin in Healthy Human Volunteers

PubMed Central

Pawar, Yogesh B.; Munjal, Bhushan; Arora, Saurabh; Karwa, Manoj; Kohli, Gunjan; Paliwal, Jyoti K.; Bansal, Arvind K.

2012-01-01

Numerous publications have reported the significant pharmacodynamic activity of Curcumin (CRM) despite low or undetectable levels in plasma. The objective of the present study was to perform a detailed pharmacokinetic evaluation of CRM after the oral administration of a highly bioavailable lipidic formulation of CRM (CRM-LF) in human subjects. Cmax, Tmax and AUC0–∞ were found to be 183.35 ± 37.54 ng/mL, 0.60 ± 0.05 h and 321.12 ± 25.55 ng/mL respectively, at a dose of 750 mg. The plasma profile clearly showed three distinct phases, viz., absorption, distribution and elimination. A close evaluation of the primary pharmacokinetic parameters provided valuable insight into the behavior of the CRM after absorption by CRM-LF. CRM-LF showed a lag time (Tlag) of 0.18 h (around 12 min). Pharmacokinetic modeling revealed that CRM-LF followed a two-compartment model with first order absorption, lag time and first order elimination. A high absorption rate constant (K01, 4.51/h) signifies that CRM-LF ensured rapid absorption of the CRM into the central compartment. This was followed by the distribution of CRM from the central to peripheral compartment (K12, 2.69/h). The rate of CRM transfer from the peripheral to central compartment (K21, 0.15/h) was slow. This encourages higher tissue levels of CRM as compared with plasma levels. The study provides an explanation of the therapeutic efficacy of CRM, despite very low/undetectable levels in the plasma. PMID:24300368

Population Pharmacokinetics of Colistin Methanesulfonate in Rats: Achieving Sustained Lung Concentrations of Colistin for Targeting Respiratory Infections

PubMed Central

W. S. Yapa, Shalini; Li, Jian; Porter, Christopher J. H.; Nation, Roger L.

2013-01-01

Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and determines the targeting advantage after direct delivery into the lungs. In addition to plasma, bronchoalveolar lavage (BAL) fluid was collected to quantify drug concentrations in lung epithelial lining fluid (ELF). The resulting data were analyzed using a population modeling approach in S-ADAPT. A three-compartment model described the disposition of both compounds in plasma following i.v. administration. The estimated mean clearance from the central compartment was 0.122 liters/h for CMS and 0.0657 liters/h for colistin. Conversion of CMS to colistin from all three compartments was required to fit the plasma data. The fraction of the i.v. dose converted to colistin in the systemic circulation was 0.0255. Two BAL fluid compartments were required to reflect drug kinetics in the ELF after i.t. dosing. A slow conversion of CMS (mean conversion time [MCTCMS] = 3.48 h) in the lungs contributed to high and sustained concentrations of colistin in ELF. The fraction of the CMS dose converted to colistin in ELF (fm,ELF = 0.226) was higher than the corresponding fractional conversion in plasma after i.v. administration. In conclusion, pulmonary administration of CMS achieves high and sustained exposures of colistin in lungs for targeting respiratory infections. PMID:23917323

A NOVEL PNYSIOLOGICALLY BASED PHARMACOKINETIC (PBPK) MODEL FOR DIMETHYLARSINIC ACID (DMA): THE LUNG AS A STORAGE COMPARTMENT

EPA Science Inventory

A NOVEL PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODEL FOR DIMETHYLARSINIC ACID (DMA): THE LUNG AS A STORAGE COMPARTMENT. Evans, M.V., Hughes, M.F., and Kenyon, E.M. USEPA, ORD, NHEERL, RTP, NC 27711

DMA is the major methylated metabolite of inorganic arsenic, a kno...

SORPTION AND DESORPTION BY IDEAL TWO-COMPARTMENT SYSTEMS: UNUSUAL BEHAVIOR AND DATA INTERPRETATION PROBLEMS

EPA Science Inventory

This paper presents an evaluation of the results of fitting curves to isotherm and kinetic data for idealized two-compartment systems of soil or sediment. Data were produced by numerically solving sets of Freundlich isotherm and first-order kinetics equations for mixtures of up ...

Compartment elasticity measured by pressure-related ultrasound to determine patients "at risk" for compartment syndrome: an experimental in vitro study.

PubMed

Sellei, Richard Martin; Hingmann, Simon Johannes; Kobbe, Philipp; Weber, Christian; Grice, John Edward; Zimmerman, Frauke; Jeromin, Sabine; Hildebrand, Frank; Pape, Hans-Christoph

2015-01-01

Decision-making in treatment of an acute compartment syndrome is based on clinical assessment, supported by invasive monitoring. Thus, evolving compartment syndrome may require repeated pressure measurements. In suspected cases of potential compartment syndromes clinical assessment alone seems to be unreliable. The objective of this study was to investigate the feasibility of a non-invasive application estimating whole compartmental elasticity by ultrasound, which may improve accuracy of diagnostics. In an in vitro model, using an artificial container simulating dimensions of the human anterior tibial compartment, intra-compartmental pressures (p) were raised subsequently up to 80 mmHg by infusion of saline solution. The compartmental depth (mm) in the cross-section view was measured before and after manual probe compression (100 mmHg) upon the surface resulting in a linear compartmental displacement (∆d). This was repeated at rising compartmental pressures. The resulting displacements were related to the corresponding intra-compartmental pressures simulated in our model. A hypothesized relationship between pressures related compartmental displacement and the elasticity at elevated compartment pressures was investigated. With rising compartmental pressures, a non-linear, reciprocal proportional relation between the displacement (mm) and the intra-compartmental pressure (mmHg) occurred. The Pearson coefficient showed a high correlation (r(2) = -0.960). The intra-observer reliability value kappa resulted in a statistically high reliability (κ = 0.840). The inter-observer value indicated a fair reliability (κ = 0.640). Our model reveals that a strong correlation between compartmental strain displacements assessed by ultrasound and the intra-compartmental pressure changes occurs. Further studies are required to prove whether this assessment is transferable to human muscle tissue. Determining the complete compartmental elasticity by ultrasound enhancement, this application may improve detection of early signs of potential compartment syndrome.

Why does walking economy improve after weight loss in obese adolescents?

PubMed

Peyrot, Nicolas; Thivel, David; Isacco, Laurie; Morin, Jean-Benoît; Belli, Alain; Duche, Pascale

2012-04-01

This study tested the hypothesis that the increase in walking economy (i.e., decrease in net metabolic rate per kilogram) after weight loss in obese adolescents is induced by a lower metabolic rate required to support the lower body weight and maintain balance during walking. Sixteen obese adolescent boys and girls were tested before and after a weight reduction program. Body composition and oxygen uptake while standing and walking at four preset speeds (0.75, 1, 1.25, and 1.5 m·s⁻¹) and at the preferred speed were quantified. Net metabolic rate and gross metabolic cost of walking-versus-speed relationships were determined. A three-compartment model was used to distinguish the respective parts of the metabolic rate associated with standing (compartment 1), maintaining balance and supporting body weight during walking (compartment 2), and muscle contractions required to move the center of mass and limbs (compartment 3). Standing metabolic rate per kilogram (compartment 1) significantly increased after weight loss, whereas net metabolic rate per kilogram during walking decreased by 9% on average across speeds. Consequently, the gross metabolic cost of walking per unit of distance-versus-speed relationship and hence preferred walking speeds did not change with weight loss. Compartment 2 of the model was significantly lower after weight loss, whereas compartment 3 did not change. The model showed that the improvement in walking economy after weight loss in obese adolescents was likely related to the lower metabolic rate of the isometric muscular contractions required to support the lower body weight and maintain balance during walking. Contrastingly, the part of the total metabolic rate associated with muscle contractions required to move the center of mass and limbs did not seem to be related to the improvement in walking economy in weight-reduced individuals.

Measuring Compartment Size and Gas Solubility in Marine Mammals

DTIC Science & Technology

2015-09-30

bends? Effect of diving behaviour and physiology on modelled gas exchange for three species: Ziphius cavirostris, Mesoplodon densirostris and Hyperoodon...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Measuring Compartment Size and Gas Solubility in Marine...is to develop methods to estimate marine mamal tissue compartment sizes, and tissue gas solubility. We aim to improve the data available for the

Model of complete separation of the hepatic veins from the systemic venous system.

PubMed

Brizard, C P; Goussef, N; Chachques, J C; Carpentier, A F

2000-12-01

In patients undergoing a Fontan operation, partial diversion of the hepatic veins to the pulmonary venous atrium has been tried with various techniques. They failed because of the development of intrahepatic collaterals leading to an unacceptable right-to-left shunting. We postulate that to avoid the formation of intrahepatic collaterals, the totality of the liver has to be drained into the same pressure compartment. We have designed a model of cavopulmonary anastomosis in which a prosthetic conduit reproduces an azygos continuation, associated with the diversion of the totality of the hepatic venous return. This article reports on the early hemodynamics and the fate of the separation of the two venous compartments in long-term survivors. Eighteen goats were operated on; the pulmonary artery and hepatic vein pressures were recorded. During month 2, an opacification of the inferior vena cava and the cavopulmonary connection was performed. Between months 6 and 14, another opacification was performed, together with pressure recording at both ends of the conduit. Postoperatively the pulmonary artery pressure was pulsatile with a mean of 10 mm Hg and the hepatic vein pressure was 0 mm Hg. The first angiogram showed patent tubes with fast progression of the contrast. Throughout the inferior vena cava injection, there was no opacification of the portal or hepatic veins. The late study showed a narrowed conduit in all animals. During the injection, a collateral was injected, feeding into the inferior mesenteric vein. No collateral circulation could be seen draining directly into the liver. The median gradient between the two ends of the conduit was 11 mm Hg. The isolation of the entire hepatic venous drainage is feasible and efficient for the separation of two pressure compartments. No intrahepatic collaterals are observed with this model at short- or long-term follow-up. The separation of the hepatic venous drainage should persist without collateral circulation as long as the inferior vena cava pressure stays at the levels observed in Fontan circulation.

Non-linear absorption pharmacokinetics of amoxicillin: consequences for dosing regimens and clinical breakpoints.

PubMed

de Velde, Femke; de Winter, Brenda C M; Koch, Birgit C P; van Gelder, Teun; Mouton, Johan W

2016-10-01

To describe the population pharmacokinetics of oral amoxicillin and to compare the PTA of current dosing regimens. Two groups, each with 14 healthy male volunteers, received oral amoxicillin/clavulanic acid tablets on two separate days 1 week apart. One group received 875/125 mg twice daily and 500/125 mg three times daily and the other group 500/125 mg twice daily and 250/125 mg three times daily. A total of 1428 amoxicillin blood samples were collected before and after administration. We analysed the concentration-time profiles using a non-compartmental pharmacokinetic method (PKSolver) and a population pharmacokinetic method (NONMEM). The PTA was computed using Monte Carlo simulations for several dosing regimens. AUC0-24 and Cmax increased non-linearly with dose. The final model included the following components: Savic's transit compartment model, Michaelis-Menten absorption, two distribution compartments and first-order elimination. The mean central volume of distribution was 27.7 L and mean clearance was 21.3 L/h. We included variability for the central volume of distribution (34.4%), clearance (25.8%), transit compartment model parameters and Michaelis-Menten absorption parameters. For 40% fT>MIC and >97.5% PTA, the breakpoints were 0.125 mg/L (500 mg twice daily), 0.25 mg/L (250 mg three times daily and 875 mg twice daily), 0.5 mg/L (500 mg three times daily) and 1 mg/L (750, 875 or 1000 mg three times daily and 500 mg four times daily). The amoxicillin absorption rate appears to be saturable. The PTAs of high-dose as well as twice-daily regimens are less favourable than regimens with lower doses and higher frequency. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

TestDose: A nuclear medicine software based on Monte Carlo modeling for generating gamma camera acquisitions and dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia, Marie-Paule, E-mail: marie-paule.garcia@univ-brest.fr; Villoing, Daphnée; McKay, Erin

Purpose: The TestDose platform was developed to generate scintigraphic imaging protocols and associated dosimetry by Monte Carlo modeling. TestDose is part of a broader project (www.dositest.com) whose aim is to identify the biases induced by different clinical dosimetry protocols. Methods: The TestDose software allows handling the whole pipeline from virtual patient generation to resulting planar and SPECT images and dosimetry calculations. The originality of their approach relies on the implementation of functional segmentation for the anthropomorphic model representing a virtual patient. Two anthropomorphic models are currently available: 4D XCAT and ICRP 110. A pharmacokinetic model describes the biodistribution of amore » given radiopharmaceutical in each defined compartment at various time-points. The Monte Carlo simulation toolkit GATE offers the possibility to accurately simulate scintigraphic images and absorbed doses in volumes of interest. The TestDose platform relies on GATE to reproduce precisely any imaging protocol and to provide reference dosimetry. For image generation, TestDose stores user’s imaging requirements and generates automatically command files used as input for GATE. Each compartment is simulated only once and the resulting output is weighted using pharmacokinetic data. Resulting compartment projections are aggregated to obtain the final image. For dosimetry computation, emission data are stored in the platform database and relevant GATE input files are generated for the virtual patient model and associated pharmacokinetics. Results: Two samples of software runs are given to demonstrate the potential of TestDose. A clinical imaging protocol for the Octreoscan™ therapeutical treatment was implemented using the 4D XCAT model. Whole-body “step and shoot” acquisitions at different times postinjection and one SPECT acquisition were generated within reasonable computation times. Based on the same Octreoscan™ kinetics, a dosimetry computation performed on the ICRP 110 model is also presented. Conclusions: The proposed platform offers a generic framework to implement any scintigraphic imaging protocols and voxel/organ-based dosimetry computation. Thanks to the modular nature of TestDose, other imaging modalities could be supported in the future such as positron emission tomography.« less

TestDose: A nuclear medicine software based on Monte Carlo modeling for generating gamma camera acquisitions and dosimetry.

