bluuebunny/crossref_metadata_2025 huggingface dataset:
CHARGE RADII OF β-STABLE NUCLEI
Authors: NIE G. K.
Published: August 2006

In a previous work it was shown that the radius of a nucleus R is determined by the α-cluster structure and can be estimated on the number of α-clusters disregarding the number of excess neutrons. A hypothesis was also made that the radius Rm of a β-stable isotope, which is actually measured at electron scattering experiments, is determined by the volume occupied by the matter of the core plus the volume occupied by the charge of the peripheral α-clusters. In this paper it is shown that the condition Rm = R restricts the number of excess neutrons filling the core to provide the β-stability. The number of peripheral clusters can vary from 1 to 5 and the value of R for heavy nuclei almost does not change, whereas the number of the excess neutrons should change with the number of peripheral clusters to provide the condition of Rm = R. It can explain the path of the β-stability and its width. The radii Rm of the stable isotopes with 12 ≤ Z ≤ 83 and the alpha-decay isotopes with 84 ≤ Z ≤ 116 that are stable to β-decay have been calculated.
NONLOCAL REGULARISATION OF NONCOMMUTATIVE FIELD THEORIES
Authors: GOVINDARAJAN T. R. , KÜRKÇÜOǦLU SEÇKIN , PANERO MARCO
Published: August 2006

We study noncommutative field theories, which are inherently nonlocal, using a Poincaré-invariant regularisation scheme which yields an effective, nonlocal theory for energies below a cutoff scale. After discussing the general features and the peculiar advantages of this regularisation scheme for theories defined in noncommutative spaces, we focus our attention on the particular case when the noncommutativity parameter is inversely proportional to the square of the cutoff, via a dimensionless parameter η. We work out the perturbative corrections at one-loop order for a scalar theory with quartic interactions, where the signature of noncommutativity appears in η-dependent terms. The implications of this approach, which avoids the problems related to uv–ir mixing, are discussed from the perspective of the Wilson renormalisation program. Finally, we remark about the generality of the method, arguing that it may lead to phenomenologically relevant predictions, when applied to realistic field theories.
STATISTICAL ENTROPY OF THE SCHWARZSCHILD BLACK HOLE
Authors: CADONI MARIANO
Published: August 2006

We derive the statistical entropy of the Schwarzschild black hole by considering the asymptotic symmetry algebra near the [Formula: see text] boundary of the spacetime at past null infinity. Using a two-dimensional description and the Weyl invariance of black hole thermodynamics this symmetry algebra can be mapped into the Virasoro algebra generating asymptotic symmetries of anti-de Sitter spacetime. Using Lagrangian methods we identify the stress–energy tensor of the boundary conformal field theory and calculate the central charge of the Virasoro algebra. The Bekenstein–Hawking result for the black hole entropy is regained using Cardy's formula. Our result strongly supports a nonlocal realization of the holographic principle.
ANALYSIS OF AN EXPERIMENTAL QUANTUM LOGIC GATE BY COMPLEMENTARY CLASSICAL OPERATIONS
Authors: HOFMANN HOLGER F. , OKAMOTO RYO , TAKEUCHI SHIGEKI
Published: August 2006

Quantum logic gates can perform calculations much more efficiently than their classical counterparts. However, the level of control needed to obtain a reliable quantum operation is correspondingly higher. In order to evaluate the performance of experimental quantum gates, it is therefore necessary to identify the essential features that indicate quantum coherent operation. In this paper, we show that an efficient characterization of an experimental device can be obtained by investigating the classical logic operations on a pair of complementary basis sets. It is then possible to obtain reliable predictions about the quantum coherent operations of the gate such as entanglement generation and Bell state discrimination even without performing these operations directly.
ANALYSIS OF HEAT CAPACITY OFYBa2Cu3O7-δSUPERCONDUCTORS: ROLE OF LATTICE AND ELECTRON CONTRIBUTION
Authors: VARSHNEY DINESH
Published: August 2006

