bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenic Hantaviruses Direct the Adherence of Quiescent Platelets to Infected Endothelial Cells
Authors: Gavrilovskaya Irina N. , Gorbunova Elena E. , Mackow Erich R.
Published: February 2010

Hantavirus infections are noted for their ability to infect endothelial cells, cause acute thrombocytopenia, and trigger 2 vascular-permeability-based diseases. However, hantavirus infections are not lytic, and the mechanisms by which hantaviruses cause capillary permeability and thrombocytopenia are only partially understood. The role of β
3
integrins in hemostasis and the inactivation of β
3
integrin receptors by pathogenic hantaviruses suggest the involvement of hantaviruses in altered platelet and endothelial cell functions that regulate permeability. Here, we determined that pathogenic hantaviruses bind to quiescent platelets via a β
3
integrin-dependent mechanism. This suggests that platelets may contribute to hantavirus dissemination within infected patients and provides a means by which hantavirus binding to β
3
integrin receptors prevents platelet activation. The ability of hantaviruses to bind platelets further suggested that cell-associated hantaviruses might recruit platelets to the endothelial cell surface. Our findings indicate that Andes virus (ANDV)- or Hantaan virus (HTNV)-infected endothelial cells specifically direct the adherence of calcein-labeled platelets. In contrast, cells comparably infected with nonpathogenic Tula virus (TULV) failed to recruit platelets to the endothelial cell surface. Platelet adherence was dependent on endothelial cell β
3
integrins and neutralized by the addition of the anti-β
3
Fab fragment, c7E3, or specific ANDV- or HTNV-neutralizing antibodies. These findings indicate that pathogenic hantaviruses displayed on the surface of infected endothelial cells bind platelets and that a platelet layer covers the surface of infected endothelial cells. This fundamentally changes the appearance of endothelial cells and has the potential to alter cellular immune responses, platelet activation, and endothelial cell functions that affect vascular permeability. Hantavirus-directed platelet quiescence and recruitment to vast endothelial cell beds further suggests mechanisms by which hantaviruses may cause thrombocytopenia and induce hypoxia. These findings are fundamental to our understanding of pathogenic-hantavirus regulation of endothelial cell responses that contribute to vascular permeability.
Deubiquitinating and Interferon Antagonism Activities of Coronavirus Papain-Like Proteases
Authors: Clementz Mark A. , Chen Zhongbin , Banach Bridget S. , Wang Yanhua , Sun Li , Ratia Kiira , Baez-Santos Yahira M. , Wang Jie , Takayama Jun , Ghosh Arun K. , Li Kui , Mesecar Andrew D. , Baker Susan C.
Published: February 2010

Coronaviruses encode multifunctional proteins that are critical for viral replication and for blocking the innate immune response to viral infection. One such multifunctional domain is the coronavirus papain-like protease (PLP), which processes the viral replicase polyprotein, has deubiquitinating (DUB) activity, and antagonizes the induction of type I interferon (IFN). Here we characterized the DUB and IFN antagonism activities of the PLP domains of human coronavirus NL63 and severe acute respiratory syndrome (SARS) coronavirus to determine if DUB activity mediates interferon antagonism. We found that NL63 PLP2 deconjugated ubiquitin (Ub) and the Ub-line molecule ISG15 from cellular substrates and processed both lysine-48- and lysine-63- linked polyubiquitin chains. This PLP2 DUB activity was dependent on an intact catalytic cysteine residue. We demonstrated that in contrast to PLP2 DUB activity, PLP2-mediated interferon antagonism did not require enzymatic activity. Furthermore, addition of an inhibitor that blocks coronavirus protease/DUB activity did not abrogate interferon antagonism. These results indicated that a component of coronavirus PLP-mediated interferon antagonism was independent of protease and DUB activity. Overall, these results demonstrate the multifunctional nature of the coronavirus PLP domain as a viral protease, DUB, and IFN antagonist and suggest that these independent activities may provide multiple targets for antiviral therapies.
Mutational Analysis of the Herpes Simplex Virus Type 1 UL25 DNA Packaging Protein Reveals Regions That Are Important after the Viral DNA Has Been Packaged
Authors: O'Hara Maureen , Rixon Frazer J. , Stow Nigel D. , Murray Jill , Murphy Mary , Preston Valerie G.
Published: February 2010

The herpes simplex virus type 1 (HSV-1) UL25 gene encodes a minor capsid protein, pUL25, that is essential for packaging the full-length viral genome. Six regions which contain disordered residues have been identified in the high-resolution structure of pUL25. To investigate the significance of these flexible regions, a panel of plasmids was generated encoding mutant proteins, with each member lacking the disordered residues in one of the six regions. In addition, UL25 constructs were produced, which specified proteins that contained missense mutations individually affecting two of the four regions on the surface of pUL25 predicted from evolutionary trace analysis to be important in protein-protein interactions. The impacts of these mutations on viral DNA packaging, virus assembly, and growth were examined. Of the nine mutant proteins analyzed, five failed to complement the growth of a UL25 deletion mutant in Vero cells. These noncomplementing proteins fell into three classes. Proteins in one class did not alter the DNA packaging phenotype of an HSV-1 UL25 deletion mutant, whereas proteins from the other two classes allowed the UL25 null mutant to package full-length viral DNA. Subsequent analysis of the latter classes of mutant proteins demonstrated that one class enabled the null virus to release enveloped virus particles from U2OS cells, whereas the other class prevented egress of mature HSV-1 capsids from the nucleus. These findings reveal a new role for pUL25 in virion assembly, consistent with its flexible structure and location on the capsid.
SDF-1/CXCL12 Production by Mature Dendritic Cells Inhibits the Propagation of X4-Tropic HIV-1 Isolates at the Dendritic Cell-T-Cell Infectious Synapse
Authors: González Nuria , Bermejo Mercedes , Calonge Esther , Jolly Clare , Arenzana-Seisdedos Fernando , Pablos José L. , Sattentau Quentin J. , Alcamí José
Published: February 2010