PubMed

Garcia, Marie-Paule; Villoing, Daphnée; McKay, Erin; Ferrer, Ludovic; Cremonesi, Marta; Botta, Francesca; Ferrari, Mahila; Bardiès, Manuel

2015-12-01

The TestDose platform was developed to generate scintigraphic imaging protocols and associated dosimetry by Monte Carlo modeling. TestDose is part of a broader project (www.dositest.com) whose aim is to identify the biases induced by different clinical dosimetry protocols. The TestDose software allows handling the whole pipeline from virtual patient generation to resulting planar and SPECT images and dosimetry calculations. The originality of their approach relies on the implementation of functional segmentation for the anthropomorphic model representing a virtual patient. Two anthropomorphic models are currently available: 4D XCAT and ICRP 110. A pharmacokinetic model describes the biodistribution of a given radiopharmaceutical in each defined compartment at various time-points. The Monte Carlo simulation toolkit gate offers the possibility to accurately simulate scintigraphic images and absorbed doses in volumes of interest. The TestDose platform relies on gate to reproduce precisely any imaging protocol and to provide reference dosimetry. For image generation, TestDose stores user's imaging requirements and generates automatically command files used as input for gate. Each compartment is simulated only once and the resulting output is weighted using pharmacokinetic data. Resulting compartment projections are aggregated to obtain the final image. For dosimetry computation, emission data are stored in the platform database and relevant gate input files are generated for the virtual patient model and associated pharmacokinetics. Two samples of software runs are given to demonstrate the potential of TestDose. A clinical imaging protocol for the Octreoscan™ therapeutical treatment was implemented using the 4D XCAT model. Whole-body "step and shoot" acquisitions at different times postinjection and one SPECT acquisition were generated within reasonable computation times. Based on the same Octreoscan™ kinetics, a dosimetry computation performed on the ICRP 110 model is also presented. The proposed platform offers a generic framework to implement any scintigraphic imaging protocols and voxel/organ-based dosimetry computation. Thanks to the modular nature of TestDose, other imaging modalities could be supported in the future such as positron emission tomography.

A fugacity-based indoor residential pesticide fate model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, Deborah H.; Furtaw, Edward J.; McKone, Thomas E.

Dermal and non-dietary pathways are potentially significant exposure pathways to pesticides used in residences. Exposure pathways include dermal contact with residues on surfaces, ingestion from hand- and object-to-mouth activities, and absorption of pesticides into food. A limited amount of data has been collected on pesticide concentrations in various residential compartments following an application. But models are needed to interpret this data and make predictions about other pesticides based on chemical properties. In this paper, we propose a mass-balance compartment model based on fugacity principles. We include air (both gas phase and aerosols), carpet, smooth flooring, and walls as model compartments.more » Pesticide concentrations on furniture and toys, and in food, are being added to the model as data becomes available. We determine the compartmental fugacity capacity and mass transfer-rate coefficient for wallboard as an example. We also present the framework and equations needed for a dynamic mass-balance model.« less

Multi-compartment microscopic diffusion imaging

PubMed Central

Kaden, Enrico; Kelm, Nathaniel D.; Carson, Robert P.; Does, Mark D.; Alexander, Daniel C.

2017-01-01

This paper introduces a multi-compartment model for microscopic diffusion anisotropy imaging. The aim is to estimate microscopic features specific to the intra- and extra-neurite compartments in nervous tissue unconfounded by the effects of fibre crossings and orientation dispersion, which are ubiquitous in the brain. The proposed MRI method is based on the Spherical Mean Technique (SMT), which factors out the neurite orientation distribution and thus provides direct estimates of the microscopic tissue structure. This technique can be immediately used in the clinic for the assessment of various neurological conditions, as it requires only a widely available off-the-shelf sequence with two b-shells and high-angular gradient resolution achievable within clinically feasible scan times. To demonstrate the developed method, we use high-quality diffusion data acquired with a bespoke scanner system from the Human Connectome Project. This study establishes the normative values of the new biomarkers for a large cohort of healthy young adults, which may then support clinical diagnostics in patients. Moreover, we show that the microscopic diffusion indices offer direct sensitivity to pathological tissue alterations, exemplified in a preclinical animal model of Tuberous Sclerosis Complex (TSC), a genetic multi-organ disorder which impacts brain microstructure and hence may lead to neurological manifestations such as autism, epilepsy and developmental delay. PMID:27282476

A novel optical assay system for the quantitative measurement of chemotaxis.

PubMed

Kanegasaki, Shiro; Nomura, Yuka; Nitta, Nao; Akiyama, Shuichi; Tamatani, Takuya; Goshoh, Yasuhiro; Yoshida, Takashi; Sato, Tsuyoshi; Kikuchi, Yuji

2003-11-01

We have developed an optically accessible, horizontal chemotaxis apparatus consisting of an etched silicon substrate and a flat glass plate, both of which form two compartments with a 5-microm-deep microchannel in between. The device is held together with a stainless steel holder with holes for injecting cells and a chemoattractant to the different compartments. Migration of cells in the channel is traced with time-lapse intervals using a CCD camera. By developing a method for aligning cells at the edge of the channel, we could successfully reduce the number of cells required for a chemotactic assay, depending on the experiment, to 100 or less. To prevent ceaseless flow of contents between the adjacent compartments via the communicating microchannel, a space at the top end of the holder was filled with medium after aligning the cells. By using a fluorescent probe, we demonstrated experimentally that a stable concentration gradient could be maintained. Furthermore, we determined theoretical details of the gradient established using a model chemokine and a computational fluid dynamics code. Reproducible kinetic results of cell migration were obtained using human neutrophils and IL-8 as a model. Migration of other cells such as eosinophils, basophils and Jurkat lymphocytes toward the appropriate chemokines were also demonstrated.

PyMUS: Python-Based Simulation Software for Virtual Experiments on Motor Unit System

PubMed Central

Kim, Hojeong; Kim, Minjung

2018-01-01

We constructed a physiologically plausible computationally efficient model of a motor unit and developed simulation software that allows for integrative investigations of the input–output processing in the motor unit system. The model motor unit was first built by coupling the motoneuron model and muscle unit model to a simplified axon model. To build the motoneuron model, we used a recently reported two-compartment modeling approach that accurately captures the key cell-type-related electrical properties under both passive conditions (somatic input resistance, membrane time constant, and signal attenuation properties between the soma and the dendrites) and active conditions (rheobase current and afterhyperpolarization duration at the soma and plateau behavior at the dendrites). To construct the muscle unit, we used a recently developed muscle modeling approach that reflects the experimentally identified dependencies of muscle activation dynamics on isometric, isokinetic and dynamic variation in muscle length over a full range of stimulation frequencies. Then, we designed the simulation software based on the object-oriented programing paradigm and developed the software using open-source Python language to be fully operational using graphical user interfaces. Using the developed software, separate simulations could be performed for a single motoneuron, muscle unit and motor unit under a wide range of experimental input protocols, and a hierarchical analysis could be performed from a single channel to the entire system behavior. Our model motor unit and simulation software may represent efficient tools not only for researchers studying the neural control of force production from a cellular perspective but also for instructors and students in motor physiology classroom settings. PMID:29695959

PyMUS: Python-Based Simulation Software for Virtual Experiments on Motor Unit System.

PubMed

Kim, Hojeong; Kim, Minjung

2018-01-01

We constructed a physiologically plausible computationally efficient model of a motor unit and developed simulation software that allows for integrative investigations of the input-output processing in the motor unit system. The model motor unit was first built by coupling the motoneuron model and muscle unit model to a simplified axon model. To build the motoneuron model, we used a recently reported two-compartment modeling approach that accurately captures the key cell-type-related electrical properties under both passive conditions (somatic input resistance, membrane time constant, and signal attenuation properties between the soma and the dendrites) and active conditions (rheobase current and afterhyperpolarization duration at the soma and plateau behavior at the dendrites). To construct the muscle unit, we used a recently developed muscle modeling approach that reflects the experimentally identified dependencies of muscle activation dynamics on isometric, isokinetic and dynamic variation in muscle length over a full range of stimulation frequencies. Then, we designed the simulation software based on the object-oriented programing paradigm and developed the software using open-source Python language to be fully operational using graphical user interfaces. Using the developed software, separate simulations could be performed for a single motoneuron, muscle unit and motor unit under a wide range of experimental input protocols, and a hierarchical analysis could be performed from a single channel to the entire system behavior. Our model motor unit and simulation software may represent efficient tools not only for researchers studying the neural control of force production from a cellular perspective but also for instructors and students in motor physiology classroom settings.

Bioavailability of dexmedetomidine after extravascular doses in healthy subjects

PubMed Central

Anttila, Markku; Penttilä, Jani; Helminen, Antti; Vuorilehto, Lauri; Scheinin, Harry

2003-01-01

Aim To determine the absolute bioavailability of extravascularly administered dexmedetomidine, a novel a2-adrenoceptor agonist, in healthy subjects. Methods Single 2 µg kg−1 doses of dexmedetomidine were given intravenously, intramuscularly, perorally and buccally (where the solution is not swallowed) to 12 healthy male subjects. The drug concentration-time data were analysed using linear one-compartment (buccal and peroral data), or two-compartment modelling (intravenous data), or noncompartmental methods (intramuscular data). Results Mean (95% CI) absolute bioavailability after peroral, buccal and intramuscular administration was 16% (12–20%), 82% (73–92%) and 104% (96–112%), respectively. Conclusion Dexmedetomidine is well absorbed systemically through the oral mucosa, and therefore buccal dosing may provide an effective, noninvasive route to administer the drug. PMID:14616431

[Study on the pharmacokinetics Oxytropis falcate total flavonoids ointment in rats].

PubMed

Li, Wei-Dong; Chen, Zhi-Peng; Qu, Min-Ming; Liu, Dan; Xiao, Yan-Yu; Cai, Bao-Chang

2011-09-01

To study the pharmacokinetics of Oxytropis falcate total flavonoids ointment after transdermal administration in rats. The content of 2',4'-dihydroxychalcone (TFC) in plasma was determined by high performance liquid chromatography. The concentration was determined at various time and the data was processed by 3P97. TFC behaved as a one-compartment and a two-compartment model after transdermal administration of total Oxytropis falcate total flavonoids ointment and solution, respectively. And the C(max) of ointment was improved about 3 times compared with that of the solution. The results show that the ointment possesses sustained release property and significantly prolong the degradation half life of TFC. The ointment is benefit to improve the analgesic and anti-inflammatory activity after transdermal administration.

Influence of the viscoelastic properties of the respiratory system on the energetically optimum breathing frequency.

PubMed

Bates, J H; Milic-Emili, J

1993-01-01

We hypothesized that the viscoelastic properties of the respiratory system should have significant implications for the energetically optimal frequency of breathing, in view of the fact that these properties cause marked dependencies of overall system resistance and elastance on frequency. To test our hypothesis we simulated two models of canine and human respiratory system mechanics during sinusoidal breathing and calculated the inspiratory work (WI) and pressure-time integral (PTI) per minute under both resting and exercise conditions. The two models were a two-compartment viscoelastic model and a single-compartment model. Requiring minute alveolar ventilation to be fixed, we found that both models predicted almost identical optimum breathing frequencies. The calculated PTI was very insensitive to increases in breathing frequency above the optimal frequencies, while WI was found to increase slowly with frequency above its optimum. In contrast, both WI and PTI increased sharply as frequency decreased below their respective optima. A sensitivity analysis showed that the model predictions were very insensitive to the elastance and resistance values chosen to characterize tissue viscoelasticity. We conclude that the WI criterion for choosing the frequency of breathing is compatible with observations in nature, whereas the optimal frequency predictions of the PTI are rather too high. Both criteria allow for a fairly wide margin of choice in frequency above the optimum values without incurring excessive additional energy expenditure. Furthermore, contrary to our expectations, the viscoelastic properties of the respiratory system tissues do not pose a noticeable problem to the respiratory controller in terms of energy expenditure.

Current concepts in the pathophysiology, evaluation, and diagnosis of compartment syndrome

NASA Technical Reports Server (NTRS)

Hargens, A. R.; Mubarak, S. J.

1998-01-01

This article reviews present knowledge of the pathophysiology and diagnosis of acute compartment syndromes. Recent results using compression of legs in normal volunteers provide objective data concerning local pressure thresholds for neuromuscular dysfunction in the anterior compartment. Results with this model indicate that a progression of neuromuscular deficits occurs when IMP increases to within 35 to 40 mm Hg of diastolic blood pressure. These findings provide useful information on the diagnosis and compression thresholds for acute compartment syndromes. Time factors are also important, however, and usually are incompletely known in most cases of acute compartment syndrome. Although the slit catheter is a very good technique for monitoring IMP during rest, these catheters and their associated extracorporeal transducer systems are not ideal. Recently developed miniature transducer-tipped catheters and, perhaps, future development of noninvasive techniques may provide accurate recordings of IMP in patients with acute compartment syndromes.