Observed temperature-dependent heat capacity C (T) behavior of high-TcYBa2Cu3O7-δcuprate superconductors has been theoretically analyzed in the temperature domain 70 ≤ T ≤ 110 K . Calculations of C (T) have been made within the two component scheme: one is the Fermionic term and the other the Bosonic (phonon) contribution. While estimating the electronic term, we use a mean field step and follow two-fluid model below and above Tc. Later on, the lattice heat capacity is estimated within harmonic approximation for high temperature expansion (T > θ/2π), the model has only one free parameter, the moments of phonon density of states. Within the two-fluid model for electronic specific heat along with reported γ value leads to a sharp discontinuity at Tc. The Coulomb correlations and electron-phonon coupling strength have significant implications on the γ. Henceforth, the present numerical analysis of specific heat from the present model shows similar results as those revealed from experiments. The accurate fitting of the specific heat data reveals that it is possible to decompose the documented specific heat into dominant lattice contribution and electronic channel. However, the specific heat from electronic term is only a fraction of lattice specific heat in YBa2Cu3O7-δhigh-Tcsuperconductors.
COOPER PAIRS AS BOSONS
Authors: de LLANO M. , SEVILLA F. J. , TAPIA S.
Published: August 2006

Although BCS pairs of fermions are known to obey neither Bose–Einstein (BE) commutation relations nor BE statistics, we show how Cooper pairs (CPs), whether the simple original ones or the CPs recently generalized in a many-body Bethe–Salpeter approach, being clearly distinct from BCS pairs at least obey BE statistics. Hence, contrary to widespread popular belief, CPs can undergo BE condensation to account for superconductivity if charged, as well as for neutral-atom fermion superfluidity where CPs, but uncharged, are also expected to form.
CAPACITIES AND GAMES ON LATTICES: A SURVEY OF RESULTS
Authors: GRABISCH MICHEL
Published: August 2006

We provide a survey of recent developments about capacities (or fuzzy measures) and cooperative games in characteristic form, when they are defined on more general structures than the usual power set of the universal set, namely lattices. In a first part, we give various possible interpretations and applications of these general concepts, and then we elaborate about the possible definitions of usual tools in these theories, such as the Choquet integral, the Möbius transform, and the Shapley value.
ANSWER SET PROGRAMMING AND COMBINATORIAL MULTICRITERIA DECISION MAKING
Authors: GRABOŚ RAFAL
Published: August 2006

The majority of approaches to multicriteria optimization are based on quantitative representations of preferences of a decision maker, in which numerical procedures of multicriteria analysis are used for aggregation purposes. However, very often qualitative data cannot be known in terms of absolute values so that a qualitative approach is needed. Moreover, the multicriteria methods are directly applicable when alternatives are individuals-then they may be explicitly listed and ordered by an agent. However, sometimes the set of alternatives has combinatorial structure and it must be selected from the set of Cartesian products of value domains of attributes satisfying certain constraints. Then, the space of possible alternatives has a size exponential in the number of variables and ranking all alternatives explicitly is a complex and tedious task. In this paper we propose logic programming with ordered disjunction as a qualitative approach to combinatorial multicriteria decision making, allowing a concise representation of the preference structures, and a human-like form of expressions, being close to natural language, hence providing a good readability and simplicity. A combinatorial multicriteria decision making problem is encoded as a logic program, in which preferences of the decision maker are represented qualitatively. The optimal decision corresponds exactly to the preferred answer set of the program, obtained via the well-known methods of multicriteria analysis.
MCDM AGGREGATION MODEL USING SITUATIONAL ME-OWA AND ME-OWGA OPERATORS
Authors: CHENG CHING-HSUE , CHANG JING-RONG
Published: August 2006

OWA (Ordered Weighted Averaging) aggregation operators have been extensively adopted to handle MCDM (multiple criteria decision making) problems. However, additive or multiplicative preferences should be aggregated with feasible operators. To resolve this problem, this study proposes a new MCDM aggregation model, capable of handling situational group MCDM problems based on the ME-OWA (maximal entropy ordered weighted averaging) and ME-OWGA (maximal entropy ordered weighted geometric averaging) operators. The proposed model is also applied not only to evaluate the service quality of airlines but also select the most appropriate desalination technology. The results of previous MCDM methods can be covered with proposed model.
CONSISTENCY IN THE ANALYTIC HIERARCHY PROCESS: A NEW APPROACH
Authors: ALONSO JOSÉ ANTONIO , LAMATA M. TERESA
Published: August 2006

