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...

Classical Michaelis-Menten and system theory approach to modeling metabolite formation kinetics.

PubMed

Popović, Jovan

2004-01-01

When single doses of drug are administered and kinetics are linear, techniques, which are based on the compartment approach and the linear system theory approach, in modeling the formation of the metabolite from the parent drug are proposed. Unlike the purpose-specific compartment approach, the methodical, conceptual and computational uniformity in modeling various linear biomedical systems is the dominant characteristic of the linear system approach technology. Saturation of the metabolic reaction results in nonlinear kinetics according to the Michaelis-Menten equation. The two compartment open model with Michaelis-Menten elimination kinetics is theorethicaly basic when single doses of drug are administered. To simulate data or to fit real data using this model, one must resort to numerical integration. A biomathematical model for multiple dosage regimen calculations of nonlinear metabolic systems in steady-state and a working example with phenytoin are presented. High correlation between phenytoin steady-state serum levels calculated from individual Km and Vmax values in the 15 adult epileptic outpatients and the observed levels at the third adjustment of phenytoin daily dose (r=0.961, p<0.01) were found.

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...

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

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)

Opening the medial tibiofemoral compartment by pie-crusting the superficial medial collateral ligament at its tibial insertion: a cadaver study.

PubMed

Roussignol, X; Gauthe, R; Rahali, S; Mandereau, C; Courage, O; Duparc, F

2015-09-01

Arthroscopic treatment of tears in the middle and posterior parts of the medial meniscus can be difficult when the medial tibiofemoral compartment is tight. Passage of the instruments may damage the cartilage. The primary objective of this cadaver study was to perform an arthroscopic evaluation of medial tibiofemoral compartment opening after pie-crusting release (PCR) of the superficial medial collateral ligament (sMCL) at its distal insertion on the tibia. The secondary objective was to describe the anatomic relationships at the site of PCR (saphenous nerve, medial saphenous vein). We studied 10 cadaver knees with no history of invasive procedures. The femur was held in a vise with the knee flexed at 45°, and the medial aspect of the knee was dissected. PCR of the sMCL was performed under arthroscopic vision, in the anteroposterior direction, at the distal tibial insertion of the sMCL, along the lower edge of the tibial insertion of the semi-tendinosus tendon. Continuous 300-N valgus stress was applied to the ankle. Opening of the medial tibiofemoral compartment was measured arthroscopically using graduated palpation hooks after sequential PCR of the sMCL. The compartment opened by 1mm after release of the anterior third, 2.3mm after release of the anterior two-thirds, and 3.9mm after subtotal release. A femoral fracture occurred in 1 case, after completion of all measurements. Both the saphenous nerve and the medial saphenous vein were located at a distance from the PCR site in all 10 knees. PCR of the sMCL is chiefly described as a ligament-balancing method during total knee arthroplasty. This procedure is usually performed at the joint line, where it opens the compartment by 4-6mm at the most, with some degree of unpredictability. PCR of the sMCL at its distal tibial insertion provides gradual opening of the compartment, to a maximum value similar to that obtained with PCR at the joint space. The lower edge of the semi-tendinosus tendon is a valuable landmark for PCR of the distal sMCL. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

[Comparative pharmacokinetics of paracetamol in humans following single oral and rectal administration (author's transl)].

PubMed

Liedtke, R; Berner, G; Haase, W; Nicolai, W; Staab, R; Wagener, H H

1979-01-01

The pharmacokinetic behaviour of N-acetyl-p-aminophenol (paracetamol) after single dose applications of 500 mg and 1000 mg dosages in the form of liquids, tablets and suppositories was compared. The estimation of the pharmacokinetic constants by a simultaneous curve fitting with a direct search procedure, based on an open two-compartment model, showed for the liquid as well as for the tablet formulation a good conformable and dosage proportional behaviour of the relative bioavailability. In opposite to the oral application, the suppositories had a significantly reduced invasion kinetics with a comparable elimination kinetics characterized by a lowering of Cmax and an increase of Tmax-values with comparable AUCs. The calculation of collapse-coefficients showed, with the exception of one suppository formulation, for all administrations a pharmacokinetic behaviour deviating from an open one-compartment model. The clinical consequences resulting from the pharmacokinetic behaviour of the different galenic formulations and routes of administrations are discussed.

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.

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 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

On the use of radiative surface temperature to estimate sensible heat flux over sparse shrubs in Nevada

NASA Technical Reports Server (NTRS)

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

1994-01-01

The accurate partitioning of available energy into sensible and latent heat flux is crucial to the understanding of 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. A three component model to estimate sensible heat flux over heterogeneous surfaces is presented. The surface was represented with two adjacent compartments. The first compartment is made up of two components, shrubs and shaded soil, the second of open 'illuminated' soil. Data collected at two different sites in Nevada (U.S.) 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.

Pharmacokinetic Interpretation of Cephradine Levels in Serum After Intravenous and Extravascular Administration in Humans

PubMed Central

Rattie, Elisabeth S.; Bernardo, Peter D.; Ravin, Louis J.

1976-01-01

Pharmacokinetic parameters were calculated from intravenous data based upon a two-compartment open model. These parameters were subsequently used to determine the absorption rates and bioavailability of cephradine administered intramuscularly and orally. The results indicate that cephradine obeys dose-independent kinetics and that biological availability is complete from all dosage forms. PMID:984770

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.

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

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.

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

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...

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...

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.

Assessment of mouse anxiety-like behavior in the light-dark box and open-field arena: role of equipment and procedure.

PubMed

Kulesskaya, Natalia; Voikar, Vootele

2014-06-22

Light-dark box and open field are conventional tests for assessment of anxiety-like behavior in the laboratory mice, based on approach-avoidance conflict. However, except the basic principles, variations in the equipment and procedures are very common. Therefore, contribution of certain methodological issues in different settings was investigated. Three inbred strains (C57BL/6, 129/Sv, DBA/2) and one outbred stock (ICR) of mice were used in the experiments. An effect of initial placement of mice either in the light or dark compartment was studied in the light-dark test. Moreover, two tracking systems were applied - position of the animals was detected either by infrared sensors in square box (1/2 dark) or by videotracking in rectangular box (1/3 dark). Both approaches revealed robust and consistent strain differences in the exploratory behavior. In general, C57BL/6 and ICR mice showed reduced anxiety-like behavior as compared to 129/Sv and DBA/2 strains. However, the latter two strains differed markedly in their behavior. DBA/2 mice displayed high avoidance of the light compartment accompanied by thigmotaxis, whereas the hypoactive 129 mice spent a significant proportion of time in risk-assessment behavior at the opening between two compartments. Starting from the light side increased the time spent in the light compartment and reduced the latency to the first transition. In the open field arena, black floor promoted exploratory behavior - increased time and distance in the center and increased rearing compared to white floor. In conclusion, modifications of the apparatus and procedure had significant effects on approach-avoidance behavior in general whereas the strain rankings remained unaffected. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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.

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.

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.

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.

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.

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.

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 .

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

A three-compartment thermometry model for the improved estimation of changes in body heat content.

PubMed

Jay, Ollie; Gariépy, Louise M; Reardon, Francis D; Webb, Paul; Ducharme, Michel B; Ramsay, Tim; Kenny, Glen P

2007-01-01

The aim of this study was to use whole body calorimetry to directly measure the change in body heat content (DeltaH(b)) during steady-state exercise and compare these values with those estimated using thermometry. The thermometry models tested were the traditional two-compartment model of "core" and "shell" temperatures, and a three-compartment model of "core," "muscle," and "shell" temperatures; with individual compartments within each model weighted for their relative influence upon DeltaH(b) by coefficients subject to a nonnegative and a sum-to-one constraint. Fifty-two participants performed 90 min of moderate-intensity exercise (40% of Vo(2 peak)) on a cycle ergometer in the Snellen air calorimeter, at regulated air temperatures of 24 degrees C or 30 degrees C and a relative humidity of either 30% or 60%. The "core" compartment was represented by temperatures measured in the esophagus (T(es)), rectum (T(re)), and aural canal (T(au)), while the "muscle" compartment was represented by regional muscle temperature measured in the vastus lateralis (T(vl)), triceps brachii (T(tb)), and upper trapezius (T(ut)). The "shell" compartment was represented by the weighted mean of 12 skin temperatures (T(sk)). The whole body calorimetry data were used to derive optimally fitting two- and three-compartment thermometry models. The traditional two-compartment model was found to be statistically biased, systematically underestimating DeltaH(b) by 15.5% (SD 31.3) at 24 degrees C and by 35.5% (SD 21.9) at 30 degrees C. The three-compartment model showed no such bias, yielding a more precise estimate of DeltaH(b) as evidenced by a mean estimation error of 1.1% (SD 29.5) at 24 degrees C and 5.4% (SD 30.0) at 30 degrees C with an adjusted R(2) of 0.48 and 0.51, respectively. It is concluded that a major source of error in the estimation of DeltaH(b) using the traditional two-compartment thermometry model is the lack of an expression independently representing the heat storage in muscle during exercise.

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.

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.

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.

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.

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

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

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.

Two-compartmental population balance modeling of a pulsed spray fluidized bed granulation based on computational fluid dynamics (CFD) analysis.

PubMed

Liu, Huolong; Li, Mingzhong

2014-11-20

In this work a two-compartmental population balance model (TCPBM) was proposed to model a pulsed top-spray fluidized bed granulation. The proposed TCPBM considered the spatially heterogeneous granulation mechanisms of the granule growth by dividing the granulator into two perfectly mixed zones of the wetting compartment and drying compartment, in which the aggregation mechanism was assumed in the wetting compartment and the breakage mechanism was considered in the drying compartment. The sizes of the wetting and drying compartments were constant in the TCPBM, in which 30% of the bed was the wetting compartment and 70% of the bed was the drying compartment. The exchange rate of particles between the wetting and drying compartments was determined by the details of the flow properties and distribution of particles predicted by the computational fluid dynamics (CFD) simulation. The experimental validation has shown that the proposed TCPBM can predict evolution of the granule size and distribution within the granulator under different binder spray operating conditions accurately. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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.

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.

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

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

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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

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.

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.

[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%.

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.

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.

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

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.

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.

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

[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.

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.

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.

Two-Compartment Pharmacokinetic Models for Chemical Engineers

ERIC Educational Resources Information Center

Kanneganti, Kumud; Simon, Laurent

2011-01-01

The transport of potassium permanganate between two continuous-stirred vessels was investigated to help chemical and biomedical engineering students understand two-compartment pharmacokinetic models. Concepts of modeling, mass balance, parameter estimation and Laplace transform were applied to the two-unit process. A good agreement was achieved…

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

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.

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.

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.

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.

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

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...

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.

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...

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.

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.

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.

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.

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.

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.

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.

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...

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.

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.

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

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.

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.

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 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.

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.

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.

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

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.

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...

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.

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.

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

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.

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

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.

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.

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.

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.

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

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.

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…

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.

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.

[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.

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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.

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.

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

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.

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...

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

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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

[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.

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.

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.

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.

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.

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.

Physiologicomathematical model for studying human exposure to organic solvents: kinetics of blood/tissue n-hexane concentrations and of 2,5-hexanedione in urine.

PubMed Central

Perbellini, L; Mozzo, P; Brugnone, F; Zedde, A

1986-01-01

The physiologicomathematical model with eight compartments described allows the simulation of the absorbtion, distribution, biotransformation, excretion of an organic solvent, and the kinetics of its metabolites. The usual compartments of the human organism (vessel rich group, muscle group, and fat group) are integrated with the lungs, the metabolising tissues, and three other compartments dealing with the metabolic kinetics (biotransformation, water, and urinary compartments). The findings obtained by mathematical simulation of exposure to n-hexane were compared with data previously reported. The concentrations of n-hexane in alveolar air and in venous blood described both in experimental and occupational exposures provided a substantial validation for the data obtained by mathematical simulation. The results of the urinary excretion of 2,5-hexanedione given by the model were in good agreement with data already reported. The simulation of an exposure to n-hexane repeated five days a week suggested that the solvent accumulates in the fat tissue. The half life of n-hexane in fat tissue equalled 64 hours. The kinetics of 2,5-hexanedione resulting from the model suggest that occupational exposure results in the presence of large amounts of 2,5-hexanedione in the body for the whole working week. PMID:3790456

Organic Pollutant Penetration through Fruit Polyester Skin: A Modified Three-compartment Diffusion Model

PubMed Central

Li, Yungui; Li, Qingqing; Chen, Baoliang

2016-01-01

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. PMID:27009902

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.

Spectroscopic Biomarkers for Monitoring Wound Healing and Infection in Combat Wounds

DTIC Science & Technology

2012-10-29

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...HO formation has been observed following orthopedic surgery (total hip arthroplasty as well as acetabular and elbow fracture surgery), burn injury

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.

Use of the light/dark test for anxiety in adult and adolescent male rats.

PubMed

Arrant, Andrew E; Schramm-Sapyta, Nicole L; Kuhn, Cynthia M

2013-11-01

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. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Systems Models for Transportation Problems : Volume 3. A Computable Command-Control System for a Social System.

DOT National Transportation Integrated Search

1976-03-01

The spectral characteristics of the urban center -- at the level of the family, the functional organized units of society, and the essential compartment balances of the urban center -- are spelled out in greater detail. These compartments are food, m...

ASEI-SEIR model with vaccination for dengue control in Shah Alam, Malaysia

NASA Astrophysics Data System (ADS)

Tay, Chai Jian; Teh, Su Yean; Koh, Hock Lye

2018-03-01

Epidemiology modelling provides an understanding of the underlying mechanisms that influence the spread of dengue disease. The most common mathematical models used are the compartment models abbreviated by ASI-SIR, ASEI-SIR and ASEI-SEIR. This paper starts with a discussion of these common models, followed by the derivation of the basic reproduction number (Ro) of each model. The value of Ro in ASI-SIR model is higher than that in ASEI-SIR and ASEI-SEIR models due to the exclusion of exposed adult mosquito in ASI-SIR model. Further, sensitivity analysis on Ro indicates that natural mortality and biting rate of adult mosquito have significant effects on dengue transmission dynamics. Next, an in-house mathematical model named MOSSEIR is developed, based upon the ASEI-SEIR compartment model, in which both mosquito and human populations are considered. The mosquito population is divided into four compartments consisting of aquatic mosquito, susceptible, exposed and infected adult mosquito; while the human population is classified into four compartments comprising susceptible, exposed, infected and recovered human. MOSSEIR is then used to replicate the number of dengue cases in 2010 for Shah Alam, a capital city of Selangor with high incidence of dengue fever. Finally, effectiveness of control strategies, including mosquito breeding sites control, fogging and vaccination, are evaluated for Shah Alam. Simulation results indicate that these three control strategies can significantly reduce dengue transmission, in theory. In reality, the effectiveness of traditional control methods such as elimination of mosquito breeding sites and fogging is below expectation due to non-compliance. Therefore, the adoption of a safe, effective and affordable vaccine remains the best prospect for controlling dengue.

Membrane curvature and its generation by BAR proteins

PubMed Central

Mim, Carsten; Unger, Vinzenz M

2012-01-01

Membranes are flexible barriers that surround the cell and its compartments. To execute vital functions such as locomotion or receptor turnover, cells need to control the shapes of their membranes. In part, this control is achieved through membrane-bending proteins, such as the bin/amphiphysin/rvs domain (BAR) proteins. Many open questions remain about the mechanisms by which membrane-bending proteins function. Addressing this shortfall, recent structures of BAR protein:membrane complexes support existing mechanistic models, but also produced novel insights into how BAR-domain proteins sense, stabilize and generate curvature. Here we review these recent findings, focusing on how BAR proteins interact with the membrane, and how the resulting scaffold structures might aid the recruitment of other proteins to the sites where membranes are bent. PMID:23058040

Compartmental and Spatial Rule-Based Modeling with Virtual Cell.

PubMed

Blinov, Michael L; Schaff, James C; Vasilescu, Dan; Moraru, Ion I; Bloom, Judy E; Loew, Leslie M

2017-10-03

In rule-based modeling, molecular interactions are systematically specified in the form of reaction rules that serve as generators of reactions. This provides a way to account for all the potential molecular complexes and interactions among multivalent or multistate molecules. Recently, we introduced rule-based modeling into the Virtual Cell (VCell) modeling framework, permitting graphical specification of rules and merger of networks generated automatically (using the BioNetGen modeling engine) with hand-specified reaction networks. VCell provides a number of ordinary differential equation and stochastic numerical solvers for single-compartment simulations of the kinetic systems derived from these networks, and agent-based network-free simulation of the rules. In this work, compartmental and spatial modeling of rule-based models has been implemented within VCell. To enable rule-based deterministic and stochastic spatial simulations and network-free agent-based compartmental simulations, the BioNetGen and NFSim engines were each modified to support compartments. In the new rule-based formalism, every reactant and product pattern and every reaction rule are assigned locations. We also introduce the rule-based concept of molecular anchors. This assures that any species that has a molecule anchored to a predefined compartment will remain in this compartment. Importantly, in addition to formulation of compartmental models, this now permits VCell users to seamlessly connect reaction networks derived from rules to explicit geometries to automatically generate a system of reaction-diffusion equations. These may then be simulated using either the VCell partial differential equations deterministic solvers or the Smoldyn stochastic simulator. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Influence of the fire location and the size of a compartment on the heat and smoke flow out of the compartment

NASA Astrophysics Data System (ADS)

Wegrzyński, Wojciech; Konecki, Marek

2018-01-01

This paper presents results of CFD and scale modelling of the flow of heat and smoke inside and outside of a compartment, in case of fire. Estimation of mass flow out of a compartment is critical, as it is the boundary condition in further considerations related to the exhaust of the smoke from a building - also in analysis related to the performance of natural ventilation in wind conditions. Both locations of the fire and the size of compartment were addressed as possible variables, which influence the mass and the temperature of smoke that leaves the room engulfed in fire. Results of the study show small to none influence of both size of the compartment and the location of the fire, on the mass flow of smoke exiting the room. On the same time, both of these parameters influence the temperature of the smoke - in larger compartments lower average temperatures of the smoke layer, but higher maximum values were observed. Results of this study may be useful also in the determination of the worst case scenarios for structural analysis, or in the investiga tion of the spread of fire through the compartment. Based on the results presented in this study, researchers can attribute an expert judgement choice of fire location, as a single scenario that is representative of a larger amount of probable scenarios.

Lumped Parameter Models of the Central Nervous System for VIIP Research

NASA Technical Reports Server (NTRS)

Vera, J.; Mulugeta, L.; Nelson, E. S.; Raykin, J.; Feola, A.; Gleason, R.; Samuels, B.; Myers, J. G.

2015-01-01

INTRODUCTION: Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit, such as to Mars and asteroids, expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome [1]. It has been hypothesized that the headward shift of cerebral spinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn induces VIIP syndrome through biomechanical pathways [1, 2]. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the realted IWS abstracts submitted by Nelson et al., Feola et al. and Ethier et al. METHODS: We have developed a nine compartment CNS model (Figure 1) capable of both time-dependent and steady state fluid transport simulations, based on the works of Stevens et al. [3]. The breakdown of compartments within the model includes: vascular (3), CSF (2), brain (1) and extracranial (3). The boundary pressure in the Central Arteries [A] node is prescribed using an oscillating pressure function PA(t) simulating the carotid pulsatile pressure wave as developed by Linninger et al. [4]. For each time step, pressures are integrated through time using an adaptive-timestep 4th and 5th order Runga-Kutta solver. Once pressures are found, constitutive equations are used to solve for flowrates (Q) between each compartment. In addition to fluid flow between the different compartments, compliance (C) interactions between neighboring compartments are represented. We are also developing a second CNS model based on the works of Linninger et al. [4] which takes a more granular approach to represent the interactions of the intracranial and spinal compartments with the inclusion of arteries, arterioles, capillaries, venules, veins, venous sinus, and ventricles. The flow through the arteries, veins and CSF compartments are governed by continuity, momentum and distensibility balance equations. Furthermore, unlike the Stevens et al. approach, the Monro-Kellie doctrine of constant cranial volume and the bi-phasic nature of the brain parenchyma are implemented. These features appear to be more consistent with the physiologic and anatomical behavior of the CNS, and follow a modeling philosophy similar to the lumped parameter eye model that is intended to be integrated with the CNS model. However, Linninger’s approach has never been implemented to include hydrostatic gradient and microgravity simulation capabilities. Therefore, we aim at implement this modeling approach for spaceflight simulations and assess its overall applicability to VIIP research. OBJECTIVES: We will present verification and validation test results for both models, as well as head-to-head comparison to explore their strengths and limitations with respect to mathematical implementation and physiological significance for VIIP research. In doing so, we hope to provide some guidance to the HRP research community on how to appropriately leverage lumped parameter models for space biomedical research.

Membrane order in the plasma membrane and endocytic recycling compartment.

PubMed

Iaea, David B; Maxfield, Frederick R

2017-01-01

The cholesterol content of membranes plays an important role in organizing membranes for signal transduction and protein trafficking as well as in modulating the biophysical properties of membranes. While the properties of model or isolated membranes have been extensively studied, there has been little evaluation of internal membranes in living cells. Here, we use a Nile Red based probe, NR12S, and ratiometric live cell imaging, to analyze the membrane order of the plasma membrane and endocytic recycling compartment. We find that after a brief incubation to allow endocytosis, NR12S is distributed between the plasma membrane and the endocytic recycling compartment. The NR12S reports that the endocytic recycling compartment is more highly ordered than the plasma membrane. We also find that the plasma membrane and the endocytic recycling compartment are differentially affected by altering cellular cholesterol levels. The membrane order of the plasma membrane, but not the endocytic recycling compartment, is altered significantly when cellular cholesterol content is increased or decreased by 20%. These results demonstrate that changes in cellular cholesterol differentially alter membrane order within different organelles.

Membrane order in the plasma membrane and endocytic recycling compartment

PubMed Central

Iaea, David B.; Maxfield, Frederick R.

2017-01-01

The cholesterol content of membranes plays an important role in organizing membranes for signal transduction and protein trafficking as well as in modulating the biophysical properties of membranes. While the properties of model or isolated membranes have been extensively studied, there has been little evaluation of internal membranes in living cells. Here, we use a Nile Red based probe, NR12S, and ratiometric live cell imaging, to analyze the membrane order of the plasma membrane and endocytic recycling compartment. We find that after a brief incubation to allow endocytosis, NR12S is distributed between the plasma membrane and the endocytic recycling compartment. The NR12S reports that the endocytic recycling compartment is more highly ordered than the plasma membrane. We also find that the plasma membrane and the endocytic recycling compartment are differentially affected by altering cellular cholesterol levels. The membrane order of the plasma membrane, but not the endocytic recycling compartment, is altered significantly when cellular cholesterol content is increased or decreased by 20%. These results demonstrate that changes in cellular cholesterol differentially alter membrane order within different organelles. PMID:29125865

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.

76 FR 10476 - Special Conditions: Boeing Model 787-8 Airplane; Overhead Crew-Rest Compartment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-25

...\\ in interior volume, the design must ensure the ability to contain a fire likely to occur within the... or unusual design features associated with installation of an overhead crew-rest (OCR) compartment... this design feature. These special conditions contain the additional safety standards that the...

Influence of biophase distribution and P-glycoprotein interaction on pharmacokinetic-pharmacodynamic modelling of the effects of morphine on the EEG

PubMed Central

Groenendaal, D; Freijer, J; de Mik, D; Bouw, M R; Danhof, M; de Lange, E C M

2007-01-01

Background and purpose: The aim was to investigate the influence of biophase distribution including P-glycoprotein (Pgp) function on the pharmacokinetic-pharmacodynamic correlations of morphine's actions in rat brain. Experimental approach: Male rats received a 10-min infusion of morphine as 4 mg kg−1, combined with a continuous infusion of the Pgp inhibitor GF120918 or vehicle, 10 or 40 mg kg−1. EEG signals were recorded continuously and blood samples were collected. Key results: Profound hysteresis was observed between morphine blood concentrations and effects on the EEG. Only the termination of the EEG effect was influenced by GF120918. Biophase distribution was best described with an extended catenary biophase distribution model, with a sequential transfer and effect compartment. The rate constant for transport through the transfer compartment (k1e) was 0.038 min−1, being unaffected by GF120918. In contrast, the rate constant for the loss from the effect compartment (keo) decreased 60% after GF120918. The EEG effect was directly related to concentrations in the effect compartment using the sigmoidal Emax model. The values of the pharmacodynamic parameters E0, Emax, EC50 and Hill factor were 45.0 μV, 44.5 μV, 451 ng ml−1 and 2.3, respectively. Conclusions and implications: The effects of GF120918 on the distribution kinetics of morphine in the effect compartment were consistent with the distribution in brain extracellular fluid (ECF) as estimated by intracerebral microdialysis. However, the time-course of morphine concentrations at the site of action in the brain, as deduced from the biophase model, is distinctly different from the brain ECF concentrations. PMID:17471181

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.

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.

Performance of an image analysis processing system for hen tracking in an environmental preference chamber.

