bluuebunny/crossref_metadata_2025 huggingface dataset:
Central WENO scheme for the integral form of contravariant shallow‐water equations
Authors: Gallerano F. , Cannata G.
Published: August 2010

A new Central Weighted Essentially Non‐Oscillatory scheme for the solution of the shallow‐water equations expressed in contravariant formulation is presented. One of the most efficient methodologies belonging to Central WENO family involves: reconstructions of cell‐averaged values of flow variables, reconstruction of point‐values of flow variables, advancing from time level tn to time level tn+1 of the cell‐averaged values. The extension of the above‐mentioned methodology into the contravariant environment implies that the contravariant shallow‐water equations must be expressed in an integral form. An element of novelty presented in this paper regards the definition of a formal integral expression of the shallow‐water equations in a contravariant formulation, in which the Christoffel symbols are avoided. The WENO reconstructions are performed by a two‐dimensional interpolating procedure taking into account the curved coordinate lines. The proposed scheme ensures the satisfaction of the exact C‐property. Several two‐dimensional test cases are used to verify the good resolution for smooth and discontinuous solutions. Copyright © 2010 John Wiley & Sons, Ltd.
The Runge–Kutta control volume discontinuous finite element method for systems of hyperbolic conservation laws
Authors: Chen Dawei , Yu Xijun , Chen Zhangxin
Published: August 2010

In this paper, a new high‐order and high‐resolution method called the Runge–Kutta control volume discontinuous finite element method (RKCVDFEM) was proposed to solve 1D and 2D systems of hyperbolic conservation laws. Its main advantage lies in the local conservation, and it is simpler than the Runge–Kutta discontinuous Galerkin finite element method (RKDGM). The theoretical analysis showed that the RKCVDFEM has formally an optimal convergence order for 1D systems. Based on logically rectangular grids of irregular quadrilaterals, a scheme for 2D systems was constructed. Some classical problems were simulated and the validity of the method was presented. Copyright © 2010 John Wiley & Sons, Ltd.
Arbitrary Lagrangian–Eulerian 3D ideal MHD algorithms
Authors: Robinson A. C. , Niederhaus J. H. J. , Weirs V. G. , Love E.
Published: August 2010

We discuss algorithmic approaches and verification results associated with the Lagrangian–Eulerian algorithms for ideal magnetohydrodynamics as implemented in the ALEGRA arbitrary Lagrangian–Eulerian code. We discuss the form of the Lagrangian step discretization including the forces and the time step control. We also discuss our constrained transport approach for remap of the magnetic flux density and a deBar‐type approach for total energy conservation which permits the capturing of shocks. We demonstrate the benefit of a predictor–corrector methodology for time discretization. Directions for further research are indicated. Copyright © 2010 John Wiley & Sons, Ltd.
Numerical models for vehicle exhaust dispersion in complex urban areas
Authors: Liu Weiming
Published: August 2010

Two numerical models are presented for predicting vehicle exhaust dispersion in complex urban areas with or without the wind field. The models not only reflect the effect of building and street canyon configuration on the pollutant propagation, but also are able to predict the turbulent energy produced by moving vehicles on the road. In particular, in the discrete model, turbulent energy and pollutant concentration produced by each vehicle are dynamically described in the Lagrangian method. The pollutant propagation is calculated with the advection–diffusion equation. The Reynolds averaged Navier–Stokes equations are numerically solved for the wind flows. The movement and heat release rate of the vehicles are treated as sources of the turbulent energy equation for the computation of turbulent energy produced by the moving vehicles. This paper reports the detailed implementation of the models. Four typical numerical tests were carried out to represent the performance of the proposed numerical models. Copyright © 2010 John Wiley & Sons, Ltd.
An unstructured finite volume model for dam‐break floods with wet/dry fronts over complex topography
Authors: Song Lixiang , Zhou Jianzhong , Li Qingqing , Yang Xiaoling , Zhang Yongchuan
Published: August 2010

A robust, well‐balanced, unstructured, Godunov‐type finite volume model has been developed in order to simulate two‐dimensional dam‐break floods over complex topography with wetting and drying. The model is based on the nonlinear shallow water equations in hyperbolic conservation form. The inviscid fluxes are calculated using the HLLC approximate Riemann solver and a second‐order spatial accuracy is achieved by implementing the MUSCL reconstruction technique. To prevent numerical oscillations near shocks, slope‐limiting techniques are used for controlling the total variation of the reconstructed field. The model utilizes an explicit two‐stage Runge–Kutta method for time stepping, whereas implicit treatments for friction source terms. The novelties of the model include the flux correction terms and the water depth reconstruction method both for partially and fully submerged cells, and the wet/dry front treatments. The proposed flux correction terms combined with the water depth reconstruction method are necessary to balance the bed slope terms and flux gradient in the hydrostatical steady flow condition. Especially, this well‐balanced property is also preserved in partially submerged cells. It is found that the developed wet/dry front treatments and implicit scheme for friction source terms are stable. The model is tested against benchmark problems, laboratory experimental data, and realistic application related to dam‐break flood wave propagation over arbitrary topography. Numerical results show that the model performs satisfactorily with respect to its effectiveness and robustness and thus has bright application prospects. Copyright © 2010 John Wiley & Sons, Ltd.
Sensitivity of the 1D shallow water equations with source terms: Solution method for discontinuous flows
Authors: Delenne C. , Finaud‐Guyot P. , Guinot V. , Cappelaere B.
Published: August 2010