Isavuconazole Population Pharmacokinetic Analysis Using Nonparametric Estimation in Patients with Invasive Fungal Disease (Results from the VITAL Study)

PubMed Central

Kovanda, Laura L.; Desai, Amit V.; Lu, Qiaoyang; Townsend, Robert W.; Akhtar, Shahzad; Bonate, Peter

2016-01-01

Isavuconazonium sulfate (Cresemba; Astellas Pharma Inc.), a water-soluble prodrug of the triazole antifungal agent isavuconazole, is available for the treatment of invasive aspergillosis (IA) and invasive mucormycosis. A population pharmacokinetic (PPK) model was constructed using nonparametric estimation to compare the pharmacokinetic (PK) behaviors of isavuconazole in patients treated in the phase 3 VITAL open-label clinical trial, which evaluated the efficacy and safety of the drug for treatment of renally impaired IA patients and patients with invasive fungal disease (IFD) caused by emerging molds, yeasts, and dimorphic fungi. Covariates examined were body mass index (BMI), weight, race, impact of estimated glomerular filtration rate (eGFR) on clearance (CL), and impact of weight on volume. PK parameters were compared based on IFD type and other patient characteristics. Simulations were performed to describe the MICs covered by the clinical dosing regimen. Concentrations (n = 458) from 136 patients were used to construct a 2-compartment model (first-order absorption compartment and central compartment). Weight-related covariates affected clearance, but eGFR did not. PK parameters and intersubject variability of CL were similar across different IFD groups and populations. Target attainment analyses demonstrated that the clinical dosing regimen would be sufficient for total drug area under the concentration-time curve (AUC)/MIC targets ranging from 50.5 for Aspergillus spp. (up to the CLSI MIC of 0.5 mg/liter) to 270 and 5,053 for Candida albicans (up to MICs of 0.125 and 0.004 mg/liter, respectively) and 312 for non-albicans Candida spp. (up to a MIC of 0.125 mg/liter). The estimations for Candida spp. were exploratory considering that no patients with Candida infections were included in the current analyses. (The VITAL trial is registered at ClinicalTrials.gov under number NCT00634049.) PMID:27185799

Integrating microbial diversity in soil carbon dynamic models parameters

NASA Astrophysics Data System (ADS)

Louis, Benjamin; Menasseri-Aubry, Safya; Leterme, Philippe; Maron, Pierre-Alain; Viaud, Valérie

2015-04-01

Faced with the numerous concerns about soil carbon dynamic, a large quantity of carbon dynamic models has been developed during the last century. These models are mainly in the form of deterministic compartment models with carbon fluxes between compartments represented by ordinary differential equations. Nowadays, lots of them consider the microbial biomass as a compartment of the soil organic matter (carbon quantity). But the amount of microbial carbon is rarely used in the differential equations of the models as a limiting factor. Additionally, microbial diversity and community composition are mostly missing, although last advances in soil microbial analytical methods during the two past decades have shown that these characteristics play also a significant role in soil carbon dynamic. As soil microorganisms are essential drivers of soil carbon dynamic, the question about explicitly integrating their role have become a key issue in soil carbon dynamic models development. Some interesting attempts can be found and are dominated by the incorporation of several compartments of different groups of microbial biomass in terms of functional traits and/or biogeochemical compositions to integrate microbial diversity. However, these models are basically heuristic models in the sense that they are used to test hypotheses through simulations. They have rarely been confronted to real data and thus cannot be used to predict realistic situations. The objective of this work was to empirically integrate microbial diversity in a simple model of carbon dynamic through statistical modelling of the model parameters. This work is based on available experimental results coming from a French National Research Agency program called DIMIMOS. Briefly, 13C-labelled wheat residue has been incorporated into soils with different pedological characteristics and land use history. Then, the soils have been incubated during 104 days and labelled and non-labelled CO2 fluxes have been measured at ten sampling time in order to follow the dynamic of residue and soil organic matter mineralization. Diversity, structure and composition of microbial communities have been characterized before incubation time. The dynamic of carbon fluxes through CO2 emissions has been modelled through a simple model. Using statistical tools, relations between parameters of the model and microbial diversity indexes and/or pedological characteristics have been developed and integrated to the model. First results show that global diversity has an impact on the models parameters. Moreover, larger fungi diversity seems to lead to larger parameters representing decomposition rates and/or carbon use efficiencies than bacterial diversity. Classically, pedological factors such as soil pH and texture must also be taken into account.

Differential synaptology of vGluT2-containing thalamostriatal afferents between the patch and matrix compartments in rats.

PubMed

Raju, Dinesh V; Shah, Deep J; Wright, Terrence M; Hall, Randy A; Smith, Yoland

2006-11-10

The striatum is divided into two compartments named the patch (or striosome) and the matrix. Although these two compartments can be differentiated by their neurochemical content or afferent and efferent projections, the synaptology of inputs to these striatal regions remains poorly characterized. By using the vesicular glutamate transporters vGluT1 and vGluT2, as markers of corticostriatal and thalamostriatal projections, respectively, we demonstrate a differential pattern of synaptic connections of these two pathways between the patch and the matrix compartments. We also demonstrate that the majority of vGluT2-immunolabeled axon terminals form axospinous synapses, suggesting that thalamic afferents, like corticostriatal inputs, terminate preferentially onto spines in the striatum. Within both compartments, more than 90% of vGluT1-containing terminals formed axospinous synapses, whereas 87% of vGluT2-positive terminals within the patch innervated dendritic spines, but only 55% did so in the matrix. To characterize further the source of thalamic inputs that could account for the increase in axodendritic synapses in the matrix, we undertook an electron microscopic analysis of the synaptology of thalamostriatal afferents to the matrix compartments from specific intralaminar, midline, relay, and associative thalamic nuclei in rats. Approximately 95% of PHA-L-labeled terminals from the central lateral, midline, mediodorsal, lateral dorsal, anteroventral, and ventral anterior/ventral lateral nuclei formed axospinous synapses, a pattern reminiscent of corticostriatal afferents but strikingly different from thalamostriatal projections arising from the parafascicular nucleus (PF), which terminated onto dendritic shafts. These findings provide the first evidence for a differential pattern of synaptic organization of thalamostriatal glutamatergic inputs to the patch and matrix compartments. Furthermore, they demonstrate that the PF is the sole source of significant axodendritic thalamic inputs to striatal projection neurons. These observations pave the way for understanding differential regulatory mechanisms of striatal outflow from the patch and matrix compartments by thalamostriatal afferents. 2006 Wiley-Liss, Inc.

19 CFR 123.63 - Examination of baggage from Canada or Mexico.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Examination of baggage from Canada or Mexico. 123...; DEPARTMENT OF THE TREASURY CUSTOMS RELATIONS WITH CANADA AND MEXICO Baggage § 123.63 Examination of baggage from Canada or Mexico. (a) Opening vehicle or compartment to examine baggage. Customs officers are...

49 CFR 176.205 - Under deck stowage requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... be equipped with an overhead water sprinkler system or fixed fire extinguishing system. (3) Each... rents, tears, and holes. (7) A fire screen must be fitted at the weather end of each vent duct leading from the hold or compartment. The fire screen must completely cover the open area. It must consist of...

49 CFR 176.205 - Under deck stowage requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... be equipped with an overhead water sprinkler system or fixed fire extinguishing system. (3) Each... rents, tears, and holes. (7) A fire screen must be fitted at the weather end of each vent duct leading from the hold or compartment. The fire screen must completely cover the open area. It must consist of...

49 CFR 176.205 - Under deck stowage requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... be equipped with an overhead water sprinkler system or fixed fire extinguishing system. (3) Each... rents, tears, and holes. (7) A fire screen must be fitted at the weather end of each vent duct leading from the hold or compartment. The fire screen must completely cover the open area. It must consist of...

49 CFR 176.205 - Under deck stowage requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... be equipped with an overhead water sprinkler system or fixed fire extinguishing system. (3) Each... rents, tears, and holes. (7) A fire screen must be fitted at the weather end of each vent duct leading from the hold or compartment. The fire screen must completely cover the open area. It must consist of...

19 CFR 123.63 - Examination of baggage from Canada or Mexico.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Examination of baggage from Canada or Mexico. 123...; DEPARTMENT OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.63 Examination of baggage from Canada or Mexico. (a) Opening vehicle or compartment to examine baggage. Customs officers are authorized...

19 CFR 123.63 - Examination of baggage from Canada or Mexico.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Examination of baggage from Canada or Mexico. 123...; DEPARTMENT OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.63 Examination of baggage from Canada or Mexico. (a) Opening vehicle or compartment to examine baggage. Customs officers are authorized...

19 CFR 123.63 - Examination of baggage from Canada or Mexico.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Examination of baggage from Canada or Mexico. 123...; DEPARTMENT OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.63 Examination of baggage from Canada or Mexico. (a) Opening vehicle or compartment to examine baggage. Customs officers are authorized...

19 CFR 123.63 - Examination of baggage from Canada or Mexico.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Examination of baggage from Canada or Mexico. 123...; DEPARTMENT OF THE TREASURY CBP RELATIONS WITH CANADA AND MEXICO Baggage § 123.63 Examination of baggage from Canada or Mexico. (a) Opening vehicle or compartment to examine baggage. Customs officers are authorized...

"Open-Box" Approach to Measuring Fluorescence Quenching Using an iPad Screen and Digital SLR Camera

ERIC Educational Resources Information Center

Koenig, Michael H.; Yi, Eun P.; Sandridge, Matthew J.; Mathew, Alexander S.; Demas, James N.

2015-01-01

Fluorescence quenching is an analytical technique and a common undergraduate laboratory exercise. Unfortunately, a typical quenching experiment requires the use of an expensive fluorometer that measures the relative fluorescence intensity of a single sample in a closed compartment unseen by the experimenter. To overcome these shortcomings, we…

Comparative evaluation of different methods for calculation of cerebral blood flow (CBF) in nonanesthetized rabbits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Angelini, G.; Lanza, E.; Rozza Dionigi, A.

1983-05-01

The measurement of cerebral blood flow (CBF) by the extracranial detection of the radioactivity of /sup 133/Xe injected into an internal carotid artery has proved to be of considerable value for the investigation of cerebral circulation in conscious rabbits. Methods are described for calculating CBF from the curves of clearance of /sup 133/Xe, and include exponential analysis (two-component model), initial slope, and stochastic method. The different methods of curve analysis were compared in order to evaluate the fitness with the theoretical model. The initial slope and stochastic methods, compared with the biexponential model, underestimate the CBF by 35% and 46%more » respectively. Furthermore, the validity of recording the clearance curve for 10 min was tested by comparing these CBF values with those obtained from the whole curve. CBF values calculated with the shortened procedure are overestimated by 17%. A correlation exists between the ''10 min'' CBF values and the CBF calculated from the whole curve; in spite of that, the values are not accurate for limited animal populations or for single animals. The extent of the two main compartments into which the CBF is divided was also measured. There is no correlation between CBF values and the extent of the relative compartment. This fact suggests that these two parameters correspond to different biological entities.« less

Use of the cellular model of body composition to describe changes in body water compartments after total fasting, very low calorie diet and low calorie diet in obese men.

PubMed

Siervo, M; Faber, P; Gibney, E R; Lobley, G E; Elia, M; Stubbs, R J; Johnstone, A M

2010-05-01

The cellular model of body composition divides the body in body cell mass (BCM), extracellular solids and extracellular fluids. This model has been infrequently applied for the evaluation of weight loss (WL) programmes. (1) To assess changes in body compartments in obese men undergoing fasting, very low calorie diet (VLCD) and low calorie diet (LCD); (2) to evaluate two cellular models for the determination of changes in BCM, fat mass (FM) and body fluids. Three groups of six, obese men participated in a total fast (F) for 6 days, a VLCD (2.5 MJ per day) for 3 weeks or an LCD (5.2 MJ per day) for 6 weeks. Body composition was measured at baseline and after small ( approximately 5%) and moderate ( approximately 10%) WL. FM was measured using a four-compartment model. Total body water (TBW) and extracellular water (ECW) were, respectively, measured by deuterium and sodium bromide dilution and intracellular water (ICW) calculated by difference. Two cellular models were used to measure BCM, FM and body fluids distribution. After about 5%WL changes in TBW were F=-3.2+/-1.2 kg (P<0.01), VLCD=-1.2+/-0.6 kg (P<0.01), LCD=-0.3+/-0.9 kg(n.s.). The contribution of TBW to total body mass loss was indirectly associated with FM loss. ECW increased during fasting (+1.5+/-3.1 kg, n.s.), decreased during the VLCD (-2.0+/-1.5 kg, P<0.05) and remained unchanged at the end of the LCD (-0.3+/-1.6 kg, n.s.). ICW significantly decreased during fasting (-4.7+/-3.9 kg, P<0.05) but did not change in the LCD and VLCD groups. The loss of BCM was more significant in the fasting group and it was directly associated with changes in ICW. After a 6-day period of fasting we observed more ICW losses and less fat mobilization compared with VLCD and LCD. The cellular model of body composition is suitable for the characterization of changes in body fluids distribution during WL.