PubMed

Kashiha, Mohammad Amin; Green, Angela R; Sales, Tatiana Glogerley; Bahr, Claudia; Berckmans, Daniel; Gates, Richard S

2014-10-01

Image processing systems have been widely used in monitoring livestock for many applications, including identification, tracking, behavior analysis, occupancy rates, and activity calculations. The primary goal of this work was to quantify image processing performance when monitoring laying hens by comparing length of stay in each compartment as detected by the image processing system with the actual occurrences registered by human observations. In this work, an image processing system was implemented and evaluated for use in an environmental animal preference chamber to detect hen navigation between 4 compartments of the chamber. One camera was installed above each compartment to produce top-view images of the whole compartment. An ellipse-fitting model was applied to captured images to detect whether the hen was present in a compartment. During a choice-test study, mean ± SD success detection rates of 95.9 ± 2.6% were achieved when considering total duration of compartment occupancy. These results suggest that the image processing system is currently suitable for determining the response measures for assessing environmental choices. Moreover, the image processing system offered a comprehensive analysis of occupancy while substantially reducing data processing time compared with the time-intensive alternative of manual video analysis. The above technique was used to monitor ammonia aversion in the chamber. As a preliminary pilot study, different levels of ammonia were applied to different compartments while hens were allowed to navigate between compartments. Using the automated monitor tool to assess occupancy, a negative trend of compartment occupancy with ammonia level was revealed, though further examination is needed. ©2014 Poultry Science Association Inc.

Interstitial diffusion and the relationship between compartment modelling and multi-scale spatial-temporal modelling of (18)F-FLT tumour uptake dynamics.

PubMed

Liu, Dan; Chalkidou, Anastasia; Landau, David B; Marsden, Paul K; Fenwick, John D

2014-09-07

Tumour cell proliferation can be imaged via positron emission tomography of the radiotracer 3'-deoxy-3'-18F-fluorothymidine (18F-FLT). Conceptually, the number of proliferating cells might be expected to correlate more closely with the kinetics of 18F-FLT uptake than with uptake at a fixed time. Radiotracer uptake kinetics are standardly visualized using parametric maps of compartment model fits to time-activity-curves (TACs) of individual voxels. However the relationship between the underlying spatiotemporal accumulation of FLT and the kinetics described by compartment models has not yet been explored. In this work tumour tracer uptake is simulated using a mechanistic spatial-temporal model based on a convection-diffusion-reaction equation solved via the finite difference method. The model describes a chain of processes: the flow of FLT between the spatially heterogeneous tumour vasculature and interstitium; diffusion and convection of FLT within the interstitium; transport of FLT into cells; and intracellular phosphorylation. Using values of model parameters estimated from the biological literature, simulated FLT TACs are generated with shapes and magnitudes similar to those seen clinically. Results show that the kinetics of the spatial-temporal model can be recovered accurately by fitting a 3-tissue compartment model to FLT TACs simulated for those tumours or tumour sub-volumes that can be viewed as approximately closed, for which tracer diffusion throughout the interstitium makes only a small fractional change to the quantity of FLT they contain. For a single PET voxel of width 2.5-5 mm we show that this condition is roughly equivalent to requiring that the relative difference in tracer uptake between the voxel and its neighbours is much less than one.

Steady state phosphorus mass balance model during hemodialysis based on a pseudo one-compartment kinetic model.

PubMed

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

2012-11-01

Mathematical models of phosphorus kinetics and mass balance during hemodialysis are in early development. We describe a theoretical phosphorus steady state mass balance model during hemodialysis based on a novel pseudo one-compartment kinetic model. The steady state mass balance model accounted for net intestinal absorption of phosphorus and phosphorus removal by both dialysis and residual kidney function. Analytical mathematical solutions were derived to describe time-dependent intradialytic and interdialytic serum phosphorus concentrations assuming hemodialysis treatments were performed symmetrically throughout a week. Results from the steady state phosphorus mass balance model are described for thrice weekly hemodialysis treatment prescriptions only. The analysis predicts 1) a minimal impact of dialyzer phosphorus clearance on predialysis serum phosphorus concentration using modern, conventional hemodialysis technology, 2) variability in the postdialysis-to-predialysis phosphorus concentration ratio due to differences in patient-specific phosphorus mobilization, and 3) the importance of treatment time in determining the predialysis serum phosphorus concentration. We conclude that a steady state phosphorus mass balance model can be developed based on a pseudo one-compartment kinetic model and that predictions from this model are consistent with previous clinical observations. The predictions from this mass balance model are theoretical and hypothesis-generating only; additional prospective clinical studies will be required for model confirmation.

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.

Spectroscopic Biomarkers for Monitoring Wound Healing and Infection in Combat Wounds

DTIC Science & Technology

2013-10-01

disruption, blastwave-associated pressure injuries, air, thrombotic, and fat embolism , and compartment syndrome. In the treatment of such complex...often associated with overt vascular injury. These injuries include traumatic amputations, open fractures , crush injuries, burns, acute vascular...patients. While Task 1c was initiated, Raman spectra of different anatomical sites of volunteers looked very similar to skin and fat . The Raman

Spectroscopic Biomarkers for Monitoring Wound Healing and Infection in Combat Wounds

DTIC Science & Technology

2011-10-01

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...injury, it develops in only 20% and 11% of patients. Rates of HO formation exceed 50% only in the setting of femoral shaft fractures with

Orthopedic injuries from the Andover, Kansas, tornado.

PubMed

Rosenfield, A L; McQueen, D A; Lucas, G L

1994-05-01

Devastating tornados struck the state of Kansas on Friday, April 26, 1991. Twenty lives were lost and many people were injured. Property damage was extensive. Overall, the outcome of those admitted to the various hospitals was good, with few orthopedic-related complications. The low complication rate can be attributed to thorough open wound management and suspicion and recognition of other potential orthopedic complications such as compartment syndrome.

Comparative Characterization of Phosphatidic Acid Sensors and Their Localization during Frustrated Phagocytosis.

PubMed

Kassas, Nawal; Tanguy, Emeline; Thahouly, Tamou; Fouillen, Laetitia; Heintz, Dimitri; Chasserot-Golaz, Sylvette; Bader, Marie-France; Grant, Nancy J; Vitale, Nicolas

2017-03-10

Phosphatidic acid (PA) is the simplest phospholipid naturally existing in living organisms, but it constitutes only a minor fraction of total cell lipids. PA has attracted considerable attention because it is a phospholipid precursor, a lipid second messenger, and a modulator of membrane shape, and it has thus been proposed to play key cellular functions. The dynamics of PA in cells and in subcellular compartments, however, remains an open question. The recent generation of fluorescent probes for PA, by fusing GFP to PA-binding domains, has provided direct evidence for PA dynamics in different intracellular compartments. Here, three PA sensors were characterized in vitro, and their preferences for different PA species in particular lipidic environments were compared. In addition, the localization of PA in macrophages during frustrated phagocytosis was examined using these PA sensors and was combined with a lipidomic analysis of PA in intracellular compartments. The results indicate that the PA sensors display some preferences for specific PA species, depending on the lipid environment, and the localization study in macrophages revealed the complexity of intracellular PA dynamics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Distal splenorenal shunt (DSS) in children: analysis of the first 21 consecutive cases.

PubMed Central

Maksoud, J G; Mies, S

1982-01-01

Twenty-one children from the ages of 4 to 12 years old were treated for esophageal hemorrhage by distal splenorenal shunt (DSS). In four patients, thrombosis of the shunt occurred within the first 24 hours after operation. In the other 17 children, long-term shunt patency was verified. Only one thrombosis has occurred in the last 15 consecutive cases. The patients were followed from one-half to six years. Late angiographic studies were performed in five patients. Forward flow through the portal vein was demonstrated in all patients. In addition, collateralization between the portomesenteric (PM) and gastrosplenic (GS) compartments was present in each case. In four patients with a wide-open shunt, the direction of collateral flow was from the PM to the GS compartment. In one child in whom the shunt was partially obstructed, the flow was from the GS to the PM compartment. In all 17 successful cases, esophageal variceal hemorrhage ceased, and there were no instances of hepatic encephalopathy. It is concluded that DSS is a safe and effective surgical procedure for the treatment of esophageal bleeding in children. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:6978110

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.

Elevated waterproof access floor system and method of making the same

NASA Technical Reports Server (NTRS)

Cohen, Marc M. (Inventor)

1987-01-01

An elevated waterproof access floor system having subfloor channels or compartments for power lines, gas lines or the like is adapted such that it can be opened and subsequently resealed without destroying the waterproofing and without destroying its aesthetic appearance. A multiplicity of tiles are supported on a support grid, and a flooring sheet is supported on the tiles. Attachment means are provided to prevent lateral but not vertical movement of the flooring sheet with respect to the tiles so that the flooring sheet can be lifted off the tiles, but when the flooring sheet is supported on the tiles, no lateral slipping will occur. The flooring sheet is made of a heat resealable material, so that it can be cut away in sections, and the tiles therebelow lifted off, to provide access to subfloor compartments.

Understanding tumor heterogeneity as functional compartments - superorganisms revisited

PubMed Central

2011-01-01

Compelling evidence broadens our understanding of tumors as highly heterogeneous populations derived from one common progenitor. In this review we portray various stages of tumorigenesis, tumor progression, self-seeding and metastasis in analogy to the superorganisms of insect societies to exemplify the highly complex architecture of a neoplasm as a system of functional "castes." Accordingly, we propose a model in which clonal expansion and cumulative acquisition of genetic alterations produce tumor compartments each equipped with distinct traits and thus distinct functions that cooperate to establish clinically apparent tumors. This functional compartment model also suggests mechanisms for the self-construction of tumor stem cell niches. Thus, thinking of a tumor as a superorganism will provide systemic insight into its functional compartmentalization and may even have clinical implications. PMID:21619636

Eave tubes for malaria control in Africa: initial development and semi-field evaluations in Tanzania.

PubMed

Sternberg, Eleanore D; Ng'habi, Kija R; Lyimo, Issa N; Kessy, Stella T; Farenhorst, Marit; Thomas, Matthew B; Knols, Bart G J; Mnyone, Ladslaus L

2016-09-01

Presented here are a series of preliminary experiments evaluating "eave tubes"-a technology that combines house screening with a novel method of delivering insecticides for control of malaria mosquitoes. Eave tubes were first evaluated with overnight release and recapture of mosquitoes in a screened compartment containing a hut and human sleeper. Recapture numbers were used as a proxy for overnight survival. These trials tested physical characteristics of the eave tubes (height, diameter, angle), and different active ingredients (bendiocarb, LLIN material, fungus). Eave tubes in a hut with closed eaves were also compared to an LLIN protecting a sleeper in a hut with open eaves. Eave tubes were then evaluated in a larger compartment containing a self-replicating mosquito population, vegetation, and multiple houses and cattle sheds. In this "model village", LLINs were introduced first, followed by eave tubes and associated house modifications. Initial testing suggested that tubes placed horizontally and at eave height had the biggest impact on mosquito recapture relative to respective controls. Comparison of active ingredients suggested roughly equivalent effects from bendiocarb, LLIN material, and fungal spores (although speed of kill was slower for fungus). The impact of treated netting on recapture rates ranged from 50 to 70 % reduction relative to controls. In subsequent experiments comparing bendiocarb-treated netting in eave tubes against a standard LLIN, the effect size was smaller but the eave tubes with closed eaves performed at least as well as the LLIN with open eaves. In the model village, introducing LLINs led to an approximate 60 % reduction in larval densities and 85 % reduction in indoor catches of host-seeking mosquitoes relative to pre-intervention values. Installing eave tubes and screening further reduced larval density (93 % relative to pre intervention values) and virtually eliminated indoor host-seeking mosquitoes. When the eave tubes and screening were removed, larval and adult catches recovered to pre-eave tube levels. These trials suggest that the "eave tube" package can impact overnight survival of host-seeking mosquitoes and can suppress mosquito populations, even in a complex environment. Further testing is now required to evaluate the robustness of these findings and demonstrate impact under field conditions.

Near-Infrared Monitoring of Model Chronic Compartment Syndrome In Exercising Skeletal Muscle

NASA Technical Reports Server (NTRS)

Hargens, Alan R.; Breit, G. A.; Gross, J. H.; Watenpaugh, D. E.; Chance, B.

1995-01-01

Chronic compartment syndrome (CCS) is characterized by muscle ischemia, usually in the anterior oompartment of the leg, caused by high intramuscular pressure during exercise. Dual-wave near-infrared (NIR) spectroscopy is an optical technique that allows noninvasive tracking of variations in muscle tissue oxygenation (Chance et al., 1988). We hypothesized that with a model CCS, muscle tissue oxygenation will show a greater decline during exercise and a slower recovery post-exercise than under normal conditions.

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.

W3MAMCAT: a world wide web based tool for mammillary and catenary compartmental modeling and expert system distinguishability.

PubMed

Russell, Solomon; Distefano, Joseph J

2006-07-01

W(3)MAMCAT is a new web-based and interactive system for building and quantifying the parameters or parameter ranges of n-compartment mammillary and catenary model structures, with input and output in the first compartment, from unstructured multiexponential (sum-of-n-exponentials) models. It handles unidentifiable as well as identifiable models and, as such, provides finite parameter interval solutions for unidentifiable models, whereas direct parameter search programs typically do not. It also tutorially develops the theory of model distinguishability for same order mammillary versus catenary models, as did its desktop application predecessor MAMCAT+. This includes expert system analysis for distinguishing mammillary from catenary structures, given input and output in similarly numbered compartments. W(3)MAMCAT provides for universal deployment via the internet and enhanced application error checking. It uses supported Microsoft technologies to form an extensible application framework for maintaining a stable and easily updatable application. Most important, anybody, anywhere, is welcome to access it using Internet Explorer 6.0 over the internet for their teaching or research needs. It is available on the Biocybernetics Laboratory website at UCLA: www.biocyb.cs.ucla.edu.

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...

78 FR 25846 - Special Conditions: Airbus, Model A340-600 Series Airplanes; Lower Deck Crew Rest Compartments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-03

... significantly delay issuance of the design approval and thus delivery of the affected aircraft. In addition, the... specific portion of the special conditions, explain the reason for any recommended change, and include... compartment configuration that affect crew member emergency egress or any other procedures affecting the...

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.

The biodistribution and dosimetry of {sup 117m}Sn DTPA with special emphasis on active marrow absorbed doses

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

Stubbs, J.; Atkins, H.

1999-01-01

{sup 117m}Sn(4+) DTPA is a new radiopharmaceutical for the palliation of pain associated with metastatic bone cancer. Recently, the Phase 2 clinical trials involving 47 patients were completed. These patients received administered activities in the range 6.7--10.6 MBq/kg of body mass. Frequent collections of urine were acquired over the first several hours postadministration and daily cumulative collections were obtained for the next 4--10 days. Anterior/posterior gamma camera images were obtained frequently over the initial 10 days. Radiation dose estimates were calculated for 8 of these patients. Each patient`s biodistribution data were mathematically simulated using a multicompartmental model. The model consistedmore » of the following compartments: central, bone, kidney, other tissues, and cumulative urine. The measured cumulative urine data were used as references for the cumulative urine excretion compartment. The total-body compartment (sum of the bone surfaces, central, kidney, and other tissues compartments) was reference to all activity not excreted in the urine.« less

APPL endosomes are not obligatory endocytic intermediates but act as stable cargo-sorting compartments

PubMed Central

Kalaidzidis, Inna; Miaczynska, Marta; Brewińska-Olchowik, Marta; Hupalowska, Anna; Ferguson, Charles; Parton, Robert G.; Kalaidzidis, Yannis

2015-01-01

Endocytosis allows cargo to enter a series of specialized endosomal compartments, beginning with early endosomes harboring Rab5 and its effector EEA1. There are, however, additional structures labeled by the Rab5 effector APPL1 whose role in endocytic transport remains unclear. It has been proposed that APPL1 vesicles are transport intermediates that convert into EEA1 endosomes. Here, we tested this model by analyzing the ultrastructural morphology, kinetics of cargo transport, and stability of the APPL1 compartment over time. We found that APPL1 resides on a tubulo-vesicular compartment that is capable of sorting cargo for recycling or degradation and that displays long lifetimes, all features typical of early endosomes. Fitting mathematical models to experimental data rules out maturation of APPL1 vesicles into EEA1 endosomes as a primary mechanism for cargo transport. Our data suggest instead that APPL1 endosomes represent a distinct population of Rab5-positive sorting endosomes, thus providing important insights into the compartmental organization of the early endocytic pathway. PMID:26459602

Biokinetic modelling development and analysis of arsenic dissolution into the gastrointestinal tract using SAAM II

NASA Astrophysics Data System (ADS)

Perama, Yasmin Mohd Idris; Siong, Khoo Kok

2018-04-01

A mathematical model comprising 8 compartments were designed to describe the kinetic dissolution of arsenic (As) from water leach purification (WLP) waste samples ingested into the gastrointestinal system. A totally reengineered software system named Simulation, Analysis and Modelling II (SAAM II) was employed to aid in the experimental design and data analysis. As a powerful tool that creates, simulate and analyze data accurately and rapidly, SAAM II computationally creates a system of ordinary differential equations according to the specified compartmental model structure and simulates the solutions based upon the parameter and model inputs provided. The experimental design of in vitro DIN approach was applied to create an artificial gastric and gastrointestinal fluids. These synthetic fluids assay were produced to determine the concentrations of As ingested into the gastrointestinal tract. The model outputs were created based upon the experimental inputs and the recommended fractional transfer rates parameter. As a result, the measured and predicted As concentrations in gastric fluids were much similar against the time of study. In contrast, the concentrations of As in the gastrointestinal fluids were only similar during the first hour and eventually started decreasing until the fifth hours of study between the measured and predicted values. This is due to the loss of As through the fractional transfer rates of q2 compartment to corresponding compartments of q3 and q5 which are involved with excretion and distribution to the whole body, respectively. The model outputs obtained after best fit to the data were influenced significantly by the fractional transfer rates between each compartment. Therefore, a series of compartmental model created with the association of fractional transfer rates parameter with the aid of SAAM II provides better estimation that simulate the kinetic behavior of As ingested into the gastrointestinal system.

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

Neonatal infrared thermography imaging: Analysis of heat flux during different clinical scenarios

NASA Astrophysics Data System (ADS)

Abbas, Abbas K.; Heimann, Konrad; Blazek, Vladimir; Orlikowsky, Thorsten; Leonhardt, Steffen

2012-11-01

IntroductionAn accurate skin temperature measurement of Neonatal Infrared Thermography (NIRT) imaging requires an appropriate calibration process for compensation of external effects (e.g. variation of environmental temperature, variable air velocity or humidity). Although modern infrared cameras can perform such calibration, an additional compensation is required for highly accurate thermography. This compensation which corrects any temperature drift should occur during the NIRT imaging process. We introduce a compensation technique which is based on modeling the physical interactions within the measurement scene and derived the detected temperature signal of the object. Materials and methodsIn this work such compensation was performed for different NIRT imaging application in neonatology (e.g. convective incubators, kangaroo mother care (KMC), and an open radiant warmer). The spatially distributed temperatures of 12 preterm infants (average gestation age 31 weeks) were measured under these different infant care arrangements (i.e. closed care system like a convective incubator, and open care system like kangaroo mother care, and open radiant warmer). ResultsAs errors in measurement of temperature were anticipated, a novel compensation method derived from infrared thermography of the neonate's skin was developed. Moreover, the differences in temperature recording for the 12 preterm infants varied from subject to subject. This variation could be arising from individual experimental setting applied to the same region of interest over the neonate's body. The experimental results for the model-based corrections is verified over the selected patient group. ConclusionThe proposed technique relies on applying model-based correction to the measured temperature and reducing extraneous errors during NIRT. This application specific method is based on different heat flux compartments present in neonatal thermography scene. Furthermore, these results are considered to be groundwork for further investigation, especially when using NIRT imaging arrangement with additional compensation settings together with reference temperature measurements.

Effect of open wedge high tibial osteotomy on the lateral compartment in sheep. Part I: Analysis of the lateral meniscus.

PubMed

Madry, Henning; Ziegler, Raphaela; Orth, Patrick; Goebel, Lars; Ong, Mei Fang; Kohn, Dieter; Cucchiarini, Magali; Pape, Dietrich

2013-01-01

To evaluate whether medial open wedge high tibial osteotomy (HTO) results in structural and biochemical changes in the lateral meniscus in adult sheep. Three experimental groups with biplanar osteotomies of the right proximal tibiae were tested: (a) closing wedge HTO resulting in 4.5° of tibial varus, (b) open wedge HTO resulting in 4.5° of tibial valgus (standard correction) and (c) open wedge HTO resulting in 9.5° of valgus (overcorrection), each of which was compared to the contralateral knees with normal limb axes. After 6 months, the lateral menisci were macroscopically and microscopically evaluated. The proteoglycan and DNA contents of the red-red and white-white zones of the anterior, middle and posterior third were determined. Semiquantitative macroscopic and microscopic grading revealed no structural differences between groups. The red-red zone of the middle third of the lateral menisci of animals that underwent overcorrection exhibited a significant 0.7-fold decrease in mean DNA contents compared with the control knee without HTO (P = 0.012). Comparative estimation of the DNA and proteoglycan contents and proteoglycan/DNA ratios of all other parts and zones of the lateral menisci did not reveal significant differences between groups. Open wedge HTO does not lead to significant macroscopic and microscopic structural changes in the lateral meniscus after 6 months in vivo. Overcorrection significantly decreases the proliferative activity of the cells in the red-red zone of the middle third in the sheep model.

Bioelectrical impedance analysis. What does it measure?

NASA Technical Reports Server (NTRS)

Schoeller, D. A.

2000-01-01

Bioelectrical impedance analysis (BIA) has been proposed for measuring fat-free mass, total body water, percent fat, body cell mass, intracellular water, and extracellular water: a veritable laboratory in a box. Although it is unlikely that BIA is quite this versatile, correlations have been demonstrated between BIA and all of these body compartments. At the same time, it is known that all of the compartments are correlated among themselves. Because of this, it is difficult to determine whether BIA is specific for any or all of these compartments. To investigate this question, we induced acute changes in total body water and its compartments over a 3-h period. Using this approach, we demonstrated that multifrequency BIA, using the Cole-Cole model to calculate the zero frequency and infinite frequency resistance, measures extracellular and intracellular water.

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.

Analysis of space radiation exposure levels at different shielding configurations by ray-tracing dose estimation method

NASA Astrophysics Data System (ADS)

Kartashov, Dmitry; Shurshakov, Vyacheslav

2018-03-01

A ray-tracing method to calculate radiation exposure levels of astronauts at different spacecraft shielding configurations has been developed. The method uses simplified shielding geometry models of the spacecraft compartments together with depth-dose curves. The depth-dose curves can be obtained with different space radiation environment models and radiation transport codes. The spacecraft shielding configurations are described by a set of geometry objects. To calculate the shielding probability functions for each object its surface is composed from a set of the disjoint adjacent triangles that fully cover the surface. Such description can be applied for any complex shape objects. The method is applied to the space experiment MATROSHKA-R modeling conditions. The experiment has been carried out onboard the ISS from 2004 to 2016. Dose measurements were realized in the ISS compartments with anthropomorphic and spherical phantoms, and the protective curtain facility that provides an additional shielding on the crew cabin wall. The space ionizing radiation dose distributions in tissue-equivalent spherical and anthropomorphic phantoms and for an additional shielding installed in the compartment are calculated. There is agreement within accuracy of about 15% between the data obtained in the experiment and calculated ones. Thus the calculation method used has been successfully verified with the MATROSHKA-R experiment data. The ray-tracing radiation dose calculation method can be recommended for estimation of dose distribution in astronaut body in different space station compartments and for estimation of the additional shielding efficiency, especially when exact compartment shielding geometry and the radiation environment for the planned mission are not known.

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.

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.

Evolution of a mini-scale biphasic dissolution model: Impact of model parameters on partitioning of dissolved API and modelling of in vivo-relevant kinetics.

PubMed

Locher, Kathrin; Borghardt, Jens M; Frank, Kerstin J; Kloft, Charlotte; Wagner, Karl G

2016-08-01

Biphasic dissolution models are proposed to have good predictive power for the in vivo absorption. The aim of this study was to improve our previously introduced mini-scale dissolution model to mimic in vivo situations more realistically and to increase the robustness of the experimental model. Six dissolved APIs (BCS II) were tested applying the improved mini-scale biphasic dissolution model (miBIdi-pH-II). The influence of experimental model parameters including various excipients, API concentrations, dual paddle and its rotation speed was investigated. The kinetics in the biphasic model was described applying a one- and four-compartment pharmacokinetic (PK) model. The improved biphasic dissolution model was robust related to differing APIs and excipient concentrations. The dual paddle guaranteed homogenous mixing in both phases; the optimal rotation speed was 25 and 75rpm for the aqueous and the octanol phase, respectively. A one-compartment PK model adequately characterised the data of fully dissolved APIs. A four-compartment PK model best quantified dissolution, precipitation, and partitioning also of undissolved amounts due to realistic pH profiles. The improved dissolution model is a powerful tool for investigating the interplay between dissolution, precipitation and partitioning of various poorly soluble APIs (BCS II). In vivo-relevant PK parameters could be estimated applying respective PK models. Copyright © 2016 Elsevier B.V. All rights reserved.