A finite volume‐based numerical technique is presented concerning the sensitivity of the solution of the one‐dimensional Shallow Water Equations with scalar transport. An approximate Riemann solver is proposed for direct sensitivity calculation even in the presence of discontinuous solutions. The Shallow Water Sensitivity Equations are first derived as well as the expressions of the sensitivity source terms, initial and boundary conditions. The numerical technique is then detailed and application examples are provided to assess the method's efficiency in estimating the sensitivity to different parameters (friction coefficient and initial and boundary conditions). The application of the dam‐break problem to a trapezoidal channel is also provided. The comparison with the analytical solution and the classical empirical approach illustrates the usefulness of the direct sensitivity calculation. Copyright © 2010 John Wiley & Sons, Ltd.
3D simulation of wind turbine rotors at full scale. Part I: Geometry modeling and aerodynamics
Authors: Bazilevs Y. , Hsu M.‐C. , Akkerman I. , Wright S. , Takizawa K. , Henicke B. , Spielman T. , Tezduyar T. E.
Published: August 2010

In this two‐part paper we present a collection of numerical methods combined into a single framework, which has the potential for a successful application to wind turbine rotor modeling and simulation. In Part 1 of this paper we focus on: 1. The basics of geometry modeling and analysis‐suitable geometry construction for wind turbine rotors; 2. The fluid mechanics formulation and its suitability and accuracy for rotating turbulent flows; 3. The coupling of air flow and a rotating rigid body. In Part 2 we focus on the structural discretization for wind turbine blades and the details of the fluid–structure interaction computational procedures. The methods developed are applied to the simulation of the NREL 5MW offshore baseline wind turbine rotor. The simulations are performed at realistic wind velocity and rotor speed conditions and at full spatial scale. Validation against published data is presented and possibilities of the newly developed computational framework are illustrated on several examples. Copyright © 2010 John Wiley & Sons, Ltd.
Evolution analysis of the main mechanisms of the jet/vortex interaction
Authors: Depommier Guillaume , Labbé Odile , Sagaut Pierre
Published: August 2010

A new analysis method of the jet/vortex interaction is presented to better understand the effect of each vortical structure on the others composing the jet and even on itself. Vortical structures are isolated from each other and the velocity field they produce is calculated by means of the Biot–Savart law. The structure influence on each another is then distinguished from the others by using its velocity field in the calculation of the vorticity momentum equations. Based on 3D‐datafields provided by a large‐eddy‐simulation (LES) of the interaction between a Lamb–Oseen vortex and a turbulent round jet, a post‐processing tool educes the vortical structures and quantifies the different vorticity momentum equations terms. The study has been limited to the first steps of the interaction regime when there are still few vortical structures so that the subsequent analysis of the post‐process results remains simple enough to be performed. The present method confirmed the intensification of azimuthal structures as they roll up around the main vortex. Core disturbance of the latter was found to be initially caused by those structures and not by core dynamic instabilities, which become dominant with the appearance of non‐linear mechanisms. Copyright © 2010 John Wiley & Sons, Ltd.
A new well‐balanced Hermite weighted essentially non‐oscillatory scheme for shallow water equations
Authors: Caleffi Valerio
Published: August 2010

Hermite weighted essentially non‐oscillatory (HWENO) methods were introduced in the literature, in the context of Euler equations for gas dynamics, to obtain high‐order accuracy schemes characterized by high compactness (e.g. Qiu and Shu, J. Comput. Phys. 2003; 193:115). For example, classical fifth‐order weighted essentially non‐oscillatory (WENO) reconstructions are based on a five‐cell stencil whereas the corresponding HWENO reconstructions are based on a narrower three‐cell stencil. The compactness of the schemes allows easier treatment of the boundary conditions and of the internal interfaces. To obtain this compactness in HWENO schemes both the conservative variables and their first derivatives are evolved in time, whereas in the original WENO schemes only the conservative variables are evolved.

In this work, an HWENO method is applied for the first time to the shallow water equations (SWEs), including the source term due to the bottom slope, to obtain a fourth‐order accurate well‐balanced compact scheme. Time integration is performed by a strong stability preserving the Runge–Kutta method, which is a five‐step and fourth‐order accurate method. Besides the classical SWE, the non‐homogeneous equations describing the time and space evolution of the conservative variable derivatives are considered here. An original, well‐balanced treatment of the source term involved in such equations is developed and tested. Several standard one‐dimensional test cases are used to verify the high‐order accuracy, the C‐property and the good resolution properties of the model. Copyright © 2010 John Wiley & Sons, Ltd.
Identification of novel carcinogen‐mediated mammary tumor susceptibility loci in the rat using the chromosome substitution technique
Authors: Adamovic Tatjana , McAllister Donna , Wang Tao , Adamovic Dragan , Rowe J. Jordi , Moreno Carol , Lazar Josef , Jacob Howard J. , Sugg Sonia L.
Published: August 2010