Antagonism of Sigma-1 Receptors Blocks Compulsive-Like Eating

PubMed Central

Cottone, Pietro; Wang, Xiaofan; Park, Jin Won; Valenza, Marta; Blasio, Angelo; Kwak, Jina; Iyer, Malliga R; Steardo, Luca; Rice, Kenner C; Hayashi, Teruo; Sabino, Valentina

2012-01-01

Binge eating disorder is an addiction-like disorder characterized by episodes of rapid and excessive food consumption within discrete periods of time which occur compulsively despite negative consequences. This study was aimed at determining whether antagonism of Sigma-1 receptors (Sig-1Rs) blocked compulsive-like binge eating. We trained male wistar rats to obtain a sugary, highly palatable diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day under fixed ratio 1 operant conditioning. Following intake stabilization, we evaluated the effects of the selective Sig-1R antagonist BD-1063 on food responding. Using a light/dark conflict test, we also tested whether BD-1063 could block the time spent and the food eaten in an aversive, open compartment, where the palatable diet was offered. Furthermore, we measured Sig-1R mRNA and protein expression in several brain areas of the two groups, 24 h after the last binge session. Palatable rats rapidly developed binge-like eating, escalating the 1 h intake by four times, and doubling the eating rate and the regularity of food responding, compared to Chow rats. BD-1063 dose-dependently reduced binge-like eating and the regularity of food responding, and blocked the increased eating rate in Palatable rats. In the light/dark conflict test, BD-1063 antagonized the increased time spent in the aversive compartment and the increased intake of the palatable diet, without affecting motor activity. Finally, Palatable rats showed reduced Sig-1R mRNA expression in prefrontal and anterior cingulate cortices, and a two-fold increase in Sig-1R protein expression in anterior cingulate cortex compared to control Chow rats. These findings suggest that the Sig-1R system may contribute to the neurobiological adaptations driving compulsive-like eating, opening new avenues of investigation towards pharmacologically treating binge eating disorder. PMID:22713906

ICAM-1 Binding Rhinoviruses A89 and B14 Uncoat in Different Endosomal Compartments

PubMed Central

Conzemius, Rick; Ganjian, Haleh; Blaas, Dieter

2016-01-01

ABSTRACT Human rhinovirus A89 (HRV-A89) and HRV-B14 bind to and are internalized by intercellular adhesion molecule 1 (ICAM-1); as demonstrated earlier, the RNA genome of HRV-B14 penetrates into the cytoplasm from endosomal compartments of the lysosomal pathway. Here, we show by immunofluorescence microscopy that HRV-A89 but not HRV-B14 colocalizes with transferrin in the endocytic recycling compartment (ERC). Applying drugs differentially interfering with endosomal recycling and with the pathway to lysosomes, we demonstrate that these two major-group HRVs productively uncoat in distinct endosomal compartments. Overexpression of constitutively active (Rab11-GTP) and dominant negative (Rab11-GDP) mutants revealed that uncoating of HRV-A89 depends on functional Rab11. Thus, two ICAM-1 binding HRVs are routed into distinct endosomal compartments for productive uncoating. IMPORTANCE Based on similarity of their RNA genomic sequences, the more than 150 currently known common cold virus serotypes were classified as species A, B, and C. The majority of HRV-A viruses and all HRV-B viruses use ICAM-1 for cell attachment and entry. Our results highlight important differences of two ICAM-1 binding HRVs with respect to their intracellular trafficking and productive uncoating; they demonstrate that serotypes belonging to species A and B, but entering the cell via the same receptors, direct the endocytosis machinery to ferry them along distinct pathways toward different endocytic compartments for uncoating. PMID:27334586

[Comparative analysis of the maternal motivation expression in WAG/Rij and Wistar rats in the place preference and open field tests].

PubMed

Dobriakova, Iu V; Tanaeva, K K; Dubynin, V A; Sarkisova, K Iu

2014-01-01

Maternal behavior in females of WAG/Rij and Wistar rats was compared in the place preference test from 2 to 8 days after delivery, as well as in the open field test from 4 to 6 days after delivery. In females of WAG/Rij rats compared with females of Wistar rats weaker expression of maternal motivation has been revealed in both tests: they spend less time in the compartment associated with pups. Moreover, in females of WAG/Rij rats, number of approaches to pups, number of pup-carryings and time spent with pups (time of contacts) were less than in females of Wistar rats. Reduced maternal motivation in females of WAG/Rij rats in the place preference test persisted in repeated testing, while in the open field test it was detected only in the first testing, indicating higher reliability of the place preference test for revealing inter-strain differences in the expression of maternal motivation. It is supposed that weaker expression of maternal behavior and preference is due to hypo-function of the mesolimbic dopaminergic bran system in WAG/Rij rats as a genetic model of depression associated with absence epilepsy.

HORIZONTAL BOILING REACTOR SYSTEM

DOEpatents

Treshow, M.

1958-11-18

Reactors of the boiling water type are described wherein water serves both as the moderator and coolant. The reactor system consists essentially of a horizontal pressure vessel divided into two compartments by a weir, a thermal neutronic reactor core having vertical coolant passages and designed to use water as a moderator-coolant posltioned in one compartment, means for removing live steam from the other compartment and means for conveying feed-water and water from the steam compartment to the reactor compartment. The system further includes auxiliary apparatus to utilize the steam for driving a turbine and returning the condensate to the feed-water inlet of the reactor. The entire system is designed so that the reactor is self-regulating and has self-limiting power and self-limiting pressure features.

Creatine pretreatment protects cortical axons from energy depletion in vitro

PubMed Central

Shen, Hua; Goldberg, Mark P.

2012-01-01

Creatine is a natural nitrogenous guanidino compound involved in bioenergy metabolism. Although creatine has been shown to protect neurons of the central nervous system (CNS) from experimental hypoxia/ischemia, it remains unclear if creatine may also protect CNS axons, and if the potential axonal protection depends on glial cells. To evaluate the direct impact of creatine on CNS axons, cortical axons were cultured in a separate compartment from their somas and proximal neurites using a modified two-compartment culture device. Axons in the axon compartment were subjected to acute energy depletion, an in vitro model of white matter ischemia, by exposure to 6 mM sodium azide for 30 min in the absence of glucose and pyruvate. Energy depletion reduced axonal ATP by 65%, depolarized axonal resting potential, and damaged 75% of axons. Application of creatine (10 mM) to both compartments of the culture at 24 h prior to energy depletion significantly reduced axonal damage by 50%. In line with the role of creatine in the bioenergy metabolism, this application also alleviated the axonal ATP loss and depolarization. Inhibition of axonal depolarization by blocking sodium influx with tetrodotoxin also effectively reduced the axonal damage caused by energy depletion. Further study revealed that the creatine effect was independent of glial cells, as axonal protection was sustained even when creatine was applied only to the axon compartment (free from somas and glial cells) for as little as 2 h. In contrast, application of creatine after energy depletion did not protect axons. The data provide the first evidence that creatine pretreatment may directly protect CNS axons from energy deficiency. PMID:22521466

Fiberfox: facilitating the creation of realistic white matter software phantoms.

PubMed

Neher, Peter F; Laun, Frederik B; Stieltjes, Bram; Maier-Hein, Klaus H

2014-11-01

Phantom-based validation of diffusion-weighted image processing techniques is an important key to innovation in the field and is widely used. Openly available and user friendly tools for the flexible generation of tailor-made datasets for the specific tasks at hand can greatly facilitate the work of researchers around the world. We present an open-source framework, Fiberfox, that enables (1) the intuitive definition of arbitrary artificial white matter fiber tracts, (2) signal generation from those fibers by means of the most recent multi-compartment modeling techniques, and (3) simulation of the actual MR acquisition that allows for the introduction of realistic MRI-related effects into the final image. We show that real acquisitions can be closely approximated by simulating the acquisition of the well-known FiberCup phantom. We further demonstrate the advantages of our framework by evaluating the effects of imaging artifacts and acquisition settings on the outcome of 12 tractography algorithms. Our findings suggest that experiments on a realistic software phantom might change the conclusions drawn from earlier hardware phantom experiments. Fiberfox may find application in validating and further developing methods such as tractography, super-resolution, diffusion modeling or artifact correction. Copyright © 2013 Wiley Periodicals, Inc.

Contamination control of the space shuttle Orbiter crew compartment

NASA Technical Reports Server (NTRS)

Bartelson, Donald W.

1986-01-01

Effective contamination control as applied to manned space flight environments is a discipline characterized and controlled by many parameters. An introduction is given to issues involving Orbiter crew compartment contamination control. An effective ground processing contamination control program is an essential building block to a successful shuttle mission. Personnel are required to don cleanroom-grade clothing ensembles before entering the crew compartment and follow cleanroom rules and regulations. Prior to crew compartment entry, materials and equipment must be checked by an orbiter integrity clerk stationed outside the white-room entrance for compliance to program requirements. Analysis and source identification of crew compartment debris studies have been going on for two years. The objective of these studies is to determine and identify particulate generating materials and activities in the crew compartment. Results show a wide spectrum of many different types of materials. When source identification is made, corrective action is implemented to minimize or curtail further contaminate generation.

Pharmacokinetics and tolerance of acyclovir, a new anti-herpesvirus agent, in humans.

PubMed Central

Laskin, O L; Longstreth, J A; Saral, R; de Miranda, P; Keeney, R; Lietman, P S

1982-01-01

The pharmacokinetics and tolerance of acyclovir administered intravenously in single doses of 2.5, 5.0, 10.0, and 15.0 mg/kg were studied in 13 volunteers. The mean concentrations (+/- standard deviations) at the end of infusion as measured by radioimmunoassay were 4.52 +/0 0.31, 8.28 +/- 2.61, 14.6 +/- 2.30, and 22.7 +/- 10.4 microgram/ml, respectively. Drug elimination during and after the infusion of acyclovir was well described by a two-compartment open model. The mean terminal plasma half-life for each of the groups was 2.85, 2.80, 3.30, and 2.38 h, respectively. Within 72 h after the start of the infusion, 70% of the administered drug was recovered in the urine as unchanged acyclovir. The renal clearance of acyclovir accounted for about 77% of the total clearance and was about threefold greater than the creatinine clearance. This confirms that acyclovir is eliminated predominantly by the kidneys in patients with normal renal function and suggests that renal secretion and glomerular filtration may both be involved. The only adverse effect found by clinical and laboratory monitoring was irritation at he intravenous site after extravasation (in two cases), which resolved without significant sequelae. PMID:7103443

A new statistical method for transfer coefficient calculations in the framework of the general multiple-compartment model of transport for radionuclides in biological systems.

PubMed

Garcia, F; Arruda-Neto, J D; Manso, M V; Helene, O M; Vanin, V R; Rodriguez, O; Mesa, J; Likhachev, V P; Filho, J W; Deppman, A; Perez, G; Guzman, F; de Camargo, S P

1999-10-01

A new and simple statistical procedure (STATFLUX) for the calculation of transfer coefficients of radionuclide transport to animals and plants is proposed. The method is based on the general multiple-compartment model, which uses a system of linear equations involving geometrical volume considerations. By using experimentally available curves of radionuclide concentrations versus time, for each animal compartment (organs), flow parameters were estimated by employing a least-squares procedure, whose consistency is tested. Some numerical results are presented in order to compare the STATFLUX transfer coefficients with those from other works and experimental data.

A review of models for near-field exposure pathways of chemicals in consumer products.

PubMed

Huang, Lei; Ernstoff, Alexi; Fantke, Peter; Csiszar, Susan A; Jolliet, Olivier

2017-01-01

Exposure to chemicals in consumer products has been gaining increasing attention, with multiple studies showing that near-field exposures from products is high compared to far-field exposures. Regarding the numerous chemical-product combinations, there is a need for an overarching review of models able to quantify the multiple transfers of chemicals from products used near-field to humans. The present review therefore aims at an in-depth overview of modeling approaches for near-field chemical release and human exposure pathways associated with consumer products. It focuses on lower-tier, mechanistic models suitable for life cycle assessments (LCA), chemical alternative assessment (CAA) and high-throughput screening risk assessment (HTS). Chemicals in a product enter the near-field via a defined "compartment of entry", are transformed or transferred to adjacent compartments, and eventually end in a "human receptor compartment". We first focus on models of physical mass transfers from the product to 'near-field' compartments. For transfers of chemicals from article interior, adequate modeling of in-article diffusion and of partitioning between article surface and air/skin/food is key. Modeling volatilization and subsequent transfer to the outdoor is crucial for transfers of chemicals used in the inner space of appliances, on object surfaces or directly emitted to indoor air. For transfers from skin surface, models need to reflect the competition between dermal permeation, volatilization and fraction washed-off. We then focus on transfers from the 'near-field' to 'human' compartments, defined as respiratory tract, gastrointestinal tract and epidermis, for which good estimates of air concentrations, non-dietary ingestion parameters and skin permeation are essential, respectively. We critically characterize for each exposure pathway the ability of models to estimate near-field transfers and to best inform LCA, CAA and HTS, summarizing the main characteristics of the potentially best-suited models. This review identifies large knowledge gaps for several near-field pathways and suggests research needs and future directions. Copyright © 2016 Elsevier B.V. All rights reserved.

Ex vivo culture platform for assessment of cartilage repair treatment strategies.

PubMed

Schwab, Andrea; Meeuwsen, Annick; Ehlicke, Franziska; Hansmann, Jan; Mulder, Lars; Smits, Anthal; Walles, Heike; Kock, Linda

2017-01-01

There is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone, which better represents the in vivo situation and enables supply of factors specific to the different needs of bone and cartilage. We investigated whether separation of the cartilage and bone compartments and/or culture media results in the maintenance of viability, structural and functional properties of cartilage tissue. Next, we evaluated for how long we can preserve cartilage matrix stability of osteochondral explants during long-term culture over 84 days. Finally, we determined the optimal defect size that does not show spontaneous self-healing in this culture system. It was demonstrated that separated compartments for cartilage and bone in combination with tissue-specific medium allow for long-term culture of osteochondral explants while maintaining cartilage viability, matrix tissue content, structure and mechanical properties for at least 56 days. Furthermore, we could create critical size cartilage defects of different sizes in the model. The osteochondral model represents a valuable preclinical ex vivo tool for studying clinically relevant cartilage therapies, such as cartilage biomaterials, for their regenerative potential, for evaluation of drug and cell therapies, or to study mechanisms of cartilage regeneration. It will undoubtedly reduce the number of animals needed for in vivo testing.

SPV: a JavaScript Signaling Pathway Visualizer.

