bluuebunny/crossref_metadata_2025 huggingface dataset:
Geminivirus AL2 and L2 Proteins Suppress Transcriptional Gene Silencing and Cause Genome-Wide Reductions in Cytosine Methylation
Authors: Buchmann R. Cody , Asad Shaheen , Wolf Jamie N. , Mohannath Gireesha , Bisaro David M.
Published: March 2009

Geminiviruses replicate single-stranded DNA genomes through double-stranded intermediates that associate with cellular histone proteins. Unlike RNA viruses, they are subject to RNA-directed methylation pathways that target viral chromatin and likely lead to transcriptional gene silencing (TGS). Here we present evidence that the related geminivirus proteins AL2 and L2 are able to suppress this aspect of host defense. AL2 and L2 interact with and inactivate adenosine kinase (ADK), which is required for efficient production of
S
-adenosyl methionine, an essential methyltransferase cofactor. We demonstrate that the viral proteins can reverse TGS of a green fluorescent protein (GFP) transgene in
Nicotiana benthamiana
when overexpressed from a
Potato virus X
vector and that reversal of TGS by geminiviruses requires L2 function. We also show that AL2 and L2 cause ectopic expression of endogenous
Arabidopsis thaliana
loci silenced by methylation in a manner that correlates with ADK inhibition. However, at one exceptional locus, ADK inhibition was insufficient and TGS reversal required the transcriptional activation domain of AL2. Using restriction-sensitive PCR and bisulfite sequencing, we showed that AL2-mediated TGS suppression is accompanied by reduced cytosine methylation. Finally, using a methylation-sensitive single-nucleotide extension assay, we showed that transgenic expression of AL2 or L2 causes global reduction in cytosine methylation. Our results provide further evidence that viral chromatin methylation is an important host defense and allow us to propose that as a countermeasure, geminivirus proteins reverse TGS by nonspecifically inhibiting cellular transmethylation reactions. To our knowledge, this is the first report that viral proteins can inhibit TGS.
Human T-Cell Leukemia Virus Type 2 Rex Carboxy Terminus Is an Inhibitory/Stability Domain That Regulates Rex Functional Activity and Viral Replication
Authors: Xie Li , Kesic Matthew , Yamamoto Brenda , Li Min , Younis Ihab , Lairmore Michael D. , Green Patrick L.
Published: March 2009

Human T-cell leukemia virus (HTLV) regulatory protein, Rex, functions to increase the expression of the viral structural and enzymatic gene products. The phosphorylation of two serine residues (S151 and S153) at the C terminus is important for the function of HTLV-2 Rex (Rex-2). The Rex-2 phosphomimetic double mutant (S151D, S153D) is locked in a functionally active conformation. Since
rex
and
tax
genes overlap, Rex S151D and S153D mutants were found to alter the Tax oncoprotein coding sequence and transactivation activities. Therefore, additional Rex-2 mutants including P152D, A157D, S151Term, and S158Term were generated and characterized (“Term” indicates termination codon). All Rex-2 mutants and wild-type (wt) Rex-2 localized predominantly to the nucleus/nucleolus, but in contrast to the detection of phosphorylated and unphosphorylated forms of wt Rex-2 (p26 and p24), mutant proteins were detected as a single phosphoprotein species. We found that Rex P152D, A157D, and S158Term mutants are more functionally active than wt Rex-2 and that the Rex-2 C terminus and its specific phosphorylation state are required for stability and optimal expression. In the context of the provirus, the more active Rex mutants (A157D or S158Term) promoted increased viral protein production, increased viral infectious spread, and enhanced HTLV-2-mediated cellular proliferation. Moreover, these Rex mutant viruses replicated and persisted in inoculated rabbits despite higher antiviral antibody responses. Thus, we identified in Rex-2 a novel C-terminal inhibitory domain that regulates functional activity and is positively regulated through phosphorylation. The ability of this domain to modulate viral replication likely plays a key role in the infectious spread of the virus and in virus-induced cellular proliferation.
The Receptor Complex Associated with Human T-Cell Lymphotropic Virus Type 3 (HTLV-3) Env-Mediated Binding and Entry Is Distinct from, but Overlaps with, the Receptor Complexes of HTLV-1 and HTLV-2
Authors: Jones Kathryn S. , Huang Ying K. , Chevalier Sébastien A. , Afonso Philippe V. , Petrow-Sadowski Cari , Bertolette Daniel C. , Gessain Antoine , Ruscetti Francis W. , Mahieux Renaud
Published: March 2009

Little is known about the transmission or tropism of the newly discovered human retrovirus, human T-cell lymphotropic virus type 3 (HTLV-3). Here, we examine the entry requirements of HTLV-3 using independently expressed Env proteins. We observed that HTLV-3 surface glycoprotein (SU) binds efficiently to both activated CD4
+
and CD8
+
T cells. This contrasts with both HTLV-1 SU, which primarily binds to activated CD4
+
T cells, and HTLV-2 SU, which primarily binds to activated CD8
+
T cells. Binding studies with heparan sulfate proteoglycans (HSPGs) and neuropilin-1 (NRP-1), two molecules important for HTLV-1 entry, revealed that these molecules also enhance HTLV-3 SU binding. However, unlike HTLV-1 SU, HTLV-3 SU can bind efficiently in the absence of both HSPGs and NRP-1. Studies of entry performed with HTLV-3 Env-pseudotyped viruses together with SU binding studies revealed that, for HTLV-1, glucose transporter 1 (GLUT-1) functions at a postbinding step during HTLV-3 Env-mediated entry. Further studies revealed that HTLV-3 SU binds efficiently to naïve CD4
+
T cells, which do not bind either HTLV-1 or HTLV-2 SU and do not express detectable levels of HSPGs, NRP-1, and GLUT-1. These results indicate that the complex of receptor molecules used by HTLV-3 to bind to primary T lymphocytes differs from that of both HTLV-1 and HTLV-2.
Herpes Simplex Virus Type 1 Glycoprotein E Mediates Retrograde Spread from Epithelial Cells to Neurites
Authors: McGraw Helen M. , Friedman Harvey M.
Published: March 2009