We here report the genetic basis for susceptibility and resistance to carcinogen‐mediated [7,12‐dimethylbenz[a]anthracene (DMBA)] mammary tumorigenesis using the full panel of SS/BN consomic rat strains, in which substitutions of individual chromosomes from the resistant BN strain onto the genomic background of the susceptible SS strain were made. Analysis of 252 consomic females identified rat mammary Quantitative Trait Loci (QTLs) affecting tumor incidence on chromosomes 3 and 5, latency on chromosomes 3, 9, 14, and 19, and multiplicity on chromosomes 13, 16, and 19. In addition, we unexpectedly identified a novel QTL on chromosome 6 controlling a lethal toxic phenotype in response to DMBA. Upon further investigation with chromosomes 6 and 13 congenic lines, in which an additional 114 rats were investigated, we mapped (1) a novel mammary tumor QTL to a region of 27.1 Mbp in the distal part of RNO6, a region that is entirely separated from the toxicity phenotype, and (2) a novel and powerful mammary tumor susceptibility locus of 4.5 Mbp that mapped to the proximal q‐arm of RNO13. Comparison of genetic strain differences using existing rat genome databases enabled us to further construct priority lists containing single breast cancer candidate genes within the defined QTLs, serving as potential functional variants for future testing. © 2010 Wiley‐Liss, Inc.
CKS1B amplification is a frequent event in cutaneous squamous cell carcinoma with aggressive clinical behaviour
Authors: Salgado Rocío , Toll Agustí , Alameda Francesc , Baró Teresa , Martín‐Ezquerra Gemma , Sanmartín Onofre , Martorell‐Calatayud Antonio , Salido Marta , Almenar Sergio , Solé Francesc , Pujol Ramon M. , Espinet Blanca
Published: August 2010

Genetic mechanisms giving rise to the development of cutaneous squamous cell carcinoma (cSCC) are poorly understood and development of genomic high resolution techniques has led to a better knowledge of the genetic basis of several human cancers. In this study, 16 cSCC were analyzed using array comparative genomic hybridization (arrayCGH). The most common aberrations found were gains of 3q11q13, 1q21.3q25, 13q34, and 19p13, and losses of 1p36p31, 3p24p21, 10p15q22, and 13q11q21. We detected gains (3/16) and amplification (1/16) of the 1q21.1q21.3 region. A potential candidate gene in this region, CKS1B (1q21.2), was selected for validation in an independent cohort and correlations with clinicopathological features were carried out. CKS1B gene and protein status were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in a series of 53 cSCC, 22 actinic keratoses (AK), and 10 normal skin samples. cSCC presented a higher frequency of chromosome 1 polysomy than AK (70% vs. 46%, P = 0.047). Association between CKS1B protein overexpression and both polysomy and amplification was demonstrated in cSCC (P < 0.001). Regarding amplifications, 11 cSCC patients (21%) presented CKS1B gene amplification. Interestingly, 8/11 (73%) patients who showed a CKS1B amplification had presented metastatic spread (mcSCC). Differences between the presence of CKS1B amplification and the presence or absence of mcSCC were observed (mcSCC [8/14] vs. cSCC [3/39]) (P < 0.001). Several drugs targeting CKS1B have been reported and may be useful for treating patients with cSCC and CKS1B amplifications. © 2010 Wiley‐Liss, Inc.
Small deletions but not methylation underlie CDKN2A/p16 loss of expression in conventional osteosarcoma
Authors: Mohseny Alexander B. , Tieken Chris , van der Velden Pieter A. , Szuhai Karoly , de Andrea Carlos , Hogendoorn Pancras C. W. , Cleton‐Jansen Anne‐Marie
Published: August 2010

Conventional osteosarcoma is characterized by rapid growth, high local aggressiveness, and metastasizing potential. Patients developing lung metastases experience poor prognosis despite extensive chemotherapy regimens and surgical interventions. Previously we identified a subgroup of osteosarcoma patients with loss of CDKN2A/p16 protein expression in the primary tumor biopsies which was significantly predictive of a very poor prognosis. Here we aimed to identify the underlying mechanism(s) of this protein loss in relation to osteosarcoma behavior. The CDKN2A locus was analyzed in osteosarcoma cases with total loss of CDKN2A/p16 expression and in cases with high protein expression using melting curve analysis‐methylation assay (MCA‐Meth), fluorescent in situ hybridization (FISH), multiplex ligation‐dependent probe amplification (MLPA), and mutation analysis. All cases with complete CDKN2A/p16 protein loss showed homozygous deletions at the CDKN2A locus. In none of the cases hyper methylation of the promoter region was seen which was confirmed by sequencing this region. Taken together we show that large or smaller deletions of the CDKN2A locus are evident in patient samples and underlie the CDKN2A/p16 protein expression loss while promoter methylation does not appear to be a mechanism of this expression loss. Genomic loss of CDKN2A instead of promoter methylation might be a plausible explanation for the rapid proliferation and high aggressiveness of osteosarcoma by simultaneous impairment CDKN2A/p14ARF function. © 2010 Wiley‐Liss, Inc.
Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis
Authors: Höftberger Romana , Fink Stephanie , Aboul‐Enein Fahmy , Botond Gergö , Olah Judit , Berki Timea , Ovadi Judit , Lassmann Hans , Budka Herbert , Kovacs Gabor G.
Published: August 2010

Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti‐TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25‐positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho‐TDP‐43, phospho‐tau, α‐synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS. © 2010 Wiley‐Liss, Inc.
Astrocyte‐derived glutathione attenuates hemin‐induced apoptosis in cerebral microvascular cells
Authors: Sukumari‐Ramesh Sangeetha , Laird Melissa D. , Singh Nagendra , Vender John R. , Alleyne Cargill H. , Dhandapani Krishnan M.
Published: August 2010