An efficient mode of HIV-1 infection of CD4 lymphocytes occurs in the context of infectious synapses, where dendritic cells (DCs) enhance HIV-1 transmission to lymphocytes. Emergence of CXCR4-using (X4) HIV-1 strains occurs late in the course of HIV-1 infection, suggesting that a selective pressure suppresses the switch from CCR5 (R5) to X4 tropism. We postulated that SDF-1/CXCL12 chemokine production by DCs could be involved in this process. We observed CXCL12 expression by DCsin vivoin the parafollicular compartment of lymph nodes. The role of mature monocyte-derived dendritic cells (mMDDCs) in transmitting R5 and X4 HIV-1 strains to autologous lymphocytes was studied using anin vitroinfection system. Using this model, we observed a strong enhancement of lymphocyte infection with R5, but not with X4, viruses. This lack of DC-mediated enhancement in the propagation of X4 viruses was proportional to CXCL12 production by mMDDCs. When CXCL12 activity was inhibited with specific neutralizing antibodies or small interfering RNAs (siRNAs), the block to mMDDC transfer of X4 viruses to lymphocytes was removed. These results suggest that CXCL12 production by DCs resident in lymph nodes represents an antiviral mechanism in the context of the infectious synapse that could account for the delayed appearance of X4 viruses.
Effect of the Internal Promoter on Insertional Gene Activation by Lentiviral Vectors with an Intact HIV Long Terminal Repeat
Authors: Knight Sean , Bokhoven Marieke , Collins Mary , Takeuchi Yasuhiro
Published: February 2010

Insertional mutagenesis by viral vectors is a problem in gene therapy. We recently reported that lentiviral vectors with an intact HIV long terminal repeat (LTR) caused insertional gene activation by transcripts from the 5′ LTR splicing to an adjacent gene. Here we demonstrate that the level of transcription from the 5′ LTR, and also insertional gene activation, is dependent on the internal promoter in the vector. We also show that there are more transcripts originating from the 5′ LTR than from, or reading through, the 3′ LTR. This study will allow the design of safer lentiviral vectors for applications in which an intact HIV LTR is required.
Expression of Type III Interferon (IFN) in the Vaginal Mucosa Is Mediated Primarily by Dendritic Cells and Displays Stronger Dependence on NF-κB than Type I IFNs
Authors: Iversen Marie B. , Ank Nina , Melchjorsen Jesper , Paludan Søren R.
Published: February 2010

Interferons (IFNs) are induced as an initial response to viral infection after recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). Here, we report that different PAMPs induce type I and III IFN expression at different ratios after mucosal administration in the vaginas of mice and that Toll-like receptor 9 (TLR9) stimulation evokes a particularly strong IFN-λ response, which is essential for optimal antiviral protection. Depletion of CD11c
+
cells
in vivo
revealed that dendritic cells (DCs) in the vaginal epithelium are a key source of type I and III IFNs during herpes simplex virus infection and after specific stimulation of TLR9. A comparison of the signaling pathways activated by TLR9 and cytoplasmic PRRs, which induced lower levels of IFN-λ, revealed that high-level induction of IFN-λ correlated with strong activation of NF-κB p65. Inhibition of the NF-κB and interferon regulatory factor 3 (IRF-3) pathways with the NEMO-binding domain peptide and small interfering RNA (siRNA), respectively, revealed that transcription of the type III IFN genes was more dependent on the NF-κB pathway than that of the type I IFN genes, which relied more on the IRF system. Thus, the type I and III IFN genes are not induced through entirely identical pathways, which indicates differential expression of these two types of IFNs under certain conditions.
PB2 Residue 271 Plays a Key Role in Enhanced Polymerase Activity of Influenza A Viruses in Mammalian Host Cells
Authors: Bussey Kendra A. , Bousse Tatiana L. , Desmet Emily A. , Kim Baek , Takimoto Toru
Published: February 2010

The direct infection of humans with highly pathogenic avian H5N1 influenza viruses has suggested viral mutation as one mechanism for the emergence of novel human influenza A viruses. Although the polymerase complex is known to be a key component in host adaptation, mutations that enhance the polymerase activity of avian viruses in mammalian hosts are not fully characterized. The genomic comparison of influenza A virus isolates has identified highly conserved residues in influenza proteins that are specific to either human or avian viruses, including 10 residues in PB2. We characterized the activity of avian polymerase complexes containing avian-to-human mutations at these conserved PB2 residues and found that, in addition to the E627K mutation, the PB2 mutation T271A enhances polymerase activity in human cells. We confirmed the effects of the T271A mutation using recombinant WSN viruses containing avian NP and polymerase genes with wild-type (WT) or mutant PB2. The 271A virus showed enhanced growth compared to that of the WT in mammalian cells in vitro. The 271A mutant did not increase viral pathogenicity significantly in mice compared to that of the 627K mutant, but it did enhance the lung virus titer. Also, cell infiltration was more evident in lungs of 271A-infected mice than in those of the WT. Interestingly, the avian-derived PB2 of the 2009 pandemic H1N1 influenza virus has 271A. The characterization of the polymerase activity of A/California/04/2009 (H1N1) and corresponding PB2 mutants indicates that the high polymerase activity of the pandemic strain in mammalian cells is, in part, dependent on 271A. Our results clearly indicate the contribution of PB2 amino acid 271 to enhanced polymerase activity and viral growth in mammalian hosts.
Role of Oxidative Stress in Rabies Virus Infection of Adult Mouse Dorsal Root Ganglion Neurons
Authors: Jackson Alan C. , Kammouni Wafa , Zherebitskaya Elena , Fernyhough Paul
Published: February 2010