PubMed

Calderone, Alberto; Cesareni, Gianni

2018-03-24

The visualization of molecular interactions annotated in web resources is useful to offer to users such information in a clear intuitive layout. These interactions are frequently represented as binary interactions that are laid out in free space where, different entities, cellular compartments and interaction types are hardly distinguishable. SPV (Signaling Pathway Visualizer) is a free open source JavaScript library which offers a series of pre-defined elements, compartments and interaction types meant to facilitate the representation of signaling pathways consisting of causal interactions without neglecting simple protein-protein interaction networks. freely available under Apache version 2 license; Source code: https://github.com/Sinnefa/SPV_Signaling_Pathway_Visualizer_v1.0. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js. sinnefa@gmail.com.

The Role of Skull Modeling in EEG Source Imaging for Patients with Refractory Temporal Lobe Epilepsy.

PubMed

Montes-Restrepo, Victoria; Carrette, Evelien; Strobbe, Gregor; Gadeyne, Stefanie; Vandenberghe, Stefaan; Boon, Paul; Vonck, Kristl; Mierlo, Pieter van

2016-07-01

We investigated the influence of different skull modeling approaches on EEG source imaging (ESI), using data of six patients with refractory temporal lobe epilepsy who later underwent successful epilepsy surgery. Four realistic head models with different skull compartments, based on finite difference methods, were constructed for each patient: (i) Three models had skulls with compact and spongy bone compartments as well as air-filled cavities, segmented from either computed tomography (CT), magnetic resonance imaging (MRI) or a CT-template and (ii) one model included a MRI-based skull with a single compact bone compartment. In all patients we performed ESI of single and averaged spikes marked in the clinical 27-channel EEG by the epileptologist. To analyze at which time point the dipole estimations were closer to the resected zone, ESI was performed at two time instants: the half-rising phase and peak of the spike. The estimated sources for each model were validated against the resected area, as indicated by the postoperative MRI. Our results showed that single spike analysis was highly influenced by the signal-to-noise ratio (SNR), yielding estimations with smaller distances to the resected volume at the peak of the spike. Although averaging reduced the SNR effects, it did not always result in dipole estimations lying closer to the resection. The proposed skull modeling approaches did not lead to significant differences in the localization of the irritative zone from clinical EEG data with low spatial sampling density. Furthermore, we showed that a simple skull model (MRI-based) resulted in similar accuracy in dipole estimation compared to more complex head models (based on CT- or CT-template). Therefore, all the considered head models can be used in the presurgical evaluation of patients with temporal lobe epilepsy to localize the irritative zone from low-density clinical EEG recordings.

Cerebrospinal Fluid Mechanics and Its Coupling to Cerebrovascular Dynamics

NASA Astrophysics Data System (ADS)

Linninger, Andreas A.; Tangen, Kevin; Hsu, Chih-Yang; Frim, David

2016-01-01

Cerebrospinal fluid (CSF) is not stagnant but displays fascinating oscillatory flow patterns inside the ventricular system and reversing fluid exchange between the cranial vault and spinal compartment. This review provides an overview of the current knowledge of pulsatile CSF motion. Observations contradicting classical views about its bulk production and clearance are highlighted. A clinical account of diseases of abnormal CSF flow dynamics, including hydrocephalus, syringomyelia, Chiari malformation type 1, and pseudotumor cerebri, is also given. We survey medical imaging modalities used to observe intracranial dynamics in vivo. Additionally, we assess the state of the art in predictive models of CSF dynamics. The discussion addresses open questions regarding CSF dynamics as they relate to the understanding and management of diseases.

Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide.

PubMed Central

Whiting, B; Lawrence, J R; Skellern, G G; Meier, J

1979-01-01

1. The metabolism and plasma kinetics of chlordiazepoxide have been determined in a group of volunteers and in a group of patients with acute alcohol intoxication. 2. Using the SAAM 26 non-linear least squares fitting programme, all chlordiazepoxide plasma concentration v time data following oral administration could be analysed in terms of a one-compartment open model with metabolic conversion of chlordiazepoxide to desmethylchlordiazepoxide. 3. Acutely intoxicated patients showed a prolonged elimination of chlordiazepoxide and a reduced clearance when compared with alcohol-free volunteers. The elimination of desmethylchlordiazepoxide, on the other hand, appeared to be faster in the alcoholics. 4. Alcohol exerts significant effects on the metabolism of chlordiazepoxide in acutely intoxicated patients. PMID:760747

Experimental investigation of an alternating evaporator duty refrigerator/freezer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lavanis, M.; Haider, I.; Radermacher, R.

1998-12-31

A bistable solenoid valve has been used to build an alternating evaporator duty (AED) domestic refrigerator/freezer. This refrigerator has two vapor compression refrigeration loops that share a common compressor, condenser, and suction line heat exchanger. Each of the refrigeration loops has an expansion device and evaporator. One evaporator is located in the fresh food compartment and the other is located in the freezer compartment. The bistable solenoid valve directs the flow of the refrigerant through one loop at a time. Only one of the two compartments is cooled at any given time. With this configuration, the food compartment is cooledmore » at a higher evaporator temperature than the freezer. Due to this, the energy efficiency of the refrigerator is improved by 8.5% over a conventional domestic refrigerator/freezer. Also, this cycle allows for completely independent temperature control of the freezer and fresh food compartments. There may be a penalty because this cycle does not allow for both loops to be simultaneously optimized. Isobutane was the only refrigerant used in this investigation.« less

The mechanics of cellular compartmentalization as a model for tumor spreading

NASA Astrophysics Data System (ADS)

Fritsch, Anatol; Pawlizak, Steve; Zink, Mareike; Kaes, Josef A.

2012-02-01

Based on a recently developed surgical method of Michael H"ockel, which makes use of cellular confinement to compartments in the human body, we study the mechanics of the process of cell segregation. Compartmentalization is a fundamental process of cellular organization and occurs during embryonic development. A simple model system can demonstrate the process of compartmentalization: When two populations of suspended cells are mixed, this mixture will eventually segregate into two phases, whereas mixtures of the same cell type will not. In the 1960s, Malcolm S. Steinberg formulated the so-called differential adhesion hypothesis which explains the segregation in the model system and the process of compartmentalization by differences in surface tension and adhesiveness of the interacting cells. We are interested in to which extend the same physical principles affect tumor growth and spreading between compartments. For our studies, we use healthy and cancerous breast cell lines of different malignancy as well as primary cells from human cervix carcinoma. We apply a set of techniques to study their mechanical properties and interactions. The Optical Stretcher is used for whole cell rheology, while Cell-cell-adhesion forces are directly measured with a modified AFM. In combination with 3D segregation experiments in droplet cultures we try to clarify the role of surface tension in tumor spreading.

Organic Pollutant Penetration through Fruit Polyester Skin: A Modified Three-compartment Diffusion Model

NASA Astrophysics Data System (ADS)

Li, Yungui; Li, Qingqing; Chen, Baoliang

2016-03-01

The surface of plants is covered by a continuous but heterogeneous cuticular membrane (CM). Serving as the first protective barrier, the uptake and transport behavior of organic pollutants at this interface continue to engage the research efforts of environmental chemist. To date, the contributions of cuticular components as a defense against the organic pollutants penetration remain unresolved. In this study, the unsteady-state penetration characteristics of phenanthrene (PHE) through isolated fruit CM was investigated. PHE penetration was differentiated by three cuticular compartments: epicuticular waxes (EW), cuticle proper (CP) and cuticular layer (CL). The driving force for PHE penetration was ascribed to the sharp concentration gradient built up endogenously by cuticular compartments with different lipophilic affinities. A modified penetration model was established and verified in terms of its general suitability for the hydrophobic chemicals and CMs of various plant species (apple, tomato and potato). The new three-compartment model demonstrates much higher accuracy in characterizing the uptake and transport behavior of semivolatile chemicals with fewer limitations in terms of environmental conditions and complexity (e.g., coexisting contaminants and temperature). This model could contribute to a more comprehensive understanding on the role of polymeric lipids in the organic pollutant sorption and transport into plants.

Organic Pollutant Penetration through Fruit Polyester Skin: A Modified Three-compartment Diffusion Model.

PubMed

Li, Yungui; Li, Qingqing; Chen, Baoliang

2016-03-24

The surface of plants is covered by a continuous but heterogeneous cuticular membrane (CM). Serving as the first protective barrier, the uptake and transport behavior of organic pollutants at this interface continue to engage the research efforts of environmental chemist. To date, the contributions of cuticular components as a defense against the organic pollutants penetration remain unresolved. In this study, the unsteady-state penetration characteristics of phenanthrene (PHE) through isolated fruit CM was investigated. PHE penetration was differentiated by three cuticular compartments: epicuticular waxes (EW), cuticle proper (CP) and cuticular layer (CL). The driving force for PHE penetration was ascribed to the sharp concentration gradient built up endogenously by cuticular compartments with different lipophilic affinities. A modified penetration model was established and verified in terms of its general suitability for the hydrophobic chemicals and CMs of various plant species (apple, tomato and potato). The new three-compartment model demonstrates much higher accuracy in characterizing the uptake and transport behavior of semivolatile chemicals with fewer limitations in terms of environmental conditions and complexity (e.g., coexisting contaminants and temperature). This model could contribute to a more comprehensive understanding on the role of polymeric lipids in the organic pollutant sorption and transport into plants.

Population pharmacokinetic/ pharmacodynamic modelling of eltrombopag in healthy volunteers and subjects with chronic liver disease

PubMed Central

Farrell, Colm; Hayes, Siobhan C; Wire, Mary; Zhang, Jianping

2014-01-01

Aims To characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of eltrombopag in chronic liver disease (CLD). Methods The PK/PD model was developed using data from 79 CLD patients using nonlinear mixed-effects modelling. Results The PK of eltrombopag were described by a two-compartment model with dual sequential first-order absorption. Gender, race and severity of CLD were predictors of the apparent clearance of eltrombopag. The PD of eltrombopag in CLD were adequately described by a four-compartment lifespan model, in which eltrombopag stimulated platelet precursor production rate. East Asian CLD patients were less sensitive to the stimulatory effect of eltrombopag. Following a daily dose regimen of 50 mg eltrombopag, the time to achieve peak platelet counts was longer for the CLD population compared with patients who had immune thrombocytopenic purpura, but was comparable to patients with hepatitis C. Likewise, it took a longer time for platelet counts to rebound back to baseline once eltrombopag treatment was discontinued. Conclusions The time course of the platelet response in CLD was different from that in immune thrombocytopenic purpura but comparable to that in hepatitis C. PMID:24117976

Water diffusion-exchange effect on the paramagnetic relaxation enhancement in off-resonance rotating frame

NASA Astrophysics Data System (ADS)

Zhang, Huiming; Xie, Yang; Ji, Tongyu

2007-06-01

The off-resonance rotating frame technique based on the spin relaxation properties of off-resonance T1 ρ can significantly increase the sensitivity of detecting paramagnetic labeling at high magnetic fields by MRI. However, the in vivo detectable dimension for labeled cell clusters/tissues in T1 ρ-weighted images is limited by the water diffusion-exchange between mesoscopic scale compartments. An experimental investigation of the effect of water diffusion-exchange between compartments on the paramagnetic relaxation enhancement of paramagnetic agent compartment is presented for in vitro/ in vivo models. In these models, the size of paramagnetic agent compartment is comparable to the mean diffusion displacement of water molecules during the long RF pulses that are used to generate the off-resonance rotating frame. The three main objectives of this study were: (1) to qualitatively correlate the effect of water diffusion-exchange with the RF parameters of the long pulse and the rates of water diffusion, (2) to explore the effect of water diffusion-exchange on the paramagnetic relaxation enhancement in vitro, and (3) to demonstrate the paramagnetic relaxation enhancement in vivo. The in vitro models include the water permeable dialysis tubes or water permeable hollow fibers embedded in cross-linked proteins gels. The MWCO of the dialysis tubes was chosen from 0.1 to 15 kDa to control the water diffusion rate. Thin hollow fibers were chosen to provide sub-millimeter scale compartments for the paramagnetic agents. The in vivo model utilized the rat cerebral vasculatures as a paramagnetic agent compartment, and intravascular agents (Gd-DTPA) 30-BSA were administrated into the compartment via bolus injections. Both in vitro and in vivo results demonstrate that the paramagnetic relaxation enhancement is predominant in the T1 ρ-weighted image in the presence of water diffusion-exchange. The T1 ρ contrast has substantially higher sensitivity than the conventional T1 contrast in detecting paramagnetic agents, especially at low paramagnetic agent volumetric fractions, low paramagnetic agent concentrations, and low RF amplitudes. Short pulse duration, short pulse recycle delay and efficient paramagnetic relaxation can reduce the influence of water diffusion-exchange on the paramagnetic enhancement. This study paves the way for the design of off-resonance rotating experiments to detect labeled cell clusters/tissue compartments in vivo at a sub-millimeter scale.

Describing the environmental fate of diuron in a tropical river catchment.

PubMed

Camenzuli, Louise; Scheringer, Martin; Gaus, Caroline; Ng, Carla A; Hungerbühler, Konrad

2012-12-01

The use of the herbicide diuron on sugarcane fields along the river catchments of the Great Barrier Reef (GBR) in Australia is an issue of concern due to high levels of diuron reported in the GBR lagoon, and has recently led to a restriction on the use of diuron during the 2011/12 wet season. An important question in this context is how much diuron is mobilised from the agricultural area by strong rainfall and floods in the wet season and transferred to the GBR lagoon. We have set up a multimedia chemical fate model for a tropical catchment to describe the fate of diuron within the Tully River catchment, Queensland, Australia. The model includes highly variable rainfall based on meteorological data from the Tully River catchment and a flood water compartment on top of the agricultural soil that is present during times for which floods were reported. The model is driven by diuron application data estimated for the Tully River catchment and is solved for time-dependent diuron concentrations in agricultural soil and seawater. Model results show that on average 25% of the diuron applied every year is transferred to the GBR lagoon with rainwater and flood water runoff. Diuron concentrations estimated for the seawater range from 0.1 ng/L to 12 ng/L and are in good agreement with concentrations measured in the GBR lagoon. The uncertainty of the diuron concentrations estimated for seawater is approximately a factor of two and mainly derives from uncertainty in the diuron degradation half-life in soil, properties of the soil compartment such as organic matter content, and the speed of the seawater current removing diuron dissolved in seawater from the seawater compartment of the model. Copyright © 2012 Elsevier B.V. All rights reserved.