Intracerebral hemorrhage (ICH) induces neurovascular injury via poorly defined mechanisms. The aim of this study was to determine whether gliovascular communication may restrict hemorrhagic vascular injury. Hemin, a hemoglobin by‐product, concentration‐ and time‐dependently increased apoptotic cell death in mouse bEnd.3 cells and in primary human brain microvascular endothelial cells, at least in part, via a caspase‐3 dependent pathway. Cell death was preceded by a NFκB‐mediated increase in inflammatory gene expression, including upregulation of inducible nitric oxide synthase (iNOS) expression and activity. Functionally, inhibition of iNOS or the addition of a peroxynitrite decomposition catalyst reduced cell death. Interestingly, co‐treatment with astrocyte‐conditioned media (ACM) reversed hemin‐induced NFκB activation, nitrotyrosine formation, and apoptotic cell death, at least in part, via the release of the endogenous antioxidant, reduced glutathione (GSH). Prior treatment of astrocytes with the GSH‐depleting agent, DL‐buthionine (S,R)‐sulfoximine or direct addition of diethyl maleate, a thiol‐depleting agent, to ACM reversed the observed protection. In contrast, neither exogenous GSH nor the GSH precursor, N‐acetylcysteine, was protective in bEnd.3 cells. Together, these data support an important role for astrocyte‐derived GSH in the maintenance of oxidative balance in the vasculature and suggest therapeutic targeting of the GSH system may reduce neurological injury following ICH. © 2010 Wiley‐Liss, Inc.
Spinal injection of TNF‐α‐activated astrocytes produces persistent pain symptom mechanical allodynia by releasing monocyte chemoattractant protein‐1
Authors: Gao Yong‐Jing , Zhang Ling , Ji Ru‐Rong
Published: August 2010

Accumulating evidence suggests that spinal astrocytes play an important role in the genesis of persistent pain, by increasing the activity of spinal cord nociceptive neurons, i.e., central sensitization. However, direct evidence of whether activation of astrocytes is sufficient to induce chronic pain symptoms is lacking. We investigated whether and how spinal injection of activated astrocytes could produce mechanical allodynia, a cardinal feature of chronic pain, in naïve mice. Spinal (intrathecal) injection of astrocytes, which were prepared from cerebral cortexes of neonatal mice and briefly stimulated by tumor necrosis factor‐alpha (TNF‐α), induced a substantial decrease in paw withdrawal thresholds, indicating the development of mechanical allodynia. This allodynia was prevented when the astrocyte cultures were pretreated with a peptide inhibitor of c‐Jun N‐terminal kinase (JNK), D‐JNKI‐1. Of note a short exposure of astrocytes to TNF‐α for 15 min dramatically increased the expression and release of the chemokine monocyte chemoattractant protein‐1 (MCP‐1), even 3 h after TNF‐α withdrawal, in a JNK‐dependent manner. In parallel, intrathecal administration of TNF‐α induced MCP‐1 expression in spinal cord astrocytes. In particular, mechanical allodynia induced by TNF‐α‐activated astrocytes was reversed by a MCP‐1 neutralizing antibody. Finally, pretreatment of astrocytes with MCP‐1 siRNA attenuated astrocytes‐induced mechanical allodynia. Taken together, our results suggest that activated astrocytes are sufficient to produce persistent pain symptom in naïve mice by releasing MCP‐1. © 2010 Wiley‐Liss, Inc.
Physiologic role for “inducible” nitric oxide synthase: A new form of astrocytic–neuronal interface
Authors: Amitai Yael
Published: August 2010

Nitric oxide (NO) has been long recognized as an atypical neuronal messenger affecting excitatory synaptic transmission, but its cellular source has remained unresolved as the neuronal isoform of NO synthase (nNOS) in many brain regions is expressed only by small subsets of inhibitory neurons. It is generally believed that the glial NO‐producing isoform (iNOS) is not expressed in the normal brain, but rather it undergoes a transcription‐mediated up‐regulation following an immunological challenge. Therefore, the involvement of iNOS in modulating normal neuronal functions has been largely ignored. Here I review evidence to the contrary: I summarize data pointing to the existence of a functioning iNOS in normal undisturbed mammalian brains, and experimental results tracing this expression to astrocytes. Finally, I review recent findings asserting that iNOS‐dependent NO modulates synaptic release from presynaptic terminals. Based on these data, I propose that astrocytes express basal levels of iNOS. Flanking synaptic elements, astrocytes are perfectly positioned to release NO and affect synaptic transmission. © 2010 Wiley‐Liss, Inc.
Glucosamine exerts a neuroprotective effect via suppression of inflammation in rat brain ischemia/reperfusion injury
Authors: Hwang So‐Young , Shin Joo‐Hyun , Hwang Ji‐Sun , Kim Song‐Yi , Shin Jin‐A , Oh Eok‐Soo , Oh Seikwan , Kim Jung‐Bin , Lee Ja‐Kyung , Han Inn‐Oc
Published: August 2010

