bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamics of an End-to-Side Anastomotic Graft for a Pulsatile Pediatric Ventricular Assist Device
Authors: Yang Ning , Deutsch Steven , Paterson Eric G. , Manning Keefe B.
Published: May 2010

Numerical simulations are performed to investigate the flow within the end-to-side proximal anastomosis of a pulsatile pediatric ventricular assist device (PVAD) to an aorta. The anastomotic model is constructed from a patient-specific pediatric aorta. The three great vessels originating from the aortic arch— brachiocephalic (innominate), left common carotid, and left subclavian arteries—are included. An implicit large eddy simulation method based on a finite volume approach is used to study the resulting turbulent flow. A resistance boundary condition is applied at each branch outlet to study flow splitting. The PVAD anastomosis is found to alter the aortic flow dramatically. More flow is diverted into the great vessels with the PVAD support. Turbulence is found in the jet impingement area at peak systole for 100% bypass, and a maximum principal normal Reynolds stress of 7081 dyn/cm2 is estimated based on ten flow cycles. This may be high enough to cause hemolysis and platelet activation. Regions prone to intimal hyperplasia are identified by combining the time-averaged wall shear stress and oscillatory shear index. These regions are found to vary, depending on the percentage of the flow bypass.
Spatiotemporal Measurement of Freezing-Induced Deformation of Engineered Tissues
Authors: Teo Ka Yaw , Dutton J. Craig , Han Bumsoo
Published: May 2010

In order to cryopreserve functional engineered tissues (ETs), the microstructure of the extracellular matrix (ECM) should be maintained, as well as the cellular viability since the functionality is closely related to the ECM microstructure. Since the post-thaw ECM microstructure is determined by the deformation of ETs during cryopreservation, freezing-induced deformation of ETs was measured with a newly developed quantum dot (QD)-mediated cell image deformetry system using dermal equivalents as a model tissue. The dermal equivalents were constructed by seeding QD-labeled fibroblasts in type I collagen matrices. After 24 h incubation, the ETs were directionally frozen by exposing them to a spatial temperature gradient (from 4°C to −20°C over a distance of 6 mm). While being frozen, the ETs were consecutively imaged, and consecutive pairs of these images were two-dimensionally cross-correlated to determine the local deformation during freezing. The results showed that freezing induced the deformation of ET, and its magnitude varied with both time and location. The maximum local dilatation was 0.006 s−1 and was always observed at the phase change interface. Due to this local expansion, the unfrozen region in front of the freezing interface experienced compression. This expansion-compression pattern was observed throughout the freezing process. In the unfrozen region, the deformation rate gradually decreased away from the freezing interface. After freezing/thawing, the ET experienced an approximately 28% decrease in thickness and 8% loss in weight. These results indicate that freezing-induced deformation caused the transport of interstitial fluid, and the interstitial fluid was extruded. In summary, the results suggest that complex cell-fluid-matrix interactions occur within ETs during freezing, and these interactions determine the post-thaw ECM microstructure and eventual post-thaw tissue functionality.
Analysis of Flow Patterns in a Patient-Specific Aortic Dissection Model
Authors: Cheng Z. , Tan F. P. P. , Riga C. V. , Bicknell C. D. , Hamady M. S. , Gibbs R. G. J. , Wood N. B. , Xu X. Y.
Published: May 2010

Aortic dissection is the most common acute catastrophic event affecting the thoracic aorta. The majority of patients presenting with an uncomplicated type B dissection are treated medically, but 25% of these patients develop subsequent aneurysmal dilatation of the thoracic aorta. This study aimed at gaining more detailed knowledge of the flow phenomena associated with this condition. Morphological features and flow patterns in a dissected aortic segment of a presurgery type B dissection patient were analyzed based on computed tomography images acquired from the patient. Computational simulations of blood flow in the patient-specific model were performed by employing a correlation-based transitional version of Menter’s hybrid k-ε/k-ω shear stress transport turbulence model implemented in ANSYS CFX 11. Our results show that the dissected aorta is dominated by locally highly disturbed, and possibly turbulent, flow with strong recirculation. A significant proportion (about 80%) of the aortic flow enters the false lumen, which may further increase the dilatation of the aorta. High values of wall shear stress have been found around the tear on the true lumen wall, perhaps increasing the likelihood of expanding the tear. Turbulence intensity in the tear region reaches a maximum of 70% at midsystolic deceleration phase. Incorporating the non-Newtonian behavior of blood into the same transitional flow model has yielded a slightly lower peak wall shear stress and higher maximum turbulence intensity without causing discernible changes to the distribution patterns. Comparisons between the laminar and turbulent flow simulations show a qualitatively similar distribution of wall shear stress but a significantly higher magnitude with the transitional turbulence model.
Computational Model of the Cerebral Ventricles in Hydrocephalus
Authors: Cheng Shaokoon , Bilston Lynne E.
Published: May 2010