In animal models of infection, glycoprotein E (gE) is required for efficient herpes simplex virus type 1 (HSV-1) spread from the inoculation site to the cell bodies of innervating neurons (retrograde direction). Retrograde spread in vivo is a multistep process, in that HSV-1 first spreads between epithelial cells at the inoculation site, then infects neurites, and finally travels by retrograde axonal transport to the neuron cell body. To better understand the role of gE in retrograde spread, we used a compartmentalized neuron culture system, in which neurons were infected in the presence or absence of epithelial cells. We found that gE-deleted HSV-1 (NS-gEnull) retained retrograde axonal transport activity when added directly to neurites, in contrast to the retrograde spread defect of this virus in animals. To better mimic the in vivo milieu, we overlaid neurites with epithelial cells prior to infection. In this modified system, virus infects epithelial cells and then spreads to neurites, revealing a 100-fold retrograde spread defect for NS-gEnull. We measured the retrograde spread defect of NS-gEnull from a variety of epithelial cell lines and found that the magnitude of the spread defect from epithelial cells to neurons correlated with epithelial cell plaque size defect, indicating that gE plays a similar role in both types of spread. Therefore, gE-mediated spread between epithelial cells and neurites likely explains the retrograde spread defect of gE-deleted HSV-1 in vivo.
Andes Virus Antigens Are Shed in Urine of Patients with Acute Hantavirus Cardiopulmonary Syndrome
Authors: Godoy Paula , Marsac Delphine , Stefas Elias , Ferrer Pablo , Tischler Nicole D. , Pino Karla , Ramdohr Pablo , Vial Pablo , Valenzuela Pablo D. T. , Ferrés Marcela , Veas Francisco , López-Lastra Marcelo
Published: March 2009

Hantavirus cardiopulmonary syndrome (HCPS) is a highly pathogenic emerging disease (40% case fatality rate) caused by New World hantaviruses. Hantavirus infections are transmitted to humans mainly by inhalation of virus-contaminated aerosol particles of rodent excreta and secretions. At present, there are no antiviral drugs or immunotherapeutic agents available for the treatment of hantaviral infection, and the survival rates for infected patients hinge largely on early virus recognition and hospital admission and aggressive pulmonary and hemodynamic support. In this study, we show that Andes virus (ANDV) interacts with human apolipoprotein H (ApoH) and that ApoH-coated magnetic beads or ApoH-coated enzyme-linked immunosorbent assay plates can be used to capture and concentrate the virus from complex biological mixtures, such as serum and urine, allowing it to be detected by both immunological and molecular approaches. In addition, we report that ANDV-antigens and infectious virus are shed in urine of HCPS patients.
The γ134.5 Protein of Herpes Simplex Virus 1 Is Required To Interfere with Dendritic Cell Maturation during Productive Infection
Authors: Jin Huali , Ma Yijie , Prabhakar Bellur S. , Feng Zongdi , Valyi-Nagy Tibor , Yan Zhipeng , Verpooten Dustin , Zhang Cuizhu , Cao Youjia , He Bin
Published: March 2009

The γ134.5 protein of herpes simplex virus 1 is an essential factor for viral virulence. In infected cells, this viral protein prevents the translation arrest mediated by double-stranded RNA-dependent protein kinase R. Additionally, it associates with and inhibits TANK-binding kinase 1, an essential component of Toll-like receptor-dependent and -independent pathways that activate interferon regulatory factor 3 and cytokine expression. Here, we show that γ134.5 is required to block the maturation of conventional dendritic cells (DCs) that initiate adaptive immune responses. Unlike wild-type virus, the γ134.5 null mutant stimulates the expression of CD86, major histocompatibility complex class II (MHC-II), and cytokines such as alpha/beta interferon in immature DCs. Viral replication in DCs inversely correlates with interferon production. These phenotypes are also mirrored in a mouse ocular infection model. Further, DCs infected with the γ134.5 null mutant effectively activate naïve T cells whereas DCs infected with wild-type virus fail to do so. Type I interferon-neutralizing antibodies partially reverse virus-induced upregulation of CD86 and MHC-II, suggesting that γ134.5 acts through interferon-dependent and -independent mechanisms. These data indicate that γ134.5 is involved in the impairment of innate immunity by inhibiting both type I interferon production and DC maturation, leading to defective T-cell activation.
Hepatitis B Virus X Protein Modulates Apoptosis in Primary Rat Hepatocytes by Regulating both NF-κB and the Mitochondrial Permeability Transition Pore
Authors: Clippinger Amy J. , Gearhart Tricia L. , Bouchard Michael J.
Published: March 2009