We investigated the neuroprotective effect of glucosamine (GlcN) in a rat middle cerebral artery occlusion model. At the highest dose used, intraperitoneal GlcN reduced infarct volume to 14.3% ± 7.4% that of untreated controls and afforded a reduction in motor impairment and neurological deficits. Neuroprotective effects were not reproduced by other amine sugars or acetylated‐GlcN, and GlcN suppressed postischemic microglial activation. Moreover, GlcN suppressed lipopolysaccharide (LPS)‐induced upregulation of proinflammatory mediators both in vivo and in culture systems using microglial or macrophage cells. The anti‐inflammatory effects of GlcN were mainly attributable to its ability to inhibit nuclear factor kappaB (NF‐κB) activation. GlcN inhibited LPS‐induced nuclear translocation and DNA binding of p65 to both NF‐κB consensus sequence and NF‐κB binding sequence of inducible nitric oxide synthase promoter. In addition, we found that GlcN strongly repressed p65 transactivation in BV2 cells using Gal4‐p65 chimeras system. P65 displayed increased O‐GlcNAcylation in response to LPS; this effect was also reversed by GlcN. The LPS‐induced increase in p65 O‐GlcNAcylation was paralleled by an increase in interaction with O‐GlcNAc transferase, which was reversed by GlcN. Finally, our results suggest that GlcN or its derivatives may serve as novel neuroprotective or anti‐inflammatory agents. © 2010 Wiley‐Liss, Inc.
Astrocytes contacting HIV‐1‐infected macrophages increase the release of CCL2 in response to the HIV‐1‐dependent enhancement of membrane‐associated TNFα in macrophages
Authors: Muratori Claudia , Mangino Giorgio , Affabris Elisabetta , Federico Maurizio
Published: August 2010

The presence of human immunodeficiency virus (HIV)‐infected macrophages in the parenchyma of central nervous system is an hallmark of acquired immunodeficiency syndrome‐related neuroinflammation. Once penetrated the blood–brain barrier (BBB), macrophages closely interact with astrocytes, beginning with those lying beneath the BBB endothelium. By investigating the consequences of the cell–cell interaction between HIV‐infected macrophages and astrocytes, we observed that the HIV‐1 expression in macrophagic cells correlated with increased chemotactic activity in supernatants of astroglial cells. Gene array analysis revealed an impressive increase in the transcription of the gene for the CCL2/MCP‐1 chemokine in astroglial cells isolated from HIV‐1‐infected co‐cultures compared with cells from uninfected co‐cultures. This phenomenon coupled with the increase in CCL2 release and depended on the cell–cell contact. In addition, it was a consequence of the HIV‐1‐induced enhancement of membrane‐associated tumor necrosis factor‐α in macrophagic cells, and correlated with increased levels of nuclear factor kappaB activation in astroglial cells. These observations could mirror a mechanism of recruitment of leukocytes through the BBB, likely contributing to the increase in both viral load and inflammation in central nervous system of HIV‐infected patients. © 2010 Wiley‐Liss, Inc.
Manganese‐induced downregulation of astroglial glutamine transporter SNAT3 involves ubiquitin‐mediated proteolytic system
Authors: Sidoryk‐Wȩgrzynowicz Marta , Lee Eun‐Sook , Ni Mingwei , Aschner Michael
Published: August 2010

SNAT3 is a major facilitator of glutamine (Gln) efflux from astrocytes, supplying Gln to neurons for neurotransmitter synthesis. Our previous investigations have shown that, in primary cortical astrocyte cultures, SNAT3 protein is degraded after exposure to manganese (Mn2+). The present studies were performed to identify the processes responsible for this effect. One of the well‐established mechanisms for protein‐level regulation is posttranslational modification via ubiquitination, which leads to the rapid degradation of proteins by the 26S proteasome pathway. Here, we show that astrocytic SNAT3 directly interacts with the ubiquitin ligase, Nedd4‐2 (neural precursor cells expressed developmentally downregulated 4‐2), and that Mn2+ increases both Nedd4‐2 mRNA and protein levels. Additionally, we have found that Mn2+ exposure elevates astrocytic ubiquitin B mRNA expression, free ubiquitin protein levels, and total protein ubiquitination. Furthermore, Mn2+ effectively decreases astrocytic mRNA expression and the phosphorylation of serum and glucocorticoid‐inducible kinase, a regulatory protein, which, in the active phosphorylated form, is responsible for the phosphorylation and subsequent inactivation of Nedd4‐2. Additional findings establish that Mn2+ increases astrocytic caspase‐like proteolytic proteasome activity and that the Mn2+‐dependent degradation of SNAT3 protein is blocked by the proteasome inhibitors, N‐acetyl‐leu‐leu‐norleucinal and lactacystin. Combined, these results demonstrate that Mn2+‐induced SNAT3 protein degradation and the dysregulation of Gln homeostasis in primary astrocyte cultures proceeds through the ubiquitin‐mediated proteolytic system. © 2010 Wiley‐Liss, Inc.
Pyridoxal‐5′‐phosphate phosphatase/chronophin induces astroglial apoptosis via actin‐depolymerizing factor/cofilin system in the rat brain following status epilepticus
Authors: Kim Ji‐Eun , Ryu Hea Jin , Kim Min‐Ju , Kim Dae‐Won , Kwon Oh‐Shin , Choi Soo Young , Kang Tae‐Cheon
Published: August 2010