Understanding the mechanisms of tissue injury in hydrocephalus is important to shed light on the pathophysiology of this neurostructural disorder. To date, most of the finite element models created to study hydrocephalus have been two-dimensional (2D). This may not be adequate as the geometry of the cerebral ventricles is unique. In this study, a three-dimensional (3D) finite element model of the cerebral ventricles during hydrocephalus is presented. Results from this model show that during hydrocephalus, the periventricular regions experience the highest stress, and stress magnitude is approximately 80 times higher than the cerebral mantle. This suggests that functional deficits observed in hydrocephalic patients could therefore be more related to the damage to periventricular white matter. In addition, the stress field simulated in the tissues based on the 3D model was found to be approximately four times lower than on the 2D model.
The Influence of the Pelvic Bone on the Computational Results of the Acetabular Component of a Total Hip Prosthesis
Authors: Barreto Sara , Folgado João , Fernandes Paulo R. , Monteiro Jacinto
Published: May 2010

The computational models developed to evaluate the hip joint performance usually neglect the presence of the pelvic bone. However, deformation depends on the stiffness of the underlying bone, and thus, the inclusion of the pelvic bone in the model influences the computed contact pressure and wear. This work discusses the influence of the pelvic bone, and how it depends on the acetabular component stiffness. It was modeled as two different polyethylene acetabular cups, considering or not a metal-backing for both 28 mm and 32 mm diametric cups. Two finite element models are developed, considering either the acetabular component rigidly fixed or attached to the deformable bone. Results present 28% and 42% difference on the contact pressure for a polyethylene cup without metal-backing when the support conditions are changed, for the 28 mm and 32 mm cups, respectively. Linear wear results present 21% and 31% difference for the same type of cups of 28 mm and 32 mm, correspondingly. The numerical results obtained in the present work show that to model the pelvic bone of the patient with a metal-backed cup did not greatly affect contact pressures and linear wear. However, when a total hip replacement is performed with an all-polyethylene acetabular cup, the presence of the pelvic bone in the model has a major influence.
Endovascular Nonthermal Irreversible Electroporation: A Finite Element Analysis
Authors: Maor Elad , Rubinsky Boris
Published: May 2010

Tissue ablation finds an increasing use in modern medicine. Nonthermal irreversible electroporation (NTIRE) is a biophysical phenomenon and an emerging novel tissue ablation modality, in which electric fields are applied in a pulsed mode to produce nanoscale defects to the cell membrane phospholipid bilayer, in such a way that Joule heating is minimized and thermal damage to other molecules in the treated volume is reduced while the cells die. Here we present a two-dimensional transient finite element model to simulate the electric field and thermal damage to the arterial wall due to an endovascular NTIRE novel device. The electric field was used to calculate the Joule heating effect, and a transient solution of the temperature is presented using the Pennes bioheat equation. This is followed by a kinetic model of the thermal damage based on the Arrhenius formulation and calculation of the Henriques and Moritz thermal damage integral. The analysis shows that the endovascular application of 90, 100 μs pulses with a potential difference of 600 V can induce electric fields of 1000 V/cm and above across the entire arterial wall, which are sufficient for irreversible electroporation. The temperature in the arterial wall reached a maximum of 66.7°C with a pulse frequency of 4 Hz. Thermal damage integral showed that this protocol will thermally damage less than 2% of the molecules around the electrodes. In conclusion, endovascular NTIRE is possible. Our study sets the theoretical basis for further preclinical and clinical trials with endovascular NTIRE.
Development of a CFD Boundary Condition to Model Transient Vapor Absorption in the Respiratory Airways
Authors: Tian Geng , Longest P. Worth
Published: May 2010

The absorption of moderately and highly soluble vapors into the walls of the conducting airways was previously shown to be a transient process over the timescale of an inhalation cycle. However, a boundary condition to predict the transient wall absorption of vapors in CFD simulations does not exist. The objective of this study was to develop and test a boundary condition that can be used to predict the transient absorption of vapors in CFD simulations of transport in the respiratory airways. To develop the boundary condition, an analytical expression for the concentration of an absorbed vapor in an air-mucus-tissue-blood (AMTB) model of the respiratory wall was developed for transient and variable air-phase concentrations. Based on the analytical expression, a flux boundary condition was developed at the air-mucus interface as a function of the far-field air-phase concentration. The new transient boundary condition was then implemented to predict absorption in a realistic model of the extrathoracic nasal airways through the larynx (nasal-laryngeal geometry). The results of the AMTB wall model verified that absorption was highly time dependent over the timescale of an inhalation cycle (approximately 1–2 s). At 1 s, transient conditions resulted in approximately 2–3 times more uptake in tissue and 20–25 times less uptake in blood than steady state conditions for both acetaldehyde and benzene. Application of this boundary condition to computational fluid dynamics simulations of the nasal-laryngeal geometry showed, as expected, that transient absorption significantly affected total deposition fractions in the mucus, tissue, and blood. Moreover, transient absorption was also shown to significantly affect the local deposition patterns of acetaldehyde and benzene. In conclusion, it is recommended that future analyses of vapors in the conducting airways consider time-dependent wall absorption based on the transient flux boundary condition developed in this study. Alternatively, a steady state absorption condition may be applied in conjunction with correction factors determined from the AMTB wall model.
Experimental Techniques for Studying Poroelasticity in Brain Phantom Gels Under High Flow Microinfusion
Authors: Ivanchenko O. , Sindhwani N. , Linninger A.
Published: May 2010