The hepatitis B virus (HBV) X protein (HBx) is a multifunctional protein that regulates numerous cellular signal transduction pathways, including those that modulate apoptosis. However, different HBx-dependent effects on apoptosis have been reported; these differences are likely the consequence of the exact conditions and cell types used in a study. Many of the previously reported studies that analyzed HBx regulation of apoptosis were conducted in immortalized or transformed cells, and the alterations that have transformed or immortalized these cells likely impact apoptotic pathways. We examined the effects of HBx on apoptotic pathways in cultured primary rat hepatocytes, a biologically relevant system that mimics normal hepatocytes in the liver. We analyzed the effects of HBx on apoptosis both when HBx was expressed in the absence of other HBV proteins and in the context of HBV replication. HBx stimulation of NF-κB inhibited the activation of apoptotic pathways in cultured primary rat hepatocytes. However, when HBx-induced activation of NF-κB was blocked, HBx stimulated apoptosis; blocking the activity of the mitochondrial permeability transition pore inhibited HBx activation of apoptosis. These results suggest that HBx can be either proapoptotic or antiapoptotic in hepatocytes, depending on the status of NF-κB, and confirm previous studies that link some HBx activities to modulation of the mitochondrial permeability transition pore. Overall, our studies define apoptotic pathways that are regulated by HBx in cultured primary hepatocytes and provide potential mechanisms for the development of HBV-associated liver cancer.
THE EFFECT OF NANO AND MICRO POROSITY ON THE SCHOTTKY BARRIER HEIGHT AND IDEALITY FACTOR IN THE I–V CHARACTERISTICS OF PtSi/p-Si IR DETECTOR
Authors: ESHGHI H. , MOHAMMADI M.
Published: March 2009

In this paper, the effect of porosity on reverse bias current–voltage characteristics of PtSi/por - Si (p-type) IR detector as a function of temperature is investigated. Our experimental data for two samples with different porosities (50% and 10%) at 300 K and 77 K are reported by Raissi et al.1 These data indicates a breakdown-like behavior. Our analytical model is based on hole thermionic emission with large ideality factor (n ≈ 200). Our calculations show that at each temperature, the Schottky barrier height, as well as the ideality factor, in sample with 10% porosity is bigger than that of 50%. These variations could be due to band gap variations of Si size effect using quantum dot model, and the presence of the relatively high (~1015 cm-2 eV-1) density of states at the silicide/por-silicon interface, respectively.
ELECTRONIC STRUCTURE AND MAGNETISM OF NixMn1-x ALLOYS
Authors: JING C. , QIAO Y. F. , LI Z. , CHEN J. P. , CAO S. X. , ZHANG J. C.
Published: March 2009

The electronic and magnetic structures of both bcc and fcc ordered Ni x Mn 1-x alloys, with x = 0, 0.25, 0.5, 0.75, and 1, are performed using the first principle linearized augmented plane-wave (LAPW) method within the framework of local spin-density functional approximation (LSDA). It is shown that fcc Ni x Mn 1-x with x = 1, 0.75 is ferromagnetic ordering, which is in good agreement with the experiments. At the equiatomic composition of Ni x Mn 1-x with x = 0.5, it is antiferromagnetic ordering. With the lower Ni composition, it presents ferrimagnetic and antiferromagnetic ordering, respectively. For bcc Ni x Mn 1-x with both rich Ni and rich Mn composition, however, it presents ferromagnetic and ferrimagnetic ordering, respectively. At the equiatomic Ni x Mn 1-x with x = 0.5, it presents ferromagnetic ordering.
DISORDERED ONE-DIMENSIONAL METALLIC-DIELECTRIC PHOTONIC CRYSTAL REFLECTOR
Authors: QI LIMEI , YANG ZIQIANG , GAO XI
Published: March 2009

The reflected properties of one-dimensional frequency-dependent metallic-dielectric photonic crystals are investigated when disorders are introduced for the first time. It is demonstrated that disordered metallic-dielectric photonic crystal provides remarkably high reflection range compared with the corresponding period metallic-dielectric one when the degree of disorder is moderately chosen, and a wider stop band will be obtained with the increasing of periods. At last, the reflected properties influenced by incident angle for different polarizations are also calculated and discussed.
CHARACTERIZATION OF LiPb2V5O15 CERAMICS USING IMPEDANCE SPECTROSCOPY
Authors: DAS P. S. , CHAKRABORTY P. K. , BEHERA BANARJI , CHOUDHARY R. N. P.
Published: March 2009

The polycrystalline sample of LiPb 2 V 5 O 15 was prepared by a mixed oxide method at low temperature (i.e. 550°C). Preliminary structural analysis confirmed the formation of the compound of an orthorhombic crystal system. The impedance parameters of the material were studied using complex impedance spectroscopy (CIS) in a wide temperature (i.e. 30–450°C) and frequency (i.e. 102–106 Hz) range. From the complex impedance plots, grain/grain boundary effects and relaxation phenomenon were observed above 30°C. Study of electrical conductivity suggests that the compound exhibits the negative temperature coefficient of resistance (NTCR) behavior like a semiconductor.
NONLINEAR RESONANCE IN THE VERY EARLY UNIVERSE: SOUNDS OF THE PRIMORDIAL MUSIC
Authors: DE OLIVEIRA H. P. , DAMIÃO SOARES I. , TONINI E. V.
Published: March 2009

Nonlinear resonance is ubiquitous in nature. Resonance is relevant to understanding phenomena in quite distinct areas such as music, cellular structure, and astrophysics, and in the very early universe. In order to see the crucial role played by resonance in cosmology, we assume that closed FRW universes with a massive inflaton field evolve according to the field equations that contain additional terms arising from high energy corrections to cosmological scenarios. As a consequence, nonsingular bounces in the early evolution of the universe are produced. We have shown that in narrow windows of the parameter space of the models, nonlinear resonance phenomena of KAM tori occur and lead to the destruction of those tori that trap the inflaton, resulting in the escape of the universe into inflation. These resonance windows are labeled by an integer n ≥ 2; n is related to the ratio of the frequencies in the scale factor/scalar field degrees of freedom.
POSSIBLE WAY OUT OF THE HAWKING PARADOX: ERASING THE INFORMATION AT THE HORIZON
Authors: HERRERA L.
Published: March 2009