In this paper, we present a statistical criterion for accepting/rejecting the pairwise reciprocal comparison matrices in the analytic hierarchy process. We have studied the consistency in random matrices of different sizes. We do not agree with the traditional criterion of accepting matrices due to their inflexibility and because it is too restrictive when the size of the matrix increases. Our system is capable of adapting the acceptance requirements to different scopes and consistency necessities. The advantages of our consistency system are the introduction of adaptability in the acceptance criterion and the simplicity of the index we have used, the eigenvalue (λmax) and the simplicity of the criterion.
ATTRIBUTE REDUCTION IN VARIABLE PRECISION ROUGH SET MODEL
Authors: INUIGUCHI MASAHIRO
Published: August 2006

In this paper, attribute reduction in variable precision rough set model is discussed. Several kinds of reducts preserving some of lower approximations, upper approximations, boundary regions and the unpredictable region are discussed. Relations among those kinds of reducts are investigated. As a basis for reduct computation, Boolean function representations of the preservation of lower approximations, upper approximations, boundary regions and the unpredictable region are discussed. Throughout this paper, the great difference between the analysis using variable precision rough sets and the classical rough set analysis is emphasized.
KERNEL METHODS FOR CLUSTERING: COMPETITIVE LEARNING AND c-MEANS
Authors: INOKUCHI RYO , MIYAMOTO SADAAKI
Published: August 2006

Recently kernel methods in support vector machines have widely been used in machine learning algorithms to obtain nonlinear models. Clustering is an unsupervised learning method which divides whole data set into subgroups, and popular clustering algorithms such as c-means are employing kernel methods. Other kernel-based clustering algorithms have been inspired from kernel c-means. However, the formulation of kernel c-means has a high computational complexity. This paper gives an alternative formulation of kernel-based clustering algorithms derived from competitive learning clustering. This new formulation obviously uses sequential updating or on-line learning to avoid high computational complexity. We apply kernel methods to related algorithms: learning vector quantization and self-organizing map. We moreover consider kernel methods for sequential c-means and its fuzzy version by the proposed formulation.
WATERMARKING NUMERICAL DATA IN THE PRESENCE OF NOISE
Authors: SEBÉ FRANCESC , DOMINGO-FERRER JOSEP , CASTELLÀ-ROCA JORDI
Published: August 2006

Data mining aims at extracting knowledge from data. Sometimes this requires the data owner to make data available to the data analyst. Unless the analyst is trusted by the data owner, the latter may wish to have his intellectual property rights protected. Watermarking is a way to provide some protection, not only for multimedia data, but also for numerical data. It consists of imperceptibly embedding a secret mark into the data to be protected. The mark can later be used to resolve any subsequent disputes on data ownership. This paper presents a watermarking method that embeds a watermark into each attribute of a multivariate continuous numerical dataset. This watermarking method is shown to be robust against random noise addition attacks. Data quality is assured to the extent that the watermarked data nearly preserve the attribute means and the covariance matrix from the original dataset. Our proposal is the first known watermarking system for multivariate numerical datasets with such robustness and quality properties.
CONTENT-BASED IMAGE RETRIEVAL OF KAOU IMAGES BY RELAXATION MATCHING OF REGION FEATURES
Authors: KAMEYAMA KEISUKE , KIM SOO-NYOUN , SUZUKI MICHITERU , TORAICHI KAZUO , YAMAMOTO TAKASHI
Published: August 2006

An improvement to the content-based image retrieval (CBIR) system for kaou images which has been developed by the authors group is introduced. Kaous are handwritten monograms found on old Japanese documents in a Chinese character-like shapes with artistic decorations. Kaous play an important role in the research of historical documents, which involve browsing and comparison of numerous samples. In this work, a novel method of kaou image modeling for CBIR is introduced, which incorporates the shade information of a closed kaou region in addition to the conventionally used contour characteristics. Dissimilarity of query and dictionary images were calculated as a weighted sum of elementary differences in the positions, contour shapes and colors of the component regions. These elementary differences were evaluated using relaxation matching and empirically defined distance functions. In the experiments, a set of 2455 kaou images were used. It was found that apparently similar kaou images could be retrieved by the proposed method, improving the retrieval quality. .
INTERVAL METHODS IN KNOWLEDGE REPRESENTATION
Authors: Kreinovich Vladik
Published: August 2006