Loss of BMP signaling through BMPR1A in osteoblasts leads to greater collagen cross-link maturation and material-level mechanical properties in mouse femoral trabecular compartments

PubMed Central

Zhang, Yanshuai; McNerny, Erin Gatenby; Terajima, Masahiko; Raghavan, Mekhala; Romanowicz, Genevieve; Zhang, Zhanpeng; Zhang, Honghao; Kamiya, Nobuhiro; Tantillo, Margaret; Zhu, Peizhi; Scott, Gregory J.; Ray, Manas K.; Lynch, Michelle; Ma, Peter X.; Morris, Michael D.; Yamauchi, Mitsuo; Kohn, David H.; Mishina, Yuji

2016-01-01

Bone morphogenetic protein (BMP) signaling pathways play critical roles in skeletal development and new bone formation. Our previous study, however, showed a negative impact of BMP signaling on bone mass because of the osteoblast-specific loss of a BMP receptor (i.e. BMPR1A) showing increased trabecular bone volume and mineral density in mice. Here, we investigated the bone quality and biomechanical properties of the higher bone mass associated with BMPR1A deficiency using the osteoblast-specific Bmpr1a conditional knockout (cKO) mouse model. Collagen biochemical analysis revealed greater levels of the mature cross-link pyridinoline in the cKO bones, in parallel with upregulation of collagen modifying enzymes. Raman spectroscopy distinguished increases in the mature to immature cross-link ratio and mineral to matrix ratio in the trabecular compartments of cKO femora, but not in the cortical compartments. The mineral crystallinity was unchanged in the cKO in either the trabecular or cortical compartments. Further, we tested the intrinsic material properties by nanoindentation and found significantly higher hardness and elastic modulus in the cKO trabecular compartments, but not in the cortical compartments. Four point bending tests of cortical compartments showed lower structural biomechanical properties (i.e. strength and stiffness) in the cKO bones due to the smaller cortical areas. However, there were no significant differences in biomechanical performance at the material level, which was consistent with the nanoindentation test results on the cortical compartment. These studies emphasize the pivotal role of BMPR1A in the determination of bone quality and mechanical integrity under physiological conditions, with different impact on femoral cortical and trabecular compartments. PMID:27113526

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

A Dynamic Model for Nitrogen‐stressed Lettuce

PubMed Central

SEGINER, IDO

2003-01-01

A previously developed dynamic lettuce model, designed to predict growth and nitrate content under the normal range of glasshouse environmental conditions, has been extended to cover high nitrogen‐stress situations. Under severe shortage of nitrogen, lettuce has been observed to grow at a very slow rate, as well as to have abnormally low water content, low reduced‐nitrogen content and negligible nitrate content. The new model mimics these observations by adding to the original model a storage compartment for ‘excess’ carbon. The resulting model has three compartments: (1) ‘vacuole’, where the soluble non‐structural material is stored, and the nitrate : carbon ratio may vary as needed to maintain a constant osmotic potential; (2) ‘structure’, a metabolically active compartment with fixed chemical composition; and (3) ‘excess‐carbon’, which serves as a long‐term storage of ‘waterless’ carbohydrates. Simulations with the model illustrate its ability to predict the effect of light, temperature and nitrogen in the nutrient solution on the long‐term growth and composition of lettuce. They also illustrate the effects of plant size, and the associated relative growth rate, on the characteristic times of transient responses resulting from step changes in the environment. PMID:12714361

Predicting the evolution of large cholera outbreaks: lessons learnt from the Haiti case study

NASA Astrophysics Data System (ADS)

Bertuzzo, Enrico; Mari, Lorenzo; Righetto, Lorenzo; Knox, Allyn; Finger, Flavio; Casagrandi, Renato; Gatto, Marino; Rodriguez-Iturbe, Ignacio; Rinaldo, Andrea

2013-04-01

Mathematical models can provide key insights into the course of an ongoing epidemic, potentially aiding real-time emergency management in allocating health care resources and possibly anticipating the impact of alternative interventions. Spatially explicit models of waterborne disease are made routinely possible by widespread data mapping of hydrology, road network, population distribution, and sanitation. Here, we study the ex-post reliability of predictions of the ongoing Haiti cholera outbreak. Our model consists of a set of dynamical equations (SIR-like, i.e. subdivided into the compartments of Susceptible, Infected and Recovered individuals) describing a connected network of human communities where the infection results from the exposure to excess concentrations of pathogens in the water, which are, in turn, driven by hydrologic transport through waterways and by mobility of susceptible and infected individuals. Following the evidence of a clear correlation between rainfall events and cholera resurgence, we test a new mechanism explicitly accounting for rainfall as a driver of enhanced disease transmission by washout of open-air defecation sites or cesspool overflows. A general model for Haitian epidemic cholera and the related uncertainty is thus proposed and applied to the dataset of reported cases now available. The model allows us to draw predictions on longer-term epidemic cholera in Haiti from multi-season Monte Carlo runs, carried out up to January 2014 by using a multivariate Poisson rainfall generator, with parameters varying in space and time. Lessons learned and open issues are discussed and placed in perspective. We conclude that, despite differences in methods that can be tested through model-guided field validation, mathematical modeling of large-scale outbreaks emerges as an essential component of future cholera epidemic control.

75 FR 6092 - Special Conditions: Model C-27J Airplane; Class E Cargo Compartment Lavatory

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... waste-receptacle design-and-material standards. (g) Section 25.854, lavatory smoke-detector and fire... lavatory, and the oxygen-supply system in the lavatory, in the event of a smoke-detector alarm in the cargo... system that shuts off power to the lavatory following a lavatory or cargo-compartment smoke-detector...

Modeling malware propagation using a carrier compartment

NASA Astrophysics Data System (ADS)

Hernández Guillén, J. D.; Martín del Rey, A.

2018-03-01

The great majority of mathematical models proposed to simulate malware spreading are based on systems of ordinary differential equations. These are compartmental models where the devices are classified according to some types: susceptible, exposed, infectious, recovered, etc. As far as we know, there is not any model considering the special class of carrier devices. This type is constituted by the devices whose operative systems is not targeted by the malware (for example, iOS devices for Android malware). In this work a novel mathematical model considering this new compartment is considered. Its qualitative study is presented and a detailed analysis of the efficient control measures is shown by studying the basic reproductive number.

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.

STS-49 MS Thuot, in LES, at CCT side hatch during JSC's egress exercises

NASA Technical Reports Server (NTRS)

1992-01-01

STS-49 Endeavour, Orbiter Vehicle (OV) 105, Mission Specialist (MS) Pierre J. Thuot, wearing launch and entry suit (LES), prepares to enter JSC's Crew Compartment Trainer (CCT) via the open side hatch as a technician looks on. Thuot along with the other STS-49 crewmembers is participating in a post-landing emergency egress exercise in JSC's Mockup and Integration Laboratory (MAIL) Bldg 9.

Burn Resuscitation Decision Support System (BRDSS)

DTIC Science & Technology

2014-11-01

agreement was to package the software into a mobile device (the BRDSS-M, trade name Burn Navigator™) with substantial input from caregivers at the USAISR...combat casualties with >30% TBSA burns developed abdominal compartment syndrome (ACS) and perished.2 Between January 2006 and June 2007, after the...or even an open-loop system, could integrate the urine output monitor and infusion pump and free up the caregiver from manual data entry tasks to

Infrared Power Generation: Study in an Insulated Compartment

DTIC Science & Technology

2015-08-17

physics, astronomy and geology , biology and medicine and art, are discussed. Technolosically. 1 the primary objective of this Project is to...astronomy and geology , low frequency and low power radiation must be considered for their interaction with a planet’s magnetic field. In...the afternoon sessions, respectively. Dr. Yvonne R. Harris, JMU’s vice Provost for Research and Scholarship , and Mr. Lynn Petersen opened the event

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.

A COMPREHENSIVE INSIGHT ON OCULAR PHARMACOKINETICS

PubMed Central

Agrahari, Vibhuti; Mandal, Abhirup; Agrahari, Vivek; Trinh, Hoang My; Joseph, Mary; Ray, Animikh; Hadji, Hicheme; Mitra, Ranjana; Pal, Dhananjay; Mitra, Ashim K.

2017-01-01

Eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment model of ocular drug delivery has been developed for describing the absorption, distribution and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems and routes of administration are discussed including factors affecting intraocular bioavailability. Factors such as pre-corneal fluid drainage, drug binding to tear proteins, systemic drug absorption, corneal factors, melanin binding, drug metabolism renders ocular delivery challenging and elaborated in this manuscript. Several compartment models are discussed those are developed in ocular drug delivery to study the pharmacokinetics parameters. There are several transporters present in both anterior and posterior segments of the eye which play a significant role in ocular pharmacokinetics and summarized briefly. Moreover, several ocular pharmacokinetics animal models and relevant studies are reviewed and discussed in addition to the pharmacokinetics of various ocular formulations. PMID:27798766

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.

The Decompression Sickness and Venous Gas Emboli Consequences of Air Breaks During 100% Oxygen Prebreathe

NASA Technical Reports Server (NTRS)

Conkin, J.; Gernhardt, M. L.; Powell, M. R.

2004-01-01

Not enough is known about the increased risk of hypobaric decompression sickness (DCS) and production of venous (VGE) and arterial (AGE) gas emboli following an air break in an otherwise normal 100% resting oxygen (O2) prebreathe (PB), and certainly a break in PB when exercise is used to accelerate nitrogen (N2) elimination from the tissues. Current Aeromedical Flight Rules at the Johnson Space Center about additional PB payback times are untested, possibly too conservative, and therefore not optimized for operational use. A 10 min air break at 90 min into a 120 min PB that includes initial dual-cycle ergometry for 10 min will show a measurable increase in the risk of DCS and VGE after ascent to 4.3 psia compared to a 10 min break at 15 min into the PB, or when there is no break in PB. Data collection with humans begins in 2005, but here we first evaluate the hypothesis using three models of tissue N2 kinetics: Model I is a simple single half-time compartment exponential model, Model II is a three compartment half-time exponential model, and Model III is a variable half-time compartment model where the percentage of maximum O2 consumption for the subject during dual-cycle ergometry exercise defines the half-time compartment. Model I with large rate constants to simulate an exercise effect always showed a late break in PB had the greatest consequence. Model II showed an early break had the greatest consequence. Model III showed there was no difference between early or late break in exercise PB. Only one of these outcomes will be observed when humans are tested. Our results will favor one of these models, and so advance our understanding of tissue N2 kinetics, and of altitude DCS after an air break in PB.

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

A preliminary investigation of the drag and ventilation characteristics of livestock haulers

NASA Technical Reports Server (NTRS)

Hoffman, J. A.; Sandin, D. R.

1983-01-01

A wind tunnel evaluation of the drag and ventilation characteristics of a conventional (unmodified) and five modified subscale model livestock haulers at 0 deg yaw angle has been made. The unmodified livestock hauler has a relatively high drag coefficient, and a low velocity recirculation region exists in the forward portion of the hauler. The use of a streamlined forebody and enclosed gap reduced the drag coefficient of one model by 42% and improved the rate at which contaminants can be flushed from the cargo compartment by a factor of 2.5. From the limited data obtained, any increase in the fraction of open area of the trailer sides was found to improve the trailer ventilation. The use of a ram air inlet can improve the ventilation within the hauler and remove the low velocity recirculation region at the expense of a modest increase in the truck's drag coefficient. A mathematical model for vehicles with ram air or NACA submerged inlets was developed and appears to adequately predict the ventilation characteristics of livestock haulers.

Orthopaedic traumatology: fundamental principles and current controversies for the acute care surgeon

PubMed Central

Pharaon, Shad K; Schoch, Shawn; Marchand, Lucas; Mirza, Amer

2018-01-01

Multiply injured patients with fractures are co-managed by acute care surgeons and orthopaedic surgeons. In most centers, orthopaedic surgeons definitively manage fractures, but preliminary management, including washouts, splinting, reductions, and external fixations, may be performed by selected acute care surgeons. The acute care surgeon should have a working knowledge of orthopaedic terminology to communicate with colleagues effectively. They should have an understanding of the composition of bone, periosteum, and cartilage, and their reaction when there is an injury. Fractures are usually fixed urgently, but some multiply injured patients are better served with a damage control strategy. Extremity compartment syndrome should be suspected in all critically injured patients with or without fractures and a low threshold for compartment pressure measurements or empiric fasciotomy maintained. Acute care surgeons performing rib fracture fixation and other chest wall injury reconstructions should follow the principles of open fracture reduction and stabilization. PMID:29766123

Can a pin-tract infection cause an acute generalized soft tissue infection and a compartment syndrome?

PubMed

Orhun, Haldun; Saka, Gürsel; Enercan, Meriç

2005-10-01

A patient who developed soft tissue infection and osteomyelitis secondary to pin tract infection after skeletal traction was evaluated. Tibial traction was performed on a patient who had exposed to a femoral pertrochanteric fracture after falling from a tree in a rural public hospital. On the first postoperative day shortly after development of soft tissue swelling, redness, and tenderness in the affected leg, compartment syndrome was noted with subsequent removal of the pin at the same health center. After arrival of the case in our center surgical decompression with an open faciatomy and proper antibiotherapy were instituted. Simultaneously hyperbaric oxygen was administered. After eradication of soft tissue infection we treated the fracture with a Richards compression screw-plate device. The patient was discharged with complete cure. This case presented how seriously a simple pin-tract infection can cause a grave clinical entity resulting in potential loss of an extremity.

Orthopaedic traumatology: fundamental principles and current controversies for the acute care surgeon.

PubMed

Pharaon, Shad K; Schoch, Shawn; Marchand, Lucas; Mirza, Amer; Mayberry, John

2018-01-01

Multiply injured patients with fractures are co-managed by acute care surgeons and orthopaedic surgeons. In most centers, orthopaedic surgeons definitively manage fractures, but preliminary management, including washouts, splinting, reductions, and external fixations, may be performed by selected acute care surgeons. The acute care surgeon should have a working knowledge of orthopaedic terminology to communicate with colleagues effectively. They should have an understanding of the composition of bone, periosteum, and cartilage, and their reaction when there is an injury. Fractures are usually fixed urgently, but some multiply injured patients are better served with a damage control strategy. Extremity compartment syndrome should be suspected in all critically injured patients with or without fractures and a low threshold for compartment pressure measurements or empiric fasciotomy maintained. Acute care surgeons performing rib fracture fixation and other chest wall injury reconstructions should follow the principles of open fracture reduction and stabilization.

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.

Measurement of regional cerebral blood flow with copper-62-PTSM and a three-compartment model.

PubMed

Okazawa, H; Yonekura, Y; Fujibayashi, Y; Mukai, T; Nishizawa, S; Magata, Y; Ishizu, K; Tamaki, N; Konishi, J

1996-07-01

We evaluated quantitatively 62Cu-labeled pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) as a brain perfusion tracer for positron emission tomography (PET). For quantitative measurement, the octanol extraction method is needed to correct for arterial radioactivity in estimating the lipophilic input function, but the procedure is not practical for clinical studies. To measure regional cerebral blood flow (rCBF) by 62Cu-PTSM with simple arterial blood sampling, a standard curve of the octanol extraction ratio and a three-compartment model were applied. We performed both 15O-labeled water PET and 62 Cu-PTSM PET with dynamic data acquisition and arterial sampling in six subjects. Data obtained in 10 subjects studied previously were used for the standard octanol extraction curve. Arterial activity was measured and corrected to obtain the true input function using the standard curve. Graphical analysis (Gjedde-Patlak plot) with the data for each subject fitted by a straight regression line suggested that 62Cu-PTSM can be analyzed by the three-compartment model with negligible K4. Using this model, K1-K3 were estimated from curve fitting of the cerebral time-activity curve and the corrected input function. The fractional uptake of 62Cu-PTSM was corrected to rCBF with the individual extraction at steady state calculated from K1-K3. The influx rates (Ki) obtained from three-compartment model and graphical analyses were compared for the validation of the model. A comparison of rCBF values obtained from 62Cu-PTSM and 150-water studies demonstrated excellent correlation. The results suggest the potential feasibility of quantitation of cerebral perfusion with 62Cu-PTSM accompanied by dynamic PET and simple arterial sampling.

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.
.

Kernel Regression Estimation of Fiber Orientation Mixtures in Diffusion MRI

PubMed Central

Cabeen, Ryan P.; Bastin, Mark E.; Laidlaw, David H.

2016-01-01

We present and evaluate a method for kernel regression estimation of fiber orientations and associated volume fractions for diffusion MR tractography and population-based atlas construction in clinical imaging studies of brain white matter. This is a model-based image processing technique in which representative fiber models are estimated from collections of component fiber models in model-valued image data. This extends prior work in nonparametric image processing and multi-compartment processing to provide computational tools for image interpolation, smoothing, and fusion with fiber orientation mixtures. In contrast to related work on multi-compartment processing, this approach is based on directional measures of divergence and includes data-adaptive extensions for model selection and bilateral filtering. This is useful for reconstructing complex anatomical features in clinical datasets analyzed with the ball-and-sticks model, and our framework’s data-adaptive extensions are potentially useful for general multi-compartment image processing. We experimentally evaluate our approach with both synthetic data from computational phantoms and in vivo clinical data from human subjects. With synthetic data experiments, we evaluate performance based on errors in fiber orientation, volume fraction, compartment count, and tractography-based connectivity. With in vivo data experiments, we first show improved scan-rescan reproducibility and reliability of quantitative fiber bundle metrics, including mean length, volume, streamline count, and mean volume fraction. We then demonstrate the creation of a multi-fiber tractography atlas from a population of 80 human subjects. In comparison to single tensor atlasing, our multi-fiber atlas shows more complete features of known fiber bundles and includes reconstructions of the lateral projections of the corpus callosum and complex fronto-parietal connections of the superior longitudinal fasciculus I, II, and III. PMID:26691524

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.

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.

76 FR 26949 - Special Conditions: Boeing Model 747-8 Series Airplanes; Overhead Flight Attendant Rest Compartment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

... comments on this proposal, include with your comments a pre-addressed, stamped postcard on which the docket number appears. We will stamp the date on the postcard and mail it back to you. Background On November 4... pots), other than a conventional lavatory or kitchenette hot water heater, within the OFAR compartment...

Comparison of different blood compartments for the detection of circulating DNA using a rat model of Pneumocystis pneumonia.

PubMed

Fréalle, E; Gantois, N; Aliouat-Denis, C M; Leroy, S; Zawadzki, C; Perkhofer, S; Aliouat, E M; Dei-Cas, E

2015-09-01

Pneumocystis is mostly found in the alveolar spaces, but circulation of viable organisms also occurs and suggests that the detection of DNA in blood could be used as a noninvasive procedure to improve the diagnosis of Pneumocystis pneumonia (PcP). In order to determine the optimal compartment for Pneumocystis DNA detection, we used a rat model of PcP and tested the presence of Pneumocystis with a quantitative mtLSU targeting real-time PCR in four blood compartments: whole blood, clot, serum and Platelet-Rich-Plasma (PRP). All samples from 4 Pneumocystis-free control rats were negative. Pneumocystis was detected in 79, 64, 57, and 57% of samples from 14 PcP rats, respectively, but DNA release was not related to pulmonary loads. These data confirm the potential usefulness of Pneumocystis DNA detection in the blood for PcP diagnosis and suggest that whole blood could be the most appropriate compartment for Pneumocystis detection. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Factors affecting the open-circuit voltage and electrode kinetics of some iron/titanium redox flow cells

NASA Technical Reports Server (NTRS)

Reid, M. A.; Gahn, R. F.

1977-01-01

Performance of the iron-titanium redox flow cell was studied as a function of acid concentration. Anion permeable membranes separated the compartments. Electrodes were graphite cloth. Current densities ranged up to 25 mA/square centimeter. Open-circuit and load voltages decreased as the acidity was increased on the iron side as predicted. On the titanium side, open-circuit voltages decreased as the acidity was increased in agreement with theory, but load voltages increased due to decreased polarization with increasing acidity. High acidity on the titanium side coupled with low acidity on the iron side gives the best load voltage, but such cells show voltage losses as they are repeatedly cycled. Analyses show that the bulk of the voltage losses are due to diffusion of acid through the membrane.

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.

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.

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.

Numerical Modeling of Ophthalmic Response to Space

NASA Technical Reports Server (NTRS)

Nelson, E. S.; Myers, J. G.; Mulugeta, L.; Vera, J.; Raykin, J.; Feola, A.; Gleason, R.; Samuels, B.; Ethier, C. R.

2015-01-01

To investigate ophthalmic changes in spaceflight, we would like to predict the impact of blood dysregulation and elevated intracranial pressure (ICP) on Intraocular Pressure (IOP). Unlike other physiological systems, there are very few lumped parameter models of the eye. The eye model described here is novel in its inclusion of the human choroid and retrobulbar subarachnoid space (rSAS), which are key elements in investigating the impact of increased ICP and ocular blood volume. Some ingenuity was required in modeling the blood and rSAS compartments due to the lack of quantitative data on essential hydrodynamic quantities, such as net choroidal volume and blood flowrate, inlet and exit pressures, and material properties, such as compliances between compartments.

Morphological elucidation of basal ganglia circuits contributing reward prediction

PubMed Central

Fujiyama, Fumino; Takahashi, Susumu; Karube, Fuyuki

2015-01-01

Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits. The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor–critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments. PMID:25698913

The development of the MELiSSA Pilot Plant Facility

NASA Astrophysics Data System (ADS)

Godia, Francesc; Dussap, Claude-Gilles; Dixon, Mike; Peiro, Enrique; Fossen, Arnaud; Lamaze, Brigitte; Brunet, Jean; Demey, Dries; Mas-Albaigès, Joan L.

MELiSSA (Micro-Ecological Life Support System Alternative) is a closed artificial ecosystem intended as a tool for the development of a bio-regenerative life support system for longterm manned missions. The MELiSSA loop is formed by five interconnected compartments, organized in three different loops (solid, liquid and gas). This compartments are microbial bioreactors and higher plant chambers. The MELiSSA Pilot Plant facility has been designed to achieve the preliminary terrestrial demonstration of the MELiSSA concept at pilot scale, using animals as a model for the crew compartent. The experience gained in the operation of such a facility will be highly relevant for planning future life support systems in Space. In this communication, the latests developments in the MELiSSA Pilot Plant will be reported. Particularly, the completion of the design phase and instalation of all the different compartments will be discussed in detail. Each of the compartments had to be designed and constructed according to very specific characteristics, associated to the biological systems to be cultured, as part of the complete MELiSSA loop (anerobic, oxygenic, thermophilic, heterotrophic, autotrophic, axenic, photosynthetic, etc.). Additionally, the sizing of each reactor (ranging from 8 to 100 Liters, depending of each particular compartment) should compile with the global integration scenario proposed, and with the final goal of connection of all compartments to provide a demonstration of the MELiSSA concept, and generate data for the design and operation of future biological life support systems.

[Effect of the ISS Russian segment configuration on the service module radiation environment].

PubMed

Mitrikas, V G

2011-01-01

Mathematical modeling of variations in the Service module radiation environment as a function of ISS Russian segment configuration was carried out using models of the RS modules and a spherical humanoid phantom. ISS reconfiguration impacted significantly only the phantom brought into the transfer compartment (ExT). The Radiation Safety Service prohibition for cosmonauts to stay in this compartment during solar flare events remains valid. In all other instances, error of dose estimation is higher as compared to dose value estimation with consideration for ISS RS reconfiguration.

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.

Investigation of Ruthenium Dissolution in Advanced Membrane Electrode Assemblies for Direct Methanol Based Fuel Cell Stacks

NASA Technical Reports Server (NTRS)

Valdez, Thomas I.; Firdosy, S.; Koel, B. E.; Narayanan, S. R.

2005-01-01

Dissolution of ruthenium was observed in the 80-cell stack. Duration testing was performed in single cell MEAs to determine the pathway of cell degradation. EDAX analysis on each of the single cell MEAs has shown that the Johnson Matthey commercial catalyst is stable in DMFC operation for 250 hours, no ruthenium dissolution was observed. Changes in the hydrophobicity of the cathode backing papers was minimum. Electrode polarization analysis revealed that the MEA performance loss is attributed to changes in the cathode catalyst layer. Ruthenium migration does not seem to occur during cell operation but can occur when methanol is absent from the anode compartment, the cathode compartment has access to air, and the cells in the stack are electrically connected to a load (Shunt Currents). The open-to-air cathode stack design allowed for: a) The MEAs to have continual access to oxygen; and b) The stack to sustain shunt currents. Ruthenium dissolution in a DMFC stack can be prevented by: a) Developing an internally manifolded stacks that seal reactant compartments when not in operation; b) Bringing the cell voltages to zero quickly when not in operation; and c) Limiting the total number of cells to 25 in an effort to limit shunt currents.

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

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.

Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and intramuscular administration to sheep.

PubMed Central

Escudero, E; Espuny, A; Vicente, S; Cárceles, C M

1999-01-01

The pharmacokinetics of a 2:1 ampicillin-sulbactam combination were studied in 6 sheep, after intravenous and intramuscular injection at a single dose rate of 20 mg/kg body weight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam). The drugs were distributed according to an open 2-compartment model after intravenous administration and a one-compartment model with first order absorption after intramuscular administration. The apparent volumes of distribution calculated by the area method of ampicillin and sulbactam were 0.32+/-0.06 L/kg and 0.42+/-0.04 L/kg, respectively and the total body clearances were 0.69+/-0.07 and 0.38+/-0.03 L/kg x h, respectively. The elimination half-lives of ampicillin after intravenous and intramuscular administration were 0.32+/-0.05 h and 0.75+/-0.27 h, respectively, whereas for sulbactam the half-lives were 0.74+/-0.10 h and 0.89+/-0.16 h, respectively. The bioavailability after intramuscular injection was high and similar in both drugs (72.76+/-9.65% for ampicillin and 85.50+/-8.35% for sulbactam). The mean peak plasma concentrations of ampicillin and sulbactam were reached at similar times (0.25+/-0.10 h and 0.24+/-0.08 h, respectively) and peak concentrations were also similar but nonproportional to the dose of both products administered (13.01+/-7.36 mg/L of ampicillin and 10.39+/-3.95 mg/L of sulbactam). Both drugs had a similar pharmacokinetic behavior after intramuscular administration in sheep. Since the plasma concentrations of sulbactam where consistently higher during the elimination phase of their disposition, consideration could be given to formulating the ampicillin-sulbactam combination in a higher than 2:1 ratio. PMID:9918330

Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

PubMed Central

Groll, Andreas H.; Gullick, Bryan M.; Petraitiene, Ruta; Petraitis, Vidmantas; Candelario, Myrna; Piscitelli, Stephen C.; Walsh, Thomas J.