Milrinone Pharmacokinetics and Pharmacodynamics in Neonates with Persistent Pulmonary Hypertension of the Newborn.

PubMed

Giaccone, Annie; Zuppa, Athena F; Sood, Beena; Cohen, Meryl S; O'Byrne, Michael L; Moorthy, Ganesh; Mathur, Amit; Kirpalani, Haresh

2017-07-01

Objective  To describe the pharmacokinetics and pharmacodynamics of milrinone in infants with persistent pulmonary hypertension of the newborn (PPHN) and to explore the impact of age on milrinone disposition. Design  Randomized, open label pilot study. Setting  Multicenter; level 3 and level 4 neonatal intensive care units. Patients  Six infants ≥34 weeks' gestational age and < 10 days of life with persistent hypoxemia receiving inhaled nitric oxide. Intervention  Intravenous milrinone lactate in one of two dosing regimens: (1) low dose, 20 mcg/kg bolus followed by 0.2 mcg/kg/minute, and (2) standard dose, 50 mcg/kg bolus followed by 0.5 mcg/kg/minute. Measurements and Main Results  The final structural model was a two-compartment disposition model with interindividual variability estimated on clearance (CL). The estimated value of CL is 7.65 mL/minute/3.4 kg (3.05 mL/minute/kg). The addition of age improved the precision of the CL estimate, and CL increased with chronological age in days. The oxygenation index was highly variable within each participant and improved with time. There were no observed safety concerns in either dosing group. Conclusion  The CL of milrinone in newborns with PPHN is reduced and increases with age. In this pilot study, we did not see significant pharmacodynamic or safety effects associated with drug exposure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Highly-accelerated quantitative 2D and 3D localized spectroscopy with linear algebraic modeling (SLAM) and sensitivity encoding

NASA Astrophysics Data System (ADS)

Zhang, Yi; Gabr, Refaat E.; Zhou, Jinyuan; Weiss, Robert G.; Bottomley, Paul A.

2013-12-01

Noninvasive magnetic resonance spectroscopy (MRS) with chemical shift imaging (CSI) provides valuable metabolic information for research and clinical studies, but is often limited by long scan times. Recently, spectroscopy with linear algebraic modeling (SLAM) was shown to provide compartment-averaged spectra resolved in one spatial dimension with many-fold reductions in scan-time. This was achieved using a small subset of the CSI phase-encoding steps from central image k-space that maximized the signal-to-noise ratio. Here, SLAM is extended to two- and three-dimensions (2D, 3D). In addition, SLAM is combined with sensitivity-encoded (SENSE) parallel imaging techniques, enabling the replacement of even more CSI phase-encoding steps to further accelerate scan-speed. A modified SLAM reconstruction algorithm is introduced that significantly reduces the effects of signal nonuniformity within compartments. Finally, main-field inhomogeneity corrections are provided, analogous to CSI. These methods are all tested on brain proton MRS data from a total of 24 patients with brain tumors, and in a human cardiac phosphorus 3D SLAM study at 3T. Acceleration factors of up to 120-fold versus CSI are demonstrated, including speed-up factors of 5-fold relative to already-accelerated SENSE CSI. Brain metabolites are quantified in SLAM and SENSE SLAM spectra and found to be indistinguishable from CSI measures from the same compartments. The modified reconstruction algorithm demonstrated immunity to maladjusted segmentation and errors from signal heterogeneity in brain data. In conclusion, SLAM demonstrates the potential to supplant CSI in studies requiring compartment-average spectra or large volume coverage, by dramatically reducing scan-time while providing essentially the same quantitative results.

Use of the light/dark test for anxiety in adult and adolescent male rats

PubMed Central

Arrant, Andrew E.; Schramm-Sapyta, Nicole L.; Kuhn, Cynthia M.

2014-01-01

The light/dark (LD) test is a commonly used rodent test of unconditioned anxiety-like behavior that is based on an approach/avoidance conflict between the drive to explore novel areas and an aversion to brightly lit, open spaces. We used the LD test to investigate developmental differences in behavior between adolescent (postnatal day (PN) 28–34) and adult (PN67–74) male rats. We investigated whether LD behavioral measures reflect anxiety-like behavior similarly in each age group using factor analysis and multiple regression. These analyses showed that time in the light compartment, percent distance in the light, rearing, and latency to emerge into the light compartment were measures of anxiety-like behavior in each age group, while total distance traveled and distance in the dark compartment provided indices of locomotor activity. We then used these measures to assess developmental differences in baseline LD behavior and the response to anxiogenic drugs. Adolescent rats emerged into the light compartment more quickly than adults and made fewer pokes into the light compartment. These age differences could reflect greater risk taking and less risk assessment in adolescent rats than adults. Adolescent rats were less sensitive than adults to the anxiogenic effects of the benzodiazepine inverse agonist N-methyl-β-carboline-3-carboxamide (FG-7142) and the α2 adrenergic antagonist yohimbine on anxiety-like behaviors validated by factor analysis, but locomotor variables were similarly affected. These data support the results of the factor analysis and indicate that GABAergic and noradrenergic modulation of LD anxiety-like behavior may be immature during adolescence. PMID:23721963

Estimation of the Number of Compartments Associated With the Apparent Diffusion Coefficient in MRI: The Theoretical and Experimental Investigations.

PubMed

Ashoor, Mansour; Khorshidi, Abdollah

2016-03-01

The goal of the present study was to estimate the number of compartments and the mean apparent diffusion coefficient (ADC) value with the use of the DWI signal curve. A useful new mathematic model that includes internal correlation among subcompartments with a distinct number of compartments was proposed. The DWI signal was simulated to estimate the approximate association between the number of subcompartments and the molecular density, with density corresponding to the ratio of the ADC values of the compartments, as determined using the Monte Carlo method. Various factors, such as energy depletion, temperature, intracellular water accumulation, changes in the tortuosity of the extracellular diffusion paths, and changes in cell membrane permeability, have all been implicated as factors contributing to changes in the ADC of water (ADCw); therefore, one may consider them as pseudocompartments in the new model proposed in this study. The lower the coefficient is, the lower the contribution of the compartment to the net signal will be. The results of the simulation indicate that when the number of compartments increases, the signal will become significantly lower, because the gradient factor (i.e., the b value) will increase. In other words, the signal curve is approximately linear at all b values when the number of compartments in which the tissues have been severely damaged is low; however, when the number of compartments is high, the curve will become constant at high b values, and the perfusion parameters will prevail on the diffusion parameters at low b values. Therefore, normal tissues will be investigated when the number of compartments and the ADC values are high and the b values are low, whereas damaged tissues will be evaluated when the number of compartments and the ADC values are low and the b values are high. The present study investigates damaged tissues at high b values for which the effect of eddy currents will also be compensated. These b values will probably be used in functional MRI.

Arbuscules of vesicular-arbuscular mycorrhizal fungi inhabit an acidic compartment within plant roots.

PubMed

Guttenberger, M

2000-08-01

The most widespread type of mycorrhiza is the so-called vesicular-arbuscular mycorrhiza. In this endomycorrhiza, fungal hyphae penetrate plant cell walls in the root cortex. There they form densely branched arbuscules. Fungus and plant plasma membrane are separated by a common interfacial apoplast. The pH of the compartment between the symbionts is of pivotal importance for nutrient transfer. Histochemical experiments were conducted to check for an acidic nature of the interface in the model system Glomus versiforme (Karst.) Berch-Allium porrum L. Two chemically different acidotropic dyes (neutral red and LysoSensor Green DND-189) stained the arbuscules intensely. The staining of arbuscules could be eliminated by addition of the protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP) or treatments leading to membrane rupture. Therefore, the staining of the arbuscules was based on the ion-trap mechanism, which indicates acidic, membrane-bound compartments. Microscopic examination of stained arbuscules at high optical resolution revealed a peripheral accumulation of the dye. Since plasmolysis rapidly destained the arbuscules, it is concluded that the dyes accumulate in the arbuscular interface, indicating the highly acidic nature of this compartment. The findings are discussed with respect to their relevance for the nutrient transfer in mycorrhizas. In addition, evidence for a discontinuity in the arbuscular interface between the stem and the branches of the arbuscule is given.

In vitro and in vivo evaluation of drug-drug interaction between dabigatran and proton pump inhibitors.

PubMed

Ollier, Edouard; Hodin, Sophie; Basset, Thierry; Accassat, Sandrine; Bertoletti, Laurent; Mismetti, Patrick; Delavenne, Xavier

2015-12-01

To quantify the drug-drug interactions between dabigatran etexilate (DE) and proton pump inhibitors (PPI) and in particular the role of P-gp activity modulation. In the first part of the study, efflux ratios of DE were evaluated using the caco-2 cell line in the presence of pantoprazole, omeprazole, rabeprazole, lansoprazole and ciclosporin A (positive control). The two PPI that reduced the efflux ratio of dabigatran to the greatest and least extent, respectively, were used during the second part of the study, comprising a single-centre, randomised, open-label study with an incomplete Latin square design. Nine healthy volunteers received DE (150 mg) alone, DE (150 mg) with the first PPI and DE (150 mg) with the second PPI in randomised sequence. Dabigatran plasma concentration and thrombin time were measured in blood samples withdrawn at 11 time points after each treatment. Models were built using a nonlinear mixed-effect modelling approach. Omeprazole and rabeprazole were the two PPI that reduced the efflux ratio of DE least and most, respectively. The PK model was based on an inverse Gaussian absorption process with one compartment. The relationship between dabigatran concentration and thrombin time was considered linear. Some PK profiles had dramatically low concentration values due to poor absorption. These profiles were clustered using a between subject model mixture with interoccasion variability. The concomitant administration of PPI did not significantly change dabigatran pharmacokinetics. DE is subject to high absorption variability, precluding evaluation of the effect of PPI on its pharmacokinetics. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Delivery of chemotherapeutics across the blood-brain barrier: challenges and advances.

PubMed

Doolittle, Nancy D; Muldoon, Leslie L; Culp, Aliana Y; Neuwelt, Edward A

2014-01-01

The blood-brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2-26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD. © 2014 Elsevier Inc. All rights reserved.

Exposure to Novelty Weakens Conditioned Fear in Long-Evans Rats

ERIC Educational Resources Information Center

Anderson, Matthew J.; Burpee, Tara E.; Wall, Matthew J.; McGraw, Justin J.

2013-01-01

The present study sought to determine whether post-training exposure to a novel or familiar object, encountered in either the location of the original fear conditioning (black compartment of a passive avoidance {PA} chamber) or in a neutral setting (open field where initial object training had occurred) would prove capable of reducing fear at…

Spectroscopic Biomarkers for Monitoring Wound Healing and Infection in Wounds

DTIC Science & Technology

2015-06-01

thrombotic, and fat embolism , and compartment syndrome. In the treatment of such complex traumatic injuries, improved assessment of global and...injuries include traumatic amputations, open fractures , crush injuries, burns, acute vascular disruption, blastwave-associated pressure injuries, air...specimens, lesion development begins adjacent to injured muscle or fat and is surrounded by fibrous connective tissue heavily besieged with

46 CFR 25.40-1 - Tanks and engine spaces.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Tanks and engine spaces. 25.40-1 Section 25.40-1...-1 Tanks and engine spaces. (a) All motorboats or motor vessels, except open boats and as provided in..., and other spaces to which explosive or flammable gases and vapors from these compartments may flow...

46 CFR 25.40-1 - Tanks and engine spaces.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Tanks and engine spaces. 25.40-1 Section 25.40-1...-1 Tanks and engine spaces. (a) All motorboats or motor vessels, except open boats and as provided in..., and other spaces to which explosive or flammable gases and vapors from these compartments may flow...

46 CFR 25.40-1 - Tanks and engine spaces.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Tanks and engine spaces. 25.40-1 Section 25.40-1...-1 Tanks and engine spaces. (a) All motorboats or motor vessels, except open boats and as provided in..., and other spaces to which explosive or flammable gases and vapors from these compartments may flow...

46 CFR 25.40-1 - Tanks and engine spaces.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Tanks and engine spaces. 25.40-1 Section 25.40-1...-1 Tanks and engine spaces. (a) All motorboats or motor vessels, except open boats and as provided in..., and other spaces to which explosive or flammable gases and vapors from these compartments may flow...

46 CFR 25.40-1 - Tanks and engine spaces.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Tanks and engine spaces. 25.40-1 Section 25.40-1...-1 Tanks and engine spaces. (a) All motorboats or motor vessels, except open boats and as provided in..., and other spaces to which explosive or flammable gases and vapors from these compartments may flow...

A method to quantify at late imaging a release rate of 18F-FDG in tissues.

PubMed

Laffon, Eric; Allard, Michèle; Marthan, Roger; Ducassou, Dominique

2005-08-01

This theoretical work shows that the rate constant for the (18)F-FDG release in tissues can be assessed without needing any arterial blood sampling. The method requires that the clearance of (18)F-FDG from plasma has occurred, whereas (18)F-FDG is still present in the tissue. This condition can be met dating from 3 h after (18)F-FDG injection, when hydration and/or phlorizin injection are applied after the routine static acquisition. The release rate constant can be obtained from a graphical analysis performed at the later decreasing phase of the tissue tracer activity. A two-compartment and a three-compartment model are developed, both in accordance with one another. To cite this article: E. Laffon et al., C. R. Biologies 328 (2005).