We show that small deviations from spherical symmetry, described by means of exact solutions to Einstein equations, provide a mechanism to "bleach" the information about the collapsing body as it falls through the apparent horizon, thereby resolving the information loss paradox. The resulting picture and its implication related to Landauer's principle in the presence of a gravitational field is discussed.
THE SELF-ORGANIZED DE SITTER UNIVERSE
Authors: AMBJØRN J. , JURKIEWICZ J. , LOLL R.
Published: March 2009

We propose a theory of quantum gravity which formulates the quantum theory as a nonperturbative path integral, where each space–time history appears with the weight exp (iS EH ), with S EH the Einstein–Hilbert action of the corresponding causal geometry. The path integral is diffeomorphism-invariant (only geometries appear) and background-independent. The theory can be investigated by computer simulations, which show that a de Sitter universe emerges on large scales. This emergence is of an entropic, self-organizing nature, with the weight of the Einstein–Hilbert action playing a minor role. Also, the quantum fluctuations around this de Sitter universe can be studied quantitatively and remain small until one gets close to the Planck scale. The structures found to describe Planck-scale gravity are reminiscent of certain aspects of condensed-matter systems.
THE EFFECT OF STRUCTURE FORMATION ON THE EXPANSION OF THE UNIVERSE
Authors: RÄSÄNEN SYKSY
Published: March 2009

Observations of the expansion rate of the universe at late times disagree by a factor of 1.5–2 with the prediction of homogeneous and isotropic models based on ordinary matter and gravity. We discuss how the departure from linearly perturbed homogeneity and isotropy due to structure formation could explain this discrepancy. We evaluate the expansion rate in a dust universe which contains nonlinear structures with a statistically homogeneous and isotropic distribution. The expansion rate is found to increase relative to the exactly homogeneous and isotropic case by a factor of 1.1–1.3 at some tens of billions of years. The time scale follows from the cold dark matter transfer function and the amplitude of primordial perturbations without additional free parameters.
THE FLUID–GRAVITY CORRESPONDENCE: THE MEMBRANE AT THE END OF THE UNIVERSE
Authors: HUBENY VERONIKA E. , RANGAMANI MUKUND , MINWALLA SHIRAZ , VAN RAAMSDONK MARK
Published: March 2009

We establish an explicit connection between the evolution of generic inhomogeneous black brane solutions in asymptotically AdS space–times and the evolution of relativistic conformal fluids in one lower dimension. Specifically, given any solution to a particular set of fluid-dynamical equations, one can construct an inhomogeneous black brane solution with a regular event horizon. This connection is reminiscent of the membrane paradigm for black holes; in our case the dynamics of the entire space–time is encoded in a fluid living at the boundary. This fluid–gravity correspondence leads to interesting implications for both gravitational physics and fluid dynamics.
CONSISTENT BOUNDARY CONDITIONS FOR COSMOLOGICAL TOPOLOGICALLY MASSIVE GRAVITY AT THE CHIRAL POINT
Authors: GRUMILLER D. , JOHANSSON N.
Published: March 2009

We show that cosmological topologically massive gravity at the chiral point allows not only Brown–Henneaux boundary conditions as consistent boundary conditions, but also slightly more general ones which encompass the logarithmic primary found in J. High Energy Phys.07 (2008) 134 as well as all its descendants.
THE HOLOGRAPHIC INTERPRETATION OF HAWKING RADIATION
Authors: FABBRI ALESSANDRO , PROCOPIO GIOVANNI PAOLO
Published: March 2009

Holography gives us a tool for viewing the Hawking effect from a new, classical perspective. In the context of Randall–Sundrum braneworld models, we show that the basic features of four-dimensional evaporating solutions are nicely translated into classical, five-dimensional language. This includes the possible dual bulk description of particles tunneling through the horizon.
NONCOMMUTATIVE GRAVITY, A "NO STRINGS ATTACHED" QUANTUM–CLASSICAL DUALITY, AND THE COSMOLOGICAL CONSTANT PUZZLE
Authors: SINGH T. P.
Published: March 2009

There ought to exist a reformulation of quantum mechanics which does not refer to an external classical space–time manifold. Such a reformulation can be achieved using the language of noncommutative differential geometry. A consequence which follows is that the "weakly quantum, strongly gravitational" dynamics of a relativistic particle whose mass is much greater than the Planck mass is dual to the "strongly quantum, weakly gravitational" dynamics of another particle whose mass is much less than the Planck mass. The masses of the two particles are inversely related to each other, and the product of their masses is equal to the square of the Planck mass. This duality explains the observed value of the cosmological constant, and also why this value is nonzero but extremely small in Planck units.
ON THE PHYSICAL INTERPRETATION OF ASYMPTOTICALLY FLAT GRAVITATIONAL FIELDS
Authors: KOZAMEH CARLOS , NEWMAN EZRA T. , SILVA-ORTIGOZA GILBERTO
Published: March 2009