Convection enhanced delivery is an attractive option for the treatment of several neurodegenerative diseases such as Parkinson, Alzheimer, and brain tumors. However, the occurrence of a backflow is a major problem impeding the widespread use of this technique. In this paper, we analyze experimentally the force impact of high flow microinfusion on the deformable gel matrix. To investigate these fluid structure interactions, two optical methods are reported. First, gel stresses during microinfusion were visualized through a linear polariscope. Second, the displacement field was tracked using 400 nm nanobeads as space markers. The corresponding strain and porosity fields were calculated from the experimental observations. Finally, experimental data were used to validate a computational model for fluid flow and deformation in soft porous media. Our studies demonstrate experimentally, the distribution and magnitude of stress and displacement fields near the catheter tip. The effect of fluid traction on porosity and hydraulic conductivity is analyzed. The increase in fluid content in the catheter vicinity enhances the gel hydraulic conductivity. Our computational model takes into account the changes in porosity and hydraulic conductivity. The simulations agree with experimental findings. The experiments quantified solid matrix deformation, due to fluid infusion. Maximum deformations occur in areas of relatively large fluid velocities leading to volumetric strain of the matrix, causing changes in hydraulic conductivity and porosity close to the catheter tip. The gradual expansion of this region with increased porosity leads to decreased hydraulic resistance that may also create an alternative pathway for fluid flow.
A Variational Approach and Finite Element Implementation for Swelling of Polymeric Hydrogels Under Geometric Constraints
Authors: Kang Min Kyoo , Huang Rui
Published: May 2010

A hydrogel consists of a cross-linked polymer network and solvent molecules. Depending on its chemical and mechanical environment, the polymer network may undergo enormous volume change. The present work develops a general formulation based on a variational approach, which leads to a set of governing equations coupling mechanical and chemical equilibrium conditions along with proper boundary conditions. A specific material model is employed in a finite element implementation, for which the nonlinear constitutive behavior is derived from a free energy function, with explicit formula for the true stress and tangent modulus at the current state of deformation and chemical potential. Such implementation enables numerical simulations of hydrogels swelling under various constraints. Several examples are presented, with both homogeneous and inhomogeneous swelling deformation. In particular, the effect of geometric constraint is emphasized for the inhomogeneous swelling of surface-attached hydrogel lines of rectangular cross sections, which depends on the width-to-height aspect ratio of the line. The present numerical simulations show that, beyond a critical aspect ratio, creaselike surface instability occurs upon swelling.
The Role of Kelvin–Helmholtz Instabilities on Shaped Charge Jet Interaction With Reactive Armor Plates
Authors: Helte Andreas , Lidén Ewa
Published: May 2010

Reactive armor panels have been used for many years as very efficient add-on armor against shaped charge warheads. The main features of the defeat mechanisms of the armor are therefore well known. The origin of the irregular disturbances on the shaped charge jet, which leads to the severe fragmentation and scattering of the jet, is however not described in literature. As this scattering of the jet provides the main protection mechanism of the armor, it is of interest to understand the details of the interaction and the origin of the disturbances. Some experimental observations have been made showing that the backward moving plate often displaces the jet relatively smoothly while it is the interaction with the forward moving plate that causes the disturbances that leads to fragmentation and scattering of the jet. In this work, a mechanism for the interaction is proposed based on the theory of Kelvin–Helmholtz instabilities, which explains the origin of the disturbances on the jet due to the interaction with the forward moving plate. Numerical simulations have been performed to show the difference in the mechanisms of backward and forward moving plates when interacting with the jet. The impact angle of the plate seems to be the dominant parameter for the onset of instabilities. A parametric study has also been performed on how different interaction and material parameters influence the development of instabilities of the interface between the jet and the armor plate. The parametric study shows that low-strength jets promote development of instabilities, a tendency that is amplified by frictional forces between the materials. The influence of the plate strength is more complex due to the influence of the structural stability on the contact forces. The effect of friction and melting of the metals in the boundary layer to the development of the instabilities is discussed. A microscopic study of the edge of the penetration channel has been made, which shows that the materials have been melted during the interaction between the plate and the jet.
Nanoscale field emission in inert gas under atmospheric pressure
Authors: Qian Li , Wang Yuquan , Liu Liang , Fan Shoushan
Published: May 2010

Stable field emission has been obtained in inert gas under atmospheric pressure with 100 nm characteristic size. An individual multiwalled carbon nanotube (MWCNT) mounted on an atomic force microscopy tip acted as the cathode. The field emitter could provide current of up to 1 μA with fluctuation lower than 6%. This MWCNT was then coated with HfC to further improve its field emission current by about four times and reduce the fluctuation to 2%. With the protection of HfC, the field emitter has a high stability under atmospheric pressure inert gas; even increasing the characteristic size to 200 nm does not affect the stability. These results, combined with the state-of-the-art fabrication technology, could help create nanoscale field emission devices.
Dynamics of Subsynaptic Vesicles and Surface Microclusters at the Immunological Synapse
Authors: Purbhoo Marco A. , Liu Hebin , Oddos Stephane , Owen Dylan M. , Neil Mark A. A. , Pageon Sophie V. , French Paul M. W. , Rudd Christopher E. , Davis Daniel M.
Published: May 2010

Vesicles dynamically deliver the T cell adaptor protein LAT to sites of T cell signalosomes.
Preventing Vitamin Overdoses?
Authors: Wong Wei
Published: May 2010