Spatial organization of chromatin domains and compartments in single chromosomes

NASA Astrophysics Data System (ADS)

Wang, Siyuan; Su, Jun-Han; Beliveau, Brian; Bintu, Bogdan; Moffitt, Jeffrey; Wu, Chao-Ting; Zhuang, Xiaowei

The spatial organization of chromatin critically affects genome function. Recent chromosome-conformation-capture studies have revealed topologically associating domains (TADs) as a conserved feature of chromatin organization, but how TADs are spatially organized in individual chromosomes remains unknown. Here, we developed an imaging method for mapping the spatial positions of numerous genomic regions along individual chromosomes and traced the positions of TADs in human interphase autosomes and X chromosomes. We observed that chromosome folding deviates from the ideal fractal-globule model at large length scales and that TADs are largely organized into two compartments spatially arranged in a polarized manner in individual chromosomes. Active and inactive X chromosomes adopt different folding and compartmentalization configurations. These results suggest that the spatial organization of chromatin domains can change in response to regulation.

Imaging regional renal function parameters using radionuclide tracers

NASA Astrophysics Data System (ADS)

Qiao, Yi

A compartmental model is given for evaluating kidney function accurately and noninvasively. This model is cast into a parallel multi-compartment structure and each pixel region (picture element) of kidneys is considered as a single kidney compartment. The loss of radionuclide tracers from the blood to the kidney and from the kidney to the bladder are modelled in great detail. Both the uptake function and the excretion function of the kidneys can be evaluated pixel by pixel, and regional diagnostic information on renal function is obtained. Gamma Camera image data are required by this model and a screening test based renal function measurement is provided. The regional blood background is subtracted from the kidney region of interest (ROI) and the kidney regional rate constants are estimated analytically using the Kuhn-Pucker multiplier method in convex programming by considering the input/output behavior of the kidney compartments. The detailed physiological model of the peripheral compartments of the system, which is not available for most radionuclide tracers, is not required in the determination of the kidney regional rate constants and the regional blood background factors within the kidney ROI. Moreover, the statistical significance of measurements is considered to assure the improved statistical properties of the estimated kidney rate constants. The relations between various renal function parameters and the kidney rate constants are established. Multiple renal function measurements can be found from the renal compartmental model. The blood radioactivity curve and the regional (or total) radiorenogram determining the regional (or total) summed behavior of the kidneys are obtained analytically with the consideration of the statistical significance of measurements using convex programming methods for a single peripheral compartment system. In addition, a new technique for the determination of 'initial conditions' in both the blood compartment and the kidney compartment is presented. The blood curve and the radiorenogram are analyzed in great detail and a physiological analysis from the radiorenogram is given. Applications of Kuhn-Tucker multiplier methods are illustrated for the renal compartmental model in the field of nuclear medicine. Conventional kinetic data analysis methods, the maximum likehood method, and the weighted integration method are investigated and used for comparisons. Moreover, the effect of the blood background subtraction is shown by using the gamma camera images in man. Several functional images are calculated and the functional imaging technique is applied for evaluating renal function in man quantitatively and visually and compared with comments from a physician.

Modeling of circulating fluised beds for post-combustion carbon capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, A.; Shadle, L.; Miller, D.

2011-01-01

A compartment based model for a circulating fluidized bed reactor has been developed based on experimental observations of riser hydrodynamics. The model uses a cluster based approach to describe the two-phase behavior of circulating fluidized beds. Fundamental mass balance equations have been derived to describe the movement of both gas and solids though the system. Additional work is being performed to develop the correlations required to describe the hydrodynamics of the system. Initial testing of the model with experimental data shows promising results and highlights the importance of including end effects within the model.

Lisdexamfetamine reduces the compulsive and perseverative behaviour of binge-eating rats in a novel food reward/punished responding conflict model.

PubMed

Heal, David J; Goddard, Simon; Brammer, Richard J; Hutson, Peter H; Vickers, Steven P

2016-07-01

Compulsive and perseverative behaviour in binge-eating, female, Wistar rats was investigated in a novel food reward/punished responding conflict model. Rats were trained to perform the conditioned avoidance response task. When proficient, the paradigm was altered to a food-associated conflict test by placing a chocolate-filled jar (empty jar for controls) in one compartment of the shuttle box. Entry into the compartment with the jar triggered the conditioning stimulus after a variable interval, and foot-shock 10 seconds later if the rat did not leave. Residence in the 'safe' compartment with no jar did not initiate trials or foot-shocks. By frequently entering the chocolate-paired compartment, binge-eating rats completed their 10 trials more quickly than non-binge controls. Binge-eating rats spent a greater percentage of the session in the chocolate-paired compartment, received foot-shocks more frequently, and tolerated foot-shocks for longer periods; all consistent with compulsive and perseverative behaviour. The d-amphetamine prodrug, lisdexamfetamine, has recently received US approval for the treatment of moderate to severe binge-eating disorder in adults. Lisdexamfetamine (0.8 mg/kg po [d-amphetamine base]) decreased chocolate consumption by binge-eating rats by 55% and markedly reduced compulsive and perseverative responding in the model. These findings complement clinical results showing lisdexamfetamine reduced compulsiveness scores in subjects with binge-eating disorder. © The Author(s) 2016.

Synchronous temperature rate control and apparatus for refrigeration with reduced energy consumption

DOEpatents

Gomes, Alberto Regio; Keres, Stephen L.; Kuehl, Steven J.; Litch, Andrew D.; Richmond, Peter J.; Wu, Guolian

2015-09-22

A refrigerator appliance configuration, and associated methods of operation, for an appliance with a controller, a condenser, at least one evaporator, a compressor, and two refrigeration compartments. The configuration may be equipped with a variable-speed or variable-capacity compressor, variable speed evaporator or compartment fans, a damper, and/or a dual-temperature evaporator with a valve system to control flow of refrigerant through one or more pressure reduction devices. The controller, by operation of the compressor, fans, damper and/or valve system, depending on the appliance configuration, synchronizes alternating cycles of cooling each compartment to a temperature approximately equal to the compartment set point temperature.

Ex-ORISKANY Artificial Reef Project: Ecological Risk Assessment

DTIC Science & Technology

2006-01-25

preferences used by PRAM and the Trophic Level determined by diet for each compartment modeled in the food chain...grouping organisms according to their habitat and diet preferences , PRAM also provided output to evaluate exposure point concentrations for the pelagic...dietary preferences used by PRAM (version 1.4C) and the Trophic Level determined by diet for each compartment modeled in the food chain. PRAM Default

EMERGING TECHNOLOGY BULLETIN: ELECTROKINETIC SOIL PROCESSING

EPA Science Inventory

Electrokinetic Soil Processing (or Electrokinetic Remediation) uses two series of electrodes (anodes and cathodes) positioned inside compartments that allow egress and ingress of pore fluids to the porous media. The compartments are filled with water or other process fluids and ...

Isolation of the Lateral Border Recycling Compartment using a diaminobenzidine-induced density shift

PubMed Central

Sullivan, David P.; Rüffer, Claas; Muller, William A.

2014-01-01

The migration of leukocytes across the endothelium and into tissue is critical to mounting an inflammatory response. The Lateral Border Recycling Compartment (LBRC), a complex vesicular-tubule invagination of the plasma membrane found at endothelial cell borders, plays an important role in the this process. Although a few proteins have been shown to be present in the LBRC, no unique marker is known. Here we detail methods that can be used to characterize a subcellular compartment that lacks an identifying marker. Initial characterization of the LBRC was performed using standard subcellular fractionation with sucrose gradients and took advantage of the observation that the compartment migrated at a lower density than other membrane compartments. To isolate larger quantities of the compartment, we modified a classic technique known as a diaminobenzidine (DAB)-induced density shift. The DAB-induced density shift allowed for specific isolation of membranes labeled with HRP conjugated antibody. Because the LBRC could be differentially labeled at 4°C and 37°C, we were able to identify proteins that are enriched in the compartment, despite lacking a unique marker. These methods serve as a model to others studying poorly characterized compartments and organelles and are applicable to a wide variety of biological systems. PMID:24915828

Bioavailability of bromhexine tablets and preliminary pharmacokinetics in humans.

PubMed

Bechgaard, E; Nielsen, A

1982-01-01

The absorption of bromhexine from Bromhexin tablets 8 mg, DAK has been compared with that from Bisolvon tablets 8 mg, Boehringer Ingelheim, in a two-way complete crossover study. Four tablets of each of the two bromhexine products, corresponding to a single dose of 32 mg of bromhexine hydrochloride (77.6 mumol), was administered to each of the 10 volunteers. The plasma concentration was followed over the 4-hour period following each administration. By means of Pratt's test for paired data no statistically significant difference (p greater than 0.10) between the two products was found with respect to maximum plasma concentration (89 and 84 nmol.1(-1), respectively), the times for their occurrence (1.3 and 1.0 h, respectively), and the area under the plasma concentration-time curves (140 and 132 nmol.1(-1).h, respectively). It is concluded that Bromhexin, DAK and Bisolvon are bioequivalent. Provisional pharmacokinetic data for bromhexine, after oral administration, in man were obtained. The first-pass effect and the biological half-life were estimated by combining plasma and 30 h urine data from four of the volunteers. The first-pass effect was estimated to be c. 75 per cent, the biological half-life to be c. 6 h, and c. 0.1 per cent of the dose was found as unmetabolized bromhexine in the urine. The data indicate that the pharmacokinetics of bromhexine may be described as a two-compartment open model.

Population pharmacokinetics and pharmacodynamics of bivalirudin in young healthy Chinese volunteers.

PubMed

Zhang, Dong-mei; Wang, Kun; Zhao, Xia; Li, Yun-fei; Zheng, Qing-shan; Wang, Zi-ning; Cui, Yi-min

2012-11-01

To investigate the population pharmacokinetics (PK) and pharmacodynamics (PD) of bivalirudin, a synthetic bivalent direct thrombin inhibitor, in young healthy Chinese subjects. Thirty-six young healthy volunteers were randomly assigned into 4 groups received bivalirudin 0.5 mg/kg, 0.75 mg/kg, and 1.05 mg/kg intravenous bolus, 0.75 mg/kg intravenous bolus followed by 1.75 mg/kg intravenous infusion per hour for 4 h. Blood samples were collected to measure bivalirudin plasma concentration and activated clotting time (ACT). Population PK-PD analysis was performed using the nonlinear mixed-effects model software NONMEM. The final models were validated with bootstrap and prediction-corrected visual predictive check (pcVPC) approaches. The final PK model was a two-compartment model without covariates. The typical PK population values of clearance (CL), apparent distribution volume of the central-compartment (V(1)), inter-compartmental clearance (Q) and apparent distribution volume of the peripheral compartment (V(2)) were 0.323 L·h(-1)·kg(-1), 0.086 L/kg, 0.0957 L·h(-1)·kg(-1), and 0.0554 L/kg, respectively. The inter-individual variabilities of these parameters were 14.8%, 24.2%, fixed to 0% and 15.6%, respectively. The final PK-PD model was a sigmoid E(max) model without the Hill coefficient. In this model, a covariate, red blood cell count (RBC(*)), had a significant effect on the EC(50) value. The typical PD population values of maximum effect (E(max)), EC(50), baseline ACT value (E(0)) and the coefficient of RBC(*) on EC(50) were 318 s, 2.44 mg/L, 134 s and 1.70, respectively. The inter-individual variabilities of E(max), EC(50), and E(0) were 6.80%, 46.4%, and 4.10%, respectively. Population PK-PD models of bivalirudin in healthy young Chinese subjects have been developed, which may provide a reference for future use of bivalirudin in China.

Disposition of pentachlorophenol in rainbow trout (Salmo gairdneri ): Effect of inhibition of metabolism

USGS Publications Warehouse

Stehly, G.R.; Hayton, W.L.

1989-01-01

The accumulation kinetics of pentachlorophenol (PCP) were investigated in rainbow trout (Salmo gairdneri ) in the absence and presence of 25 mg/l salicylamide, an inhibitor of PCP metabolism. After exposure to 5 mu g/l PCP over 1-96 h, the amount of PCP in the whole fish, its concentration in water and the total amount of metabolites (water, whole fish and bile) were measured. Equations for these variables, based on a two compartment pharmacokinetic model, were fitted simultaneously to the data using the computer program NONLIN, which uses an iterative nonlinear least squares technique. Salicylamide decreased the metabolic clearance of PCP, which resulted in an increase in the bioconcentration factor (BCF); this increase was partially offset by a salicylamide-induced decrease in the apparent volume of distribution of PCP. A clearance-volume compartment model permitted partitioning of the BCF in terms of the underlying physiologic and biochemical processes (uptake clearance, metabolic clearance and apparent volume of distribution).

Minimum energy control for a two-compartment neuron to extracellular electric fields

NASA Astrophysics Data System (ADS)

Yi, Guo-Sheng; Wang, Jiang; Li, Hui-Yan; Wei, Xi-Le; Deng, Bin

2016-11-01

The energy optimization of extracellular electric field (EF) stimulus for a neuron is considered in this paper. We employ the optimal control theory to design a low energy EF input for a reduced two-compartment model. It works by driving the neuron to closely track a prescriptive spike train. A cost function is introduced to balance the contradictory objectives, i.e., tracking errors and EF stimulus energy. By using the calculus of variations, we transform the minimization of cost function to a six-dimensional two-point boundary value problem (BVP). Through solving the obtained BVP in the cases of three fundamental bifurcations, it is shown that the control method is able to provide an optimal EF stimulus of reduced energy for the neuron to effectively track a prescriptive spike train. Further, the feasibility of the adopted method is interpreted from the point of view of the biophysical basis of spike initiation. These investigations are conducive to designing stimulating dose for extracellular neural stimulation, which are also helpful to interpret the effects of extracellular field on neural activity.