This section is maintained by Vladik Kreinovich. Please send your abstracts (or copies of papers that you want to see reviewed here) to vladik@utep.edu, or by regular mail to: V. Kreinovich, Department of Computer Science, University of Texas, El Paso, TX 79968, USA.
PERTURBED SCHRÖDINGER EQUATION WITH SINGULAR POTENTIAL AND INITIAL DATA
Authors: STOJANOVIĆ MIRJANA
Published: August 2006

We consider linear Schrödinger equation perturbed by delta distribution with singular potential and the initial data. Due to the singularities appearing in the equation, we introduce two kinds of approximations: the parameter's approximation for potential and the initial data given by mollifiers of different growth and the approximation for the Green function for Schrödinger equation with regularized derivatives. These approximations reduce the perturbed Schrödinger equation to the family of singular integral equations. We prove the existence-uniqueness theorems in Colombeau space [Formula: see text], 1 ≤ p,q ≤ ∞, employing novel stability estimates (w.r.) to singular perturbations for ε → 0, which imply the statements in the framework of Colombeau generalized functions. In particular, we prove the existence-uniqueness result in [Formula: see text] and [Formula: see text] algebra of Colombeau.
MULTIPLE HOMOCLINICS IN A HAMILTONIAN SYSTEM WITH ASYMPTOTICALLY OR SUPER LINEAR TERMS
Authors: DING YANHENG
Published: August 2006

This paper is concerned with homoclinic orbits in the Hamiltonian system [Formula: see text] where H is periodic in t with Hz(t, z) = L(t)z + Rz(t, z), Rz(t, z) = o(|z|) as z → 0. We find a condition on the matrix valued function L to describe the spectrum of operator [Formula: see text] so that a proper variational formulation is presented. Supposing Rz is asymptotically linear as |z| → ∞ and symmetric in z, we obtain infinitely many homoclinic orbits. We also treat the case where Rz is super linear as |z| → ∞ with assumptions different from those studied previously in relative work, and prove existence and multiplicity of homoclinic orbits. Our arguments are based on some recent information on strongly indefinite functionals in critical point theory.
GLOBAL STEADY-STATE STABILIZATION AND CONTROLLABILITY OF 1D SEMILINEAR WAVE EQUATIONS
Authors: CORON JEAN-MICHEL , TRÉLAT EMMANUEL
Published: August 2006

This paper is concerned with the exact boundary controllability of semilinear wave equations in one space dimension. We prove that it is possible to move from any steady-state to any other one by means of a boundary control, provided that they are in the same connected component of the set of steady-states. The proof is based on an expansion of the solution in a one-parameter Riesz basis of generalized eigenvectors, and on an effective feedback stabilization procedure which is implemented.
QUASISYMMETRIC SEWING IN RIGGED TEICHMÜLLER SPACE
Authors: RADNELL DAVID , SCHIPPERS ERIC
Published: August 2006

One of the basic geometric objects in conformal field theory (CFT) is the moduli space of Riemann surfaces whose n boundaries are "rigged" with analytic parametrizations. The fundamental operation is the sewing of such surfaces using the parametrizations to identify points. An alternative model is the moduli space of n-punctured Riemann surfaces together with local biholomorphic coordinates at the punctures. We refer to both of these moduli spaces as the "rigged Riemann moduli space".

By generalizing to quasisymmetric boundary parametrizations, and defining rigged Teichmüller spaces in both the border and puncture pictures, we prove the following results: (1) The Teichmüller space of a genus-g surface bordered by n closed curves covers the rigged Riemann and rigged Teichmüller moduli spaces of surfaces of the same type, and induces complex manifold structures on them; (2) With this complex structure, the sewing operation is holomorphic; (3) The border and puncture pictures of the rigged moduli and rigged Teichmüller spaces are biholomorphically equivalent.