Actin‐depolymerizing factor (ADF)/cofilin is a small cytoskeletal protein that is a stimulus‐responsive mediator of actin dynamics. ADF/cofilin also translocates into mitochondria and nuclei in response to apoptotic stimuli for cytochrome c release. These ADF/cofilin translocations are negatively regulated by phosphorylation. Recently, it has been reported that pyridoxal‐5′‐phosphate (PLP) phosphatase/chronophin (PLPP/CIN) regulates phosphorylation of ADF/cofilin levels. Therefore, we investigated whether PLPP/CIN contributes to apoptosis‐like events via modulation of ADF/cofilin phosphorylation following status epilepticus (SE). In the present study, apoptosis‐like astroglial damages were detected in the dentate gyrus after SE. Upregulation of ADF/cofilin and PLPP/CIN expression in the cytoplasm and nucleus were accompanied by apoptosis‐like events. PLPP/CIN level showed a direct proportionality to nuclear translocation of ADF/cofilin. Moreover, nuclear accumulation of apoptosis‐inducing factor was simultaneously observed with that of ADF/cofilin. Tat‐PLPP/CIN pretreatment accelerated astroglial apoptosis‐like degeneration following SE, although Tat‐PLPP/CIN transduction alone could not induce apoptosis or necrosis in astrocytes. Therefore, our findings suggest that nuclear accumulation of ADF/cofilin itself may not induce apoptogenic events, but may play a synergic role in apoptosis‐like astroglial loss following SE. © 2010 Wiley‐Liss, Inc.
Functional connectivity of cortical motor areas in the resting state in Parkinson's disease
Authors: Wu Tao , Long Xiangyu , Wang Liang , Hallett Mark , Zang Yufeng , Li Kuncheng , Chan Piu
Published: August 2010

Parkinson's disease (PD) patients have difficulty in initiating movements. Previous studies have suggested that the abnormal brain activity may happen not only during performance of self‐initiated movements but also in the before movement (baseline or resting) state. In the current study, we investigated the functional connectivity of brain networks in the resting state in PD. We chose the rostral supplementary motor area (pre‐SMA) and bilateral primary motor cortex (M1) as “seed” regions, because the pre‐SMA is important in motor preparation, whereas the M1 is critical in motor execution. FMRIs were acquired in 18 patients and 18 matched controls. We found that in the resting state, the pattern of connectivity with both the pre‐SMA or the M1 was changed in PD. Connectivity with the pre‐SMA in patients with PD compared to normal subjects was increased connectivity to the right M1 and decreased to the left putamen, right insula, right premotor cortex, and left inferior parietal lobule. We only found stronger connectivity in the M1 with its own local region in patients with PD compared to controls. Our findings demonstrate that the interactions of brain networks are abnormal in PD in the resting state. There are more connectivity changes of networks related to motor preparation and initiation than to networks of motor execution in PD. We postulate that these disrupted connections indicate a lack of readiness for movement and may be partly responsible for difficulty in initiating movements in PD. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Amygdala and hippocampus volumetry and diffusivity in relation to dreaming
Authors: De Gennaro Luigi , Cipolli Carlo , Cherubini Andrea , Assogna Francesca , Cacciari Claudia , Marzano Cristina , Curcio Giuseppe , Ferrara Michele , Caltagirone Carlo , Spalletta Gianfranco
Published: August 2010

Microstructural analyses by MRI brain scans and by DTI analysis of MR images were used to investigate the possible relationship between deep gray matter structures (amygdala and hippocampus) and dreaming in healthy subjects. Thirty‐four subjects ranging in age 20s to 70s underwent to a MRI protocol for the assessment of volume and mean diffusivity (MD) in the amygdala and hippocampus and were asked to fill out a dream diary via audiotape recording upon morning awakening for two weeks. Multiple regression analyses evaluated the relationships between anatomical measures and quantitative and qualitative measures of the reported dreams. The main result points to a dissociation between some quantitative and qualitative aspects of dream reports. While the mean number of dreams recalled per day did not show any significant relationship with the neuroanatomical measures, significant associations with some qualitative features of the recalled dreams (emotional load, bizarreness, and vividness) and, to some extent, with the length of dream reports were observed. Particularly, a higher MD of the left amygdala, reflecting a decreased microstructural integrity, was associated with shorter dream reports and lower scores on emotional load. Bizarreness of dream reports was negatively correlated with the left amygdala volume and positively correlated with the right amygdala MD. Some specific, although weaker, relationships were also found between bizarreness and hippocampal measures. These findings indicate some direct relationships between volumetric and ultrastructural measures of the hippocampus‐amygdala complex and specific qualitative features of dreaming. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Regional gray matter density associated with emotional intelligence: Evidence from voxel‐based morphometry
Authors: Takeuchi Hikaru , Taki Yasuyuki , Sassa Yuko , Hashizume Hiroshi , Sekiguchi Atsushi , Fukushima Ai , Kawashima Ryuta
Published: August 2010

Emotional Intelligence (EI) is the ability to monitor one's own and others' emotions and the ability to use the gathered information to guide one's thinking and action. EI is thought to be important for social life making it a popular subject of research. However, despite the existence of previous functional imaging studies on EI, the relationship between regional gray matter morphology and EI has never been investigated. We used voxel‐based morphometry (VBM) and a questionnaire (Emotional Intelligence Scale) to measure EI to identify the gray matter correlates of each factor of individual EI (Intrapersonal factor, Interpersonal factor, Situation Management factor). We found significant negative relationships between the Intrapersonal factor and regional gray matter density (rGMD) (1‐a) in an anatomical cluster that included the right anterior insula, (1‐b) in the right cerebellum, (1‐c) in an anatomical cluster that extends from the cuneus to the precuneus, (1‐d) and in an anatomical cluster that extends from the medial prefrontal cortex to the left lateral fronto‐polar cortex. We also found significant positive correlations between the Interpersonal factor and rGMD in the right superior temporal sulcus, and significant negative correlations between the Situation Management factor and rGMD in the ventromedial prefrontal cortex. These findings suggest that each factor of EI in healthy young people is related to the specific brain regions known to be involved in the networks of social cognition and self‐related recognition, and in the somatic marker circuitry. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Cognitive impairment in multiple sclerosis is associated to different patterns of gray matter atrophy according to clinical phenotype
Authors: Riccitelli Gianna , Rocca Maria A. , Pagani Elisabetta , Rodegher Maria E. , Rossi Paolo , Falini Andrea , Comi Giancarlo , Filippi Massimo
Published: August 2010