A problem in general relativity is how to extract physical information from solutions to the Einstein equations. Most often information is found from special conditions, e.g., special vector fields, symmetries or approximate symmetries. Our concern is with asymptotically flat space–times with approximate symmetry: the BMS group. For these spaces the Bondi four-momentum vector and its evolution, found at infinity, describes the total energy–momentum and the energy–momentum radiated. By generalizing the simple idea of the transformation of (electromagnetic) dipoles under a translation, we define (analogous to center of charge) the center of mass for asymptotically flat Einstein–Maxwell fields. This gives kinematical meaning to the Bondi four-momentum, i.e., the four-momentum and its evolution is described in terms of a center of mass position vector, its velocity and spin-vector. From dynamical arguments, a unique (for our approximation) total angular momentum and evolution equation in the form of a conservation law is found.
COVARIANT ANOMALIES, HORIZONS AND HAWKING RADIATION
Authors: BANERJEE RABIN
Published: March 2009

Hawking radiation is obtained from anomalies resulting from a breaking of diffeomorphism symmetry near the event horizon of a black hole. Such anomalies, manifested as a nonconservation of the energy–momentum tensor, occur in two different forms — covariant and consistent. The crucial role of covariant anomalies near the horizon is revealed, since this is the only input required to obtain the Hawking flux, thereby highlighting the universality of this effect. A brief description of the application of this method to obtain thermodynamic entities like entropy or temperature is provided.
WEB SERVICE COMPOSITION AS A COMPOSITION OF VALID AND ROBUST SEMANTIC LINKS
Authors: LÉCUÉ FREDDY , DELTEIL ALEXANDRE , LÉGER ALAIN , BOISSIER OLIVIER
Published: March 2009

Automated composition of Web services or the process of forming new value-added Web services is one of the most promising challenges facing the Semantic Web today. Semantics enables Web service to describe capabilities together with their processes, hence one of the key elements for the automated composition of Web services. In this paper, we focus on the functional level of Web services i.e. services are described according to some input, output parameters semantically enhanced by concepts in a domain ontology. Web service composition is then viewed as a composition of semantic links wherein the latter links refer to semantic matchmaking between Web service parameters (i.e. outputs and inputs) in order to model their connection and interaction. The key idea is that the matchmaking enables, at run time, finding semantic compatibilities among independently defined Web service descriptions. By considering such a level of composition, a formal model to perform the automated composition of Web services i.e. Semantic Link Matrix, is introduced. The latter model is required as a starting point to apply problem-solving techniques such as regression (or progression)-based search for Web service composition. The model supports a semantic context in order to find correct, complete, consistent and robust plans as solutions. In this paper, an innovative and formal model for an AI (Artificial Intelligence) planning-oriented composition is presented. Our system is implemented and interacting with Web services which are dedicated to Telecom scenarios. The preliminary evaluation results showed high efficiency and effectiveness of the proposed approach.
SPECIFICATION AND VERIFICATION OF DYNAMICS IN AGENT MODELS
Authors: BOSSE TIBOR , JONKER CATHOLIJN M. , VAN DER MEIJ LOURENS , SHARPANSKYKH ALEXEI , TREUR JAN
Published: March 2009

Within many domains, among which biological, cognitive, and social areas, multiple interacting processes occur among agents with dynamics that are hard to handle. This paper presents the predicate logical Temporal Trace Language (TTL) for the formal specification and analysis of dynamic properties of agents and multi-agent systems. This language supports the specification of both qualitative and quantitative aspects, and therefore subsumes specification languages based on differential equations and qualitative, logical approaches. A software environment has been developed for TTL, which supports editing TTL properties and enables the formal verification of properties against a set of traces. The TTL environment proved its value in a number of projects within different biological, cognitive and social domains.
PROVIDING INTEGRATED LIFE CYCLE SUPPORT IN PROCESS-AWARE INFORMATION SYSTEMS
Authors: WEBER BARBARA , REICHERT MANFRED , RINDERLE-MA STEFANIE , WILD WERNER
Published: March 2009

The need for more flexibility of process-aware information systems (PAISs) has been discussed for several years and different approaches for adaptive process management have emerged. However, only few of them provide support for both changes of individual process instances and the propagation of process type changes to a collection of related process instances. Furthermore, knowledge about process changes has not yet been exploited by any of these systems. This paper presents the ProCycle approach which overcomes this practical limitation by capturing the whole process life cycle and all kinds of changes in an integrated way. Users are not only allowed to deviate from the predefined process in exceptional situations, but are also assisted in retrieving and reusing knowledge about previously performed changes in this context. If similar instance deviations occur frequently, process engineers will be supported in deriving improved process models from them. This, in turn, allows engineers to evolve the PAIS (including the knowledge about the changes) over time. Feasability of the ProCycle approach is demonstrated by a proof-of-concept prototype which combines adaptive process management technology with concepts and methods provided by case-based reasoning (CBR) technology.
ON THE FOURTH POWER MOMENT OF Δx AND E(x) IN SHORT INTERVALS
Authors: TANIGAWA YOSHIO , ZHAI WENGUANG
Published: March 2009

Let Δ(x) and E(x) be error terms of the sum of divisor function and the mean square of the Riemann zeta function, respectively. In this paper, their fourth power moments for short intervals of Jutila's type are considered. We get an asymptotic formula for U in some range.
SPECIAL VALUES OF THE POLYGAMMA FUNCTIONS
Authors: RAM MURTY M. , SARADHA N.
Published: March 2009

Let q be a natural number and [Formula: see text]. We consider the Dirichlet series ∑n ≥ 1 f(n)/ns and relate its value when s is a natural number, to the special values of the polygamma function. For certain types of functions f, we evaluate the special value explicitly and use this to study linear independence over ℚ of L(k,χ) as χ ranges over Dirichlet characters mod q which have the same parity as k.
ON THE EULER PRODUCT OF THE DEDEKIND ZETA FUNCTION
Authors: LI XIAN-JIN
Published: March 2009