Dietary absorption of vitamins A and D decreases bile acid synthesis through nuclear receptor–mediated transcriptional regulation.
Wnt Signaling Heterogeneity
Authors: Gough Nancy R.
Published: May 2010

The tumor microenvironment controls the intensity of cancer-associated Wnt signaling.
Keeping Balance in the Innate Immune System
Authors: Ray L. Bryan
Published: May 2010

A receptor protein helps avoid excessive activation of immune responses to invading pathogens.
Dangerous Dengue Provocation
Authors: Ash Caroline
Published: May 2010

Variable maturation of a dengue viral antigen results in incomplete neutralization and promotes secondary pathology.
Taking It Slow
Authors: Ray L. Bryan
Published: May 2010

The time delay in transcriptional regulatory systems sets important constraints on biological control systems.
Intracellular Concentrations of Posaconazole in Different Compartments of Peripheral Blood
Authors: Farowski Fedja , Cornely Oliver A. , Vehreschild Jörg J. , Hartmann Pia , Bauer Tim , Steinbach Angela , Rüping Maria J. G. T. , Müller Carsten
Published: May 2010

Therapeutic drug monitoring (TDM) of antifungal plasma concentrations is increasingly recommended. However, data on antifungal concentrations in the other compartments of the peripheral blood are limited. Hence, we collected 23 blood samples from 14 patients receiving posaconazole for prophylaxis of fungal infections. These samples were separated by double-discontinuous Ficoll-Hypaque density gradient centrifugation. The intracellular posaconazole concentrations of the obtained cells, i.e., the peripheral blood mononuclear cells (PBMCs), polymorphonuclear leukocytes (PMNs), and red blood cells (RBCs), were determined by liquid chromatography-tandem mass spectrometry. The intracellular concentrations of the PBMCs and PMNs were significantly higher than those of surrounding media (
P
< 0.001). The ratios between the intracellular and extracellular concentrations (C/E) were 22.5 ± 21.2, 7.66 ± 6.50, and 0.09 ± 0.05 for the PBMCs, PMNs, and RBCs, respectively. Posaconazole reaches high concentrations within human PBMCs and PMNs and is, to a lesser extent, present in RBCs. The high intracellular concentrations might contribute to posaconazole efficacy and distribution.
The VirSR Two-Component Signal Transduction System Regulates NetB Toxin Production in
Clostridium perfringens
Authors: Cheung Jackie K. , Keyburn Anthony L. , Carter Glen P. , Lanckriet Anouk L. , Van Immerseel Filip , Moore Robert J. , Rood Julian I.
Published: May 2010

Clostridium perfringens
causes several diseases in domestic livestock, including necrotic enteritis in chickens, which is of concern to the poultry industry due to its health implications and associated economic cost. The novel pore-forming toxin NetB is a critical virulence factor in the pathogenesis of this disease. In this study, we have examined the regulation of NetB toxin production. In
C. perfringens
, the quorum sensing-dependent VirSR two-component signal transduction system regulates genes encoding several toxins and extracellular enzymes. Analysis of the sequence upstream of the
netB
gene revealed the presence of potential DNA binding sites, or VirR boxes, that are recognized by the VirR response regulator.
In vitro
binding experiments showed that purified VirR was able to recognize and bind to these
netB
-associated VirR boxes. Furthermore, using a reporter gene assay, the
netB
VirR boxes were shown to be functional. Mutation of the
virR
gene in two avian
C. perfringens
strains was shown to significantly reduce the production of the NetB toxin; culture supernatants derived from these strains were no longer cytotoxic to Leghorn male hepatoma cells. Complementation with the
virRS
operon restored the toxin phenotypes to wild type. The results also showed that the VirSR two-component system regulates the expression of
netB
at the level of transcription. We postulate that in the gastrointestinal tract of infected birds, NetB production is upregulated when the population of
C. perfringens
cells reaches a threshold level that leads to activation of the VirSR system.
Pseudomonas aeruginosa
Evasion of Phagocytosis Is Mediated by Loss of Swimming Motility and Is Independent of Flagellum Expression
Authors: Amiel Eyal , Lovewell Rustin R. , O'Toole George A. , Hogan Deborah A. , Berwin Brent
Published: May 2010

Pseudomonas aeruginosa
is a pathogenic Gram-negative bacterium that causes severe opportunistic infections in immunocompromised individuals; in particular, severity of infection with
P. aeruginosa
positively correlates with poor prognosis in cystic fibrosis (CF) patients. Establishment of chronic infection by this pathogen is associated with downregulation of flagellar expression and of other genes that regulate
P. aeruginosa
motility. The current paradigm is that loss of flagellar expression enables immune evasion by the bacteria due to loss of engagement by phagocytic receptors that recognize flagellar components and loss of immune activation through flagellin-mediated Toll-like receptor (TLR) signaling. In this work, we employ bacterial and mammalian genetic approaches to demonstrate that loss of motility, not the loss of the flagellum
per se
, is the critical factor in the development of resistance to phagocytosis by
P. aeruginosa
. We demonstrate that isogenic
P. aeruginosa
mutants deficient in flagellar function, but retaining an intact flagellum, are highly resistant to phagocytosis by both murine and human phagocytic cells at levels comparable to those of flagellum-deficient mutants. Furthermore, we show that loss of MyD88 signaling in murine phagocytes does not recapitulate the phagocytic deficit observed for either flagellum-deficient or motility-deficient
P. aeruginosa
mutants. Our data demonstrate that loss of bacterial motility confers a dramatic resistance to phagocytosis that is independent of both flagellar expression and TLR signaling. These findings provide an explanation for the well-documented observation of nonmotility in clinical
P. aeruginosa
isolates and for how this phenotype confers upon the bacteria an advantage in the context of immune evasion.
Generation ofTrypanosoma cruzi-Specific CD8+T-Cell Immunity Is Unaffected by the Absence of Type I Interferon Signaling
Authors: Martin Diana L. , Murali-Krishna Kaja , Tarleton Rick L.
Published: May 2010