Objective: To investigate whether cognitive impairment in multiple sclerosis (MS) patients is associated to different patterns of gray matter (GM) atrophy and T2‐visible lesion distribution according to the clinical phenotype. Experimental Design: Twenty‐two relapsing remitting (RR), 29 secondary progressive (SP), and 22 primary progressive (PP) MS patients, and 39 healthy controls underwent high‐field structural magnetic resonance imaging and an extensive neuropsychological battery. Voxel‐wise distribution of GM damage and T2‐lesions was compared between cognitively impaired (CI) and cognitively preserved (CP) patients according to their clinical phenotype. Principal Observations: Thirty‐nine MS patients were CI. In all MS groups, regional GM loss was correlated with cognitive impairment. Different patterns of regional distribution of GM atrophy and T2‐visible lesions were found between CI vs. CP MS patients, according to their clinical phenotype. No areas were significantly more atrophied in CI SPMS vs. CI RRMS patients. Conversely, compared with CI PPMS, CI SPMS patients had a significant GM loss in several regions of the fronto‐temporal lobes, the left hypothalamus and thalami. While in RRMS and SPMS patients there was a correspondence between presence of T2 visible lesions and GM atrophy in several areas, this was not the case in PPMS patients. Conclusion: Distinct patterns of regional distribution of GM damage and T2‐visible lesions are associated with cognitive impairment in MS patients with different clinical phenotypes. The correspondence between lesion formation and GM atrophy distribution varies in the different forms of MS. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
1‐Heteroakylation of tris(trimethylsilyl)phosphine
Authors: Prishchenko Andrey A. , Livantsov Mikhail V. , Novikova Olga P. , Livantsova Ludmila I. , Petrosyan Valery S.
Published: August 2010

The 1‐heteroalkylation of the tris‐(trimethylsilyl)phosphine was thoroughly investigated using heterosubstituted methylamines, chloromethyl alkyl ethers, methyl chloroformate, paraformaldehyde, and dialkylformamides. Convenient methods for the synthesis of tris(dialkylaminomethyl)phosphines, tris(alkoxymethyl)phosphines, tris(methoxycarbonyl) phosphine, and several phosphaethylenes were proposed on the basis of the 1‐heteroalkylation of tris(trimethylsilyl)phosphine as a valuable synthon. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:441–445, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20636
Feasibility of submandibular gland preservation in neck dissection: A prospective anatomic‐pathologic study
Authors: Dhiwakar Muthuswamy , Ronen Ohad , Malone James , Rao Krishna , Bell Stephen , Phillips Roy , Shevlin Bruce , Robbins K. Thomas
Published: August 2010

Background.

The submandibular gland is commonly removed during neck dissection involving sublevel IB. However, removal reduces basal salivary secretion and therapeutic options for minimizing xerostomia. The purpose of this study was to determine whether all lymph nodes in sublevel IB can be extirpated without removing the submandibular gland.

Methods.

Twenty consecutive patients undergoing 33 neck dissections were prospectively enrolled. Sublevel IB dissection was performed by 3 sequential steps: (1) removal of targeted lymph node groups (preglandular and postglandular, prevascular and postvascular), (2) removal of submandibular gland, and (3) removal of residual lymphoadipose tissue in the surgical bed.

Results.

Complete removal of lymph nodes in sublevel IB was achieved before excising the submandibular gland in all of the 30 eligible neck dissections. The submandibular gland and the surgical bed contained no residual lymph nodes.

Conclusion.

In suitable cases, it is technically feasible to remove all lymph nodes in sublevel IB and preserve the submandibular gland. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Contemporary management of sinonasal cancer
Authors: Robbins K. Thomas , Ferlito Alfio , Silver Carl E. , Takes Robert P. , Strojan Primoẑ , Snyderman Carl H. , de Bree Remco , Haigentz Missak , Langendijk Johannes A. , Rinaldo Alessandra , Shaha Ashok R. , Hanna Ehab Y. , Werner Jochen A. , Suárez Carlos
Published: August 2010

Background.

Sinonasal cancer is a relatively uncommon entity encountered by head and neck oncologists, rhinologists, and skull base surgeons. Recent innovations in surgical and nonsurgical therapeutic modalities raise the question of whether there has been any measurable improvement for treatment outcomes.

Methods.

A retrospective review of data from recent studies that focus on surgery, radiation, and chemotherapy, or combinations thereof, was conducted.

Results.

Surgery continues to be the preferred treatment and provides the best results, albeit with an inherent bias based on patient selection. For advanced disease (T4 lesions), the survival rate remains only modest. Complications of treatment, including both surgical and radiation therapy, have been reduced.

Conclusions.