[The structure of the gastric mucosa of the llamas (Lama guanocoe and Lama lamae). I. Forestomach].

PubMed

Luciano, L; Voss-Wermbter, G; Behnke, M; von Engelhardt, W; Reale, E

1979-01-01

The mucous membrane of the first and second compartments (ventral regions) as well as of the third compartment of Lama guanacoe and Lama lamae stomach shows tubular glands opening into pits. Below the surface epithelium blood capillaries of the fenestrated type form a regular network, each mesh of which surrounds a gastric pit. From a morphological point of view (thin section and freeze-fracture replicas) the columnar cells of the surface epithelium and those of the pits closest to the capillaries are largely similar to the epithelial cells of the rabbit gallbladder. This similarity suggests that at the level of the columnar cells sodium-dependent water reabsorption occurs. This reabsorption has already been demonstrated in the abovementioned compartments by physiological methods. The surface and foveolae epithelial cells as well as some cells of the tubular glands have a secretory function. Their secretory granules contain mucosubstances, as indicated by light-(PAS- and Alcian blue reactions) and electron microscopic (PA-TCH-Ag-reaction) histochemistry. The secretory granules originate from the Golgi complex which shows a positive histochemical reaction in its innermost sacculi at the electron microscope level. Endocrine cells (s. second part of this investigation) are rare. The mucosal membrane of each muscular lip separating the glandular sacs in the first compartment shows a stratified, not keratinized, squamous epithelium.

Ketone bodies and two-compartment tumor metabolism

PubMed Central

Martinez-Outschoorn, Ubaldo E.; Lin, Zhao; Whitaker-Menezes, Diana; Howell, Anthony; Lisanti, Michael P.; Sotgia, Federica

2012-01-01

We have previously suggested that ketone body metabolism is critical for tumor progression and metastasis. Here, using a co-culture system employing human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts, we provide new evidence to directly support this hypothesis. More specifically, we show that the enzymes required for ketone body production are highly upregulated within cancer-associated fibroblasts. This appears to be mechanistically controlled by the stromal expression of caveolin-1 (Cav-1) and/or serum starvation. In addition, treatment with ketone bodies (such as 3-hydroxy-butyrate, and/or butanediol) is sufficient to drive mitochondrial biogenesis in human breast cancer cells. This observation was also validated by unbiased proteomic analysis. Interestingly, an MCT1 inhibitor was sufficient to block the onset of mitochondrial biogenesis in human breast cancer cells, suggesting a possible avenue for anticancer therapy. Finally, using human breast cancer tumor samples, we directly confirmed that the enzymes associated with ketone body production (HMGCS2, HMGCL and BDH1) were preferentially expressed in the tumor stroma. Conversely, enzymes associated with ketone re-utilization (ACAT1) and mitochondrial biogenesis (HSP60) were selectively associated with the epithelial tumor cell compartment. Our current findings are consistent with the “two-compartment tumor metabolism” model. Furthermore, they suggest that we should target ketone body metabolism as a new area for drug discovery, for the prevention and treatment of human cancers. PMID:23082721

The two-pore channel TPC1 is required for efficient protein processing through early and recycling endosomes.

PubMed

Castonguay, Jan; Orth, Joachim H C; Müller, Thomas; Sleman, Faten; Grimm, Christian; Wahl-Schott, Christian; Biel, Martin; Mallmann, Robert Theodor; Bildl, Wolfgang; Schulte, Uwe; Klugbauer, Norbert

2017-08-30

Two-pore channels (TPCs) are localized in endo-lysosomal compartments and assumed to play an important role for vesicular fusion and endosomal trafficking. Recently, it has been shown that both TPC1 and 2 were required for host cell entry and pathogenicity of Ebola viruses. Here, we investigate the cellular function of TPC1 using protein toxins as model substrates for distinct endosomal processing routes. Toxin uptake and activation through early endosomes but not processing through other compartments were reduced in TPC1 knockout cells. Detailed co-localization studies with subcellular markers confirmed predominant localization of TPC1 to early and recycling endosomes. Proteomic analysis of native TPC1 channels finally identified direct interaction with a distinct set of syntaxins involved in fusion of intracellular vesicles. Together, our results demonstrate a general role of TPC1 for uptake and processing of proteins in early and recycling endosomes, likely by providing high local Ca 2+ concentrations required for SNARE-mediated vesicle fusion.

Air-displacement plethysmography pediatric option in 2-6 years old using the four-compartment model as a criterion method.

PubMed

Fields, David A; Allison, David B

2012-08-01

The objective of this study was to determine the accuracy, precision, bias, and reliability of percent fat (%fat) determined by air-displacement plethysmography (ADP) with the pediatric option against the four-compartment model in 31 children (4.1 ± 1.2 years, 103.3 ± 10.2 cm, 17.5 ± 3.4 kg). %Fat was determined by (BOD POD Body Composition System; COSMED USA, Concord, CA) with the pediatric option. Total body water (TBW) was determined by isotope dilution ((2)H(2)O; 0.2 g/kg) while bone mineral was determined by dual-energy X-ray absorptiometry (DXA) (Lunar iDXA v13.31; GE, Fairfield, CT and analyzed using enCore 2010 software). The four-compartment model by Lohman was used as the criterion measure of %fat. The regression for %fat by ADP vs. %fat by the four-compartment model did not deviate from the line of identity where: y = 0.849(x) + 4.291. ADP explained 75.2% of the variance in %fat by the four-compartment model while the standard error of the estimate (SEE) was 2.09 %fat. The Bland-Altman analysis showed %fat by ADP did not exhibit any bias across the range of fatness (r = 0.04; P = 0.81). The reliability of ADP was assessed by the coefficient of variation (CV), within-subject SD, and Cronbach's α. The CV was 3.5%, within-subject SD was 0.9%, and Cronbach's α was 0.95. In conclusion, ADP with the pediatric option is accurate, precise, reliable, and without bias in estimating %fat in children 2-6 years old.

Prediction of water loss and viscoelastic deformation of apple tissue using a multiscale model.

PubMed

Aregawi, Wondwosen A; Abera, Metadel K; Fanta, Solomon W; Verboven, Pieter; Nicolai, Bart

2014-11-19

A two-dimensional multiscale water transport and mechanical model was developed to predict the water loss and deformation of apple tissue (Malus × domestica Borkh. cv. 'Jonagold') during dehydration. At the macroscopic level, a continuum approach was used to construct a coupled water transport and mechanical model. Water transport in the tissue was simulated using a phenomenological approach using Fick's second law of diffusion. Mechanical deformation due to shrinkage was based on a structural mechanics model consisting of two parts: Yeoh strain energy functions to account for non-linearity and Maxwell's rheological model of visco-elasticity. Apparent parameters of the macroscale model were computed from a microscale model. The latter accounted for water exchange between different microscopic structures of the tissue (intercellular space, the cell wall network and cytoplasm) using transport laws with the water potential as the driving force for water exchange between different compartments of tissue. The microscale deformation mechanics were computed using a model where the cells were represented as a closed thin walled structure. The predicted apparent water transport properties of apple cortex tissue from the microscale model showed good agreement with the experimentally measured values. Deviations between calculated and measured mechanical properties of apple tissue were observed at strains larger than 3%, and were attributed to differences in water transport behavior between the experimental compression tests and the simulated dehydration-deformation behavior. Tissue dehydration and deformation in the high relative humidity range ( > 97% RH) could, however, be accurately predicted by the multiscale model. The multiscale model helped to understand the dynamics of the dehydration process and the importance of the different microstructural compartments (intercellular space, cell wall, membrane and cytoplasm) for water transport and mechanical deformation.

Dissociation of Color and Figure-Ground Effects in the Watercolor Illusion

PubMed Central

von der Heydt, Rüdiger; Pierson, Rachel

2005-01-01

Two phenomena can be observed in the watercolor illusion: illusory color spreading and figure-ground organization. We performed experiments to determine whether the figure-ground effect is a consequence of the color illusion or due to an independent mechanism. Subjects were tested with displays consisting of six adjacent compartments, three that generated the illusion alternating with three that served for comparison. In a first set of experiments, the illusory color was measured by finding the matching physical color in the alternate compartments. Figureness (probability of ‘figure’ responses, 2AFC) of the watercolor compartments was then determined with and without the matching color in the alternate compartments. The color match reduced figureness, but did not abolish it. There was a range of colors in which the watercolor compartments dominated as figures over the alternate compartments although the latter appeared more saturated in color. In another experiment, the effect of tinting alternate compartments was measured in displays without watercolor illusion. Figureness increased with color contrast, but its value at the equivalent contrast fell short of the figureness value obtained for the watercolor pattern. Thus, in both experiments figureness produced by the watercolor pattern was stronger than expected from the color effect, suggesting independent mechanisms. Considering the neurophysiology, we propose that the color illusion follows from the principles of representation of surface color in the visual cortex, while the figure-ground effect results from two mechanisms of border ownership assignment, one that is sensitive to asymmetric shape of edge profile, the other to consistency of color borders. PMID:16862843

An assessment of the trophic structure of the Bay of Biscay continental shelf food web: Comparing estimates derived from an ecosystem model and isotopic data

NASA Astrophysics Data System (ADS)

Lassalle, G.; Chouvelon, T.; Bustamante, P.; Niquil, N.

2014-01-01

Comparing outputs of ecosystem models with estimates derived from experimental and observational approaches is important in creating valuable feedback for model construction, analyses and validation. Stable isotopes and mass-balanced trophic models are well-known and widely used as approximations to describe the structure of food webs, but their consistency has not been properly established as attempts to compare these methods remain scarce. Model construction is a data-consuming step, meaning independent sets for validation are rare. Trophic linkages in the French continental shelf of the Bay of Biscay food webs were recently investigated using both methodologies. Trophic levels for mono-specific compartments representing small pelagic fish and marine mammals and multi-species functional groups corresponding to demersal fish and cephalopods, derived from modelling, were compared with trophic levels calculated from independent carbon and nitrogen isotope ratios. Estimates of the trophic niche width of those species, or groups of species, were compared between these two approaches as well. A significant and close-to-one positive (rSpearman2 = 0.72 , n = 16, p < 0.0001) correlation was found between trophic levels estimated by Ecopath modelling and those derived from isotopic signatures. Differences between estimates were particularly low for mono-specific compartments. No clear relationship existed between indices of trophic niche width derived from both methods. Given the wide recognition of trophic levels as a useful concept in ecosystem-based fisheries management, propositions were made to further combine these two approaches.

Physiologically Based Pharmacokinetic (PBPK) Modeling of ...

EPA Pesticide Factsheets

Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, inter-individual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data.Objectives: To evaluate the utility of genetically diverse mouse strains for estimating toxicokinetic population variability for risk assessment, using trichloroethylene (TCE) metabolism as a case study. Methods: We used data on oxidative and glutathione conjugation metabolism of TCE in 16 inbred and one hybrid mouse strains to calibrate and extend existing physiologically-based pharmacokinetic (PBPK) models. We added one-compartment models for glutathione metabolites and a two-compartment model for dichloroacetic acid (DCA). A Bayesian population analysis of inter-strain variability was used to quantify variability in TCE metabolism. Results: Concentration-time profiles for TCE metabolism to oxidative and glutathione conjugation metabolites varied across strains. Median predictions for the metabolic flux through oxidation was less variable (5-fold range) than that through glutathione conjugation (10-fold range). For oxidative metabolites, median predictions of trichloroacetic acid production was less variable (2-fold range) than DCA production (5-fold range), although uncertainty bounds for DCA exceeded the predicted variability. Conclusions:

Multimedia fate modeling of perfluorooctanoic acid (PFOA) and perfluorooctane sulphonate (PFOS) in the shallow lake Chaohu, China.

PubMed

Kong, Xiangzhen; Liu, Wenxiu; He, Wei; Xu, Fuliu; Koelmans, Albert A; Mooij, Wolf M

2018-06-01

Freshwater shallow lake ecosystems provide valuable ecological services to human beings. However, these systems are subject to severe contamination from anthropogenic sources. Per- and polyfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulphonate (PFOS), are among the contaminants that have received substantial attention, primarily due to abundant applications, environment persistence, and potential threats to ecological and human health. Understanding the environmental behavior of these contaminants in shallow freshwater lake environments using a modeling approach is therefore critical. Here, we characterize the fate, transport and transformation of both PFOA and PFOS in the fifth largest freshwater lake in China (Chaohu) during a two-year period (2013-2015) using a fugacity-based multimedia fate model. A reasonable agreement between the measured and modeled concentrations in various compartments confirms the model's reliability. The model successfully quantifies the environmental processes and identifies the major sources and input pathways of PFOA and PFOS to the Chaohu water body. Sensitivity analysis reveals the critical role of nonlinear Freundlich sorption, which contributes to a variable fraction of the model true uncertainty in different compartments (8.1%-93.6%). Through additional model scenario analyses, we further elucidate the importance of nonlinear Freundlich sorption that is essential for the reliable model performance. We also reveal the distinct composition of emission sources for the two contaminants, as the major sources are indirect soil volatilization and direct release from human activities for PFOA and PFOS, respectively. The present study is expected to provide implications for local management of PFASs pollution in Lake Chaohu and to contribute to developing a general model framework for the evaluation of PFASs in shallow lakes. Copyright © 2018 Elsevier Ltd. All rights reserved.