It is well known that the Euler product formula for the Riemann zeta function ζ(s) is still valid for ℜ(s) = 1 and s ≠ 1. In this paper, we extend this result to zeta functions of number fields. In particular, we show that the Dedekind zeta function ζk(s) for any algebraic number field k can be written as the Euler product on the line ℜ(s) = 1 except at the point s = 1. As a corollary, we obtain the Euler product formula on the line ℜ(s) = 1 for Dirichlet L-functions L(s, χ) of real characters.
A CHARACTERIZATION OF THE MODULAR UNITS
Authors: FOLSOM AMANDA
Published: March 2009

We provide an exact formula for the complex exponents in the modular product expansion of the modular units in terms of the Kubert–Lang structure theory, and deduce a characterization of the modular units in terms of the growth of these exponents, answering a question posed by Kohnen.
CRYPTANALYSIS OF RSA WITH CONSTRAINED KEYS
Authors: NITAJ ABDERRAHMANE
Published: March 2009

Let n = pq be an RSA modulus with unknown prime factors of equal bit-size. Let e be the public exponent and d be the secret exponent satisfying ed ≡ 1 mod ϕ(n) where ϕ(n) is the Euler totient function. To reduce the decryption time or the signature generation time, one might be tempted to use a small private exponent d. Unfortunately, in 1990, Wiener showed that private exponents smaller than [Formula: see text] are insecure and in 1999, Boneh and Durfee improved the bound to n0.292. In this paper, we show that instances of RSA with even large private exponents can be efficiently broken if there exist positive integers X, Y such that |eY - XF(u)| and Y are suitably small where F is a function of publicly known expression for which there exists an integer u ≠ 0 satisfying F(u) ≈ n and pu or qu is computable from F(u) and n. We show that the number of such exponents is at least O(n3/4-ε) when F(u) = p(q - u).
MAGNETISM IN GRAPHENE SYSTEMS
Authors: KAN ERJUN , LI ZHENYU , YANG JINLONG
Published: March 2009

Graphene has attracted great interest in materials science, owing to its novel electronic structures. Recently, magnetism discovered in graphene-based systems has opened up the possibility of their spintronics application. This paper provides a comprehensive review of the magnetic behaviors and electronic structures of graphene systems, including two-dimensional graphene, one-dimensional graphene nanoribbons, and zero-dimensional graphene nanoclusters. Theoretical research suggests that such metal-free magnetism mainly comes from the localized states or edges states. By applying an external electric field, or by chemical modification, we can turn the zigzag nanoribbon systems into half metal, thus obtaining a perfect spin filter.
MORPHOLOGY CONTROL OF CARBON NANOTUBES THROUGH FOCUSED ION BEAMS
Authors: LOYA M. , PARK J. E. , CHEN L. H. , BRAMMER K. S. , BANDARU P. R. , JIN S.
Published: March 2009

This research demonstrates the capability of controlled, focused ion beam (FIB)–assisted tailoring of morphologies in both multiwall carbon nanotubes (CNTs) and Y junction nonlinear CNT systems through defect engineering. We have shown that a 30 keV FIB Ga + ion beam at low ion milling currents of 1 pA can be used to partially reduce the CNT diameter, to provide electrical conduction bottleneck morphologies for linear CNTs, and to introduce both additive and subractive defects at Y junction locations of Y-CNT samples. Our aim is for this work to provide motivation for additional research to determine the effects of ion-beam-induced changes in modulating the physical and chemical properties of nanotubes.
LABEL-FREE BIOMOLECULAR DETECTION USING CARBON NANOTUBE FIELD EFFECT TRANSISTORS
Authors: BYON HYE RYUNG , KIM SUPHIL , CHOI HEE CHEUL
Published: March 2009

Carbon nanotube field effect transistor (FET) type biosensors have been widely investigated as one of the promising platforms for highly sensitive personalized disease-monitoring electronic devices. Combined with high level cutting edge information technology (IT) infra systems, carbon nanotube transistor biosensors afford a great opportunity to contribute to human disease care by providing early diagnostic capability. Several key prerequisites that should be clarified for the real application include sensitivity, reliability, reproducibility, and expandability to multiplex detection systems. In this brief review, we introduce the types, fabrication, and detection methods of single-walled carbon nanotube FET (SWNT-FET) devices. As surface functionalization of the devices by which nonspecific bindings (NSBs) are efficiently prohibited is also another important issue regarding reliable biosensors, we discuss several key strategies about surface passivation along with examples of various biomolecules such as proteins, DNA, small molecules, aptamers, viruses, and cancer and neurodegenerative disease markers which have been successfully sensed by SWNT-FET devices. Finally, we discuss proposed detection mechanisms, according to which strategies for fabricating sensor devices having high sensitivity are determined. Two main mechanisms — charge transfer (or electrostatic gate effect) and Schottky barrier effect, depending on the place where biomolecules are adsorbed — will be covered.
Mechanisms of human complement factor B induction in sepsis and inhibition by activated protein C
Authors: Goring Kim , Huang Yong , Mowat Connie , Léger Caroline , Lim Teik-How , Zaheer Raza , Mok Dereck , Tibbles Lee Anne , Zygun David , Winston Brent W.
Published: March 2009