There is a need to improve the efficacy of treatment for this disease. Recommendations for the future direction of therapeutic investigations are outlined. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Long‐term survival of a patient with leptomeningeal involvement by nasopharyngeal carcinoma after treatment with high‐dose intravenous methotrexate
Authors: Fakhry Carole , Bajaj Gopal , Aygun Nafi , Westra William , Gillison Maura
Published: August 2010

Background.

Nasopharyngeal carcinoma with leptomeningeal involvement is rare and typically has poor prognosis.

Methods and Results.

We present a case report of a patient with nasopharyngeal carcinoma who was treated with high‐dose intravenous methotrexate and remains asymptomatic and without clinical evidence of disease 6 years later.

Conclusions.

Systemic high‐dose methotrexate should be evaluated in the treatment of advanced nasopharyngeal carcinoma with central nervous involvement. © 2010 Wiley Periodicals, Inc. Head Neck, 2012
Classification of papillary thyroid microcarcinoma according to size and fine‐needle aspiration cytology: Behavior and therapeutic implications
Authors: Friguglietti Celso Ubirajara Moretto , Dutenhefner Simone Elisa , Brandão Lenine Garcia , Kulcsar Marco Aurélio Vamondes
Published: August 2010

Background.

The purpose of this study was to assess and classify cases of papillary microcarcinoma according to size (up to 0.5 cm and between 0.6 and 1.0 cm) and fine‐needle aspiration cytology (FNAC). These results were then correlated with clinical and histopathologic factors of worse prognosis.

Methods.

A total of 448 cases of papillary thyroid carcinoma were studied retrospectively.

Results.

Of the 448 patients, 173 presented with carcinomas of ≤0.5 cm and 275 patients presented with carcinomas sized between 0.6 and 1.0 cm (>0.5 cm). Lymph node metastasis was diagnosed in 6% of the carcinoma cases of ≤0.5 cm and in 16% of the cases with tumors of >0.5 cm. A total of 281 cases tested positive for papillary carcinoma by FNAC, and in 113 cases, the carcinoma was diagnosed during the histopathologic examination. A positive FNAC for carcinoma was correlated with a higher incidence of lymph node metastasis (16% vs 5%).

Conclusion.

The diagnosis of papillary carcinoma using the preoperative biopsy enables a more precise oncological procedure with greater chance of biological cure. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Aspiration after supracricoid partial laryngectomy: Incidence, risk factors, management, and outcomes
Authors: Benito José , Holsinger F. Christopher , Pérez‐Martín Augustin , Garcia Dominique , Weinstein Gregory S. , Laccourreye Ollivier
Published: August 2010

Background.

The aim of this study was to evaluate the incidence, risk factors, management, and outcome of postoperative aspiration in patients managed with a supracricoid partial laryngectomy (SCPL) for selected invasive squamous carcinoma of the larynx.

Methods.

In all, 457 patients underwent SCPL at an academic, tertiary referral care center, 1975–2000. The incidence of aspiration defined in accord with Pearson's scale was recorded. Univariate and multivariate analyses were performed for potential statistical relation with various variables. The management and outcome of aspiration are presented.

Results.

Normal swallowing without aspiration was noted in 259 patients (58.9%). Grades 1, 2, and 3 aspiration occurred in 87, 48, and 53 patients (19%, 10.5%, and 11.6%), respectively. A significant relationship was noted between aspiration and increased age, performing cricohyoidopexy, not repositioning the pyriform sinuses, and resecting an arytenoid cartilage. A prediction model, based on multinomial logistic regression, found that the probability that severe aspiration cases (grade 2–3) exceeded the subclinical ones (grade 0–1) occurred only when a cricohyoidopexy with partial or total arytenoid resection was performed in patients >70 years of age (p = .0000001). Management of aspiration required a temporary gastrostomy, a permanent gastrostomy, and a completion total laryngectomy in 65, 3, and 7 of 188 patients (34.5%, 1.6%, and 3.7%, respectively) who aspirated, and 65, 3, and 7 of 457 of the entire population (14.2%, 0.6%, and 1.5%, respectively). Aspiration‐related death was not encountered in the current series.

Conclusions.

Aspiration after SCPL is a common but rarely severe event, with a low incidence for permanent gastrostomy or completion laryngectomy. Aspiration can be minimized with careful patient selection and precise surgical technique. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Retropharyngeal lymph node metastases in head and neck malignancies
Authors: Coskun H. Hakan , Ferlito Alfio , Medina Jesus E. , Robbins K. Thomas , Rodrigo Juan P. , Strojan Primož , Suárez Carlos , Takes Robert P. , Woolgar Julia A. , Shaha Ashok R. , de Bree Remco , Rinaldo Alessandra , Silver Carl E.
Published: August 2010

Retropharyngeal lymph node (RPLN) metastasis of primary head and neck cancer often receives less consideration than lymph node metastasis in the neck. With improvements in imaging techniques and reports of surgical pathology, there is an improved understanding of the risk and subsequently the need for treatment of RPLNs. The rates of RPLN metastasis from carcinomas of the nasopharynx, oropharynx, hypopharynx, postcricoid region, maxillary sinus, and cervical esophagus are sufficiently high to warrant routine treatment, either electively or therapeutically, of this region. Through improved diagnostic techniques and heightened awareness of RPLN metastasis, patients at risk of having these metastases can be treated more effectively. © 2010 Wiley Periodicals, Inc. Head Neck, 2010