These results are necessary in rigorously defining CFT (in the sense of G. Segal), as well as for the construction of CFT from vertex operator algebras.
The New Bioinformatics: Integrating Ecological Data from the Gene to the Biosphere
Authors: Jones Matthew B. , Schildhauer Mark P. , Reichman O.J. , Bowers Shawn
Published: August 2006

Bioinformatics, the application of computational tools to the management and analysis of biological data, has stimulated rapid research advances in genomics through the development of data archives such as GenBank, and similar progress is just beginning within ecology. One reason for the belated adoption of informatics approaches in ecology is the breadth of ecologically pertinent data (from genes to the biosphere) and its highly heterogeneous nature. The variety of formats, logical structures, and sampling methods in ecology create significant challenges. Cultural barriers further impede progress, especially for the creation and adoption of data standards. Here we describe informatics frameworks for ecology, from subject-specific data warehouses, to generic data collections that use detailed metadata descriptions and formal ontologies to catalog and cross-reference information. Combining these approaches with automated data integration techniques and scientific workflow systems will maximize the value of data and open new frontiers for research in ecology.
The Role of Hybridization in the Evolution of Reef Corals
Authors: Willis Bette L. , van Oppen Madeleine J.H. , Miller David J. , Vollmer Steve V. , Ayre David J.
Published: August 2006

The importance of hybridization in the evolution of plant species is widely accepted, but its contributions to animal species evolution remain less recognized. Here we review evidence that hybridization has contributed to the evolution of reef corals, a group underpinning the coral reef ecosystem. Increasingly threatened by human and climate-related impacts, there is need to understand the evolutionary processes that have given rise to their diversity and contribute to their resilience. Reticulate evolutionary pathways among the ecologically prominent, mass-spawning genus Acropora suggest that hybridization, although rare on ecological timescales, has been instrumental in their diversification on evolutionary timescales. Evidence that coral hybrids colonize marginal habitats distinct from those of parental species' and that hybridization may be more frequent at peripheral boundaries of species' ranges supports a role for hybridization in range expansion and adaptation to changing environments. We conclude that outcomes of hybridization are significant for the future resilience of reef corals and warrant inclusion in conservation strategies.
Toward a Comprehensive Set of Asthma Susceptibility Genes
Authors: Bossé Yohan , Hudson Thomas J.
Published: August 2006

Epidemiological and twin studies have demonstrated that asthma is under genetic and environmental influences. Numerous candidate gene association studies as well as genome-wide linkage scans have followed, aiming to elucidate the genetic architecture underlying this complex disease. Several promising asthma susceptibility genes were identified, and a comprehensive catalogue of these genes seems a realistic goal within 5 to 10 years. However, a key challenge is to understand the combination of genes and environmental factors that gives rise to the disease in a specific individual. Currently, most of the reports of asthma susceptibility genes are either preliminary or controversial, with little knowledge about the genetic mechanisms leading to abnormal function of the gene that promotes the development of asthma. Replications of published associations are relatively few. Many factors, including the inherent complexity of asthma as well as methodological issues, can explain these inconsistencies. Promising genetic tools are emerging with the completion of the International HapMap Project that will increase the scope of gene-discovery investigations. It is hoped that these tools, combined with validation studies in additional populations, will enable the creation of a comprehensive catalogue of susceptibility genes for asthma. Notwithstanding the difficulties in making sense of the vast amount of new genetic data, we already see the emergence of new biological pathways of atopy, airway remodeling, and asthma that may lead to novel therapeutic approaches.
Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11β-HSD-2 activity
Authors: Thiesson Helle C. , Jensen Boye L. , Bistrup Claus , Ottosen Peter D. , McNeilly Alison D. , Andrew Ruth , Seckl Jonathan , Skøtt Ole
Published: August 2006