To investigate the potential role of the local expression of alternative complement factor B (hBf) in human sepsis, we examined the induction of Bf gene expression in human peripheral blood monocytes (PBMCs) from patients with septic shock and the mechanisms of hBf gene regulation by tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and lipopolysaccharide (LPS) in human monocytes. PBMCs from septic shock patients showed increased hBf mRNA expression when compared with control patients. Costimulation with TNF-α and IFN-γ or stimulation with LPS demonstrated a time- and dose-dependent induction of hBf mRNA expression in human PBMCs. A region of the hBf promoter between −735 and +128 bp was found to mediate IFN-γ, TNF-α, and LPS responsiveness as well as the synergistic effect of IFN-γ/TNF-α on hBf promoter activity. Site-directed mutagenesis of a IFN-γ-activation site (GAS) cis element (−90 to −82 bp) abrogated IFN-γ responsiveness. Mutagenesis of a nuclear factor (NF)-κB cis element at −466 to −456 bp abrogated TNF-α and LPS responsiveness of the Bf promoter. Thus hBf gene expression is induced in PBMCs from septic shock patients, and the induction of hBf by IFN-γ, TNF-α, and LPS is through GAS and NF-κB cis-binding sites on the hBf promoter. Furthermore, activated protein C (APC) inhibited LPS-stimulated hBf promoter activity and protein expression in human monocytes suggesting that the beneficial effect of APC therapy in sepsis may in part be due to inhibition of complement induction and/or activation via the alternative pathway.
Regulation of cardiac fibroblast collagen synthesis by adenosine: roles for Epac and PI3K
Authors: Villarreal Francisco , Epperson Sara A. , Ramirez-Sanchez Israel , Yamazaki Katrina G. , Brunton Laurence L.
Published: March 2009

Rat cardiac fibroblasts (CF) express multiple adenosine (ADO) receptors. Pharmacological evidence suggests that activation of A2 receptors may inhibit collagen synthesis via adenylyl cyclase-induced elevation of cellular cAMP. We have characterized the signaling pathways involved in ADO-mediated inhibition of collagen synthesis in primary cultures of adult rat CF. ANG II stimulates collagen production in these cells. Coincubation with agents that elevate cellular cAMP [the ADO agonist, 5′- N-ethylcarboxamidoadensoine (NECA), and forskolin] inhibited the stimulatory effects of ANG II. However, direct stimulators and inhibitors of protein kinase A (PKA) did not alter ANG II-induced collagen synthesis, indicating that PKA does not mediate the inhibitory effects of NECA. Inhibitors of AMP-kinase (AMPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) do not alter NECA-inhibited collagen synthesis. However, activation of exchange factor directly activated by cAMP (Epac) mimicked the effects of NECA on ANG II-stimulated collagen synthesis. Inhibition of phosphoinositol-3 kinase (PI3K) reduced the inhibitory effects of NECA on ANG II-induced collagen synthesis, suggesting that NECA acts via PI3K. Furthermore, inhibition of PI3K also relieved the inhibitory effect of Epac activation on ANG II-stimulated collagen synthesis. Thus it appears that ADO activates the A2R-Gs-adenylyl cyclase pathway and that the resultant cAMP reduces collagen synthesis via a PKA-independent, Epac-dependent pathway that feeds through PI3K.
Voltage-gated sodium channel modulation by σ-receptors in cardiac myocytes and heterologous systems
Authors: Johannessen Molly , Ramachandran Subramaniam , Riemer Logan , Ramos-Serrano Andrea , Ruoho Arnold E. , Jackson Meyer B.
Published: March 2009

The σ-receptor, a broadly distributed integral membrane protein with a novel structure, is known to modulate various voltage-gated K+and Ca2+channels through a mechanism that involves neither G proteins nor phosphorylation. The present study investigated the modulation of the heart voltage-gated Na+channel (Nav1.5) by σ-receptors. The σ1-receptor ligands [SKF-10047 and (+)-pentazocine] and σ1/σ2-receptor ligands (haloperidol and ditolylguanidine) all reversibly inhibited Nav1.5 channels to varying degrees in human embryonic kidney 293 (HEK-293) cells and COS-7 cells, but the σ1-receptor ligands were less effective in COS-7 cells. The same four ligands also inhibited Na+current in neonatal mouse cardiac myocytes. In σ1-receptor knockout myocytes, the σ1-receptor-specific ligands were far less effective in modulating Na+current, but the σ1/σ2-receptor ligands modulated Na+channels as well as in wild type. Photolabeling with the σ1-receptor photoprobe [125I]-iodoazidococaine demonstrated that σ1-receptors were abundant in heart and HEK-293 cells, but scarce in COS-7 cells. This difference was consistent with the greater efficacy of σ1-receptor-specific ligands in HEK-293 cells than in COS-7 cells. σ-Receptors modulated Na+channels despite the omission of GTP and ATP from the patch pipette solution. σ-Receptor-mediated inhibition of Na+current had little if any voltage dependence and produced no change in channel kinetics. Na+channels represent a new addition to the large number of voltage-gated ion channels modulated by σ-receptors. The modulation of Nav1.5 channels by σ-receptors in the heart suggests an important pathway by which drugs can alter cardiac excitability and rhythmicity.
Perspectives in mammalian IGFBP-3 biology: local vs. systemic action
Authors: Yamada Paulette M. , Lee Kuk-Wha
Published: March 2009