Rabies virus infection of dorsal root ganglia (DRG) was studiedin vitrowith cultured adult mouse DRG neurons. Recentin vivostudies of transgenic mice that express the yellow fluorescent protein indicate that neuronal process degeneration, involving both dendrites and axons, occurs in mice infected with the challenge virus standard (CVS) strain of rabies virus by footpad inoculation. Because of the similarities of the morphological changes in experimental rabies and in diabetic neuropathy and other diseases, we hypothesize that neuronal process degeneration occurs as a result of oxidative stress. DRG neurons were cultured from adult ICR mice. Two days after plating, they were infected with CVS. Immunostaining was evaluated with CVS- and mock-infected cultures for neuron specific β-tubulin, rabies virus antigen, and amino acid adducts of 4-hydroxy-2-nonenal (4-HNE) (marker of lipid peroxidation and hence oxidative stress). Neuronal viability (by trypan blue exclusion), terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, and axonal growth were also assessed with the cultures. CVS infected 33 to 54% of cultured DRG neurons. Levels of neuronal viability and TUNEL staining were similar in CVS- and mock-infected DRG neurons. There were significantly more 4-HNE-labeled puncta at 2 and 3 days postinfection in CVS-infected cultures than in mock-infected cultures, and axonal outgrowth was reduced at these time points in CVS infection. Axonal swellings with 4-HNE-labeled puncta were also associated with aggregations of actively respiring mitochondria. We have found evidence that rabies virus infectionin vitrocauses axonal injury of DRG neurons through oxidative stress. Oxidative stress may be importantin vivoin rabies and may explain previous observations of the degeneration of neuronal processes.
Numerous Conserved and Divergent MicroRNAs Expressed by Herpes Simplex Viruses 1 and 2
Authors: Jurak Igor , Kramer Martha F. , Mellor Joseph C. , van Lint Alison L. , Roth Frederick P. , Knipe David M. , Coen Donald M.
Published: February 2010

Certain viruses use microRNAs (miRNAs) to regulate the expression of their own genes, host genes, or both. Previous studies have identified a limited number of miRNAs expressed by herpes simplex viruses 1 and 2 (HSV-1 and -2), some of which are conserved between these two viruses. To more comprehensively analyze the miRNAs expressed by HSV-1 or HSV-2 during productive and latent infection, we applied a massively parallel sequencing approach. We were able to identify 16 and 17 miRNAs expressed by HSV-1 and HSV-2, respectively, including all previously known species, and a number of previously unidentified virus-encoded miRNAs. The genomic positions of most miRNAs encoded by these two viruses are within or proximal to the latency-associated transcript region. Nine miRNAs are conserved in position and/or sequence, particularly in the seed region, between these two viruses. Interestingly, we did not detect an HSV-2 miRNA homolog of HSV-1 miR-H1, which is highly expressed during productive infection, but we did detect abundant expression of miR-H6, whose seed region is conserved with HSV-1 miR-H1 and might represent a functional analog. We also identified a highly conserved miRNA family arising from the viral origins of replication. In addition, we detected several pairs of complementary miRNAs and we found miRNA-offset RNAs (moRs) arising from the precursors of HSV-1 and HSV-2 miR-H6 and HSV-2 miR-H4. Our results reveal elements of miRNA conservation and divergence that should aid in identifying miRNA functions.
Influence of a small amount of tethered chains on wetting transitions: A density functional approach
Authors: Borówko Małgorzata , Patrykiejew Andrzej , Sokołowski Stefan , Staszewski Tomasz
Published: February 2010

A density functional approach to adsorption and phase behavior of a simple fluid from gas phase on a surface modified with a small amount of grafted chains is presented. The chains are modeled as freely jointed tangent spheres with end segments attached to the surface. The segments and gas molecules interact via the Lennard–Jones potential. We have found that the presence of preadsorbed chains considerably affects wettability of solid surfaces. An increase in the amount of grafted chains leads to a crossover between prewetting and layering transitions. This crossover occurs by merging of successive layering transitions.
Letting the sunshine in: shining a new light on physician–industry relationships: Table 1
Authors: Bruguera Carolyn M , Hirsch Joshua A
Published: February 2010

The pending federal healthcare reform legislation includes Physician Payment Sunshine provisions that would mandate public disclosure of virtually all payments by industry to US physicians on government websites. The requirements reflect a growing trend toward public disclosure of payments following high-profile government investigations of allegedly improper payments and undisclosed conflicts of interests. The pending law world require broad disclosure and will affect most physicians. Industry and physicians groups have offered qualified support to the legislation.
GRAVITATIONAL CORRECTION TO SU(5) GAUGE COUPLING UNIFICATION
Authors: BHATT JITESH R. , PATRA SUDHANWA , SARKAR UTPAL
Published: February 2010

The gravitational corrections to the gauge coupling constants of Abelian and non-Abelian gauge theories have been shown to diverge quadratically. Since this result will have interesting consequences, this has been analyzed by several authors from different approaches. We propose to discuss this issue from a phenomenological approach. We analyze the SU(5) gauge coupling unification and argue that the gravitational corrections to gauge coupling constants may not vanish when higher dimensional non-renormalizable terms are included in the problem.
IS DARK ENERGY FROM COSMIC HAWKING RADIATION?
Authors: LEE JAE-WEON , KIM HYEONG-CHAN , LEE JUNGJAI
Published: February 2010