Downregulation of the renal glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2) during liver cirrhosis may allow activation of the mineralocorticoid receptor (MR) by glucocorticoids and contribute to sodium retention. We tested this hypothesis in male Wistar rats with decompensated liver cirrhosis and ascites 7 wk after bile duct ligation (BDL). Renal 11β-HSD-2 mRNA, protein, and activity were significantly decreased in decompensated rats. The urinary Na+/K+ ratio was reduced by 40%. Renal epithelial sodium channel (ENaC) mRNA and immunostaining were only slightly affected. Complete metabolic studies, including fecal excretion, showed that the BDL rats had avid renal sodium retention. Treatment of the BDL rats with dexamethasone suppressed endogenous glucocorticoid production, normalized total sodium balance and renal sodium excretion, and reduced ascites formation to the same degree as direct inhibition of MR with K-canrenoate. Total potassium balance was negative in the BDL rats, whereas renal potassium excretion was unchanged. In the distal colon, expression of ENaC was increased in BDL rats. Fecal potassium excretion was increased in cirrhotic rats, and this was corrected by treatment with K-canrenoate but not dexamethasone. We conclude that development of sodium retention and decompensation in cirrhotic rats is associated with downregulation of renal 11β-HSD-2 activity and inappropriate activation of renal sodium reabsorption by endogenous glucocorticoids. In addition, the overall potassium loss in the BDL model is due to increased fecal potassium excretion, which is associated with upregulation of ENaC in distal colon.
Electrophysiological Mechanisms of Delayed Excitotoxicity: Positive Feedback Loop Between NMDA Receptor Current and Depolarization-Mediated Glutamate Release
Authors: Norris C. M. , Blalock E. M. , Thibault O. , Brewer L. D. , Clodfelter G. V. , Porter N. M. , Landfield P. W.
Published: August 2006

Delayed excitotoxic neuronal death after insult from exposure to high glutamate concentrations appears important in several CNS disorders. Although delayed excitotoxicity is known to depend on NMDA receptor (NMDAR) activity and Ca2+elevation, the electrophysiological mechanisms underlying postinsult persistence of NMDAR activation are not well understood. Membrane depolarization and nonspecific cationic current in the postinsult period were reported previously, but were not sensitive to NMDAR antagonists. Here, we analyzed mechanisms of the postinsult period using parallel current- and voltage-clamp recording and Ca2+imaging in primary hippocampal cultured neurons. We also compared more vulnerable older neurons [about 22 days in vitro (DIV)] to more resistant younger (about 15 DIV) neurons, to identify processes selectively associated with cell death in older neurons. During exposure to a modest glutamate insult (20 μM, 5 min), similar degrees of Ca2+elevation, membrane depolarization, action potential block, and increased inward current occurred in younger and older neurons. However, after glutamate withdrawal, these processes recovered rapidly in younger but not in older neurons. The latter also exhibited a concurrent postinsult increase in spontaneous miniature excitatory postsynaptic currents, reflecting glutamate release. Importantly, postinsult NMDAR antagonist administration reversed all of these persisting responses in older cells. Conversely, repolarization of the membrane by voltage clamp immediately after glutamate exposure reversed the NMDAR-dependent Ca2+elevation. Together, these data suggest that, in vulnerable neurons, excitotoxic insult induces a sustained positive feedback loop between NMDAR-dependent current and depolarization-mediated glutamate release, which persists after withdrawal of exogenous glutamate and drives Ca2+elevation and delayed excitotoxicity.
Δ9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria
Authors: Jia Wentao , Hegde Venkatesh L. , Singh Narendra P. , Sisco Daniel , Grant Steven , Nagarkatti Mitzi , Nagarkatti Prakash S.
Published: August 2006