2001-01-01

The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (Cmax) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increased Vdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi. PMID:11158761

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.

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.

A decoy trap for breeding-season mallards in North Dakota

USGS Publications Warehouse

Sharp, D.E.; Lokemoen, J.T.

1987-01-01

A modified decoy trap was effective for capturing wild adult male and female mallards (Anas platyrhynchos) during the 1980-81 breeding seasons in North Dakota. Key features contributing to the trap's success included a central decoy cylinder, large capture compartments with spring-door openings, an adjustable trigger mechanism with a balanced door attachment that was resistant to trap movement, and the use of F1, wild-stock or game-farm female decoys.

Practical Modeling Concepts for Connective Tissue Stem Cell and Progenitor Compartment Kinetics

PubMed Central

2003-01-01

Stem cell activation and development is central to skeletal development, maintenance, and repair, as it is for all tissues. However, an integrated model of stem cell proliferation, differentiation, and transit between functional compartments has yet to evolve. In this paper, the authors review current concepts in stem cell biology and progenitor cell growth and differentiation kinetics in the context of bone formation. A cell-based modeling strategy is developed and offered as a tool for conceptual and quantitative exploration of the key kinetic variables and possible organizational hierarchies in bone tissue development and remodeling, as well as in tissue engineering strategies for bone repair. PMID:12975533

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

Hydrological modelling in forested systems | Science ...

EPA Pesticide Factsheets

This chapter provides a brief overview of forest hydrology modelling approaches for answering important global research and management questions. Many hundreds of hydrological models have been applied globally across multiple decades to represent and predict forest hydrological processes. The focus of this chapter is on process-based models and approaches, specifically 'forest hydrology models'; that is, physically based simulation tools that quantify compartments of the forest hydrological cycle. Physically based models can be considered those that describe the conservation of mass, momentum and/or energy. The purpose of this chapter is to provide a brief overview of forest hydrology modeling approaches for answering important global research and management questions. The focus of this chapter is on process-based models and approaches, specifically “forest hydrology models”, i.e., physically-based simulation tools that quantify compartments of the forest hydrological cycle.

77 FR 29331 - Publication of the Petition for Waiver From Sanyo E&E Corporation From the Department of Energy...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-17

... these hybrid models is cable of achieving temperatures at or below 38 [deg]F, the wine storage compartment of these single-cabinet units can only achieve a minimum temperature of 45 [deg]F. As a result, it... energy consumption be measured when each compartment temperature is set at 38 [deg]F. In order to...

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.

A Multi-Compartment 3-D Finite Element Model of Rectocele and Its Interaction with Cystocele

PubMed Central

Luo, Jiajia; Chen, Luyun; Fenner, Dee E.; Ashton-Miller, James A.; DeLancey, John O. L.

2015-01-01

We developed a subject-specific 3-D finite element model to understand the mechanics underlying formation of female pelvic organ prolapse, specifically a rectocele and its interaction with a cystocele. The model was created from MRI 3-D geometry of a healthy 45 year-old multiparous woman. It included anterior and posterior vaginal walls, levator ani muscle, cardinal and uterosacral ligaments, anterior and posterior arcus tendineus fascia pelvis, arcus tendineus levator ani, perineal body, perineal membrane and anal sphincter. Material properties were mostly from the literature. Tissue impairment was modeled as decreased tissue stiffness based on previous clinical studies. Model equations were solved using Abaqus v 6.11. The sensitivity of anterior and posterior vaginal wall geometry was calculated for different combinations tissue impairments under increasing intraabdominal pressure. Prolapse size was reported as POP-Q point at point Bp for rectocele and point Ba for cystocele. Results show that a rectocele resulted from impairments of the levator ani and posterior compartment support. For 20% levator and 85% posterior support impairments, simulated rectocele size (at POP-Q point: Bp) increased 0.29 mm/cm H2O without apical impairment and 0.36 mm/cm H2O with 60% apical impairment, as intraabdominal pressures increased from 0 to 150 cm H2O. Apical support impairment could result in the development of either a cystocele or rectocele. Simulated repair of posterior compartment support decreased rectocele but increased a preexisting cystocele. We conclude that development of rectocele and cystocele depend on the presence of anterior, posterior, levator and/or or apical support impairments, as well as the interaction of the prolapse with the opposing compartment. PMID:25757664

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

Delayed unlatching mechanism

DOEpatents

Bzorgi, Fariborz M.

2015-05-19

In various embodiments an apparatus is presented for securing a structure such as a door, window, hatch, or gate that moves between an open and a closed position relative to a fixed structure to provide or deny access to a compartment, a room, an outdoor area, or a facility. Various embodiments provide a delay in opening the closure of sufficient duration to frustrate a rapid activation that might be desired by a person who is attempting to pass through the closure for some illicit purpose. Typically, hydraulics are used to activate the apparatus and no electrical energy or electronic signals are employed. In one embodiment, a plurality of actuations of a hand lever operates a hydraulic pump that moves a locking bolt from a first position in which a locking bolt is engaged with a recess in the fixed structure (preventing opening of a gate) to a second position in which the locking bolt is disengaged from the recess to permit opening of the gate.

Non-perturbative Quantification of Ionic Charge Transfer through Nm-Scale Protein Pores Using Graphene Microelectrodes

NASA Astrophysics Data System (ADS)

Ping, Jinglei; Johnson, A. T. Charlie; A. T. Charlie Johnson Team

Conventional electrical methods for detecting charge transfer through protein pores perturb the electrostatic condition of the solution and chemical reactivity of the pore, and are not suitable to be used for complex biofluids. We developed a non-perturbative methodology ( fW input power) for quantifying trans-pore electrical current and detecting the pore status (i.e., open vs. closes) via graphene microelectrodes. Ferritin was used as a model protein featuring a large interior compartment, well-separated from the exterior solution with discrete pores as charge commuting channels. The charge flowing through the ferritin pores transfers into the graphene microelectrode and is recorded by an electrometer. In this example, our methodology enables the quantification of an inorganic nanoparticle-protein nanopore interaction in complex biofluids. The authors acknowledge the support from the Defense Advanced Research Projects Agency (DARPA) and the U.S. Army Research Office under Grant Number W911NF1010093.

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.

Satisfactory functional and radiological outcomes can be expected in young patients under 45 years old after open wedge high tibial osteotomy in a long-term follow-up.

PubMed

Hantes, Michael E; Natsaridis, Prodromos; Koutalos, Antonios A; Ono, Yohei; Doxariotis, Nikolaos; Malizos, Konstantinos N

2017-11-30

To report the long-term outcomes of medial open wedge high tibial osteotomy (MOWHTO) for the treatment of medial compartment knee osteoarthritis in patients younger than 45 years old. It was hypothesized that the correction of knee alignment would result in preservation of knee function in a long-term follow-up. Patients under 45 years old, who underwent MOWHTO for symptomatic medial compartment knee osteoarthritis between 2001 and 2005 were retrospectively reviewed after a minimum of 10 years. The osteotomy was performed utilizing a locking plate without the use of bone graft. Patients were evaluated pre- and postoperatively using the International Knee Documentation Committee Score, the Oxford Knee Score, the Knee injury Osteoarthritis Outcome Score and the Short Form-12 Score. Standardized standing whole-limb radiographs were also obtained to assess mechanical tibiofemoral angle (mTFA) and the grade of osteoarthritis. A total of 20 patients (18 males, 2 females, mean age 35.4 years) with a mean follow-up of 12.3 years were included in the study. During the follow-up period, one patient required conversion to total knee replacement (95% survival rate). All clinical outcome scores (IKDC, KOOS, OKS, and SF-12) significantly improved postoperatively (p < 0.05), with no significant deterioration over time. Preoperative varus alignment with an mTFA of - 5.8 ± 2.4° was corrected to 2.5 ± 1.9° immediately after surgery (p < 0.05), and remained 2.2 ± 1.7° at the last follow-up. Furthermore, no significant radiographic progression of osteoarthritis was observed. MWOHTO with a locking plate is an effective joint preservation method to treat medial compartment OA in active patients less than 45 years. Clinical and radiological results are satisfactory and the survival rate is 95%, 12 years after the procedure. Level IV therapeutic, retrospective, cohort study.

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.

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.

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.

Numerical cell model investigating cellular carbon fluxes in Emiliania huxleyi.

PubMed

Holtz, Lena-Maria; Wolf-Gladrow, Dieter; Thoms, Silke

2015-01-07

Coccolithophores play a crucial role in the marine carbon cycle and thus it is interesting to know how they will respond to climate change. After several decades of research the interplay between intracellular processes and the marine carbonate system is still not well understood. On the basis of experimental findings given in literature, a numerical cell model is developed that describes inorganic carbon fluxes between seawater and the intracellular sites of calcite precipitation and photosynthetic carbon fixation. The implemented cell model consists of four compartments, for each of which the carbonate system is resolved individually. The four compartments are connected to each other via H(+), CO2, and HCO3(-) fluxes across the compartment-confining membranes. For CO2 accumulation around RubisCO, an energy-efficient carbon concentrating mechanism is proposed that relies on diffusive CO2 uptake. At low external CO2 concentrations and high light intensities, CO2 diffusion does not suffice to cover the carbon demand of photosynthesis and an additional uptake of external HCO3(-) becomes essential. The model is constrained by data of Emiliania huxleyi, the numerically most abundant coccolithophore species in the present-day ocean. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

Modeling the dynamic volatile fatty acids profiles with pH and hydraulic retention time in an anaerobic baffled reactor during the startup period.

PubMed

Shi, En; Li, Jianzheng; Leu, Shao-Yuan; Antwi, Philip

2016-12-01

To predict the dynamic profiles in volatile fatty acids (VFAs) with pH and hydraulic retention time (HRT) during the startup of a 4-compartment ABR, a mathematical model was constructed by introducing pH and thermodynamic inhibition functions into the biochemical processes derived from the ADM1. The calibration of inhibition parameter for propionate uptake effectively improved the prediction accuracy of VFAs. The developed model could simulate the VFAs profiles very well no matter the observable change of pH or/and HRT. The simulation results indicated that both H 2 -producing acetogenesis and methanogenesis in the ABR would be inhibited with a pH less than 4.61, and the propionate oxidation could be thermodynamically restricted even with a neutral pH. A decreased HRT would enhanced the acidogenesis and H 2 -producing acetogenesis in the first 3 compartments, but no observable increase in effluent VFAs could be found due to the synchronously enhanced methanogenesis in the last compartment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of recirculation configurations for biological nutrient removal in a membrane bioreactor.

PubMed

Bekir Ersu, Cagatayhan; Ong, Say Kee; Arslankaya, Ertan; Brown, Patrick

2008-03-01

A 12-L lab-scale membrane bioreactor (MBR), consisting of an anaerobic and anoxic compartment followed by an oxic plate-frame membrane compartment, was evaluated for carbonaceous and nutrient removals by varying the recirculation of mixed liquor and permeate. The hydraulic retention times (HRTs) for the anaerobic, anoxic, and oxic compartments were 2, 2, and 8h, respectively. The solids residence time (SRT) for the oxic compartment was 25 days. Five different recirculation configurations were tested by recirculating mixed liquor and/or permeate recirculation equal to the influent flow rate (identified as 100%) into different locations of the anaerobic and anoxic compartments. Of the five configurations, the configuration with 100% mixed liquor recirculation to the anaerobic compartment and 100% permeate recirculation to the anoxic compartment gave the highest percentage removal with an average 92.3+/-0.5% soluble chemical oxygen demand (sCOD), 75.6+/-0.4% total nitrogen (TN), and 62.4+/-1.3% total phosphorus (TP) removal. When the mixed liquor and permeate recirculation rates were varied for the same configuration, the highest TP removal was obtained for 300% mixed liquor recirculation and 100% permeate recirculation (300%/100%) with a TP removal of 88.1+/-1.3% while the highest TN removal (90.3+/-0.3%) was obtained for 200%/300% recirculation. TN and TP concentrations as low as 4.2+/-0.1 and 1.4+/-0.2mg/L respectively were obtained. Mass loading rates were generally low in the range of 0.11-0.22kgCOD/kgMLSS/d due to high biomass concentrations within the oxic reactor (approx. 8000mg/L). The BioWin model was calibrated against one set of the experimental data and was found to predict the experimental data of effluent TN, TP, and NO(3)(-)-N but over-predicted sCOD and NH(3)-N for various recirculation rates. The anoxic heterotrophic yield for the calibrated model was 0.2kg biomass COD/kg COD utilized while the maximum growth rates were found to be 0.45day(-1) for mu(max-autotroph), 3.2day(-1) for mu(max-heterotroph), and 1.5day(-1) for mu(max-PAO).

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.

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.

A mathematical model for CTL effect on a latently infected cell inclusive HIV dynamics and treatment

NASA Astrophysics Data System (ADS)

Tarfulea, N. E.

2017-10-01

This paper investigates theoretically and numerically the effect of immune effectors, such as the cytotoxic lymphocyte (CTL), in modeling HIV pathogenesis (via a newly developed mathematical model); our results suggest the significant impact of the immune response on the control of the virus during primary infection. Qualitative aspects (including positivity, boundedness, stability, uncertainty, and sensitivity analysis) are addressed. Additionally, by introducing drug therapy, we analyze numerically the model to assess the effect of treatment consisting of a combination of several antiretroviral drugs. Our results show that the inclusion of the CTL compartment produces a higher rebound for an individual's healthy helper T-cell compartment than drug therapy alone. Furthermore, we quantitatively characterize successful drugs or drug combination scenarios.

Geometric approach to segmentation and protein localization in cell culture assays.

PubMed

Raman, S; Maxwell, C A; Barcellos-Hoff, M H; Parvin, B

2007-01-01

Cell-based fluorescence imaging assays are heterogeneous and require the collection of a large number of images for detailed quantitative analysis. Complexities arise as a result of variation in spatial nonuniformity, shape, overlapping compartments and scale (size). A new technique and methodology has been developed and tested for delineating subcellular morphology and partitioning overlapping compartments at multiple scales. This system is packaged as an integrated software platform for quantifying images that are obtained through fluorescence microscopy. Proposed methods are model based, leveraging geometric shape properties of subcellular compartments and corresponding protein localization. From the morphological perspective, convexity constraint is imposed to delineate and partition nuclear compartments. From the protein localization perspective, radial symmetry is imposed to localize punctate protein events at submicron resolution. Convexity constraint is imposed against boundary information, which are extracted through a combination of zero-crossing and gradient operator. If the convexity constraint fails for the boundary then positive curvature maxima are localized along the contour and the entire blob is partitioned into disjointed convex objects representing individual nuclear compartment, by enforcing geometric constraints. Nuclear compartments provide the context for protein localization, which may be diffuse or punctate. Punctate signal are localized through iterative voting and radial symmetries for improved reliability and robustness. The technique has been tested against 196 images that were generated to study centrosome abnormalities. Corresponding computed representations are compared against manual counts for validation.

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.

SSM-based electrophysiology.

PubMed

Schulz, Patrick; Garcia-Celma, Juan J; Fendler, Klaus

2008-10-01

An assay technique for the electrical characterization of electrogenic transport proteins on solid supported membranes is presented. Membrane vesicles, proteoliposomes or membrane fragments containing the transporter are adsorbed to the solid supported membrane and are activated by providing a substrate or a ligand via a rapid solution exchange. This technique opens up new possibilities where conventional electrophysiology fails like transporters or ion channels from bacteria and from intracellular compartments. Its rugged design and potential for automation make it suitable for drug screening.

STS-49 MS Thornton, in LES, at the CCT side hatch during JSC egress exercises

NASA Technical Reports Server (NTRS)

1992-01-01

STS-49 Endeavour, Orbiter Vehicle (OV) 105, Mission Specialist (MS) Kathryn C. Thornton, wearing launch and entry suit (LES) and with foot propped on open side hatch, prepares to enter JSC's Crew Compartment Trainer (CCT) located in the Mockup and Integration Laboratory (MAIL) Bldg 9. Thornton along with other STS-49 crewmembers is participating in post-landing emergency egress training. Photo taken by NASA JSC contract photographer Mark Sowa.

Mathematical modelling of the influenced of diffusion rate on macro nutrient availability in paddy field

NASA Astrophysics Data System (ADS)

Renny; Supriyanto

2018-04-01

Nutrition is the chemical compounds that needed by the organism for the growth process. In plants, nutrients are organic or inorganic compounds that are absorbed from the roots of the soil. It consist of macro and micro nutrient. Macro nutrients are nutrition that needed by plants in large quantities, such as, nitrogen, calcium, pottacium, magnesium, and sulfur. The total soil nutrient is the difference between the input nutrient and the output nutrients. Input nutrients are nutrient that derived from the decomposition of organic substances. Meanwhile, the output nutrient consists of the nutrients that absorbed by plant roots (uptake), the evaporated nutrients (volatilized) and leached nutrients. The nutrient transport can be done through diffusion process. The diffusion process is essential in removing the nutrient from one place to the root surface. It will cause the rate of absorption of nutrient by the roots will be greater. Nutrient concept in paddy filed can be represented into a mathematical modelling, by making compartment models. The rate of concentration change in the compartment model forms a system of homogeneous linear differential equations. In this research, we will use Laplaces transformation to solve the compartment model and determined the dynamics of macro nutrition due to diffusion process.

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.

A probabilistic approach to assess antibiotic resistance development risks in environmental compartments and its application to an intensive aquaculture production scenario.

PubMed

Rico, Andreu; Jacobs, Rianne; Van den Brink, Paul J; Tello, Alfredo

2017-12-01

Estimating antibiotic pollution and antibiotic resistance development risks in environmental compartments is important to design management strategies that advance our stewardship of antibiotics. In this study we propose a modelling approach to estimate the risk of antibiotic resistance development in environmental compartments and demonstrate its application in aquaculture production systems. We modelled exposure concentrations for 12 antibiotics used in Vietnamese Pangasius catfish production using the ERA-AQUA model. Minimum selective concentration (MSC) distributions that characterize the selective pressure of antibiotics on bacterial communities were derived from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) Minimum Inhibitory Concentration dataset. The antibiotic resistance development risk (RDR) for each antibiotic was calculated as the probability that the antibiotic exposure distribution exceeds the MSC distribution representing the bacterial community. RDRs in pond sediments were nearly 100% for all antibiotics. Median RDR values in pond water were high for the majority of the antibiotics, with rifampicin, levofloxacin and ampicillin having highest values. In the effluent mixing area, RDRs were low for most antibiotics, with the exception of amoxicillin, ampicillin and trimethoprim, which presented moderate risks, and rifampicin and levofloxacin, which presented high risks. The RDR provides an efficient means to benchmark multiple antibiotics and treatment regimes in the initial phase of a risk assessment with regards to their potential to develop resistance in different environmental compartments, and can be used to derive resistance threshold concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multiphoton fluorescence lifetime imaging of chemotherapy distribution in solid tumors

NASA Astrophysics Data System (ADS)

Carlson, Marjorie; Watson, Adrienne L.; Anderson, Leah; Largaespada, David A.; Provenzano, Paolo P.

2017-11-01

Doxorubicin is a commonly used chemotherapeutic employed to treat multiple human cancers, including numerous sarcomas and carcinomas. Furthermore, doxorubicin possesses strong fluorescent properties that make it an ideal reagent for modeling drug delivery by examining its distribution in cells and tissues. However, while doxorubicin fluorescence and lifetime have been imaged in live tissue, its behavior in archival samples that frequently result from drug and treatment studies in human and animal patients, and murine models of human cancer, has to date been largely unexplored. Here, we demonstrate imaging of doxorubicin intensity and lifetimes in archival formalin-fixed paraffin-embedded sections from mouse models of human cancer with multiphoton excitation and multiphoton fluorescence lifetime imaging microscopy (FLIM). Multiphoton excitation imaging reveals robust doxorubicin emission in tissue sections and captures spatial heterogeneity in cells and tissues. However, quantifying the amount of doxorubicin signal in distinct cell compartments, particularly the nucleus, often remains challenging due to strong signals in multiple compartments. The addition of FLIM analysis to display the spatial distribution of excited state lifetimes clearly distinguishes between signals in distinct compartments such as the cell nuclei versus cytoplasm and allows for quantification of doxorubicin signal in each compartment. Furthermore, we observed a shift in lifetime values in the nuclei of transformed cells versus nontransformed cells, suggesting a possible diagnostic role for doxorubicin lifetime imaging to distinguish normal versus transformed cells. Thus, data here demonstrate that multiphoton FLIM is a highly sensitive platform for imaging doxorubicin distribution in normal and diseased archival tissues.

Transit-time and age distributions for nonlinear time-dependent compartmental systems.

PubMed

Metzler, Holger; Müller, Markus; Sierra, Carlos A

2018-02-06

Many processes in nature are modeled using compartmental systems (reservoir/pool/box systems). Usually, they are expressed as a set of first-order differential equations describing the transfer of matter across a network of compartments. The concepts of age of matter in compartments and the time required for particles to transit the system are important diagnostics of these models with applications to a wide range of scientific questions. Until now, explicit formulas for transit-time and age distributions of nonlinear time-dependent compartmental systems were not available. We compute densities for these types of systems under the assumption of well-mixed compartments. Assuming that a solution of the nonlinear system is available at least numerically, we show how to construct a linear time-dependent system with the same solution trajectory. We demonstrate how to exploit this solution to compute transit-time and age distributions in dependence on given start values and initial age distributions. Furthermore, we derive equations for the time evolution of quantiles and moments of the age distributions. Our results generalize available density formulas for the linear time-independent case and mean-age formulas for the linear time-dependent case. As an example, we apply our formulas to a nonlinear and a linear version of a simple global carbon cycle model driven by a time-dependent input signal which represents fossil fuel additions. We derive time-dependent age distributions for all compartments and calculate the time it takes to remove fossil carbon in a business-as-usual scenario.

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.

Physiological Intracellular Crowdedness is Defined by the Perimeter-to-Area Ratio of Sub-Cellular Compartments

PubMed Central

Hiroi, Noriko; Okuhara, Takahiro; Kubojima, Takeshi; Iba, Keisuke; Tabira, Akito; Yamashita, Shuji; Okada, Yasunori; Kobayashi, Tetsuya J.; Funahashi, Akira

2012-01-01

The intracellular environment is known to be a crowded and inhomogeneous space. Such an in vivo environment differs from a well-diluted, homogeneous environment for biochemical reactions. However, the effects of both crowdedness and the inhomogeneity of environment on the behavior of a mobile particle have not yet been investigated sufficiently. As described in this paper, we constructed artificial reaction spaces with fractal models, which are assumed to be non-reactive solid obstacles in a reaction space with crevices that function as operating ranges for mobile particles threading the space. Because of the homogeneity of the structures of artificial reaction spaces, the models succeeded in reproducing the physiological fractal dimension of solid structures with a smaller number of non-reactive obstacles than in the physiological condition. This incomplete compatibility was mitigated when we chose a suitable condition of a perimeter-to-area ratio of the operating range to our model. Our results also show that a simulation space is partitioned into convenient reaction compartments as an in vivo environment with the exact amount of solid structures estimated from TEM images. The characteristics of these compartments engender larger mean square displacement of a mobile particle than that of particles in smaller compartments. Subsequently, the particles start to show confined particle-like behavior. These results are compatible with our previously presented results, which predicted that a physiological environment would produce quick response and slow exhaustion reactions. PMID:22936917

Study the Seasonal Variability of Plankton and Forage Fish in the Gulf of Khambhat Using Npzfd Model

NASA Astrophysics Data System (ADS)

Kumar, V.; Kumar, S.

2016-02-01

Numerical modelling of marine ecology exploits several assumptions and it is indeed quite challenging to include marine ecological phenomena into a mathematical framework with too many unknown parameters. The governing ordinary differential equations represent the interaction of the biological and chemical processes in a marine environment. The key concern in the development of a numerical models are parameterizations based on output, viz., mathematical modelling of ecological system mainly depends on parameters and its variations. Almost, all constituents of each trophic level of marine food web are depended on phytoplankton, which are mostly influenced by initial slope of P-I curve and nutrient stock in the study domain. Whereas, the earlier plankton dynamic models rarely include a compartment of small fish and as an agent in zooplankton mortality, which is most important for the modelling of higher trophic level of marine species. A compartment of forage fish in the modelling of plankton dynamics has been given more realistic mortality rates of plankton, viz., they feed upon phytoplankton and zooplankton. The inclusion of an additional compartment increases complexity of earlier plankton dynamics model as it introduces additional unknown parameters, which has been specified for performing the numerical simulations.As a case study we applied our analysis to explain the aquatic ecology of Gulf of Khambhat (19o 48' N - 22o20' N, 65o E - 72o40' E), west coast of India, which has rich bio-diversity and a high productive area in the form of plankton and forage fish. It has elevated turbidity and varying geography location, viz., one of the regions among world's ocean with high biological productivity.The model presented in this study is able to bring out the essential features of the observed data; that includes the bimodal oscillations in the observed data, monthly mean chlorophyll-a in the SeaWiFs/MODIS Aqua data and in-situ data of plankton. The additional compartment of forage fish and detritus in NPZFD model represents a major structural difference from the earlier NPZ model.

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.

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.

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

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

A Stochastic Model For Extracting Sediment Delivery Timescales From Sediment Budgets

NASA Astrophysics Data System (ADS)

Pizzuto, J. E.; Benthem, A.; Karwan, D. L.; Keeler, J. J.; Skalak, K.