It is suggested that dark energy is the energy of the Hawking radiation from a cosmic horizon. Despite its extremely low Gibbons–Hawking temperature, this radiation could have the appropriate magnitude [Formula: see text]and the equation of state to explain the observed cosmological data if there is a Planck scale UV-cutoff, where H is the Hubble parameter.
NUCLEON AXIAL COUPLINGS AND [(½,0) ⊕ (0,½)]-[(1,½) ⊕ (½,1)] CHIRAL MULTIPLET MIXING
Authors: DMITRAŠINOVIĆ V. , HOSAKA A. , NAGATA K.
Published: February 2010

Three-quark nucleon interpolating fields in QCD have well-defined SU L(2) × SU R(2) and U A(1) chiral transformation properties. Mixing of the [(1,½) ⊕ (½,1)] chiral multiplet with one of four available [(½,0) ⊕ (0,½)] or [(0,½) ⊕ (½,0)] representations can be used to fit the isovector axial coupling [Formula: see text] and thus predict the isoscalar axial coupling [Formula: see text] of the nucleon, in reasonable agreement with experiment. We also use a chiral meson–baryon interaction to calculate the masses and one-pion-interaction terms of J = ½ baryons belonging to the [(0,½) ⊕ (½,0)] and [(1,½) ⊕ (½,1)] chiral multiplets and fit two of the diagonalized masses to the lowest-lying nucleon resonances thus predicting the third J = ½ resonance at 2030 MeV, not far from the (one-star PDG) state Δ(2150).
ASYMPTOTIC BEHAVIORS AND CLASSICAL LIMITS OF SOLUTIONS TO A QUANTUM DRIFT-DIFFUSION MODEL FOR SEMICONDUCTORS
Authors: NISHIBATA SHINYA , SHIGETA NAOTAKA , SUZUKI MASAHIRO
Published: February 2010

This paper discusses a time global existence, asymptotic behavior and a singular limit of a solution to the initial boundary value problem for a quantum drift-diffusion model of semiconductors over a one-dimensional bounded domain. Firstly, we show a unique existence and an asymptotic stability of a stationary solution for the model. Secondly, it is shown that the time global solution for the quantum drift-diffusion model converges to that for a drift-diffusion model as the scaled Planck constant tends to zero. This singular limit is called a classical limit. Here these theorems allow the initial data to be arbitrarily large in the suitable Sobolev space. We prove them by applying an energy method.
A GENERATION THEOREM FOR GROUPS OF FINITE MORLEY RANK
Authors: BURDGES JEFFREY , CHERLIN GREGORY
Published: February 2010

We deal with two forms of the "uniqueness cases" in the classification of large simple K*-groups of finite Morley rank of odd type, where large means the 2-rank m2(G) is at least three. This substantially extends results known for even larger groups having Prüfer 2-rank at least three, so as to cover the two groups PSp4and G2. With an eye towards more distant developments, we carry out this analysis for L*-groups, a context which is substantially broader than the K* setting.
WAVELETS WITH VANISHING MOMENTS ON THE HEISENBERG GROUP
Authors: LIU YU , PENG LIZHONG
Published: February 2010

Discrete vanishing moments and sum rules are established on the Heisenberg group and the relationship between them is investigated in this paper. Also, the compactly supported wavelets with 2 vanishing moments corresponding to the separable filter {am,nhl} on the Heisenberg group are constructed by using the theory of discrete vanishing moments and sum rules.
IMAGE MIRRORING AND ROTATION IN THE WAVELET DOMAIN
Authors: JACOB THEJU , RAO K. R. , KIM DO NYEON
Published: February 2010

JPEG2000, the international standard for still image compression, uses wavelet transform. The filters used by JPEG2000 for transformation are the 9/7 Daubechies filter and the 5/3 Le Gall filter. In this paper, we present a method for image mirroring and rotation in the wavelet domain, by manipulating the transformation coefficients. Our technique requires no additional complexity and the perfect reconstruction property is preserved.
WAVELET CHARACTERIZATION OF HARDY SPACE H1 AND ITS APPLICATION IN VARIATIONAL IMAGE DECOMPOSITION
Authors: ZHANG TAO , FAN QIBIN , GAO QIULI
Published: February 2010

In this paper, we examine the wavelet characterization of Hardy space H1, and show that the H1-norm is a good choice for modelizing the oscillating patterns. Furthermore, we give the discrete representation of H1-norm by using wavelet coefficients, and apply it to the variational image decomposition models. Finally, we give the iterative algorithm, and present various numerical results on images to demonstrate the potential of our methods.
GENERALIZED p-FRAME IN SEPARABLE COMPLEX BANACH SPACES
Authors: XIAO XIANG-CHUN , ZHU YU-CAN , ZENG XIAO-MING
Published: February 2010

The concept of g-frame and g-Riesz basis in a complex Hilbert space was introduced by Sun.18 In this paper, we generalize the g-frame and g-Riesz basis in a complex Hilbert space to a complex Banach space. Using operators theory and methods of functional analysis, we give some characterizations of a g-frame or a g-Riesz basis in a complex Banach space. We also give a result about the stability of g-frame in a complex Banach space.
PROPOSAL OF WARNING METHOD FOR REAR-SIDE OBSTACLES USING DRIVER'S PERCEPTUAL RISK MODEL
Authors: NISHIYAMA AKIHIRO , WADA TAKAHIRO , TSUTSUMI SHIGEYOSHI , DOI SHUN'ICHI
Published: February 2010