Trypanosoma cruziis a protozoan parasite that causes human Chagas’ disease, a leading source of congestive heart failure in Central and South America. CD8+T cells are critical for control ofT. cruziinfection, and CD8+T cells recognizing the immunodominanttrans-sialidase gene-encoded peptide TSKB20 (ANYKFTLV) account for approximately 30% of the total CD8+T-cell population at the peak of infection in C57BL/6 mice. Type I interferons (IFN-I) are pleiotropic cytokines that play a critical role in both innate and adaptive immunity against a variety of infections, but their induction and their role in infection are dictated by the infectious agent. Because type I IFNs and IFN-responsive genes are evident early afterT. cruziinfection of host cells, we examined the influence of IFN-I on the development of CD8+T-cell responses during this infection. Mice lacking the receptor for IFN-I (IFNARKO) and their wild-type counterparts both developed chronic infections and generated similar frequencies of immunodominant TSKB20- and subdominant TSKB18-specific CD8+T cells followingT. cruziinfection. In contrast, peak TSKB20-specific CD8+T-cell responses generated during infection with vaccinia virus engineered to express TSKB20 were approximately 2.5-fold lower in IFNARKO mice than B6 mice, although after viral clearance, the frequencies of TSKB20-specific CD8+T cells stabilized at similar levels. Together, these data suggest that IFN-I induction and biology are dependent upon the microbial context and emphasize the need to investigate various infection models for a full understanding of CD8+T-cell development.
A SPLITTING METHOD FOR THE CAHN–HILLIARD EQUATION WITH INERTIAL TERM
Authors: GRASSELLI MAURIZIO , PIERRE MORGAN
Published: May 2010

P. Galenko et al. proposed a Cahn–Hilliard model with inertial term in order to model spinodal decomposition caused by deep supercooling in certain glasses. Here we analyze a finite element space semidiscretization of their model, based on a scheme introduced by C. M. Elliott et al. for the Cahn–Hilliard equation. We prove that the semidiscrete solution converges weakly to the continuous solution as the discretization parameter tends to 0. We obtain optimal a priori error estimates in energy norm and related norms, assuming enough regularity on the solution. We also show that the semidiscrete solution converges to an equilibrium as time goes to infinity and we give a simple finite difference version of the scheme.
Reframing health to embrace design of our own well-being
Authors: Dubberly Hugh , Mehta Rajiv , Evenson Shelley , Pangaro Paul
Published: May 2010

Editor's Note: Improving healthcare is a wicked problem [1]. Healthcare's many stakeholders can't agree on a solution, because they don't agree on the problem. They come to the discussion from different points of view, with different frames. Wicked problems can be "solved" only by reframing, by providing a new way of understanding the problem that stakeholders can share [1]. This article describes a growing trend: framing health in terms of well-being and broadening healthcare to include self-management. Self-management reframes patients as designers, an example of a shift also occurring in design practice---reframing users as designers. The article concludes with thoughts on what these changes may mean when designing for health.---Hugh Dubberly
Mobile collaboration
Authors: Ali-Hassan Hossam , Nevo Dorit , Nevo Saggi
Published: May 2010

With advances in the areas of telecommunications, computing and miniaturization of computers, the use of mobile technology is becoming prevalent within organizations. Consequently, a shift towards a nomadic computing environment, capable of supporting workers anywhere and anytime, is commonly observed. While many of the issues associated with such environments are technological in nature, this paper focuses on the social aspect of the shift to a nomadic computing environment, and examines its impact of employees' ability to effectively collaborate with one another. Studying changes at the individual level, we argue that an increase in workers' social mobility, brought upon by the move to a nomadic computing environment, is likely to have a negative effect on their social capital. Social capital has been shown to positively impact collaboration in various settings, including the workplace. We further argue that the above negative effect is contingent upon the type of mobile technology used by nomadic workers. The paper concludes with suggestions for model extensions and avenues for future research.
PDZ protein mediated activity-dependent LTP/LTD developmental switch at rat retinocollicular synapses
Authors: Xue Lei , Zhang Fan , Chen Xianhua , Lin Junji , Shi Jian
Published: May 2010