2015-12-01

Watershed managers need to quantify sediment storage and delivery timescales to understand the time required for best management practices to improve downstream water quality. To address this need, we route sediment downstream using a random walk through a series of valley compartments spaced at 1 km intervals. The probability of storage within each compartment, q, is specified from a sediment budget and is defined as the ratio of the volume deposited to the annual sediment flux. Within each compartment, the probability of sediment moving directly downstream without being stored is p=1-q. If sediment is stored within a compartment, its "resting time" is specified by a stochastic exponential waiting time distribution with a mean of 10 years. After a particle's waiting time is over, it moves downstream to the next compartment by fluvial transport. Over a distance of "n" compartments, a sediment particle may be stored from 0 to n times with the probability of each outcome (store or not store) specified by the binomial distribution. We assign q = 0.02, a stream velocity of 0.5 m/s, an event "intermittency "of 0.01, and assume a balanced sediment budget. Travel time probability density functions have a steep peak at the shortest times, representing rapid transport in the channel of the fraction of sediment that moves downstream without being stored. However, the probability of moving downstream "n" km without storage is pn (0.90 for 5 km, 0.36 for 50 km, 0.006 for 250 km), so travel times are increasingly dominated by storage with increasing distance. Median travel times for 5, 50, and 250 km are 0.03, 4.4, and 46.5 years. After a distance of approximately 2/q or 100 km (2/0.02/km), the median travel time is determined by storage timescales, and active fluvial transport is irrelevant. Our model extracts travel time statistics from sediment budgets, and can be cast as a differential equation and solved numerically for more complex systems.

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

Proposal of a calculation method to determine the structural components' contribution on the deceleration of a passenger compartment based on the energy-derivative method.

PubMed

Nagasaka, Kei; Mizuno, Koji; Ito, Daisuke; Saida, Naoya

2017-05-29

In car crashes, the passenger compartment deceleration significantly influences the occupant loading. Hence, it is important to consider how each structural component deforms in order to control the passenger compartment deceleration. In frontal impact tests, the passenger compartment deceleration depends on the energy absorption property of the front structures. However, at this point in time there are few papers describing the components' quantitative contributions on the passenger compartment deceleration. Generally, the cross-sectional force is used to examine each component's contribution to passenger compartment deceleration. However, it is difficult to determine each component's contribution based on the cross-sectional forces, especially within segments of the individual members itself such as the front rails, because the force is transmitted continuously and the cross-sectional forces remain the same through the component. The deceleration of a particle can be determined from the derivative of the kinetic energy. Using this energy-derivative method, the contribution of each component on the passenger compartment deceleration can be determined. Using finite element (FE) car models, this method was applied for full-width and offset impact tests. This method was also applied to evaluate the deceleration of the powertrain. The finite impulse response (FIR) coefficient of the vehicle deceleration (input) and the driver chest deceleration (output) was calculated from Japan New Car Assessment Program (JNCAP) tests. These were applied to the component's contribution on the vehicle deceleration in FE analysis, and the component's contribution to the deceleration of the driver's chest was determined. The sum of the contribution of each component coincides with the passenger compartment deceleration in all types of impacts; therefore, the validity of this method was confirmed. In the full-width impact, the contribution of the crush box was large in the initial phases, and the contribution of the passenger compartment was large in the final phases. For the powertrain deceleration, the crush box had a positive contribution and the passenger compartment had a negative contribution. In the offset test, the contribution of the honeycomb and the passenger compartment deformation to the passenger compartment deceleration was large. Based on the FIR analysis, the passenger compartment deformation contributed the most to the chest deceleration of the driver dummy in the full-width impact. Based on the energy-derivative method, the contribution of the components' deformation to deceleration of the passenger compartment can be calculated for various types of crash configurations more easily, directly, and quantitatively than by using conventional methods. In addition, by combining the energy-derivative method and FIR, each structure's contribution to the occupant deceleration can be obtained. The energy-derivative method is useful in investigating how the deceleration develops from component deformations and also in designing deceleration curves for various impact configurations.

Photoelectrodialytic cell

DOEpatents

Murphy, George W.

1983-01-01

A multicompartment photoelectrodialytic demineralization cell is provided with a buffer compartment interposed between the product compartment and a compartment containing an electrolyte solution. Semipermeable membranes separate the buffer compartment from the product and electrolyte compartments. The buffer compartment is flushed to prevent leakage of the electrolyte compartment from entering the product compartment.

A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET.

PubMed

Green, Leeta Alison; Nguyen, Khoi; Berenji, Bijan; Iyer, Meera; Bauer, Eileen; Barrio, Jorge R; Namavari, Mohammad; Satyamurthy, Nagichettiar; Gambhir, Sanjiv S

2004-09-01

Reporter probe 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (18F-FHBG) and reporter gene mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) have been used for imaging reporter gene expression with PET. Current methods for quantitating the images using the percentage injected dose per gram of tissue do not distinguish between the effects of probe transport and subsequent phosphorylation. We therefore investigated tracer kinetic models for 18F-FHBG dynamic microPET data and noninvasive methods for determining blood time-activity curves in an adenoviral gene delivery model in mice. 18F-FHBG (approximately 7.4 MBq [approximately 200 microCi]) was injected into 4 mice; 18F-FHBG concentrations in plasma and whole blood were measured from mouse heart left ventricle (LV) direct sampling. Replication-incompetent adenovirus (0-2 x 10(9) plaque-forming units) with the E1 region deleted (n = 8) or replaced by HSV1-sr39tk (n = 18) was tail-vein injected into mice. Mice were dynamically scanned using microPET (approximately 7.4 MBq [approximately 200 microCi] 18F-FHBG) over 1 h; regions of interest were drawn on images of the heart and liver. Serial whole blood 18F-FHBG concentrations were measured in 6 of the mice by LV sampling, and 1 least-squares ratio of the heart image to the LV time-activity curve was calculated for all 6 mice. For 2 control mice and 9 mice expressing HSV1-sr39tk, heart image (input function) and liver image time-activity curves (tissue curves) were fit to 2- and 3-compartment models using Levenberg-Marquardt nonlinear regression. The models were compared using an F statistic. HSV1-sr39TK enzyme activity was determined from liver samples and compared with model parameter estimates. For another 3 control mice and 6 HSV1-sr39TK-positive mice, the model-predicted relative percentage of metabolites was compared with high-performance liquid chromatography analysis. The ratio of 18F-FHBG in plasma to whole blood was 0.84 +/- 0.05 (mean +/- SE) by 30 s after injection. The least-squares ratio of the heart image time-activity curve to the LV time-activity curve was 0.83 +/- 0.02, consistent with the recovery coefficient for the partial-volume effect (0.81) based on independent measures of heart geometry. A 3-compartment model best described 18F-FHBG kinetics in mice expressing HSV1-sr39tk in the liver; a 2-compartment model best described the kinetics in control mice. The 3-compartment model parameter, k3, correlated well with the HSV1-sr39TK enzyme activity (r2 = 0.88). 18F-FHBG equilibrates rapidly between plasma and whole blood in mice. Heart image time-activity curves corrected for partial-volume effects well approximate LV time-activity curves and can be used as input functions for 2- and 3-compartment models. The model parameter k3 from the 3-compartment model can be used as a noninvasive estimate for HSV1-sr39TK reporter protein activity and can predict the relative percentage of metabolites.

Allothermal steam gasification of biomass in cyclic multi-compartment bubbling fluidized-bed gasifier/combustor - new reactor concept.

PubMed

Iliuta, Ion; Leclerc, Arnaud; Larachi, Faïçal

2010-05-01

A new reactor concept of allothermal cyclic multi-compartment fluidized bed steam biomass gasification is proposed and analyzed numerically. The concept combines space and time delocalization to approach an ideal allothermal gasifier. Thermochemical conversion of biomass in periodic time and space sequences of steam biomass gasification and char/biomass combustion is simulated in which the exothermic combustion compartments provide heat into an array of interspersed endothermic steam gasification compartments. This should enhance unit heat integration and thermal efficiency and procure N(2)-free biosyngas with recourse neither to oxygen addition in steam gasification nor contact between flue and syngas. The dynamic, one-dimensional, multi-component, non-isothermal model developed for this concept accounts for detailed solid and gas flow dynamics whereupon gasification/combustion reaction kinetics, thermal effects and freeboard-zone reactions were tied. Simulations suggest that allothermal operation could be achieved with switch periods in the range of a minute supporting practical feasibility for portable small-scale gasification units. Copyright 2009 Elsevier Ltd. All rights reserved.

Photoelectrodialytic cell

DOEpatents

Murphy, G.W.

1983-09-13

A multicompartment photoelectrodialytic demineralization cell is provided with a buffer compartment interposed between the product compartment and a compartment containing an electrolyte solution. Semipermeable membranes separate the buffer compartment from the product and electrolyte compartments. The buffer compartment is flushed to prevent leakage of the electrolyte compartment from entering the product compartment. 3 figs.

Assessment of hemoglobin responsiveness to epoetin alfa in patients on hemodialysis using a population pharmacokinetic pharmacodynamic model.

PubMed

Wu, Liviawati; Mould, Diane R; Perez Ruixo, Juan Jose; Doshi, Sameer

2015-10-01

A population pharmacokinetic pharmacodynamic (PK/PD) model describing the effect of epoetin alfa on hemoglobin (Hb) response in hemodialysis patients was developed. Epoetin alfa pharmacokinetics was described using a linear 2-compartment model. PK parameter estimates were similar to previously reported values. A maturation-structured cytokinetic model consisting of 5 compartments linked in a catenary fashion by first-order cell transfer rates following a zero-order input process described the Hb time course. The PD model described 2 subpopulations, one whose Hb response reflected epoetin alfa dosing and a second whose response was unrelated to epoetin alfa dosing. Parameter estimates from the PK/PD model were physiologically reasonable and consistent with published reports. Numerical and visual predictive checks using data from 2 studies were performed. The PK and PD of epoetin alfa were well described by the model. © 2015, The American College of Clinical Pharmacology.

Effect of Posterior Horn Medial Meniscus Root Tear on In Vivo Knee Kinematics.

PubMed

Marsh, Chelsea A; Martin, Daniel E; Harner, Christopher D; Tashman, Scott

2014-07-01

Medial meniscus root tear (MMRT) is a recently recognized yet frequently missed meniscal tear pattern that biomechanically creates an environment approaching meniscal deficiency. The purpose of this study was to assess the effect of MMRT on tibiofemoral kinematics and arthrokinematics during daily activities by comparing the injured knees of subjects with isolated MMRT to their uninjured contralateral knees. The hypothesis was that the injured knee will demonstrate significantly more lateral tibial translation and adduction than the uninjured knee, and that the medial compartment will exhibit significantly different arthrokinematics than the lateral compartment in the affected limb. Cross-sectional study; Level of evidence, 3. Seven subjects with isolated MMRT were recruited and volumetric, density-based 3-dimensional models of their distal femurs and proximal tibia were created from computed tomography scans. High-speed, biplane radiographs were obtained of both their affected and unaffected knees. Moving 3-dimensional models of tibiofemoral kinematics were calculated using model-based tracking to assess overall kinematic variables and specific measures of tibiofemoral joint contact. The affected knees of the subjects were then compared to their unaffected contralateral knees. Affected knees demonstrated significantly more lateral tibial translation than the uninjured contralateral limb in all dynamic activities. Additionally, the medial compartment displayed greater amounts of mobility than the lateral compartment in the injured limbs. This study suggests that MMRT causes significant changes in in vivo knee kinematics and arthrokinematics and that the magnitude of these changes is influenced by dynamic task difficulty. Medial meniscus root tears lead to significant changes in joint arthrokinematics, with increased lateral tibial translation and greater medial compartment excursion. With complete root tears, essentially 100% of circumferential fibers are lost. This study will further our knowledge of meniscal deficiency and osteoarthritis and provide a baseline for more common forms of medial meniscal injuries (vertical, horizontal, radial), with various degrees of circumferential fiber function remaining.

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.

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

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.

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.

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.

A physiologically based toxicokinetic model for methylmercury in female American kestrels

USGS Publications Warehouse

Nichols, J.W.; Bennett, R.S.; Rossmann, R.; French, J.B.; Sappington, K.G.

2010-01-01

A physiologically based toxicokinetic (PBTK) model was developed to describe the uptake, distribution, and elimination of methylmercury (CH 3Hg) in female American kestrels. The model consists of six tissue compartments corresponding to the brain, liver, kidney, gut, red blood cells, and remaining carcass. Additional compartments describe the elimination of CH3Hg to eggs and growing feathers. Dietary uptake of CH 3Hg was modeled as a diffusion-limited process, and the distribution of CH3Hg among compartments was assumed to be mediated by the flow of blood plasma. To the extent possible, model parameters were developed using information from American kestrels. Additional parameters were based on measured values for closely related species and allometric relationships for birds. The model was calibrated using data from dietary dosing studies with American kestrels. Good agreement between model simulations and measured CH3Hg concentrations in blood and tissues during the loading phase of these studies was obtained by fitting model parameters that control dietary uptake of CH 3Hg and possible hepatic demethylation. Modeled results tended to underestimate the observed effect of egg production on circulating levels of CH3Hg. In general, however, simulations were consistent with observed patterns of CH3Hg uptake and elimination in birds, including the dominant role of feather molt. This model could be used to extrapolate CH 3Hg kinetics from American kestrels to other bird species by appropriate reassignment of parameter values. Alternatively, when combined with a bioenergetics-based description, the model could be used to simulate CH 3Hg kinetics in a long-term environmental exposure. ?? 2010 SETAC.

Using Rising Limb Analysis to Estimate Uptake of Reactive Solutes in Advective and Transient Storage Sub-compartments of Stream Ecosystems

NASA Astrophysics Data System (ADS)

Thomas, S. A.; Valett, H.; Webster, J. R.; Mulholland, P. J.; Dahm, C. N.

2001-12-01

Identifying the locations and controls governing solute uptake is a recent area of focus in studies of stream biogeochemistry. We introduce a technique, rising limb analysis (RLA), to estimate areal nitrate uptake in the advective and transient storage (TS) zones of streams. RLA is an inverse approach that combines nutrient spiraling and transient storage modeling to calculate total uptake of reactive solutes and the fraction of uptake occurring within the advective sub-compartment of streams. The contribution of the transient storage zones to solute loss is determined by difference. Twelve-hour coinjections of conservative (Cl-) and reactive (15NO3) tracers were conducted seasonally in several headwater streams among which AS/A ranged from 0.01 - 2.0. TS characteristics were determined using an advection-dispersion model modified to include hydrologic exchange with a transient storage compartment. Whole-system uptake was determined by fitting the longitudinal pattern of NO3 to first-order, exponential decay model. Uptake in the advective sub-compartment was determined by collecting a temporal sequence of samples from a single location beginning with the arrival of the solute front and concluding with the onset of plateau conditions (i.e. the rising limb). Across the rising limb, 15NO3:Cl was regressed against the percentage of water that had resided in the transient storage zone (calculated from the TS modeling). The y-intercept thus provides an estimate of the plateau 15NO3:Cl ratio in the absence of NO3 uptake within the transient storage zone. Algebraic expressions were used to calculate the percentage of NO3 uptake occurring in the advective and transient storage sub-compartments. Application of RLA successfully estimated uptake coefficients for NO3 in the subsurface when the physical dimensions of that habitat were substantial (AS/A > 0.2) and when plateau conditions at the sampling location consisted of waters in which at least 25% had resided in the transient storage zone. In those cases, the TS zone accounted for 8 - 47 % of overall NO3 uptake and uptake rates within the subsurface ranged from 0.7 - 14.3 mg N m-2 d-1.

The folding landscape of the epigenome

NASA Astrophysics Data System (ADS)

Olarte-Plata, Juan D.; Haddad, Noelle; Vaillant, Cédric; Jost, Daniel

2016-04-01

The role of the spatial organization of chromatin in gene regulation is a long-standing but still open question. Experimentally it has been shown that the genome is segmented into epigenomic chromatin domains that are organized into hierarchical sub-nuclear spatial compartments. However, whether this non-random spatial organization only reflects or indeed contributes—and how—to the regulation of genome function remains to be elucidated. To address this question, we recently proposed a quantitative description of the folding properties of the fly genome as a function of its epigenomic landscape using a polymer model with epigenomic-driven attractions. We propose in this article, to characterize more deeply the physical properties of the 3D epigenome folding. Using an efficient lattice version of the original block copolymer model, we study the structural and dynamical properties of chromatin and show that the size of epigenomic domains and asymmetries in sizes and in interaction strengths play a critical role in the chromatin organization. Finally, we discuss the biological implications of our findings. In particular, our predictions are quantitatively compatible with experimental data and suggest a different mean of self-interaction in euchromatin versus heterochromatin domains.

Optimization Parameters of Air-conditioning and Heat Insulation Systems of a Pressurized Cabins of Long-distance Airplanes

NASA Astrophysics Data System (ADS)

Gusev, Sergey A.; Nikolaev, Vladimir N.

2018-01-01

The method for determination of an aircraft compartment thermal condition, based on a mathematical model of a compartment thermal condition was developed. Development of solution techniques for solving heat exchange direct and inverse problems and for determining confidence intervals of parametric identification estimations was carried out. The required performance of air-conditioning, ventilation systems and heat insulation depth of crew and passenger cabins were received.

Fasciotomy Reduces Compartment Pressures and Improves Recovery in a Porcine Model of Extremity Vascular Injury and Ischemia/Reperfusion

DTIC Science & Technology

2012-10-01

the study. Ill. ~Ut’i.Jt.t.;l I 1:111V1~ Vascular injury, Extremity\\ Ischemia-rcperfusion, Therapeutic reperfusion, Statin \\ Recovery\\ Neuromuscular...Health Sciences, Bethesda, Maryland Keywords: Vascular injury, Extremity, Ischemia-reperfusion, Therapeutic reperfusion, Statin , Recovery...compartment pressure (pɘ.05) which were directly related to degree of muscle degeneration (pɘ.05) and inversely related to nerve recovery (p<.05

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

Ionic contrast terahertz near-field imaging of axonal water fluxes

PubMed Central

Masson, Jean-Baptiste; Sauviat, Martin-Pierre; Martin, Jean-Louis; Gallot, Guilhem

2006-01-01

We demonstrate the direct and noninvasive imaging of functional neurons by ionic contrast terahertz near-field microscopy. This technique provides quantitative measurements of ionic concentrations in both the intracellular and extracellular compartments and opens the way to direct noninvasive imaging of neurons during electrical, toxin, or thermal stresses. Furthermore, neuronal activity results from both a precise control of transient variations in ionic conductances and a much less studied water exchange between the extracellular matrix and the intraaxonal compartment. The developed ionic contrast terahertz microscopy technique associated with a full three-dimensional simulation of the axon-aperture near-field system allows a precise measurement of the axon geometry and therefore the direct visualization of neuron swelling induced by temperature change or neurotoxin poisoning. Water influx as small as 20 fl per μm of axonal length can be measured. This technique should then provide grounds for the development of advanced functional neuroimaging methods based on diffusion anisotropy of water molecules. PMID:16547134

A draft map of the mouse pluripotent stem cell spatial proteome

PubMed Central

Christoforou, Andy; Mulvey, Claire M.; Breckels, Lisa M.; Geladaki, Aikaterini; Hurrell, Tracey; Hayward, Penelope C.; Naake, Thomas; Gatto, Laurent; Viner, Rosa; Arias, Alfonso Martinez; Lilley, Kathryn S.

2016-01-01

Knowledge of the subcellular distribution of proteins is vital for understanding cellular mechanisms. Capturing the subcellular proteome in a single experiment has proven challenging, with studies focusing on specific compartments or assigning proteins to subcellular niches with low resolution and/or accuracy. Here we introduce hyperLOPIT, a method that couples extensive fractionation, quantitative high-resolution accurate mass spectrometry with multivariate data analysis. We apply hyperLOPIT to a pluripotent stem cell population whose subcellular proteome has not been extensively studied. We provide localization data on over 5,000 proteins with unprecedented spatial resolution to reveal the organization of organelles, sub-organellar compartments, protein complexes, functional networks and steady-state dynamics of proteins and unexpected subcellular locations. The method paves the way for characterizing the impact of post-transcriptional and post-translational modification on protein location and studies involving proteome-level locational changes on cellular perturbation. An interactive open-source resource is presented that enables exploration of these data. PMID:26754106

Genome contact map explorer: a platform for the comparison, interactive visualization and analysis of genome contact maps

PubMed Central

Kumar, Rajendra; Sobhy, Haitham

2017-01-01

Abstract Hi-C experiments generate data in form of large genome contact maps (Hi-C maps). These show that chromosomes are arranged in a hierarchy of three-dimensional compartments. But to understand how these compartments form and by how much they affect genetic processes such as gene regulation, biologists and bioinformaticians need efficient tools to visualize and analyze Hi-C data. However, this is technically challenging because these maps are big. In this paper, we remedied this problem, partly by implementing an efficient file format and developed the genome contact map explorer platform. Apart from tools to process Hi-C data, such as normalization methods and a programmable interface, we made a graphical interface that let users browse, scroll and zoom Hi-C maps to visually search for patterns in the Hi-C data. In the software, it is also possible to browse several maps simultaneously and plot related genomic data. The software is openly accessible to the scientific community. PMID:28973466

Evolutionary dynamics of 3D genome architecture following polyploidization in cotton.

PubMed

Wang, Maojun; Wang, Pengcheng; Lin, Min; Ye, Zhengxiu; Li, Guoliang; Tu, Lili; Shen, Chao; Li, Jianying; Yang, Qingyong; Zhang, Xianlong

2018-02-01

The formation of polyploids significantly increases the complexity of transcriptional regulation, which is expected to be reflected in sophisticated higher-order chromatin structures. However, knowledge of three-dimensional (3D) genome structure and its dynamics during polyploidization remains poor. Here, we characterize 3D genome architectures for diploid and tetraploid cotton, and find the existence of A/B compartments and topologically associated domains (TADs). By comparing each subgenome in tetraploids with its extant diploid progenitor, we find that genome allopolyploidization has contributed to the switching of A/B compartments and the reorganization of TADs in both subgenomes. We also show that the formation of TAD boundaries during polyploidization preferentially occurs in open chromatin, coinciding with the deposition of active chromatin modification. Furthermore, analysis of inter-subgenomic chromatin interactions has revealed the spatial proximity of homoeologous genes, possibly associated with their coordinated expression. This study advances our understanding of chromatin organization in plants and sheds new light on the relationship between 3D genome evolution and transcriptional regulation.

The formation of the light-sensing compartment of cone photoreceptors coincides with a transcriptional switch

PubMed Central

Daum, Janine M; Keles, Özkan; Holwerda, Sjoerd JB; Kohler, Hubertus; Rijli, Filippo M

2017-01-01

High-resolution daylight vision is mediated by cone photoreceptors. The molecular program responsible for the formation of their light sensor, the outer segment, is not well understood. We correlated daily changes in ultrastructure and gene expression in postmitotic mouse cones, between birth and eye opening, using serial block-face electron microscopy (EM) and RNA sequencing. Outer segments appeared rapidly at postnatal day six and their appearance coincided with a switch in gene expression. The switch affected over 14% of all expressed genes. Genes that switched off were rich in transcription factors and neurogenic genes. Those that switched on contained genes relevant for cone function. Chromatin rearrangements in enhancer regions occurred before the switch was completed, but not after. We provide a resource comprised of correlated EM, RNAseq, and ATACseq data, showing that the growth of a key compartment of a postmitotic cell involves an extensive switch in gene expression and chromatin accessibility. PMID:29106373

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.

Dynamics of an SAITS alcoholism model on unweighted and weighted networks

NASA Astrophysics Data System (ADS)

Huo, Hai-Feng; Cui, Fang-Fang; Xiang, Hong

2018-04-01

A novel SAITS alcoholism model on networks is introduced, in which alcoholics are divided into light problem alcoholics and heavy problem alcoholics. Susceptible individuals can enter into the compartment of heavy problem alcoholics directly by contacting with light problem alcoholics or heavy problem alcoholics and the heavy problem alcoholics who receive treatment can relapse into the compartment of heavy problem alcoholics are also considered. First, the dynamics of our model on unweighted networks, including the basic reproduction number, existence and stability of equilibria are studied. Second, the models with fixed weighted and adaptive weighted networks are introduced and investigated. At last, some simulations are presented to illustrate and extend our results. Our results show that it is very important to treat alcoholics to quit the drinking.

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.