Warning systems have been proposed to reduce driver cognitive and judgment load as driver systems for traffic safety. The system's efficacy could be decreased if the driver feels annoyance and/or mistrust with inappropriate warning timing, etc. This paper explores the possibility of personalized warning timing to cope with this problem. First, we propose a new warning method for rear-side obstacles using a driver's perceptual risk model that we derived from the analysis of the driver's deceleration behavior. Validity of the warning method will be shown by driving simulator experiments. In addition, there exists individual difference in expectation of meaning of warning. Thus, differences of the efficacy and driver's response behaviors against warning will be analyzed based on the difference of their expectation.
A NOVEL DENSITY GRADIENT-BASED COLOR EDGE DETECTION APPROACH
Authors: SUN DA , CHENG H. D. , LIU JIAFENG , TANG XIANGLONG
Published: February 2010

The intensity gradient-based methods are commonly used in edge detection of images. However, these methods are not very suitable for color images and they change the shapes of object contours in large scales. In this paper, a novel density gradient-based method is proposed to solve these problems. The proposed method locates the edges using the density gradients of image pixels instead of the color/intensity gradients. Comparing with the traditional methods, the proposed approach can be applied more effectively to all types of images: gray level, color and multispectral images; and the detection results are invariant to the detection scales as well. It may find wide applications in computer vision and image processing.
MULTIPLE STRUCTURE ALIGNMENT BASED ON GEOMETRICAL CORRELATION OF SECONDARY STRUCTURE ELEMENTS
Authors: PAI TUN-WEN , CHANG RUEI-HSIANG , CHEN CHIEN-MING , SU PO-HAN , WANG LEE-JYI , LAY KUEN-TSAIR , LAN KUO-TORNG
Published: February 2010

Protein structure alignment facilitates the analysis of protein functionality. Through superimposed structures and the comparison of variant components, common or specific features of proteins can be identified. Several known protein families exhibit analogous tertiary structures but divergent primary sequences. These proteins in the same structural class are unable to be aligned by sequence-based methods. The main objective of the present study was to develop an efficient and effective algorithm for multiple structure alignment based on geometrical correlation of secondary structures, which are conserved in evolutionary heritage. The method utilizes mutual correlation analysis of secondary structure elements (SSEs) and selects representative segments as the key anchors for structural alignment. The system exploits a fast vector transformation technique to represent SSEs in vector format, and the mutual geometrical relationship among vectors is projected onto an angle-distance map. Through a scoring function and filtering mechanisms, the best candidates of vectors are selected, and an effective constrained multiple structural alignment module is performed. The correctness of the algorithm was verified by the multiple structure alignment of proteins in the SCOP database. Several protein sets with low sequence identities were aligned, and the results were compared with those obtained by three well-known structural alignment approaches. The results show that the proposed method is able to perform multiple structural alignments effectively and to obtain satisfactory results, especially for proteins possessing low sequence identity.
LASER-INDUCED ADIABATIC POPULATION TRANSFER IN ASYMMETRIC QUANTUM WELLS
Authors: GAMBHIR MONICA , LAHON SIDDHARTHA , JHA PRADEEP KUMAR , MOHAN MAN
Published: February 2010

The basic technique of stimulated Raman adiabatic passage for laser-induced adiabatic population transfer between discrete quantum states of an asymmetric double quantum well has been used in our study. The results show that the proper time-delay, overlap, and detuning of two pulses allows the coherent transfer between the states of a double quantum well system, leading to the possibility of implementation of semiconductor–based quantum logic gates and high efficiency optical switches. The impact of phase relaxation on the population transfer efficiency is also studied.
SILICON QUANTUM DOTS GROWTH IN SiNx DIELECTRIC: A REVIEW
Authors: PANCHAL A. K. , RAI D. K. , MATHEW M. , SOLANKI C. S.
Published: February 2010

This paper reviews research works carried out on silicon quantum dots ( Si -QDs) embedded in the silicon nitride ( SiN x) dielectric matrix films with different fabrication techniques and different characteristics. The advantages of SiN x as a dielectric compared to silicon dioxide ( SiO 2) for Si -QDs from a device point of view are discussed. Various fabrication techniques along with different optimized deposition conditions are summarized. The typical results of structural characteristics of the films with Raman spectroscopy and Transmission Electron Microscopy (TEM) are discussed. The origin of photoluminescence (PL) from the films and the chemical compositional analysis such as X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Secondary Ion Mass Spectroscopy (SIMS) analysis of the films are also made available in brief. The charge conduction mechanism in the films with metal–insulator–semiconductor (MIS) structure, with their electrical characterization like capacitance–voltage (C–V) and current–voltage (I–V) measurements are presented.
LOCAL DOPING AND OPTIMAL ANNEALING OF A MESH MULTILAYER STRUCTURE TO DECREASE THE SPATIAL DIMENSIONS OF INTEGRATED p–n-JUNCTIONS
Authors: PANKRATOV E. L.
Published: February 2010

It has been recently shown that inhomogeneity of a multilayer structure and optimization of annealing time give us the possibility to decrease the depth of p–n-junctions, which were produced in the structures. The additional to the considered effect is increasing of homogeneity of dopant distribution in enriched by the dopant area of p–n-junction. In the present paper analysis of dopant redistribution in a multilayer structures during production a series of p–n-junctions, which was produced in the multilayer structures, has been done. We consider an approach to increase the sharpness of both diffused-junction and implanted-junction rectifiers, which comprise in a bipolar transistor or thyristor, and increasing of homogeneity of dopants distributions in enriched by the dopants areas of p–n-junctions. The approach gives us possibility to increase the degree of integration of p–n-junctions, which was produced as elements of integrated circuits. Optimization of annealing time for simultaneously increasing of the sharpness and homogeneity has been done.
p38 MAP kinase is necessary for melanoma-mediated regulation of VE-cadherin disassembly
Authors: Khanna Payal , Yunkunis Tara , Muddana Hari S. , Peng Hsin Hsin , August Avery , Dong Cheng
Published: February 2010