The insertion of amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors into the plasma membrane and removal via internalization are essential for regulating synaptic strength, which underlies the basic mechanism of learning and memory. The retinocollicular pathway undergoes synaptic refinement during development and shows a wide variety of long-term synaptic changes; however, still little is known about its underlying molecular regulation. Here we report a rapid developmental long-term potentiation (LTP)/long-term depression (LTD) switch and its intracellular mechanism at the rat retinocollicular pathway from postnatal day 5 (P5) to P14. Before P9, neurons always exhibited LTP, whereas LTD was observed only after P10. Blockade of GluR2/3-glutamate receptor-interacting protein (GRIP)/AMPA-receptor-binding protein (ABP)/protein interacting with C kinase 1 (PICK1) interactions with pep2-SVKI could sustain the LTP after P10. This suggests that the LTP/LTD switch relied on PDZ protein activities. Selective interruption of GluR2/3-PICK1 binding by pep2-EVKI blocked the long-lasting effects of both LTP and LTD, suggesting a role for PICK1 in the maintenance of long-term synaptic plasticity. Interestingly, synaptic expression of GRIP increased more than twofold from P7 to P11, whereas ABP and PICK1 expression levels remained stable. Blockade of spontaneous retinal input suppressed this increase and abolished the LTP/LTD switch. These results suggest that the increased GRIP synaptic expression may be a key regulatory factor in mediating the activity-dependent developmental LTP/LTD switch, whereas PICK1 may be required for both LTP and LTD to maintain their long-term effects.
Autophagy in health and disease. 4. The role of pancreatic β-cell autophagy in health and diabetes
Authors: Fujitani Yoshio , Ueno Takashi , Watada Hirotaka
Published: May 2010

Autophagy is an evolutionarily conserved machinery for degradation and recycling of various cytoplasmic components such as long-lived proteins and organelles. In pancreatic β-cells, as in most other cells, autophagy is also important for the low basal turnover of ubiquitinated proteins and damaged organelles under normal conditions. Insulin resistance results in upregulation of autophagic activity in β-cells. Induced autophagy in β-cells plays a pivotal role in the adaptive expansion of β-cell mass. Nevertheless, it is not clear whether autophagy is protective or detrimental in response to cellular stresses in β-cells. In this review, we describe the crucial roles of autophagy in normal function of β-cells and discuss how dysfunction of the autophagic machinery could lead to the development of diabetes mellitus.
Functional NMDA receptors in rat erythrocytes
Authors: Makhro Asya , Wang Jue , Vogel Johannes , Boldyrev Alexander A. , Gassmann Max , Kaestner Lars , Bogdanova Anna
Published: May 2010

N-methyl-d-aspartate (NMDA) receptors are ligand-gated nonselective cation channels mediating fast neuronal transmission and long-term potentiation in the central nervous system. These channels have a 10-fold higher permeability for Ca2+ compared with Na+ or K+ and binding of the agonists (glutamate, homocysteine, homocysteic acid, NMDA) triggers Ca2+ uptake. The present study demonstrates the presence of NMDA receptors in rat erythrocytes. The receptors are most abundant in both erythroid precursor cells and immature red blood cells, reticulocytes. Treatment of erythrocytes with NMDA receptor agonists leads to a rapid increase in intracellular Ca2+ resulting in a transient shrinkage via Gardos channel activation. Additionally, the exposure of erythrocytes to NMDA receptor agonists causes activation of the nitric oxide (NO) synthase facilitating either NO production in l-arginine-containing medium or superoxide anion (O2·−) generation in the absence of l-arginine. Conversely, treatment with an NMDA receptor antagonist MK-80, or the removal of Ca2+ from the incubation medium causes suppression of Ca2+ accumulation and prevents attendant changes in cell volume and NO/O2·− production. These results suggest that the NMDA receptor activity in circulating erythrocytes is regulated by the plasma concentrations of homocysteine and homocysteic acid. Moreover, receptor hyperactivation may contribute to an increased incidence of thrombosis during hyperhomocysteinemia.
A mechanosensitive ion channel regulating cell volume
Authors: Hua Susan Z. , Gottlieb Philip A. , Heo Jinseok , Sachs Frederick
Published: May 2010

Cells respond to a hyposmotic challenge by swelling and then returning toward the resting volume, a process known as the regulatory volume decrease or RVD. The sensors for this process have been proposed to include cationic mechanosensitive ion channels that are opened by membrane tension. We tested this hypothesis using a microfluidic device to measure cell volume and the peptide GsMTx4, a specific inhibitor of cationic mechanosensitive channels. GsMTx4 had no effect on RVD in primary rat astrocytes or Madin-Darby canine kidney (MDCK) cells but was able to completely inhibit RVD and the associated Ca2+uptake in normal rat kidney (NRK-49F) cells in a dose-dependent manner. Gadolinium (Gd3+), a nonspecific blocker of many mechanosensitive channels, inhibited RVD and Ca2+uptake in all three cell types, demonstrating the existence of at least two types of volume sensors. Single-channel stretch-activated currents are present in outside-out patches from NRK-49F, MDCK, and astrocytes, and they are reversibly inhibited by GsMTx4. While mechanosensitive channels are involved in volume regulation, their role for volume sensing is specialized. The NRK cells form a stable platform from which to screen drugs that affect volume regulation via mechanosensory channels and as a sensitive system to clone the channel.
Prostaglandin E2 induces interleukin-6 expression in human chondrocytes via cAMP/protein kinase A- and phosphatidylinositol 3-kinase-dependent NF-κB activation
Authors: Wang Pu , Zhu Fei , Konstantopoulos Konstantinos
Published: May 2010