The Selector Gene apterous and Notch Are Required to Locally Increase Mechanical Cell Bond Tension at the Drosophila Dorsoventral Compartment Boundary

PubMed Central

Michel, Marcus; Aliee, Maryam; Rudolf, Katrin; Bialas, Lisa; Jülicher, Frank; Dahmann, Christian

2016-01-01

The separation of cells with distinct fates and functions is important for tissue and organ formation during animal development. Regions of different fates within tissues are often separated from another along straight boundaries. These compartment boundaries play a crucial role in tissue patterning and growth by stably positioning organizers. In Drosophila, the wing imaginal disc is subdivided into a dorsal and a ventral compartment. Cells of the dorsal, but not ventral, compartment express the selector gene apterous. Apterous expression sets in motion a gene regulatory cascade that leads to the activation of Notch signaling in a few cell rows on either side of the dorsoventral compartment boundary. Both Notch and apterous mutant clones disturb the separation of dorsal and ventral cells. Maintenance of the straight shape of the dorsoventral boundary involves a local increase in mechanical tension at cell bonds along the boundary. The mechanisms by which cell bond tension is locally increased however remain unknown. Here we use a combination of laser ablation of cell bonds, quantitative image analysis, and genetic mutants to show that Notch and Apterous are required to increase cell bond tension along the dorsoventral compartment boundary. Moreover, clonal expression of the Apterous target gene capricious results in cell separation and increased cell bond tension at the clone borders. Finally, using a vertex model to simulate tissue growth, we find that an increase in cell bond tension at the borders of cell clones, but not throughout the cell clone, can lead to cell separation. We conclude that Apterous and Notch maintain the characteristic straight shape of the dorsoventral compartment boundary by locally increasing cell bond tension. PMID:27552097

Physically based modeling in catchment hydrology at 50: Survey and outlook

NASA Astrophysics Data System (ADS)

Paniconi, Claudio; Putti, Mario

2015-09-01

Integrated, process-based numerical models in hydrology are rapidly evolving, spurred by novel theories in mathematical physics, advances in computational methods, insights from laboratory and field experiments, and the need to better understand and predict the potential impacts of population, land use, and climate change on our water resources. At the catchment scale, these simulation models are commonly based on conservation principles for surface and subsurface water flow and solute transport (e.g., the Richards, shallow water, and advection-dispersion equations), and they require robust numerical techniques for their resolution. Traditional (and still open) challenges in developing reliable and efficient models are associated with heterogeneity and variability in parameters and state variables; nonlinearities and scale effects in process dynamics; and complex or poorly known boundary conditions and initial system states. As catchment modeling enters a highly interdisciplinary era, new challenges arise from the need to maintain physical and numerical consistency in the description of multiple processes that interact over a range of scales and across different compartments of an overall system. This paper first gives an historical overview (past 50 years) of some of the key developments in physically based hydrological modeling, emphasizing how the interplay between theory, experiments, and modeling has contributed to advancing the state of the art. The second part of the paper examines some outstanding problems in integrated catchment modeling from the perspective of recent developments in mathematical and computational science.

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.

The association of magnetic resonance imaging (MRI)-detected structural pathology of the knee with crepitus in a population-based cohort with knee pain: the MoDEKO study.

PubMed

Crema, M D; Guermazi, A; Sayre, E C; Roemer, F W; Wong, H; Thorne, A; Singer, J; Esdaile, J M; Marra, M D; Kopec, J A; Nicolaou, S; Cibere, J

2011-12-01

Osteoarthritis (OA) is the most common arthropathy of the knee joint(1). Symptoms reported by patients and signs noted during physical examination guide clinicians in identifying subjects with knee OA(2-4). Pain is one of the most important symptoms reported by subjects with knee OA(2,3). Although very common, pain is a non-specific symptom, related to pathology in several structures within the knee joint, and includes synovitis(5), subchondral bone marrow lesions(6), and joint effusion(7). Further, pain is a subjective symptom that cannot be directly measured or assessed during physical examination. Crepitus or crepitation in association with arthritis is defined as a crackling or grinding sound on joint movement with a sensation in the joint. Crepitus may occur with or without pain and is a common finding during physical examination in subjects with knee OA(2-4,8,9). It is not known whether crepitus is related to pathology in various structures within the knee. The aim of our study was to determine the cross-sectional associations of structural pathologies within the knee with crepitus in a population-based cohort with knee pain, using magnetic resonance imaging (MRI). Subjects with knee pain were recruited as a random population sample, with crepitus assessed in each compartment of the knee using a validated and standardized approach during physical examination(10). MRI of the knee was performed to assess cartilage morphology, meniscal morphology, osteophytes, cruciate ligaments, and collateral ligaments. For both compartment-specific and whole-knee analyses, a multiple logistic regression analysis was performed to assess the associations of MRI-detected structural pathology with crepitus, adjusting for potential confounders. Variables were selected by backwards elimination within each compartment and in the overall knee models, and only statistically significant variables remained in the "selected" models; remaining variables in these models are adjusted for each other. An increased risk for compartment-specific crepitus was associated with osteophytes at the patellofemoral (PF) and lateral tibiofemoral (LTF) joints. Crepitus was associated with osteophytes and medial collateral ligament (MCL) pathology at the medial tibiofemoral (MTF) compartment, but cartilage damage was negatively associated with crepitus at this compartment. In the selected whole-knee model, only meniscal tears were associated with an increased risk for general crepitus. Thus, it seems that crepitus may be associated with pathology in several internal structures. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

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.

In vivo tibiofemoral cartilage-to-cartilage contact area of females with medial osteoarthritis under acute loading using MRI.

PubMed

Shin, Choongsoo S; Souza, Richard B; Kumar, Deepak; Link, Thomas M; Wyman, Bradley T; Majumdar, Sharmila

2011-12-01

To investigate the effect of acute loading on in vivo tibiofemoral contact area changes in both compartments, and to determine whether in vivo tibiofemoral contact area differs between subjects with medial knee osteoarthritis (OA) and healthy controls. Ten subjects with medial knee OA (KL3) and 11 control subjects (KL0) were tested. Coronal three-dimensional spoiled gradient-recalled (3D-SPGR) and T(2) -weighted fast spin-echo FSE magnetic resonance imaging (MRI) of the knee were acquired under both unloaded and loaded conditions. Tibiofemoral cartilage contact areas were measured using image-based 3D models. Tibiofemoral contact areas in both compartments significantly increased under loading (P < 0.001) and the increased contact area in the medial compartment was significantly larger than in the lateral compartment (P < 0.05). Medial compartment contact area was significantly larger in KL3 subjects than KL0 subjects, both at unloaded and loaded conditions (P < 0.05). Contact areas measured from 3D-SPGR and T(2) -weighted FSE images were strongly correlated (r = 0.904). Females with medial OA increased tibiofemoral contact area in the medial compartment compared to healthy subjects under both unloaded and loaded conditions. The contact area data presented in this study may provide a quantitative reference for further cartilage contact biomechanics such as contact stress analysis and cartilage biomechanical function difference between osteoarthritic and healthy knees. Copyright © 2011 Wiley Periodicals, Inc.

Ecposure Related Dose Estimating Model

EPA Science Inventory

ERDEM is a physiologically based pharmacokinetic (PBPK) modeling system consisting of a general model and an associated front end. An actual model is defined when the user prepares an input command file. Such a command file defines the chemicals, compartments and processes that...

Simulation, identification and statistical variation in cardiovascular analysis (SISCA) - A software framework for multi-compartment lumped modeling.

PubMed

Huttary, Rudolf; Goubergrits, Leonid; Schütte, Christof; Bernhard, Stefan

2017-08-01

It has not yet been possible to obtain modeling approaches suitable for covering a wide range of real world scenarios in cardiovascular physiology because many of the system parameters are uncertain or even unknown. Natural variability and statistical variation of cardiovascular system parameters in healthy and diseased conditions are characteristic features for understanding cardiovascular diseases in more detail. This paper presents SISCA, a novel software framework for cardiovascular system modeling and its MATLAB implementation. The framework defines a multi-model statistical ensemble approach for dimension reduced, multi-compartment models and focuses on statistical variation, system identification and patient-specific simulation based on clinical data. We also discuss a data-driven modeling scenario as a use case example. The regarded dataset originated from routine clinical examinations and comprised typical pre and post surgery clinical data from a patient diagnosed with coarctation of aorta. We conducted patient and disease specific pre/post surgery modeling by adapting a validated nominal multi-compartment model with respect to structure and parametrization using metadata and MRI geometry. In both models, the simulation reproduced measured pressures and flows fairly well with respect to stenosis and stent treatment and by pre-treatment cross stenosis phase shift of the pulse wave. However, with post-treatment data showing unrealistic phase shifts and other more obvious inconsistencies within the dataset, the methods and results we present suggest that conditioning and uncertainty management of routine clinical data sets needs significantly more attention to obtain reasonable results in patient-specific cardiovascular modeling. Copyright © 2017 Elsevier Ltd. All rights reserved.

A physiologically based pharmacokinetic model for developmental exposure to BDE-47 in rats

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

Emond, Claude, E-mail: claude.emond@umontreal.c; BioSimulation Consulting Inc., Newark, DE 19711; Raymer, James H.

2010-02-01

Polybrominated diphenyl ethers (PBDEs) are used commercially as additive flame retardants and have been shown to transfer into environmental compartments, where they have the potential to bioaccumulate in wildlife and humans. Of the 209 possible PBDEs, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is usually the dominant congener found in human blood and milk samples. BDE-47 has been shown to have endocrine activity and produce developmental, reproductive, and neurotoxic effects. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for BDE-47 in male and female (pregnant and non-pregnant) adult rats to facilitate investigations of developmental exposure. This model consistsmore » of eight compartments: liver, brain, adipose tissue, kidney, placenta, fetus, blood, and the rest of the body. Concentrations of BDE-47 from the literature and from maternal-fetal pharmacokinetic studies conducted at RTI International were used to parameterize and evaluate the model. The results showed that the model simulated BDE-47 tissue concentrations in adult male, maternal, and fetal compartments within the standard deviations of the experimental data. The model's ability to estimate BDE-47 concentrations in the fetus after maternal exposure will be useful to design in utero exposure/effect studies. This PBPK model is the first one designed for any PBDE pharmaco/toxicokinetic description. The next steps will be to expand this model to simulate BDE-47 pharmacokinetics and distributions across species (mice), and then extrapolate it to humans. After mouse and human model development, additional PBDE congeners will be incorporated into the model and simulated as a mixture.« less

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.

Simulating the effects of light intensity and carbonate system composition on particulate organic and inorganic carbon production in Emiliania huxleyi.

PubMed

Holtz, Lena-Maria; Wolf-Gladrow, Dieter; Thoms, Silke

2015-05-07

Coccolithophores play an important role in the marine carbon cycle. Variations in light intensity and external carbonate system composition alter intracellular carbon fluxes and therewith the production rates of particulate organic and inorganic carbon. Aiming to find a mechanistic explanation for the interrelation between dissolved inorganic carbon fluxes and particulate carbon production rates, we develop a numerical cell model for Emiliania huxleyi, one of the most abundant coccolithophore species. The model consists of four cellular compartments, for each of which the carbonate system is resolved dynamically. The compartments are connected to each other and to the external medium via substrate fluxes across the compartment-confining membranes. By means of the model we are able to explain several pattern observed in particulate organic and inorganic carbon production rates for different strains and under different acclimation conditions. Particulate organic and inorganic carbon production rates for instance decrease at very low external CO2 concentrations. Our model suggests that this effect is caused mainly by reduced HCO3(-) uptake rates, not by CO2 limitation. The often observed decrease in particulate inorganic carbon production rates under Ocean Acidification is explained by a downregulation of cellular HCO3(-) uptake. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

Smith, Jordan N.; Hinderliter, Paul M.; Timchalk, Charles

Sensitivity to chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to computationally predict disposition of CPF and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, age-dependent body weight was calculated from a generalized Gompertz function, and compartments (liver, brain, fat, blood, diaphragm, rapid, and slow) were scaled based on body weight from polynomial functions on a fractional body weight basis. Bloodmore » flows among compartments were calculated as a constant flow per compartment volume. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Model simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ≥ 0.55 mg/kg of chlorpyrifos (significantly higher than environmental exposure levels), 6 mo old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent oral doses of chlorpyrifos. At lower doses that are more relevant to environmental exposures, the model predicts that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict CPF disposition and biological response over various postnatal life-stages.« less

Impact of Trichodesmium Sp. on Pacific Primary production

NASA Astrophysics Data System (ADS)

Dutheil, C.; Menkes, C.; Aumont, O.; Shiozaki, T.; Bonnet, S.; Rodier, M.; Bopp, L.; Lorrain, A.

2016-12-01

Recent sea-experiments have suggested that the South Pacific is one of the world's hot spot for nitrogen fixation. In that region, diazotrophs Trichodesmium Sp. have been shown to be one of its major contributors. Here we assess the climatological impact of these diazotrophs in the Pacific by using a 1°x1° coupled model dynamical-biogeochemical model ROMS-PISCES in which an explicit a Trichodesmium compartment is implemented. Firstly, we validate our model on the main limiting components (phosphate, iron, and temperature) of Trichodesmium growth. Phosphate patterns show modelled values and structures in qualitatively good agreement with observations. Iron concentrations are in good agreement with the observations. We also validate our model on nitrogen fixation rates. The regional spatial patterns of strong fixation are coherent with the observations. In the South Pacific, the model is able to reproduce the strong east-west gradient. Secondly, we evaluate the climatological effects of Trichodesmium on the biogeochemical conditions of the Tropical Pacific by adding with the explicit Trichodesmium compartment. The implementation of this compartment improves the model ability to reproduce the observed chlorophyll fields in the South West Pacific and the northern hemisphere, especially around Hawaii. In regions where there are strong nitrogen fixation rates, we observe an increase in the primary production by more than 100%, and an increase by more than 60 % in the production due to nanophytoplankton and diatoms, between the simulation with trichodesmium and without nitrogen fixation.

Starling forces drive intracranial water exchange during normal and pathological states.

PubMed

Linninger, Andreas A; Xu, Colin; Tangen, Kevin; Hartung, Grant

2017-12-31

To quantify the exchange of water between cerebral compartments, specifically blood, tissue, perivascular pathways, and cerebrospinal fluid-filled spaces, on the basis of experimental data and to propose a dynamic global model of water flux through the entire brain to elucidate functionally relevant fluid exchange phenomena. The mechanistic computer model to predict brain water shifts is discretized by cerebral compartments into nodes. Water and species flux is calculated between these nodes across a network of arcs driven by Hagen-Poiseuille flow (blood), Darcy flow (interstitial fluid transport), and Starling's Law (transmembrane fluid exchange). Compartment compliance is accounted for using a pressure-volume relationship to enforce the Monro-Kellie doctrine. This nonlinear system of differential equations is solved implicitly using MATLAB software. The model predictions of intraventricular osmotic injection caused a pressure rise from 10 to 22 mmHg, followed by a taper to 14 mmHg over 100 minutes. The computational results are compared to experimental data with R2=0.929. Moreover, simulated osmotic therapy of systemic (blood) injection reduced intracranial pressure from 25 to 10 mmHg. The modeled volume and intracranial pressure changes following cerebral edema agree with experimental trends observed in animal models with R2=0.997. The model successfully predicted time course and the efficacy of osmotic therapy for clearing cerebral edema. Furthermore, the mathematical model implicated the perivascular pathways as a possible conduit for water and solute exchange. This was a first step to quantify fluid exchange throughout the brain.

The exocytotic fusion pore modeled as a lipidic pore.

PubMed Central

Nanavati, C; Markin, V S; Oberhauser, A F; Fernandez, J M

1992-01-01

Freeze-fracture electron micrographs from degranulating cells show that the lumen of the secretory granule is connected to the extracellular compartment via large (20 to 150 nm diameter) aqueous pores. These exocytotic fusion pores appear to be made up of a highly curved bilayer that spans the plasma and granule membranes. Conductance measurements, using the patch-clamp technique, have been used to study the fusion pore from the instant it conducts ions. These measurements reveal the presence of early fusion pores that are much smaller than those observed in electron micrographs. Early fusion pores open abruptly, fluctuate, and then either expand irreversibly or close. The molecular structure of these early fusion pores is unknown. In the simplest extremes, these early fusion pores could be either ion channel like protein pores or lipidic pores. Here, we explored the latter possibility, namely that of the early exocytotic fusion pore modeled as a lipid-lined pore whose free energy was composed of curvature elastic energy and work done by tension. Like early exocytotic fusion pores, we found that these lipidic pores could open abruptly, fluctuate, and expand irreversibly. Closure of these lipidic pores could be caused by slight changes in lipid composition. Conductance distributions for stable lipidic pores matched those of exocytotic fusion pores. These findings demonstrate that lipidic pores can exhibit the properties of exocytotic fusion pores, thus providing an alternate framework with which to understand and interpret exocytotic fusion pore data. PMID:1420930

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.

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.

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.

[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.

Fractal analysis of lateral movement in biomembranes.

PubMed

Gmachowski, Lech

2018-04-01

Lateral movement of a molecule in a biomembrane containing small compartments (0.23-μm diameter) and large ones (0.75 μm) is analyzed using a fractal description of its walk. The early time dependence of the mean square displacement varies from linear due to the contribution of ballistic motion. In small compartments, walking molecules do not have sufficient time or space to develop an asymptotic relation and the diffusion coefficient deduced from the experimental records is lower than that measured without restrictions. The model makes it possible to deduce the molecule step parameters, namely the step length and time, from data concerning confined and unrestricted diffusion coefficients. This is also possible using experimental results for sub-diffusive transport. The transition from normal to anomalous diffusion does not affect the molecule step parameters. The experimental literature data on molecular trajectories recorded at a high time resolution appear to confirm the modeled value of the mean free path length of DOPE for Brownian and anomalous diffusion. Although the step length and time give the proper values of diffusion coefficient, the DOPE speed calculated as their quotient is several orders of magnitude lower than the thermal speed. This is interpreted as a result of intermolecular interactions, as confirmed by lateral diffusion of other molecules in different membranes. The molecule step parameters are then utilized to analyze the problem of multiple visits in small compartments. The modeling of the diffusion exponent results in a smooth transition to normal diffusion on entering a large compartment, as observed in experiments.

Modeling Microgravity Induced Fluid Redistribution Autoregulatory and Hydrostatic Enhancements

NASA Technical Reports Server (NTRS)

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

2017-01-01

Space flight induces a marked cephalad (headward) redistribution of blood and interstitial fluid potentially resulting in a loss of venous tone and reduction in heart muscle efficiency upon introduction into the microgravity environment. Using various types of computational models, we are investigating how this fluid redistribution may induce intracranial pressure changes, relevant to reported reductions in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome. Methods: We utilize a lumped parameter cardiovascular system (CVS) model, augmented by compartments comprising the cerebral spinal fluid (CSF) space, as the primary tool to describe how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. Models of ocular fluid pressures and biomechanics then accept the output of the above model as boundary condition input to allow more detailed, local analysis (see IWS Abstract by Ethier et al.). Recently, we enhanced the capabilities our previously reported CVS model through the implementation of robust autoregulatory mechanisms and a more fundamental approach to the implementation of hydrostatic mechanisms. Modifying the approach of Blanco et al., we implemented auto-regulation in a quasi-static manner, as an averaged effect across the span of one heartbeat. This approach reduced the higher frequency perturbations from the regulatory mechanism and was intended to allow longer simulation times (days) than models that implement within-beat regulatory mechanisms (minutes). A more fundamental approach to hydrostatics was implemented by a quasi-1D approach, in which compartment descriptions include compartment length, orientation and relative position, allowed for modeling of body orientation, relative body positioning and, in the future, alternative gravity environments. At this time the inclusion of hydrostatic mechanisms supplies additional capabilities to train and validate the CVS model with terrestrial data. Results and Conclusions: With the implementation of auto-regulation and hydrostatic modeling capabilities, the model performs as expected in the maintaining the CA (Central Artery) compartment pressure when simulating orientations ranging from supine to standing. The model appears to generally overpredict heart rate and thus cardiac output, possibly indicating sensitivity to the nominal heart rate, which is used as an initial set point of the regulation mechanisms. Despite this sensitivity, the model performs consistently for many hours of simulation time, indicating the success of our quasi-static implementation approach.

Assessment of disintegration of rapidly disintegrating tablets by a visiometric liquid jet-mediated disintegration apparatus.

PubMed

Desai, Parind M; Liew, Celine V; Heng, Paul W S

2013-02-14

The aim of this study was to develop a responsive disintegration test apparatus that is particularly suitable for rapidly disintegrating tablets (RDTs). The designed RDT disintegration apparatus consisted of disintegration compartment, stereomicroscope and high speed video camera. Computational fluid dynamics (CFD) was used to simulate 3 different designs of the compartment and to predict velocity and pressure patterns inside the compartment. The CFD preprocessor established the compartment models and the CFD solver determined the numerical solutions of the governing equations that described disintegration medium flow. Simulation was validated by good agreement between CFD and experimental results. Based on the results, the most suitable disintegration compartment was selected. Six types of commercial RDTs were used and disintegration times of these tablets were determined using the designed RDT disintegration apparatus and the USP disintegration apparatus. The results obtained using the designed apparatus correlated well to those obtained by the USP apparatus. Thus, the applied CFD approach had the potential to predict the fluid hydrodynamics for the design of optimal disintegration apparatus. The designed visiometric liquid jet-mediated disintegration apparatus for RDT provided efficient and precise determination of very short disintegration times of rapidly disintegrating dosage forms. Copyright © 2012 Elsevier B.V. All rights reserved.

B Cell Development in the Bone Marrow Is Regulated by Homeostatic Feedback Exerted by Mature B Cells

PubMed Central

Shahaf, Gitit; Zisman-Rozen, Simona; Benhamou, David; Melamed, Doron; Mehr, Ramit

2016-01-01

Cellular homeostasis in the B cell compartment is strictly imposed to balance cell production and cell loss. However, it is not clear whether B cell development in the bone marrow is an autonomous process or subjected to regulation by the peripheral B cell compartment. To specifically address this question, we used mice transgenic for human CD20, where effective depletion of B lineage cells is obtained upon administration of mouse anti-human CD20 antibodies, in the absence of any effect on other cell lineages and/or tissues. We followed the kinetics of B cell return to equilibrium by BrdU labeling and flow cytometry and analyzed the resulting data by mathematical modeling. Labeling was much faster in depleted mice. Compared to control mice, B cell-depleted mice exhibited a higher proliferation rate in the pro-/pre-B compartment, and higher cell death and lower differentiation in the immature B cell compartment. We validated the first result by analysis of the expression of Ki67, the nuclear protein expressed in proliferating cells, and the second using Annexin V staining. Collectively, our results suggest that B lymphopoiesis is subjected to homeostatic feedback mechanisms imposed by mature B cells in the peripheral compartment. PMID:27047488

Proceedings of the Annual Conference on Environmental Toxicology (5th) Held at Fairborn, OH on 24-26 September 1974

DTIC Science & Technology

1974-12-01

259 Paul M. Newberne 19 - STATISTICAL MODELS FOR ESTIMATING CARCINOGENIC RISKS FROM ANIMAL DATA ................... 285 .David G. Hoel V AMRL-TR-74-125... Paul M., D. V. M., Ph. D. SHANK, Ronald C., Ph. D. Professor of Pathology Associate Professor of Toxicology Laboratory of Animal Pathology Departments of...significance for water quality management . Each compartment represents the concentration of a measurable constituent. Lines connecting compartments represent

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

SIZE DEPENDENT MODEL OF HAZARDOUS SUBSTANCES IN Q AQUATIC FOOD CHAIN

EPA Science Inventory

A model of toxic substance accumulation is constructed that introduces organism size as an additional independent variable. The model represents an ecological continuum through size dependency; classical compartment analyses are therefore a special case of the continuous model. S...

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

Python as a federation tool for GENESIS 3.0.

PubMed

Cornelis, Hugo; Rodriguez, Armando L; Coop, Allan D; Bower, James M

2012-01-01

The GENESIS simulation platform was one of the first broad-scale modeling systems in computational biology to encourage modelers to develop and share model features and components. Supported by a large developer community, it participated in innovative simulator technologies such as benchmarking, parallelization, and declarative model specification and was the first neural simulator to define bindings for the Python scripting language. An important feature of the latest version of GENESIS is that it decomposes into self-contained software components complying with the Computational Biology Initiative federated software architecture. This architecture allows separate scripting bindings to be defined for different necessary components of the simulator, e.g., the mathematical solvers and graphical user interface. Python is a scripting language that provides rich sets of freely available open source libraries. With clean dynamic object-oriented designs, they produce highly readable code and are widely employed in specialized areas of software component integration. We employ a simplified wrapper and interface generator to examine an application programming interface and make it available to a given scripting language. This allows independent software components to be 'glued' together and connected to external libraries and applications from user-defined Python or Perl scripts. We illustrate our approach with three examples of Python scripting. (1) Generate and run a simple single-compartment model neuron connected to a stand-alone mathematical solver. (2) Interface a mathematical solver with GENESIS 3.0 to explore a neuron morphology from either an interactive command-line or graphical user interface. (3) Apply scripting bindings to connect the GENESIS 3.0 simulator to external graphical libraries and an open source three dimensional content creation suite that supports visualization of models based on electron microscopy and their conversion to computational models. Employed in this way, the stand-alone software components of the GENESIS 3.0 simulator provide a framework for progressive federated software development in computational neuroscience.

Python as a Federation Tool for GENESIS 3.0

PubMed Central

Cornelis, Hugo; Rodriguez, Armando L.; Coop, Allan D.; Bower, James M.

2012-01-01

The GENESIS simulation platform was one of the first broad-scale modeling systems in computational biology to encourage modelers to develop and share model features and components. Supported by a large developer community, it participated in innovative simulator technologies such as benchmarking, parallelization, and declarative model specification and was the first neural simulator to define bindings for the Python scripting language. An important feature of the latest version of GENESIS is that it decomposes into self-contained software components complying with the Computational Biology Initiative federated software architecture. This architecture allows separate scripting bindings to be defined for different necessary components of the simulator, e.g., the mathematical solvers and graphical user interface. Python is a scripting language that provides rich sets of freely available open source libraries. With clean dynamic object-oriented designs, they produce highly readable code and are widely employed in specialized areas of software component integration. We employ a simplified wrapper and interface generator to examine an application programming interface and make it available to a given scripting language. This allows independent software components to be ‘glued’ together and connected to external libraries and applications from user-defined Python or Perl scripts. We illustrate our approach with three examples of Python scripting. (1) Generate and run a simple single-compartment model neuron connected to a stand-alone mathematical solver. (2) Interface a mathematical solver with GENESIS 3.0 to explore a neuron morphology from either an interactive command-line or graphical user interface. (3) Apply scripting bindings to connect the GENESIS 3.0 simulator to external graphical libraries and an open source three dimensional content creation suite that supports visualization of models based on electron microscopy and their conversion to computational models. Employed in this way, the stand-alone software components of the GENESIS 3.0 simulator provide a framework for progressive federated software development in computational neuroscience. PMID:22276101

A combined pharmacokinetic/pharmacodynamic model of levodopa motor response and dyskinesia in Parkinson's disease patients.