Vascular endothelial (VE)-cadherin is localized to the endothelial borders and the adherens junctions, which are regulated by changes in mitogen-activated protein (MAP) kinases, GTPases, and intracellular calcium. We previously showed that melanoma cells induce VE-cadherin disassembly through contact with human umbilical vein endothelial cells in coculture. However, the exact mechanism by which melanoma cells signal endothelial cells to induce VE-cadherin junction disassembly is not well understood. In this study, VE-cadherin junction disassembly was further examined under fluorescence microscopy. We found that melanoma-induced VE-cadherin junction disassembly and upregulation of p38 MAP kinase in endothelial cells is regulated by both soluble factors from melanomas, particularly interleukin (IL)-8, IL-6, and IL-1β, and through vascular cell adhesion molecule-1. Neutralizing melanoma-secreted soluble factors reduced endothelial gap formation. Endothelial cells transfected with MAP kinase kinase 6, a direct activator of p38 MAP kinase, increased VE-cadherin-mediated gap formation, facilitating melanoma transendothelial migration. In contrast, endothelial cells transfected with small-interfering RNA against p38 MAP kinase expression largely prevented melanoma transendothelial migration in Boyden chamber experiments. These findings indicate that p38 MAP kinase proteins regulate VE-cadherin junction disassembly, facilitating melanoma migration across endothelial cells.
Extracellular acidosis activates ASIC-like channels in freshly isolated cerebral artery smooth muscle cells
Authors: Chung Wen-Shuo , Farley Jerry M. , Swenson Alyssa , Barnard John M. , Hamilton Gina , Chiposi Rumbidzayi , Drummond Heather A.
Published: February 2010

Recent studies suggest that certain acid-sensing ion channels (ASIC) are expressed in vascular smooth muscle cells (VSMCs) and are required for VSMC functions. However, electrophysiological evidence of ASIC channels in VSMCs is lacking. The purpose of this study was to test the hypothesis that isolated cerebral artery VSMCs express ASIC-like channels. To address this hypothesis, we used RT-PCR, Western blotting, immunolabeling, and conventional whole cell patch-clamp technique. We found extracellular H+-induced inward currents in 46% of cells tested ( n = 58 of 126 VSMCs, pH 6.5–5.0). The percentage of responsive cells and the current amplitude increased as the external H+ concentration increased (pH6.0, n = 28/65 VSMCs responsive, mean current density = 8.1 ± 1.2 pA/pF). Extracellular acidosis (pH6.0) shifted the whole cell reversal potential toward the Nernst potential of Na+ ( n = 6) and substitution of extracellular Na+ by N-methyl-d-glucamine abolished the inward current ( n = 6), indicating that Na+ is a major charge carrier. The broad-spectrum ASIC blocker amiloride (20 μM) inhibited proton-induced currents to 16.5 ± 8.7% of control ( n = 6, pH6.0). Psalmotoxin 1 (PcTx1), an ASIC1a inhibitor and ASIC1b activator, had mixed effects: PcTx1 either 1) abolished H+-induced currents (11% of VSMCs, 5/45), 2) enhanced or promoted activation of H+-induced currents (76%, 34/45), or 3) failed to promote H+ activation in nonresponsive VSMCs (13%, 6/45). These findings suggest that freshly dissociated cerebral artery VSMCs express ASIC-like channels, which are predominantly formed by ASIC1b.
Proteomic analysis of V-ATPase-rich cells harvested from the kidney and epididymis by fluorescence-activated cell sorting
Authors: Da Silva Nicolas , Pisitkun Trairak , Belleannée Clémence , Miller Lance R. , Nelson Raoul , Knepper Mark A. , Brown Dennis , Breton Sylvie
Published: February 2010

Proton-transporting cells are located in several tissues where they acidify the extracellular environment. These cells express the vacuolar H+-ATPase (V-ATPase) B1 subunit (ATP6V1B1) in their plasma membrane. We provide here a comprehensive catalog of the proteins that are expressed in these cells, after their isolation by enzymatic digestion and fluorescence-activated cell sorting (FACS) from transgenic B1-enhanced green fluorescent protein (EGFP) mice. In these mice, type A and B intercalated cells and connecting segment cells of the kidney, and narrow and clear cells of the epididymis, which all express ATP6V1B1, also express EGFP, while all other cell types are negative. The proteome of renal and epididymal EGFP-positive (EGFP+) cells was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared with their respective EGFP-negative (EGFP−) cell populations. A total of 2,297 and 1,564 proteins were detected in EGFP+ cells from the kidney and epididymis, respectively. Out of these proteins, 202 and 178 were enriched by a factor greater than 1.5 in EGFP+ cells compared with EGFP− cells, in the kidney and epididymis respectively, and included subunits of the V-ATPase (B1, a4, and A). In addition, several proteins involved in intracellular trafficking, signaling, and cytoskeletal dynamics were identified. A novel common protein that was enriched in renal and epididymal EGFP+ cells is the progesterone receptor, which might be a potential candidate for the regulation of V-ATPase-dependent proton transport. These proteomic databases provide a framework for comprehensive future analysis of the common and distinct functions of V-ATPase-B1-expressing cells in the kidney and epididymis.
Upregulation of parathyroid VDR expression by extracellular calcium is mediated by ERK1/2-MAPK signaling pathway
Authors: Cañadillas Sagrario , Canalejo Rocio , Rodriguez-Ortiz Maria Encarnacion , Martinez-Moreno Julio Manuel , Estepa Jose Carlos , Zafra Rafael , Perez Jose , Muñoz-Castañeda Juan Rafael , Canalejo Antonio , Rodriguez Mariano , Almaden Yolanda
Published: February 2010