Insulin-like growth factor (IGF) binding protein (IGFBP)-3 has traditionally been defined by its role as a binding protein and its association with IGF delivery and availability. Development of non-IGF binding IGFBP-3 analogs and the use of cell lines devoid of type 1 IGF receptors (IGF-R) have led to critical advances in the field of IGFBP-3 biology. These studies show that IGFBP-3 has IGF-independent roles in inhibiting cell proliferation in cancer cell lines. Nuclear transcription factor, retinoid X receptor (RXR)-α, and IGFBP-3 functionally interact to reduce prostate tumor growth and prostate-specific antigen in vivo. Moreover, IGFBP-3 inhibits insulin-stimulated glucose uptake into adipocytes independent of IGF. The purpose of this review is to highlight IGFBP-3 as a novel effector molecule and not just another “binding protein” by discussing its IGF-independent actions on metabolism and cell growth. Although this review presents studies that assume the role of IGFBP-3 as either an endocrine or autocrine/paracrine molecule, these systems may not exist as distinct entities, justifying the examination of IGFBP-3 in an integrated model. Also, we provide an overview of factors that regulate IGFBP-3 availability, including its production, methylation, and ubiquitination. We conclude with the role of IGFBP-3 in whole body systems and possible future applications of IGFBP-3 in physiology.
Bcl-2 family on guard at the ER
Authors: Szegezdi Eva , MacDonald David C. , Ní Chonghaile Tríona , Gupta Sanjeev , Samali Afshin
Published: March 2009

The endoplasmic reticulum (ER) is the main site for protein folding, lipid biosynthesis, and calcium storage in the cell. Disturbances of these critical cellular functions lead to ER stress. The ER responds to disturbances in its homeostasis by launching an adaptive signal transduction pathway, known as the unfolded protein response (UPR). The UPR strives to maintain ER function during stress; however, if the stress is not resolved, apoptotic responses are activated that involve cross talk between the ER and mitochondria. In addition, ER stress is also known to induce autophagy to counteract XBP-1-mediated ER expansion and assist in the degradation of unfolded proteins. One family of proteins involved in the regulation of apoptosis is that of B-cell lymphoma protein 2 (Bcl-2). Complex interactions among the three subgroups within the Bcl-2 family [the antiapoptotic, the multidomain proapoptotic, and the Bcl-2 homology domain 3 (BH3)-only members] control the signaling events of apoptosis upstream of mitochondrial outer membrane permeabilization. These proteins were found to have diverse subcellular locations to aid in the response to varied intrinsic and extrinsic stimuli. Of recent interest is the presence of the Bcl-2 family at the ER. Here, we review the involvement of proteins from each of the three Bcl-2 family subgroups in the maintenance of ER homeostasis and their participation in ER stress signal transduction pathways.
D1/D2-dopamine receptor agonist dihydrexidine stimulates inspiratory motor output and depresses medullary expiratory neurons
Authors: Lalley Peter M.
Published: March 2009

It is now accepted that dopamine plays an important neuromodulatory role in the central nervous control of respiration. D1, D2, and D4 subtypes of the receptor seem to be important players, but the assignment of various respiratory tasks to specific subtypes of the dopamine receptor is a work in progress. In the present investigation, dihydrexidine (DHD), a full dopamine receptor agonist with affinity for both D1- and D2-subtypes of receptor, was tested for its effects on inspiratory neurons and motor output and on membrane potential properties of medullary bulbospinal expiratory augmenting expiratory neurons in the pentobarbital anesthetized adult cat. The effects of DHD were compared with those of the highly selective D1-dopamine receptor (D1R) agonists SKF-38393 and 6-chloro-APB. DHD increased the intensity and duration of inspiratory motor output. Phrenic nerve discharge intensity was increased and prolonged, contributing to elevated inspiratory effort and duration when spontaneous breathing was monitored with tracheal pressure measurements. Intracellular recording from rostral medullary inspiratory neurons revealed that DHD, like SKF-38393, increases and prolongs inspiratory phase membrane depolarization, resulting in a longer and more intense discharge of action potentials. Remarkably, DHD had opposite effects on Aug-E neurons. Membrane potential was hyperpolarized, and action potential discharges were suppressed or abolished. In association with reduction of discharge intensity, action potential half width was reduced and after-hyperpolarization increased. The stimulatory action of DHD on inspiratory motor output is attributed to D1R effects, while the depression of Aug-E neurons seems to be linked to D2R actions on the postsynaptic membrane.
Social stress-induced bladder dysfunction: potential role of corticotropin-releasing factor
Authors: Wood Susan K. , Baez Madelyn A. , Bhatnagar Seema , Valentino Rita J.
Published: March 2009

Psychological stress can impact on visceral function with pathological consequences, although the mechanisms underlying this are poorly understood. Here we demonstrate that social stress produces marked changes in bladder structure and function. Male rats were subjected to repeated (7 days) social defeat stress using the resident-intruder model. Measurement of the voiding pattern indicated that social stress produced urinary retention. Consistent with this, bladder size was increased in rats exposed to social stress. Moreover, this was negatively correlated to the latency to assume a subordinate posture, implying an association between passive behavior and bladder dysfunction. In vivo cystometry revealed distinct changes in urodynamic function in rats exposed to social stress, including increased bladder capacity, micturition volume, intermicturition interval, and the presence of non-micturition-related contractions, resembling overactive bladder. In contrast to social stress, repeated restraint (7 days) did not affect voiding, bladder weight, or urodynamics. The stress-related neuropeptide corticotropin-releasing factor (CRF) is present in spinal projections of Barrington's nucleus that regulate the micturition reflex and has an inhibitory influence in this pathway. Social stress, but not restraint, increased the number of CRF-immunoreactive neurons in Barrington's nucleus. Additionally, social stress increased CRF mRNA in Barrington's nucleus. Together, the results imply that social stress-induced CRF upregulation in Barrington's nucleus neurons results in urinary retention and, eventually, bladder dysfunction, perhaps as a visceral component of a behavioral coping response. This mechanism may underlie dysfunctional voiding in children and/or contribute to the development of stress-induced bladder disorders in adulthood.