PubMed

Simon, N; Viallet, F; Boulamery, A; Eusebio, A; Gayraud, D; Azulay, J-P

2016-04-01

Levodopa is the reference treatment for Parkinson's disease. However, after several years of treatment, dyskinesia may occur and strategies to overcome this side effect still need to be explored. We identified a unique population pharmacokinetic/pharmacodynamic model in Parkinson's disease to investigate the relationship and dissociability of motor response and dyskinesia. Thirty parkinsonian patients (Hoehn and Yahr stages 3-4), treated with levodopa and suffering from peak-dose dyskinesia, were included in a prospective open-label study. They received a single dose of levodopa equal to 150 % of their usual daily dose. Blood samples, motor evaluations (UPDRS III scale) and peak-dose dyskinesia (Goetz scale) were examined after administration. A population pharmacokinetic/pharmacodynamic (PK/PD) model was developed using NONMEM software. Pharmacokinetic analysis identified a one-compartment model with the following parameter values [bootstrap 95 % CI]: absorption rate constant (KA) 1.86 1/h [1.08-3.25], clearance 36.6 L/h [31.3-42.8], and volume of distribution 42.9 L [34.3-52.3]. Between-subject variability was 122 % [71-183] and 38 % [26-47] for KA and clearance, respectively. Residual variability was 1120 μg/L [886-1290]. UPDRS III and dyskinesia were best described with an effect compartment and similar KE0 values of 1.37 1/h [1.01-1.77]. For UPDRS III, the E0, EC50, Emax, and Hill coefficient were 31.4 [28.4-35.3], 1410 μg/L [1200-1700], 0.72 [0.71-0.75], and 4.26 [3.20-5.58], respectively. For dyskinesia, the EC50 and Emax were 6280 μg/L [3420-37,900] and 17.9 [12.3-80.8], respectively. Residual variability was 3.15 [2.75-3.53] for UPDRS III and 2.66 [1.94-3.51] for dyskinesia. No covariates influenced the parameters. In patients treated with levodopa and suffering from dyskinesia, the motor response and dyskinesia have close onsets and duration effects. Maximal motor response tends to be inevitably associated with dyskinesia.

Rugged Energy Landscapes in Multiphase Porous Media Flow: A Discrete-Domain Description

NASA Astrophysics Data System (ADS)

Cueto-Felgueroso, L.; Juanes, R.

2015-12-01

Immiscible displacements in porous media involve a complex sequence of pore-scale events, from the smooth, reversible displacement of interfaces to abrupt interfacial reconfigurations and rapid pore invasion cascades. Discontinuous changes in pressure or saturation have been referred to as Haines jumps, and they emerge as a key mechanism to understand the origin of hysteresis in porous media flow. Hysteresis persists at the many-pore scale: when multiple cycles of drainage and imbibition of a porous sample are conducted, a dense hysteresis diagram emerges. The interpretation of hysteresis as a consequence of irreversible transitions and multistability is at the heart of early hysteresis models, and in recent experiments, and points to an inherently non-equilibrium behavior. For a given volume fraction of fluids occupying the pore space, many stable configurations are possible, due to the tortuous network of nonuniform pores and throats that compose the porous medium, and to complex wetting and capillary transitions. Multistability indicates that porous media systems exhibit rugged energy landscapes, where the system may remain pinned at local energy minima for long times. We address the question of developing a zero-dimensional model that inherits the path-dependence and `'bursty'' behavior of immiscible displacements, and propose a discrete-domain model that captures the role of metastability and local equilibria in the origin of hysteresis. We describe the porous medium and fluid system as a discrete set of weakly connected, multistable compartments, charaterized by a unique free energy function. This description does not depend explicitly on past saturations, turning points, or drainage/imbibition labels. The system behaves hysteretically, and we rationalize its behavior as sweeping a complex metastability diagram, with dissipation arising from discrete switches among metastable branches. The hysteretic behavior of the pressure-saturation curve is controlled by the topography of the energy landscape, through the number of metastable regions of the compartments and characteristic height of the energy barriers separating the different basins. Our model opens the door to fully explore the interplay between hysteresis and fluctuations in multiphase displacements in porous media.

DynaSim: A MATLAB Toolbox for Neural Modeling and Simulation

PubMed Central

Sherfey, Jason S.; Soplata, Austin E.; Ardid, Salva; Roberts, Erik A.; Stanley, David A.; Pittman-Polletta, Benjamin R.; Kopell, Nancy J.

2018-01-01

DynaSim is an open-source MATLAB/GNU Octave toolbox for rapid prototyping of neural models and batch simulation management. It is designed to speed up and simplify the process of generating, sharing, and exploring network models of neurons with one or more compartments. Models can be specified by equations directly (similar to XPP or the Brian simulator) or by lists of predefined or custom model components. The higher-level specification supports arbitrarily complex population models and networks of interconnected populations. DynaSim also includes a large set of features that simplify exploring model dynamics over parameter spaces, running simulations in parallel using both multicore processors and high-performance computer clusters, and analyzing and plotting large numbers of simulated data sets in parallel. It also includes a graphical user interface (DynaSim GUI) that supports full functionality without requiring user programming. The software has been implemented in MATLAB to enable advanced neural modeling using MATLAB, given its popularity and a growing interest in modeling neural systems. The design of DynaSim incorporates a novel schema for model specification to facilitate future interoperability with other specifications (e.g., NeuroML, SBML), simulators (e.g., NEURON, Brian, NEST), and web-based applications (e.g., Geppetto) outside MATLAB. DynaSim is freely available at http://dynasimtoolbox.org. This tool promises to reduce barriers for investigating dynamics in large neural models, facilitate collaborative modeling, and complement other tools being developed in the neuroinformatics community. PMID:29599715

DynaSim: A MATLAB Toolbox for Neural Modeling and Simulation.

PubMed

Sherfey, Jason S; Soplata, Austin E; Ardid, Salva; Roberts, Erik A; Stanley, David A; Pittman-Polletta, Benjamin R; Kopell, Nancy J

2018-01-01

DynaSim is an open-source MATLAB/GNU Octave toolbox for rapid prototyping of neural models and batch simulation management. It is designed to speed up and simplify the process of generating, sharing, and exploring network models of neurons with one or more compartments. Models can be specified by equations directly (similar to XPP or the Brian simulator) or by lists of predefined or custom model components. The higher-level specification supports arbitrarily complex population models and networks of interconnected populations. DynaSim also includes a large set of features that simplify exploring model dynamics over parameter spaces, running simulations in parallel using both multicore processors and high-performance computer clusters, and analyzing and plotting large numbers of simulated data sets in parallel. It also includes a graphical user interface (DynaSim GUI) that supports full functionality without requiring user programming. The software has been implemented in MATLAB to enable advanced neural modeling using MATLAB, given its popularity and a growing interest in modeling neural systems. The design of DynaSim incorporates a novel schema for model specification to facilitate future interoperability with other specifications (e.g., NeuroML, SBML), simulators (e.g., NEURON, Brian, NEST), and web-based applications (e.g., Geppetto) outside MATLAB. DynaSim is freely available at http://dynasimtoolbox.org. This tool promises to reduce barriers for investigating dynamics in large neural models, facilitate collaborative modeling, and complement other tools being developed in the neuroinformatics community.

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

In-situ electrochemically active surface area evaluation of an open-cathode polymer electrolyte membrane fuel cell stack

NASA Astrophysics Data System (ADS)

Torija, Sergio; Prieto-Sanchez, Laura; Ashton, Sean J.

2016-09-01

The ability to evaluate the electrochemically active surface area (ECSA) of fuel cell electrodes is crucial toward characterising designs and component suites in-situ, particularly when evaluating component durability in endurance testing, since it is a measure of the electrode area available to take part in the fuel cell reactions. Conventional methods to obtain the ECSA using cyclic voltammetry, however, rely on potentiostats that cannot be easily scaled to simultaneously evaluate all cells in a fuel cell stack of practical size, which is desirable in fuel cell development. In-situ diagnostics of an open-cathode fuel cell stack are furthermore challenging because the cells do not each possess an enclosed cathode compartment; instead, the cathodes are rather open to the environment. Here we report on a diagnostic setup that allows the electrochemically active surface area of each cell anode or cathode in an open-cathode fuel cell stack to be evaluated in-situ and simultaneously, with high resolution and reproducibility, using an easily scalable chronopotentiometry methodology and a gas-tight stack enclosure.

Virtual reality anatomy: is it comparable with traditional methods in the teaching of human forearm musculoskeletal anatomy?

PubMed

Codd, Anthony M; Choudhury, Bipasha

2011-01-01

The use of cadavers to teach anatomy is well established, but limitations with this approach have led to the introduction of alternative teaching methods. One such method is the use of three-dimensional virtual reality computer models. An interactive, three-dimensional computer model of human forearm anterior compartment musculoskeletal anatomy was produced using the open source 3D imaging program "Blender." The aim was to evaluate the use of 3D virtual reality when compared with traditional anatomy teaching methods. Three groups were identified from the University of Manchester second year Human Anatomy Research Skills Module class: a "control" group (no prior knowledge of forearm anatomy), a "traditional methods" group (taught using dissection and textbooks), and a "model" group (taught solely using e-resource). The groups were assessed on anatomy of the forearm by a ten question practical examination. ANOVA analysis showed the model group mean test score to be significantly higher than the control group (mean 7.25 vs. 1.46, P < 0.001) and not significantly different to the traditional methods group (mean 6.87, P > 0.5). Feedback from all users of the e-resource was positive. Virtual reality anatomy learning can be used to compliment traditional teaching methods effectively. Copyright © 2011 American Association of Anatomists.

Membrane Compartmentalization Reducing the Mobility of Lipids and Proteins within a Model Plasma Membrane.

PubMed

Koldsø, Heidi; Reddy, Tyler; Fowler, Philip W; Duncan, Anna L; Sansom, Mark S P

2016-09-01

The cytoskeleton underlying cell membranes may influence the dynamic organization of proteins and lipids within the bilayer by immobilizing certain transmembrane (TM) proteins and forming corrals within the membrane. Here, we present coarse-grained resolution simulations of a biologically realistic membrane model of asymmetrically organized lipids and TM proteins. We determine the effects of a model of cytoskeletal immobilization of selected membrane proteins using long time scale coarse-grained molecular dynamics simulations. By introducing compartments with varying degrees of restraints within the membrane models, we are able to reveal how compartmentalization caused by cytoskeletal immobilization leads to reduced and anomalous diffusional mobility of both proteins and lipids. This in turn results in a reduced rate of protein dimerization within the membrane and of hopping of membrane proteins between compartments. These simulations provide a molecular realization of hierarchical models often invoked to explain single-molecule imaging studies of membrane proteins.

Modeling intrinsic electrophysiology of AII amacrine cells: preliminary results.

PubMed

Apollo, Nick; Grayden, David B; Burkitt, Anthony N; Meffin, Hamish; Kameneva, Tatiana

2013-01-01

In patients who have lost their photoreceptors due to retinal degenerative diseases, it is possible to restore rudimentary vision by electrically stimulating surviving neurons. AII amacrine cells, which reside in the inner plexiform layer, split the signal from rod bipolar cells into ON and OFF cone pathways. As a result, it is of interest to develop a computational model to aid in the understanding of how these cells respond to the electrical stimulation delivered by a prosthetic implant. The aim of this work is to develop and constrain parameters in a single-compartment model of an AII amacrine cell using data from whole-cell patch clamp recordings. This model will be used to explore responses of AII amacrine cells to electrical stimulation. Single-compartment Hodgkin-Huxley-type neural models are simulated in the NEURON environment. Simulations showed successful reproduction of the potassium currentvoltage relationship and some of the spiking properties observed in vitro.

[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.

Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants

PubMed Central

Stage, C; Bergmann, TK; Ferrero‐Milliani, L; Bjerre, D; Thomsen, R; Dalhoff, KP; Rasmussen, HB; Jürgens, G

2016-01-01

The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d‐MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two‐compartment disposition model with absorption transit compartments. Novel effects of rs115629050 and CES1 diplotypes, as well as previously reported effects of rs71647871 and body weight, were included in the final model. Assessment of the independent and combined effect of CES1 covariates identified several specific risk factors that may result in severely increased d‐MPH plasma exposure. PMID:27754602

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.

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.

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.

Quantification of Dynamic 11C-Phenytoin PET Studies.

PubMed

Mansor, Syahir; Boellaard, Ronald; Froklage, Femke E; Bakker, Esther D M; Yaqub, Maqsood; Voskuyl, Rob A; Schwarte, Lothar A; Verbeek, Joost; Windhorst, Albert D; Lammertsma, Adriaan

2015-09-01

The overexpression of P-glycoprotein (Pgp) is thought to be an important mechanism of pharmacoresistance in epilepsy. Recently, (11)C-phenytoin has been evaluated preclinically as a tracer for Pgp. The aim of the present study was to assess the optimal plasma kinetic model for quantification of (11)C-phenytoin studies in humans. Dynamic (11)C-phenytoin PET scans of 6 healthy volunteers with arterial sampling were acquired twice on the same day and analyzed using single- and 2-tissue-compartment models with and without a blood volume parameter. Global and regional test-retest (TRT) variability was determined for both plasma to tissue rate constant (K1) and volume of distribution (VT). According to the Akaike information criterion, the reversible single-tissue-compartment model with blood volume parameter was the preferred plasma input model. Mean TRT variability ranged from 1.5% to 16.9% for K1 and from 0.5% to 5.8% for VT. Larger volumes of interest showed better repeatabilities than smaller regions. A 45-min scan provided essentially the same K1 and VT values as a 60-min scan. A reversible single-tissue-compartment model with blood volume seems to be a good candidate model for quantification of dynamic (11)C-phenytoin studies. Scan duration may be reduced to 45 min without notable loss of accuracy and precision of both K1 and VT, although this still needs to be confirmed under pathologic conditions. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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.

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.

A generic biokinetic model for carbon-14 labelled compounds

NASA Astrophysics Data System (ADS)

Manger, Ryan Paul

Carbon-14, a radioactive nuclide, is used in many industrial applications. Due to its wide range of uses in industry, many workers are at risk of accidental internal exposure to 14C. Being a low energy beta emitter, 14C is not a significant external radiation hazard, but the internal consequences posed by 14C are important, especially because of its long half life of 5730 years [46]. The current biokinetic model recommended by the International Commission on Radiological Protection (ICRP) is a conservative estimate of how radiocarbon is treated by the human body. The ICRP generic radiocarbon model consists of a single compartment representing the entire human body. This compartment has a biological half life of 40 days yielding an effective dose coefficient of 5.8x10-10 Sv B q-1 [44, 45, 49, 53, 54]. This overestimates the dose of all radiocarbon compounds that have been studied [96]. An improved model has been developed that includes and alimentary tract, a urinary bladder, CO2 model, and an "Other" compartment used to model systemic tissues. The model can be adapted to replicate any excretion curve and excretion pattern. In addition, the effective dose coefficient produced by the updated model is near the mean effective dose coefficient of carbon compounds that have been considered in this research. The major areas of improvement are: more anatomically significant, a less conservative dose coefficient, and the ability to manipulate the model for known excretion data. Due to the wide variety of carbon compounds, it is suggested that specific biokinetic models be implemented for known radiocarbon substances. If the source of radiocarbon is dietary, then the physiologically based model proposed by Whillans [102] that splits all ingested radiocarbon compounds into carbohydrates, fats, and proteins should be used.

Mechanism-based pharmacokinetic-pharmacodynamic modeling of the antinociceptive effect of buprenorphine in healthy volunteers.

PubMed

Yassen, Ashraf; Olofsen, Erik; Romberg, Raymonda; Sarton, Elise; Danhof, Meindert; Dahan, Albert

2006-06-01

The objective of this investigation was to characterize the pharmacokinetic-pharmacodynamic relation of buprenorphine's antinociceptive effect in healthy volunteers. Data on the time course of the antinociceptive effect after intravenous administration of 0.05-0.6 mg/70 kg buprenorphine in healthy volunteers was analyzed in conjunction with plasma concentrations by nonlinear mixed-effects analysis. A three-compartment pharmacokinetic model best described the concentration time course. Four structurally different pharmacokinetic-pharmacodynamic models were evaluated for their appropriateness to describe the time course of buprenorphine's antinociceptive effect: (1) E(max) model with an effect compartment model, (2) "power" model with an effect compartment model, (3) receptor association-dissociation model with a linear transduction function, and (4) combined biophase equilibration/receptor association-dissociation model with a linear transduction function. The latter pharmacokinetic-pharmacodynamic model described the time course of effect best and was used to explain time dependencies in buprenorphine's pharmacodynamics. The model converged, yielding precise estimation of the parameters characterizing hysteresis and the relation between relative receptor occupancy and antinociceptive effect. The rate constant describing biophase equilibration (k(eo)) was 0.00447 min(-1) (95% confidence interval, 0.00299-0.00595 min(-1)). The receptor dissociation rate constant (k(off)) was 0.0785 min(-1) (95% confidence interval, 0.0352-0.122 min(-1)), and k(on) was 0.0631 ml . ng(-1) . min(-1) (95% confidence interval, 0.0390-0.0872 ml . ng(-1) . min(-1)). This is consistent with observations in rats, suggesting that the rate-limiting step in the onset and offset of the antinociceptive effect is biophase distribution rather than slow receptor association-dissociation. In the dose range studied, no saturation of receptor occupancy occurred explaining the lack of a ceiling effect for antinociception.

Increased anxiety-related behavior in male and female adult rats following early and late adolescent exposure to 3,4-methylenedioxymethamphetamine (MDMA).

PubMed

Kolyaduke, Olga V; Hughes, Robert N

2013-02-01

Subsequent behavioral effects in adulthood of daily exposure to MDMA during early or late adolescence were assessed in both male and female rats. From either postnatal day (PND) 35 (early adolescence) or PND45 (late adolescence), PVG/c rats of each sex were exposed via intraperitoneal injections to saline or 10mg/kg MDMA for 10 consecutive days. They were regularly weighed during treatment and again on PND90. At this age, their anxiety-related behavior was determined from frequencies of ambulation, rearing, grooming, defecation and occupancy of the center and corners of an open field, as well as entries into and time spent in the light compartment of a light-dark box. Spatial and working memories were assessed by preferences for a novel Y-maze arm, and by recognition of a novel object. MDMA-exposed rats gained less weight during treatment than saline controls but were heavier on PND90 depending on their sex or age when treated. As shown by decreased open-field ambulation (for males only) and increased defecation plus fewer entries into the light compartment of the light-dark box and entries into both arms of a Y maze, MDMA exposure increased adult anxiety-related behavior particularly for rats treated during late adolescence. There was no evidence of any effects on either spatial or working memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Modeling the pharmacokinetics of extended release pharmaceutical systems

NASA Astrophysics Data System (ADS)

di Muria, Michela; Lamberti, Gaetano; Titomanlio, Giuseppe

2009-03-01

The pharmacokinetic (PK) models predict the hematic concentration of drugs after the administration. In compartment modeling, the body is described by a set of interconnected “vessels” or “compartments”; the modeling consisting of transient mass balances. Usually the orally administered drugs were considered as immediately available: this cannot describe the administration of extended-release systems. In this work we added to the traditional compartment models the ability to account for a delay in administration, relating this delay to in vitro data. Firstly, the method was validated, applying the model to the dosage of nicotine by chewing-gum; the model was tuned by in vitro/in vivo data of drugs (divalproex-sodium and diltiazem) with medium-rate release kinetics, then it was applied in describing in vivo evolutions due to the assumption of fast- and slow-release systems. The model reveals itself predictive, the same of a Level A in vitro/in vivo correlation, but being physically based, it is preferable to a purely statistical method.

Finite element analysis of unicompartmental knee arthroplasty.

PubMed

Hopkins, Andrew R; New, Andrew M; Rodriguez-y-Baena, Ferdinando; Taylor, Mark

2010-01-01

Concerns over accelerated damage to the untreated compartment of the knee following unicompartmental knee arthroplasty (UKA), as well as the relatively poor success rates observed for lateral as opposed to the medial arthroplasty, remain issues for attention. Finite element analysis (FEA) was used to assess changes to the kinematics and potential for cartilage damage across the knee joint in response to the implantation of the Oxford Mobile Bearing UKA. FE models of lateral and medial compartment arthroplasty were developed, in addition to a healthy natural knee model, to gauge changes incurred through the arthroplasty. Varus-valgus misalignments were introduced to the femoral components to simulate surgical inaccuracy or over-correction. Boundary conditions from the Stanmore knee simulator during the stance phase of level gait were used. AP translations of the tibia in the medial UKA models were comparable to the behaviour of the natural knee models (+/-0.6mm deviation from pre-operative motion). Following lateral UKA, 4.1mm additional posterior translation of the tibia was recorded than predicted for the natural knee. IE rotations of the medial UKA models were less consistent with the pre-operative knee model than the lateral UKA models (7.7 degrees vs. 3.6 degrees deviation). Varus misalignment of the femoral prosthesis was more influential than valgus for medial UKA kinematics, whereas in lateral UKA, a valgus misalignment of the femoral prosthesis was most influential on the kinematics. Resection of the cartilage in the medial compartment reduced the overall risk of progressive OA in the knee, whereas removing the cartilage from the lateral compartment, and in particular introducing a valgus femoral misalignment, increased the overall risk of progressive OA in the knee. Based on these results, under the conditions tested herein, both medial and lateral UKA can be said to induce kinematics of the knee which could be considered broadly comparable to those of the natural knee, and that even a 10 degrees varus-valgus misalignment of the femoral component may not induce highly irregular kinematics. However, elevated posterior translation of the tibia in lateral UKA and large excursions of the insert may explain the higher incidence of bearing dislocation observed in some clinical studies. (c) 2009 IPEM. All rights reserved.

Comparing models for perfluorooctanoic acid pharmacokinetics using Bayesian analysis

EPA Science Inventory

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 Haskel...

A PHYSIOLOGICALLY BASED TOXICOKINETIC MODEL FOR LAKE TROUT (SALVELINUS NAMAYCUSH)

EPA Science Inventory

A physiologically based toxicokinetic (PB-TK) model for fish, incorporating chemical exchange at the gill and accumulation in five tissue compartments, was used to examine the effect of natural variability in physiological, morphological, and physico-chemical parameters on model ...

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

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.

Design/Development of Spacecraft and Module Crew Compartments

NASA Technical Reports Server (NTRS)

Goodman, Jerry R.

2010-01-01

This slide presentation reviews the design and development of crew compartments for spacecraft and for modules. The Crew Compartment or Crew Station is defined as the spacecraft interior and all other areas the crewman interfaces inside the cabin, or may potentially interface.It uses examples from all of the human rated spacecraft. It includes information about the process, significant drivers for the design, habitability, definitions of models, mockups, prototypes and trainers, including pictures of each stage in the development from Apollo, pictures of the space shuttle trainers, and International Space Station trainers. It further reviews the size and shape of the Space Shuttle orbiter crew compartment, and the Apollo command module and the lunar module. It also has a chart which reviews the International Space Station (ISS) internal volume by stage. The placement and use of windows is also discussed. Interestingly according to the table presented, the number 1 rated piece of equipment for recreation was viewing windows. The design of crew positions and restraints, crew translation aids and hardware restraints is shown with views of the restraints and handholds used from the Apollo program through the ISS.

Uncertainty quantification in flux balance analysis of spatially lumped and distributed models of neuron-astrocyte metabolism.

PubMed

Calvetti, Daniela; Cheng, Yougan; Somersalo, Erkki

2016-12-01

Identifying feasible steady state solutions of a brain energy metabolism model is an inverse problem that allows infinitely many solutions. The characterization of the non-uniqueness, or the uncertainty quantification of the flux balance analysis, is tantamount to identifying the degrees of freedom of the solution. The degrees of freedom of multi-compartment mathematical models for energy metabolism of a neuron-astrocyte complex may offer a key to understand the different ways in which the energetic needs of the brain are met. In this paper we study the uncertainty in the solution, using techniques of linear algebra to identify the degrees of freedom in a lumped model, and Markov chain Monte Carlo methods in its extension to a spatially distributed case. The interpretation of the degrees of freedom in metabolic terms, more specifically, glucose and oxygen partitioning, is then leveraged to derive constraints on the free parameters to guarantee that the model is energetically feasible. We demonstrate how the model can be used to estimate the stoichiometric energy needs of the cells as well as the household energy based on the measured oxidative cerebral metabolic rate of glucose and glutamate cycling. Moreover, our analysis shows that in the lumped model the net direction of lactate dehydrogenase (LDH) in the cells can be deduced from the glucose partitioning between the compartments. The extension of the lumped model to a spatially distributed multi-compartment setting that includes diffusion fluxes from capillary to tissue increases the number of degrees of freedom, requiring the use of statistical sampling techniques. The analysis of the distributed model reveals that some of the conclusions valid for the spatially lumped model, e.g., concerning the LDH activity and glucose partitioning, may no longer hold.

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.