We have previously demonstrated that the activation of rat parathyroid calcium-sensing receptor (CaSR) upregulates VDR expression in vivo (Garfia B, Cañadillas S, Luque F, Siendones E, Quesada M, Almadén Y, Aguilera-Tejero E, Rodríguez M. J Am Soc Nephrol 13: 2945–2952, 2002; Rodriguez ME, Almaden Y, Cañadillas S, Canalejo A, Siendones E, Lopez I, Aguilera-Tejero E, Martin D, Rodriguez M. Am J Physiol Renal Physiol 292: F1390–F1395, 2007). The present study was designed to characterize the signaling system that mediates the stimulation of parathyroid VDR gene expression by extracellular calcium. Experiments were performed in vitro by the incubation of rat parathyroid glands and in vivo with normal and uremic (Nx) rats receiving injections of CaCl2or EDTA to obtain hypercalcemic or hypocalcemic clamps. A high calcium concentration increased VDR expression. The addition of arachidonic acid (AA) to the low-calcium medium produced an increase in VDR mRNA of the same magnitude as that observed with high calcium. The addition of ionophore to the low-calcium medium also increased VDR mRNA expression. High calcium or the addition of AA to the low-calcium medium induced the activation (phosphorylation) of ERK1/2-MAPK. The specific inhibition of the ERK1/2-MAPK activity prevented the stimulation of VDR expression by high calcium or AA. These results suggest that AA regulates parathyroid VDR gene expression through the activation of the ERK1/2-MAPK. CaSR activation induced the activation of transcription factor Sp1, but not of NF-κB p50 or p65 or activator protein-1. The addition of AA to the low-calcium medium increased specific DNA-binding activity of Sp1 to almost the same level as high calcium, which was prevented by the inhibition of ERK1/2. Furthermore, mithramycin A (a Sp1 inhibitor) prevented the upregulation of VDR mRNA by high calcium. Finally, both sham and Nx hypercalcemic rats showed similar increased levels of VDR mRNA compared with sham and Nx hypocalcemic rats. Our results demonstrate that extracellular calcium stimulates VDR expression in parathyroid glands through the elevation of the cytosolic calcium level and the stimulation of the PLA2-AA-dependent ERK1/2-pathway. Furthermore, the transcription factor Sp1 mediates this effect.
An “As Soon As Possible” Effect in Human Intertemporal Decision Making: Behavioral Evidence and Neural Mechanisms
Authors: Kable Joseph W. , Glimcher Paul W.
Published: February 2010

Many decisions involve a trade-off between the quality of an outcome and the time at which that outcome is received. In psychology and behavioral economics, the most widely studied models hypothesize that the values of future gains decline as a roughly hyperbolic function of delay from the present. Recently, it has been proposed that this hyperbolic-like decline in value arises from the interaction of two separate neural systems: one specialized to value immediate rewards and the other specialized to value delayed rewards. Here we report behavioral and functional magnetic resonance imaging results that are inconsistent with both the standard behavioral models of discounting and the hypothesis that separate neural systems value immediate and delayed rewards. Behaviorally, we find that human subjects do not necessarily make the impulsive preference reversals predicted by hyperbolic-like discounting. We also find that blood oxygenation level dependent activity in ventral striatum, medial prefrontal, and posterior cingulate cortex does not track whether an immediate reward was present, as proposed by the separate neural systems hypothesis. Activity in these regions was correlated with the subjective value of both immediate and delayed rewards. Rather than encoding only the relative value of one reward compared with another, these values are represented on a more absolute scale. These data support an alternative behavioral–neural model (which we call “ASAP”), in which subjective value declines hyperbolically relative to the soonest currently available reward and a small number of valuation areas serve as a final common pathway through which these subjective values guide choice.
Afferent Regulation of Leg Motor Cortex Excitability After Incomplete Spinal Cord Injury
Authors: Roy François D. , Yang Jaynie F. , Gorassini Monica A.
Published: February 2010

An incomplete spinal cord injury (SCI) impairs neural conduction along spared ascending sensory pathways to disrupt the control of residual motor movements. To characterize how SCI affects the activation of the motor cortex by spared ascending sensory pathways, we examined how stimulation of leg afferents facilitates the excitability of the motor cortex in subjects with incomplete SCI. Homo- and heteronymous afferents to the tibialis anterior (TA) representation in the motor cortex were electrically stimulated, and the responses were compared with uninjured controls. In addition, we examined if cortical excitability could be transiently increased by repetitively pairing stimulation of spared ascending sensory pathways with transcranial magnetic stimulation (TMS), an intervention termed paired associative stimulation (PAS). In uninjured subjects, activating the tibial nerve at the ankle 45–50 ms before a TMS pulse in a conditioning-test paradigm facilitated the motor-evoked potential (MEP) in the heteronymous TA muscle by twofold on average. In contrast, prior tibial nerve stimulation did not facilitate the TA MEP in individuals with incomplete SCI ( n = 8 SCI subjects), even in subjects with less severe injuries. However, we provide evidence that ascending sensory inputs from the homonymous common peroneal nerve (CPN) can, unlike the heteronymous pathways, facilitate the motor cortex to modulate the TA MEP ( n = 16 SCI subjects) but only in subjects with less severe injuries. Finally, by repetitively coupling CPN stimulation with coincident TA motor cortex activation during PAS, we show that 7 of 13 SCI subjects produced appreciable (>20%) facilitation of the MEP following the intervention. The increase in corticospinal tract excitability by PAS was transient (<20 min) and tended to be more prevalent in SCI subjects with stronger functional ascending sensory pathways.
A Common Single Nucleotide Polymorphism Can Exacerbate Long-QT Type 2 Syndrome Leading to Sudden Infant Death
Authors: Nof Eyal , Cordeiro Jonathan M. , Pérez Guillermo J. , Scornik Fabiana S. , Calloe Kirstine , Love Barry , Burashnikov Elena , Caceres Gabriel , Gunsburg Moshe , Antzelevitch Charles
Published: February 2010