Elevated levels of prostaglandin (PG)E2 and interleukin (IL)-6 have been reported in the cartilage and synovial fluid from patients with arthritic disorders. PGE2 regulates IL-6 production in numerous different cells including macrophages and synovial fibroblasts. Although PGE2 stimulates IL-6 expression in human chondrocytes, the underlying signaling pathway of this process has yet to be delineated. Here, we investigate the mechanism of IL-6 induction in human T/C-28a2 chondrocytes treated with exogenously added PGE2. PGE2 induces IL-6 mRNA and protein expression via a cAMP-dependent pathway, reaching maximal levels after 60 min of stimulation before declining to baseline levels at 6 h. Forskolin, an adenylyl cyclase activator, also stimulates IL-6 expression in human chondrocytes in a dose- and time-dependent fashion. Inhibition of downstream effectors of cAMP activity such as protein kinase A (PKA) or phosphatidylinositol 3 kinase (PI3K) blocks PGE2- and forskolin-induced IL-6 upregulation. Simultaneous inhibition of PKA and PI3K reduces IL-6 expression in stimulated chondrocytes well below the basal levels of untreated cells. Gel shift, supershift, and chromatin immunoprecipitation assays reveal the activation and binding of the nuclear factor (NF)-κB p65 subunit to the IL-6 promoter, which is markedly suppressed by selective PI3K or PKA pharmacological inhibitors. p65 knockdown completely abrogates IL-6 mRNA synthesis in PGE2- and forskolin-primed chondrocytes. Cumulatively, our data show that PGE2 and forskolin induce IL-6 expression in human chondrocytes via cAMP/PKA and PI3K-dependent pathways, which in turn regulate the activation and binding of p65 to the IL-6 promoter.
Activation of NMDA Receptors Is Necessary for the Recovery of Cortical Binocularity
Authors: Krahe Thomas E. , Medina Alexandre E.
Published: May 2010

Classic experiments have indicated that monocular deprivation (MD) for a few days during a critical period of development results in a decrease in the strength of connections mediating responses to the deprived eye, leading to a dramatic breakdown of cortical neuron binocularity. Despite the substantial functional change in the visual cortex, recovery from the effects of MD can be obtained if binocular vision is promptly restored. While great efforts have been made to elucidate the mechanisms regulating loss of deprived eye function, the mechanisms that underlie the recovery of cortical binocularity are poorly understood. Here, we examined whether activation of the N-methyl-d-aspartate receptor (NMDAR) is required for the recovery of cortical binocularity by pharmacologically blocking the NMDAR using d,l-2-amino-5-phosphonopentanoic (APV). Ferrets ( n = 10) were monocularly deprived for 6 days, and osmotic minipumps, filled with APV (5.6 mg/ml) or saline, were surgically implanted into the primary visual cortex. One day after surgery, the deprived eye was reopened, and the animals were allowed 24 h of binocular vision. Extracellular recordings showed that intracortical infusion of the NMDAR antagonist, APV, prevented recovery of cortical binocularity while preserving neuronal responsiveness. These findings provide an important new insight for a specific role of NMDARs in the recovery of cortical binocularity from the effects of MD.
Convergence of Pyramidal and Medial Brain Stem Descending Pathways Onto Macaque Cervical Spinal Interneurons
Authors: Riddle C. Nicholas , Baker Stuart N.
Published: May 2010

We investigated the control of spinal interneurons by corticospinal and medial brain stem descending tracts in two macaque monkeys. Stimulating electrodes were implanted in the left pyramidal tract (PT), and the right medial longitudinal fasciculus (MLF), which contains reticulospinal, vestibulospinal, and some tectospinal fibers. Single unit discharge was recorded from 163 interneurons in the intermediate zone of the right spinal cord (segmental levels C6–C8) in the awake state; inputs from descending pathways were assessed from the responses to stimulation through the PT and MLF electrodes. Convergent input from both pathways was the most common finding (71/163 cells); responses to PT and MLF stimulation were of similar amplitude. Interneuron discharge was also recorded while the animal performed a reach and grasp task with the right hand; the output connections of the recorded cells were determined by delivering intraspinal microstimulation (ISMS) at the recording sites. Convergent input from MLF/PT stimulation was also common when analysis was restricted to cells that increased their rate during grasp (14/23 cells) or to cells recorded at sites where ISMS elicited finger or wrist movements (23/57 cells). We conclude that medial brain stem and corticospinal descending pathways have largely overlapping effects on spinal interneurons, including those involved in the control of the hand. This may imply a more important role for the brain stem in coordinating hand movements in primates than commonly assumed; brain stem pathways could contribute to the restoration of function seen after lesions to the corticospinal tract.
Spontaneous Ryanodine-Receptor-Dependent Ca2+-Activated K+ Currents and Hyperpolarizations in Rat Medial Preoptic Neurons
Authors: Klement Göran , Druzin Michael , Haage David , Malinina Evgenya , Århem Peter , Johansson Staffan
Published: May 2010