Comparison of multiple methods to measure maternal fat mass in late gestation12

PubMed Central

Marshall, Nicole E; Murphy, Elizabeth J; King, Janet C; Haas, E Kate; Lim, Jeong Y; Wiedrick, Jack; Thornburg, Kent L; Purnell, Jonathan Q

2016-01-01

Background: Measurements of maternal fat mass (FM) are important for studies of maternal and fetal health. Common methods of estimating FM have not been previously compared in pregnancy with measurements using more complete body composition models. Objectives: The goal of this pilot study was to compare multiple methods that estimate FM, including 2-, 3- and 4-compartment models in pregnant women at term, and to determine how these measures compare with FM by dual-energy X-ray absorptiometry (DXA) 2 wk postpartum. Design: Forty-one healthy pregnant women with prepregnancy body mass index (in kg/m2) 19 to 46 underwent skinfold thickness (SFT), bioelectrical impedance analysis (BIA), body density (Db) via air displacement plethysmography (ADP), and deuterium dilution of total body water (TBW) with and without adjustments for gestational age using van Raaij (VRJ) equations at 37–38 wk of gestation and 2 wk postpartum to derive 8 estimates of maternal FM. Deming regression analysis and Bland-Altman plots were used to compare methods of FM assessment. Results: Systematic differences in FM estimates were found. Methods for FM estimates from lowest to highest were 4-compartment, DXA, TBW(VRJ), 3-compartment, Db(VRJ), BIA, air displacement plethysmography body density, and SFT ranging from a mean ± SD of 29.5 ± 13.2 kg via 4-compartment to 39.1 ± 11.7 kg via SFT. Compared with postpartum DXA values, Deming regressions revealed no substantial departures from trend lines in maternal FM in late pregnancy for any of the methods. The 4-compartment method showed substantial negative (underestimating) constant bias, and the air displacement plethysmography body density and SFT methods showed positive (overestimating) constant bias. ADP via Db(VRJ) and 3-compartment methods had the highest precision; BIA had the lowest. Conclusions: ADP that uses gestational age-specific equations may provide a reasonable and practical measurement of maternal FM across a spectrum of body weights in late pregnancy. SFT would be acceptable for use in larger studies. This trial was registered at clinicaltrials.gov as NCT02586714. PMID:26888714

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.

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.

Effect of human bone marrow mesenchymal stromal cells on cytokine production by peripheral blood naive, memory, and effector T cells.

PubMed

Laranjeira, Paula; Pedrosa, Monia; Pedreiro, Susana; Gomes, Joana; Martinho, Antonio; Antunes, Brigida; Ribeiro, Tania; Santos, Francisco; Trindade, Helder; Paiva, Artur

2015-01-05

The different distribution of T cells among activation/differentiation stages in immune disorders may condition the outcome of mesenchymal stromal cell (MSC)-based therapies. Indeed, the effect of MSCs in the different functional compartments of T cells is not completely elucidated. We investigated the effect of human bone marrow MSCs on naturally occurring peripheral blood functional compartments of CD4(+) and CD8(+) T cells: naive, central memory, effector memory, and effector compartments. For that, mononuclear cells (MNCs) stimulated with phorbol myristate acetate (PMA) plus ionomycin were cultured in the absence/presence of MSCs. The percentage of cells expressing tumor necrosis factor-alpha (TNF-α), interferon gamma (IFNγ), and interleukin-2 (IL-2), IL-17, IL-9, and IL-6 and the amount of cytokine produced were assessed by flow cytometry. mRNA levels of IL-4, IL-10, transforming growth factor-beta (TGF-β), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in purified CD4(+) and CD8(+) T cells, and phenotypic and mRNA expression changes induced by PMA + ionomycin stimulation in MSCs, were also evaluated. MSCs induced the reduction of the percentage of CD4(+) and CD8(+) T cells producing TNF-α, IFNγ, and IL-2 in all functional compartments, except for naive IFNγ(+)CD4(+) T cells. This inhibitory effect differentially affected CD4(+) and CD8(+) T cells as well as the T-cell functional compartments; remarkably, different cytokines showed distinct patterns of inhibition regarding both the percentage of producing cells and the amount of cytokine produced. Likewise, the percentages of IL-17(+), IL-17(+)TNF-α(+), and IL-9(+) within CD4(+) and CD8(+) T cells and of IL-6(+)CD4(+) T cells were decreased in MNC-MSC co-cultures. MSCs decreased IL-10 and increased IL-4 mRNA expression in stimulated CD4(+) and CD8(+) T cells, whereas TGF-β was reduced in CD8(+) and augmented in CD4(+) T cells, with no changes for CTLA4. Finally, PMA + ionomycin stimulation did not induce significant alterations on MSCs phenotype but did increase indoleamine-2,3-dioxygenase (IDO), inducible costimulatory ligand (ICOSL), IL-1β, IL-8, and TNF-α mRNA expression. Overall, our study showed that MSCs differentially regulate the functional compartments of CD4(+) and CD8(+) T cells, which may differentially impact their therapeutic effect in immune disorders. Furthermore, the influence of MSCs on IL-9 expression can open new possibilities for MSC-based therapy in allergic diseases.

Starling forces drive intracranial water exchange during normal and pathological states

PubMed Central

Linninger, Andreas A.; Xu, Colin; Tangen, Kevin; Hartung, Grant

2017-01-01

Aim To quantify the exchange of water between cerebral compartments, specifically blood, tissue, perivascular pathways, and cerebrospinal fluid-filled spaces, on the basis of experimental data and to propose a dynamic global model of water flux through the entire brain to elucidate functionally relevant fluid exchange phenomena. Methods The mechanistic computer model to predict brain water shifts is discretized by cerebral compartments into nodes. Water and species flux is calculated between these nodes across a network of arcs driven by Hagen-Poiseuille flow (blood), Darcy flow (interstitial fluid transport), and Starling’s Law (transmembrane fluid exchange). Compartment compliance is accounted for using a pressure-volume relationship to enforce the Monro-Kellie doctrine. This nonlinear system of differential equations is solved implicitly using MATLAB software. Results The model predictions of intraventricular osmotic injection caused a pressure rise from 10 to 22 mmHg, followed by a taper to 14 mmHg over 100 minutes. The computational results are compared to experimental data with R2 = 0.929. Moreover, simulated osmotic therapy of systemic (blood) injection reduced intracranial pressure from 25 to 10 mmHg. The modeled volume and intracranial pressure changes following cerebral edema agree with experimental trends observed in animal models with R2 = 0.997. Conclusion The model successfully predicted time course and the efficacy of osmotic therapy for clearing cerebral edema. Furthermore, the mathematical model implicated the perivascular pathways as a possible conduit for water and solute exchange. This was a first step to quantify fluid exchange throughout the brain. PMID:29308830

Investigation of tDCS volume conduction effects in a highly realistic head model

NASA Astrophysics Data System (ADS)

Wagner, S.; Rampersad, S. M.; Aydin, Ü.; Vorwerk, J.; Oostendorp, T. F.; Neuling, T.; Herrmann, C. S.; Stegeman, D. F.; Wolters, C. H.

2014-02-01

Objective. We investigate volume conduction effects in transcranial direct current stimulation (tDCS) and present a guideline for efficient and yet accurate volume conductor modeling in tDCS using our newly-developed finite element (FE) approach. Approach. We developed a new, accurate and fast isoparametric FE approach for high-resolution geometry-adapted hexahedral meshes and tissue anisotropy. To attain a deeper insight into tDCS, we performed computer simulations, starting with a homogenized three-compartment head model and extending this step by step to a six-compartment anisotropic model. Main results. We are able to demonstrate important tDCS effects. First, we find channeling effects of the skin, the skull spongiosa and the cerebrospinal fluid compartments. Second, current vectors tend to be oriented towards the closest higher conducting region. Third, anisotropic WM conductivity causes current flow in directions more parallel to the WM fiber tracts. Fourth, the highest cortical current magnitudes are not only found close to the stimulation sites. Fifth, the median brain current density decreases with increasing distance from the electrodes. Significance. Our results allow us to formulate a guideline for volume conductor modeling in tDCS. We recommend to accurately model the major tissues between the stimulating electrodes and the target areas, while for efficient yet accurate modeling, an exact representation of other tissues is less important. Because for the low-frequency regime in electrophysiology the quasi-static approach is justified, our results should also be valid for at least low-frequency (e.g., below 100 Hz) transcranial alternating current stimulation.

[«Surgical» analysis of the new clinical practice guide on compartmental syndrome].

PubMed

García-Ureña, Miguel Ángel; López-Monclús, Javier; Robín, Álvaro

2014-04-01

The new published guidelines of compartment syndrome are supposed to be a helpful tool in order to make decisions in patients with abdominal hypertension. From a surgical perspective of view, an important effort has been made in order to reach consensus in different phases in which there is no clear answer in evidence-based medicine. It is mandatory the use of a universal classification of open abdomen and there are three main concepts that must be observed: make a decompressive laparotomy when conservative measures have failed, attempt to closure the abdomen as soon as possible and the use of negative-pressure treatments that facilitates the management of an open abdomen. Although most of recommendations that have been delivered are not high grades, the present guide is an important assistant for the management of intra-abdominal hypertension and several lines of investigation are opened in order to answer the doubts that have been addressed. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

A Physiologically Based Model for Methylmercury in Female American Kestrels

EPA Science Inventory

A physiologically based toxicokinetic (PBTK) model was developed to describe the uptake, distribution, and elimination of methylmercury (CH3Hg) in female American kestrels. The model consists of six tissue compartments corresponding to the brain, liver, kidney, gut, red blood cel...

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

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.

Multimedia fate modeling and risk assessment of a commonly used azole fungicide climbazole at the river basin scale in China.

PubMed

Zhang, Qian-Qian; Ying, Guang-Guo; Chen, Zhi-Feng; Liu, You-Sheng; Liu, Wang-Rong; Zhao, Jian-Liang

2015-07-01

Climbazole is an antidandruff active ingredient commonly used in personal care products, but little is known about its environmental fate. The aim of this study was to evaluate the fate of climbazole in water, sediment, soil and air compartments of the whole China by using a level III multimedia fugacity model. The usage of climbazole was calculated to be 345 t in the whole China according to the market research data, and after wastewater treatment a total emission of 245 t was discharged into the receiving environment with approximately 93% into the water compartment and 7% into the soil compartment. The developed fugacity model was successfully applied to estimate the contamination levels and mass inventories of climbazole in various environmental compartments of the river basins in China. The predicted environmental concentration ranges of climbazole were: 0.20-367 ng/L in water, and 0.009-25.2 ng/g dry weight in sediment. The highest concentration was mainly found in Haihe River basin and the lowest was in basins of Tibet and Xinjiang regions. The mass inventory of climbazole in the whole China was estimated to be 294 t, with 6.79% in water, 83.7% in sediment, 9.49% in soil, and 0.002% in air. Preliminary risk assessment showed high risks in sediment posed by climbazole in 2 out of 58 basins in China. The medium risks in water and sediment were mostly concentrated in north China. To the best of our knowledge, it is the first report on the emissions and multimedia fate of climbazole in the river basins of the whole China. Copyright © 2015 Elsevier B.V. All rights reserved.

Image-based evaluations of distribution and cytotoxicity of Irinotecan (CPT-11) in a multi-compartment micro-cell coculture device.

PubMed

Nakayama, Hidenari; Kimura, Hiroshi; Fujii, Teruo; Sakai, Yasuyuki

2014-06-01

We recently developed a polydimethylsiloxane (PDMS)-based three-compartment microfluidic cocultivation device enabling real-time interactions of different cell populations as an advanced physiologically-relevant cell-based assay. This device had valves and small magnetic stirrer-based internal pumps for easy and flexible perfusion operations. In this study, we applied this device for the evaluation of Irinotecan (CPT-11) toxicity to the lung, because it is detoxified by the liver and accumulated in the fat in humans. We successfully cultured representative three different tissue model cells in each compartment under the individual culture conditions and also in entire perfusion. Growth inhibition of rat lung epithelial cell line L-2, was measured when administered with 50 μM CPT-11 under various cocultivation conditions with respect to the presences and absence of primary rat hepatocytes (liver tissue model) and adipocyte-like cells (fat tissue model) induced from a mouse fibroblast cell line, 3T3-L1. Although CPT-11 showed moderate toxicity to the pure culture of L-2 cells in the device after 72 h of perfusion culture, this was lowered mainly in the presence of the liver tissue. Inhibition of the L-2 cell growth agreed with the area under curve (AUC) values obtained from fluorescent image-based analyses in each compartment. These results demonstrate that developed simple and flexible microfluidic cocultivation device, with appropriate image-based analyses, can be used in evaluating toxicokinetic behaviors of drug candidates in systemic levels. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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.

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.

Exploration of optimal dosing regimens of haloperidol, a D2 Antagonist, via modeling and simulation analysis in a D2 receptor occupancy study.

PubMed

Lim, Hyeong-Seok; Kim, Su Jin; Noh, Yook-Hwan; Lee, Byung Chul; Jin, Seok-Joon; Park, Hyun Soo; Kim, Soohyeon; Jang, In-Jin; Kim, Sang Eun

2013-03-01

To evaluate the potential usage of D(2) receptor occupancy (D2RO) measured by positron emission tomography (PET) in antipsychotic development. In this randomized, parallel group study, eight healthy male volunteers received oral doses of 0.5 (n = 3), 1 (n = 2), or 3 mg (n = 3) of haloperidol once daily for 7 days. PET's were scanned before haloperidol, and on days 8, 12, with serial pharmacokinetic sampling on day 7. Pharmacokinetics and binding potential to D(2) receptor in putamen and caudate nucleus over time were analyzed using NONMEM, and simulations for the profiles of D2RO over time on various regimens of haloperidol were conducted to find the optimal dosing regimens. One compartment model with a saturable binding compartment, and inhibitory E(max) model in the effect compartment best described the data. Plasma haloperidol concentrations at half-maximal inhibition were 0.791 and 0.650 ng/ml, in putamen and caudate nucleus. Simulation suggested haloperidol 2 mg every 12 h is near the optimal dose. This study showed that sparse D2RO measurements in steady state pharmacodynamic design after multiple dosing could reveal the possibility of treatment effect of D(2) antagonist, and could identify the potential optimal doses for later clinical studies by modeling and simulation.

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.

Adaptive reconfiguration of the human NK-cell compartment in response to cytomegalovirus: a different perspective of the host-pathogen interaction.

PubMed

Muntasell, Aura; Vilches, Carlos; Angulo, Ana; López-Botet, Miguel

2013-05-01

As discussed in this review, human cytomegalovirus (HCMV) infection in healthy individuals is associated with a variable and persistent increase of NK cells expressing the CD94/NKG2C activating receptor. The expansion of NKG2C(+) NK cells reported in other infectious diseases is systematically associated with HCMV co-infection. The functionally mature NKG2C(bright) NK-cell subset expanding in HCMV(+) individuals displays inhibitory Ig-like receptors (KIR and LILRB1) specific for self HLA class I, and low levels of NKp46 and NKp30 activating receptors. Such reconfiguration of the NK-cell compartment appears particularly marked in immunocompromised patients and in children with symptomatic congenital infection, thus suggesting that its magnitude may be inversely related with the efficiency of the T-cell-mediated response. This effect of HCMV infection is reminiscent of the pattern of response of murine Ly49H(+) NK cells against murine CMV (MCMV), and it has been hypothesized that a cognate interaction of the CD94/NKG2C receptor with HCMV-infected cells may drive the expansion of the corresponding NK-cell subset. Yet, the precise role of NKG2C(+) cells in the control of HCMV infection, the molecular mechanisms underlying the NK-cell compartment redistribution, as well as its putative influence in the response to other pathogens and tumors remain open issues. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44.

PubMed

Stoeck, Alexander; Keller, Sascha; Riedle, Svenja; Sanderson, Michael P; Runz, Steffen; Le Naour, Francois; Gutwein, Paul; Ludwig, Andreas; Rubinstein, Eric; Altevogt, Peter

2006-02-01

Ectodomain shedding is a proteolytic mechanism by which transmembrane molecules are converted into a soluble form. Cleavage is mediated by metalloproteases and proceeds in a constitutive or inducible fashion. Although believed to be a cell-surface event, there is increasing evidence that cleavage can take place in intracellular compartments. However, it is unknown how cleaved soluble molecules get access to the extracellular space. By analysing L1 (CD171) and CD44 in ovarian carcinoma cells, we show in the present paper that the cleavage induced by ionomycin, APMA (4-aminophenylmercuric acetate) or MCD (methyl-beta-cyclodextrin) is initiated in an endosomal compartment that is subsequently released in the form of exosomes. Calcium influx augmented the release of exosomes containing functionally active forms of ADAM10 (a disintegrin and metalloprotease 10) and ADAM17 [TACE (tumour necrosis factor a-converting enzyme)] as well as CD44 and L1 cytoplasmic cleavage fragments. Cleavage could also proceed in released exosomes, but only depletion of ADAM10 by small interfering RNA blocked cleavage under constitutive and induced conditions. In contrast, cleavage of L1 in response to PMA occurred at the cell surface and was mediated by ADAM17. We conclude that different ADAMs are involved in distinct cellular compartments and that ADAM10 is responsible for shedding in vesicles. Our findings open up the possibility that exosomes serve as a platform for ectodomain shedding and as a vehicle for the cellular export of soluble molecules.

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.

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.

[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.

Mathematical properties and parameter estimation for transit compartment pharmacodynamic models.

PubMed

Yates, James W T

2008-07-03

One feature of recent research in pharmacodynamic modelling has been the move towards more mechanistically based model structures. However, in all of these models there are common sub-systems, such as feedback loops and time-delays, whose properties and contribution to the model behaviour merit some mathematical analysis. In this paper a common pharmacodynamic model sub-structure is considered: the linear transit compartment. These models have a number of interesting properties as the length of the cascade chain is increased. In the limiting case a pure time-delay is achieved [Milsum, J.H., 1966. Biological Control Systems Analysis. McGraw-Hill Book Company, New York] and the initial behaviour becoming increasingly sensitive to parameter value perturbation. It is also shown that the modelled drug effect is attenuated, though the duration of action is longer. Through this analysis the range of behaviours that such models are capable of reproducing are characterised. The properties of these models and the experimental requirements are discussed in order to highlight how mathematical analysis prior to experimentation can enhance the utility of mathematical modelling.

Stimulated echo diffusion tensor imaging and SPAIR T2-weighted imaging in Chronic Exertional Compartment Syndrome of the lower leg muscles

PubMed Central

Sigmund, Eric E.; Sui, Dabang; Ukpebor, Obehi; Baete, Steven; Fieremans, Els; Babb, James S.; Mechlin, Michael; Liu, Kecheng; Kwon, Jane; Mcgorty, KellyAnne; Hodnett, Phil; Bencardino, Jenny

2013-01-01

Purpose To evaluate the performance of diffusion tensor imaging (DTI) in the evaluation of chronic exertional compartment syndrome (CECS) as compared to T2-weighted imaging. Materials and Methods Using an IRB-approved HIPAA-compliant protocol, spectral adiabatic inversion recovery (SPAIR) T2-weighted imaging (T2w) and stimulated echo DTI were applied to 8 healthy volunteers and 14 suspected CECS patients before and after exertion. Longitudinal and transverse diffusion eigenvalues, mean diffusivity (MD), and fractional anisotropy (FA) were measured in 7 calf muscle compartments, which in patients were classified by their response on T2w: normal (<20% change), and CECS (>20% change). Mixed model analysis of variance compared subject groups and compartments in terms of response factors (post-/pre-exercise ratios) of DTI parameters. Results All diffusivities significantly increased (p<0.0001) and FA decreased (p=.0014) with exercise. Longitudinal diffusion responses were significantly smaller than transversal diffusion responses (p<0.0001). 19 of 98 patient compartments were classified as CECS on T2w. MD increased by 3.8±3.4% (volunteer), 7.4±4.2 % (normal), and 9.1±7.0% (CECS) with exercise. Conclusion DTI shows promise as an ancillary imaging method in the diagnosis and understanding of the pathophysiology in CECS. Future studies may explore its utility in predicting response to treatment. PMID:23440764

Spatial Heterogeneity in Drug Concentrations Can Facilitate the Emergence of Resistance to Cancer Therapy

PubMed Central

Fu, Feng; Nowak, Martin A.; Bonhoeffer, Sebastian

2015-01-01

Acquired resistance is one of the major barriers to successful cancer therapy. The development of resistance is commonly attributed to genetic heterogeneity. However, heterogeneity of drug penetration of the tumor microenvironment both on the microscopic level within solid tumors as well as on the macroscopic level across metastases may also contribute to acquired drug resistance. Here we use mathematical models to investigate the effect of drug heterogeneity on the probability of escape from treatment and the time to resistance. Specifically we address scenarios with sufficiently potent therapies that suppress growth of all preexisting genetic variants in the compartment with the highest possible drug concentration. To study the joint effect of drug heterogeneity, growth rate, and evolution of resistance, we analyze a multi-type stochastic branching process describing growth of cancer cells in multiple compartments with different drug concentrations and limited migration between compartments. We show that resistance is likely to arise first in the sanctuary compartment with poor drug penetrations and from there populate non-sanctuary compartments with high drug concentrations. Moreover, we show that only below a threshold rate of cell migration does spatial heterogeneity accelerate resistance evolution, otherwise deterring drug resistance with excessively high migration rates. Our results provide new insights into understanding why cancers tend to quickly become resistant, and that cell migration and the presence of sanctuary sites with little drug exposure are essential to this end. PMID:25789469

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.

Advanced tissue engineering scaffold design for regeneration of the complex hierarchical periodontal structure.

PubMed

Costa, Pedro F; Vaquette, Cédryck; Zhang, Qiyi; Reis, Rui L; Ivanovski, Saso; Hutmacher, Dietmar W

2014-03-01

This study investigated the ability of an osteoconductive biphasic scaffold to simultaneously regenerate alveolar bone, periodontal ligament and cementum. A biphasic scaffold was built by attaching a fused deposition modelled bone compartment to a melt electrospun periodontal compartment. The bone compartment was coated with a calcium phosphate (CaP) layer for increasing osteoconductivity, seeded with osteoblasts and cultured in vitro for 6 weeks. The resulting constructs were then complemented with the placement of PDL cell sheets on the periodontal compartment, attached to a dentin block and subcutaneously implanted into athymic rats for 8 weeks. Scanning electron microscopy, X-ray diffraction, alkaline phosphatase and DNA content quantification, confocal laser microscopy, micro computerized tomography and histological analysis were employed to evaluate the scaffold's performance. The in vitro study showed that alkaline phosphatase activity was significantly increased in the CaP-coated samples and they also displayed enhanced mineralization. In the in vivo study, significantly more bone formation was observed in the coated scaffolds. Histological analysis revealed that the large pore size of the periodontal compartment permitted vascularization of the cell sheets, and periodontal attachment was achieved at the dentin interface. This work demonstrates that the combination of cell sheet technology together with an osteoconductive biphasic scaffold could be utilized to address the limitations of current periodontal regeneration techniques. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

RLC model of visco-elastic properties of the chest wall

NASA Astrophysics Data System (ADS)

Aliverti, Andrea; Ferrigno, Giancarlo

1996-04-01

The quantification of the visco-elastic properties (resistance (R), inertia (L) and compliance (C)) of the different chest wall compartments (pulmonary rib cage,diaphragmatic rib cage and abdomen) is important to study the status of the passive components of the respiratory system, particularly in selected pathologies. Applying the viscoelastic-electrical analogy to the chest wall, we used an identification method in order to estimate the R, L and C parameters of the different parts of the chest, basing on different models; the input and output measured data were constituted by the volume variations of the different chest wall compartments and by the nasal pressure during controlled intermittent positive pressure ventilation by nasal mask, while the parameters of the system (R, L and C of the different compartments) were to be estimated. Volumes were measured with a new method, recently validated, based on an opto-electronic motion analyzer, able to compute with high accuracy and null invasivity the absolute values and the time variations of the volumes of each of the three compartments. The estimation of the R, L and C parameters has been based on a least-squared criterion, and the minimization has been based on a robustified iterative Gauss-Newton algorithm. The validation of the estimation procedure (fitting) has ben performed computing the percentage root mean square value of the error between the output real data and the output estimated data. The method has been applied to 2 healthy subjects. Also preliminary results have been obtained from 20 subjects affected by neuromuscular diseases (Duchenne Muscular Dystrophy (DMD) and Spinal Muscle Atrophy (SMA)). The results show that: (a) the best-fitting electrical models of the respiratory system are made up by one or three parallel RLC branches supplied by a voltage generator (so considering inertial properties, particularly in the abdominal compartment, and not considering patient/machine connection); (b) there is a significant difference between DMD and SMA groups (the value of resistance and rigidity of the thorax is much higher in SMA patients); (c) the inclusion of the connection patient-ventilator make the models ill-conditioned. We conclude that this method allows a quantitative evaluation of rib cage and abdominal passive characteristics with a good accuracy and through a dynamic measurement and that it could give significant data in physiology and clinics.

Pharmacokinetic properties of methadone hydrochloride after single intramuscular administration in adult dairy goats.

PubMed

Kock, M; Thompson, E; Vulliet, P R; Brooks, D L

1994-10-01

Pharmacokinetic parameters of methadone were studied in adult dairy goats. Five goats were each given methadone hydrochloride as a single 0.2 mg/kg of body weight dosage by intramuscular (IM) administration. Plasma methadone concentrations were determined for 96 h after dosing. Plasma methadone concentrations after IM administration were best described by an open one-compartment model. Overall elimination half-life (t1/2) was 1.38 h. Peak plasma concentrations were reached 0.25 h after dosing, and the actual plasma concentration averaged 37.8 ng/ml (SD = 12.76) at that time. The data obtained from this study suggest that plasma concentrations, similar to those that are analgesic in humans, can be achieved after IM administration of methadone at a dose rate of 0.2 mg/kg of body weight. In addition, these plasma concentrations can be maintained for up to 3 h after a single injection and, therefore, may provide satisfactory analgesia for such period.

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.