Background—

Identification of infants at risk for sudden arrhythmic death remains one of the leading challenges of modern medicine. We present a family in which a common polymorphism (single nucleotide polymorphism) inherited from the father, combined with a stop codon mutation inherited from the mother (both asymptomatic), led to 2 cases of sudden infant death.

Methods and Results—

KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, CACNA1c, CACNB2b
, and
KCNJ2
genes were amplified and analyzed by direct sequencing. Functional electrophysiological studies were performed with the single nucleotide polymorphism and mutation expressed singly and in combination in Chinese ovary (CHO-K1) and COS-1 cells. An asymptomatic woman presenting after the death of her 2-day-old infant and spontaneous abortion of a second baby in the first trimester was referred for genetic analysis. The newborn infant had nearly incessant ventricular tachycardia while in utero and a prolonged QTc (560 ms). The mother was asymptomatic but displayed a prolonged QTc. Genetic screening of the mother revealed a heterozygous nonsense mutation (P926AfsX14) in
KCNH2
, predicting a stop codon. The father was asymptomatic with a normal QTc but had a heterozygous polymorphism (K897T) in
KCNH2
. The baby who died at 2 days of age and the aborted fetus inherited both K897T and P926AfsX14. Heterologous coexpression of K897T and P926AfsX14 led to loss of function of HERG current much greater than expression of K897T or P926AfsX14 alone.

Conclusions—

Our data suggest that a common polymorphism (K897T) can markedly accentuate the loss of function of mildly defective HERG channels, leading to long-QT syndrome–mediated arrhythmias and sudden infant death.
Effect of Combined Aspirin and Extended-Release Dipyridamole Versus Clopidogrel on Functional Outcome and Recurrence in Acute, Mild Ischemic Stroke
Authors: Bath Philip M.W. , Cotton Daniel , Martin Reneé H. , Palesch Yuko , Yusuf Salim , Sacco Ralph , Diener Hans-Christoph , Estol Conrado , Roberts Robin
Published: February 2010

Background and Purpose—

Long-term antiplatelet therapy is effective at reducing recurrence after ischemic stroke. However, the relative safety and efficacy of combined aspirin-dipyridamole or clopidogrel are not known in patients with acute ischemic stroke.

Methods—

The factorial PRoFESS secondary prevention trial assessed antiplatelet and blood pressure–lowering strategies in 20 332 patients, 1360 of whom were randomized within 72 hours of ischemic stroke to combined aspirin (Asp; 25 mg BID) and extended-release dipyridamole (ER-DP; 200 mg BID, n=672) or clopidogrel (75 mg/d, n=688). The primary outcome for this post hoc subgroup analysis was functional outcome at 30 days; secondary outcomes included recurrence and death by 90 days. Analyses were adjusted for baseline prognostic variables and blood pressure treatment assignment.

Results—

Patients were representative of the whole trial (age 67 years, National Institutes of Health Stroke Scale score 3, small-artery occlusion 59%), and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. By 90 days, treatment was no longer being taken in 121 (18%) patients randomized to Asp/ER-DP and in 86 (12.5%) assigned to clopidogrel (
P
=0.006). Combined death or dependency (shift analysis of modified Rankin Scale score at day 30) did not differ between treatment groups (odds ratio [OR]=0.97; 95% CI, 0.79 to 1.19). Nonsignificant trends to reduced recurrence (OR=0.56; 95% CI, 0.26 to 1.18) and vascular events (OR=0.71; 95% CI, 0.36 to 1.37) were present with Asp/ER-DP. Rates of death, major bleeding, and serious adverse events did not differ between treatment groups.

Conclusions—

Treatment with combined Asp/ER-DP vs clopidogrel in 1360 patients with acute, mild ischemic stroke did not differ in terms of effects on functional outcome, recurrence, death, bleeding, or serious adverse events. Both treatments were practical to administer.
Switched control of fluid networks
Authors: Blanchini Franco , Viaro Umberto
Published: February 2010

A switched-control technique for fluid distribution systems is presented. It is based on a compartment model of the distribution network consisting of a number of interconnected reservoirs. The unforced flows among reservoirs and environment only depend (non-linearly) on the stored water levels (state variables), which are also influenced by the water demands (disturbances) and by the forced flows of the water pumped into or out of the reservoirs (controlled variables). The control objective is to drive the system to the equilibrium state and keep it there. This goal can be achieved by means of a state-feedback control, which entails switching the controlled inputs among given values according to the current system state. Necessary and sufficient stabilizability conditions are provided. The global asymptotic stability of the overall control system is proved by resorting to a suitable control-Lyapunov function. An experiment is worked out to show the performance of the adopted control policy.