The aim of the present study was to clarify the identity of slow spontaneous currents, the underlying mechanism and possible role for impulse generation in neurons of the rat medial preoptic nucleus (MPN). Acutely dissociated neurons were studied with the perforated patch-clamp technique. Spontaneous outward currents, at a frequency of ∼0.5 Hz and with a decay time constant of ∼200 ms, were frequently detected in neurons when voltage-clamped between approximately −70 and −30 mV. The dependence on extracellular K+ concentration was consistent with K+ as the main charge carrier. We concluded that the main characteristics were similar to those of spontaneous miniature outward currents (SMOCs), previously reported mainly for muscle fibers and peripheral nerve. From the dependence on voltage and from a pharmacological analysis, we concluded that the currents were carried through small-conductance Ca2+-activated (SK) channels, of the SK3 subtype. From experiments with ryanodine, xestospongin C, and caffeine, we concluded that the spontaneous currents were triggered by Ca2+ release from intracellular stores via ryanodine receptor channels. An apparent voltage dependence was explained by masking of the spontaneous currents as a consequence of steady SK-channel activation at membrane potentials > −30 mV. Under current-clamp conditions, corresponding transient hyperpolarizations occasionally exceeded 10 mV in amplitude and reduced the frequency of spontaneous impulses. In conclusion, MPN neurons display spontaneous hyperpolarizations triggered by Ca2+ release via ryanodine receptors and SK3-channel activation. Thus such events may affect impulse firing of MPN neurons.
Compensatory Motor Control After Stroke: An Alternative Joint Strategy for Object-Dependent Shaping of Hand Posture
Authors: Raghavan Preeti , Santello Marco , Gordon Andrew M. , Krakauer John W.
Published: May 2010

Efficient grasping requires planned and accurate coordination of finger movements to approximate the shape of an object before contact. In healthy subjects, hand shaping is known to occur early in reach under predominantly feedforward control. In patients with hemiparesis after stroke, execution of coordinated digit motion during grasping is impaired as a result of damage to the corticospinal tract. The question addressed here is whether patients with hemiparesis are able to compensate for their execution deficit with a qualitatively different grasp strategy that still allows them to differentiate hand posture to object shape. Subjects grasped a rectangular, concave, and convex object while wearing an instrumented glove. Reach-to-grasp was divided into three phases based on wrist kinematics: reach acceleration (reach onset to peak horizontal wrist velocity), reach deceleration (peak horizontal wrist velocity to reach offset), and grasp (reach offset to lift-off). Patients showed reduced finger abduction, proximal interphalangeal joint (PIP) flexion, and metacarpophalangeal joint (MCP) extension at object grasp across all three shapes compared with controls; however, they were able to partially differentiate hand posture for the convex and concave shapes using a compensatory strategy that involved increased MCP flexion rather than the PIP flexion seen in controls. Interestingly, shape-specific hand postures did not unfold initially during reach acceleration as seen in controls, but instead evolved later during reach deceleration, which suggests increased reliance on sensory feedback. These results indicate that kinematic analysis can identify and quantify within-limb compensatory motor control strategies after stroke. From a clinical perspective, quantitative study of compensation is important to better understand the process of recovery from brain injury. From a motor control perspective, compensation can be considered a model for how joint redundancy is exploited to accomplish the task goal through redistribution of work across effectors.
Co-Induction of LTP and LTD and Its Regulation by Protein Kinases and Phosphatases
Authors: Grey Kathryn B. , Burrell Brian D.
Published: May 2010

The cellular properties of long-term potentiation (LTP) following pairing of pre- and postsynaptic activity were examined at a known glutamatergic synapse in the leech, specifically between the pressure (P) mechanosensory and anterior pagoda (AP) neurons. Stimulation of the presynaptic P cell (25 Hz) concurrent with a 2 nA depolarization of the postsynaptic AP cell significantly potentiated the P-to-AP excitatory postsynaptic potential (EPSP) in an N-methyl-d-aspartate receptor (NMDAR)-dependent manner based on inhibitory effects of the NMDAR antagonist MK801 and inhibition of the NMDAR glycine binding site by 7-chlorokynurenic acid. LTP was blocked by injection of bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (BAPTA) into the postsynaptic (AP) cell, indicating a requirement for postsynaptic elevation of intracellular Ca2+. Autocamtide-2-related inhibitory peptide (AIP), a specific inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII), and Rp-cAMP, an inhibitor of protein kinase A (PKA), also blocked pairing-induced potentiation, indicating a requirement for activation of CaMKII and PKA. Interestingly, application of AIP during pairing resulted in significantly depressed synaptic transmission. Co-application of AIP with the protein phosphatase inhibitor okadaic acid restored synaptic transmission to baseline levels, suggesting an interaction between CaMKII and protein phosphatases during induction of activity-dependent synaptic plasticity. When postsynaptic activity preceded presynaptic activity, NMDAR-dependent long-term depression (LTD) was observed that was blocked by okadaic acid. Postsynaptic injection of botulinum toxin blocked P-to-AP potentiation while postsynaptic injection of pep2-SVKI, an inhibitor of AMPA receptor endocytosis, inhibited LTD, supporting the hypothesis that glutamate receptor trafficking contributes to both LTP and LTD at the P-to-AP synapse in the leech.
Convergence Theorems on Asymptotically Pseudocontractive Mappings in the Intermediate Sense
Authors: Qin Xiaolong , Cho SunYoung , Kim JongKyu
Published: May 2010

A new nonlinear mapping is introduced. The convergence of Ishikawa iterative processes for the class of asymptotically pseudocontractive mappings in the intermediate sense is studied. Weak convergence theorems are established. A strong convergence theorem is also established without any compact assumption by considering the so-called hybrid projection methods.