Plant-derived cannabinoids, including Δ9-tetrahydrocannabinol (THC), induce apoptosis in leukemic cells, although the precise mechanism remains unclear. In the current study, we investigated the effect of THC on the upstream and downstream events that modulate the extracellular signal-regulated kinase (ERK) module of mitogen-activated protein kinase pathways primarily in human Jurkat leukemia T cells. The data showed that THC down-regulated Raf-1/mitogen-activated protein kinase/ERK kinase (MEK)/ERK/RSK pathway leading to translocation of Bad to mitochondria. THC also decreased the phosphorylation of Akt. However, no significant association of Bad translocation with phosphatidylinositol 3-kinase/Akt and protein kinase A signaling pathways was noted when treated cells were examined in relation to phosphorylation status of Bad by Western blot and localization of Bad to mitochondria by confocal analysis. Furthermore, THC treatment decreased the Bad phosphorylation at Ser112 but failed to alter the level of phospho-Bad on site Ser136 that has been reported to be associated with phosphatidylinositol 3-kinase/Akt signal pathway. Jurkat cells expressing a constitutively active MEK construct were found to be resistant to THC-mediated apoptosis and failed to exhibit decreased phospho-Bad on Ser112 as well as Bad translocation to mitochondria. Finally, use of Bad small interfering RNA reduced the expression of Bad in Jurkat cells leading to increased resistance to THC-mediated apoptosis. Together, these data suggested that Raf-1/MEK/ERK/RSK-mediated Bad translocation played a critical role in THC-induced apoptosis in Jurkat cells. (Mol Cancer Res 2006;4(8):549–62)
Tumor Necrosis Factor-α Differentially Modulates CD44 Expression in Ovarian Cancer Cells
Authors: Muthukumaran Neelakandan , Miletti-González Karl E. , Ravindranath Abhilash K. , Rodríguez-Rodríguez Lorna
Published: August 2006

Chronic inflammation is implicated in the pathophysiology of ovarian cancer. Tumor necrosis factor-α (TNF-α), a major inflammatory cytokine, is abundant in the ovarian cancer microenvironment. TNF-α modulates the expression of CD44 in normal T lymphocytes and CD44 is implicated in ovarian carcinogenesis and metastases. However, little is known about the role of TNF-α in CD44 expression of cancer cells. Recent clinical work using TNF-α inhibitors for the treatment of ovarian cancer makes the study of TNF-α interactions with CD44 crucial to determining treatment a success or a failure. We studied the effect of TNF-α on ovarian cancer cells viability, CD44 expression, and in vitro migration/invasion. Our results revealed that TNF-α differentially modulates the expression of CD44 in TNF-α-resistant ovarian cancer cells, affecting their in vitro migration, invasion, and binding to hyaluronic acid. TNF-α up-regulation of CD44 expression was dependent on the activation of c-Jun NH2-terminal kinase (JNK) and this activation was accompanied by an increase in their invasive phenotype. On the contrary, if TNF-α failed to induce JNK phosphorylation, the end result was down-regulation of both CD44 expression and the invasive phenotype. These results were confirmed by the use of JNK inhibitors and a TNF receptor competitive inhibitor. (Mol Cancer Res 2006;4(8):511–20)
Mitotic Arrest, Apoptosis, and Sensitization to Chemotherapy of Melanomas by Methionine Deprivation Stress
Authors: Kokkinakis Demetrius M. , Brickner Anthony G. , Kirkwood John M. , Liu XiaoYan , Goldwasser Jason E. , Kastrama Anastasiya , Sander Cindy , Bocangel Dora , Chada Sunil
Published: August 2006

Methionine deprivation stress (MDS) eliminates mitotic activity in melanoma cells regardless of stage, grade, or TP53 status, whereas it has a negligible effect on normal skin fibroblasts. In most cases, apoptosis accounts for the elimination of up to 90% of tumor cells from the culture within 72 hours after MDS, leaving a scattered population of multinucleated resistant cells. Loss of mitosis in tumor cells is associated with marked reduction of cyclin-dependent kinase (CDK) 1 transcription and/or loss of its active form (CDK1-P-Thr161), which is coincident with up-regulation of CDKN1A, CDKN1B, and CDKN1C (p21, p27, and p57). Expression of the proapoptotic LITAF, IFNGR, EREG, TNFSF/TNFRSF10 and TNFRSF12, FAS, and RNASEL is primarily up-regulated/induced in cells destined to undergo apoptosis. Loss of Aurora kinase B and BIRC5, which are required for histone H3 phosphorylation, is associated with the accumulation of surviving multinucleated cells. Nevertheless, noncycling survivors of MDS are sensitized to temozolomide, carmustin, and cisplatin to a much greater extent than normal skin fibroblasts possibly because of the suppression of MGMT/TOP1/POLB, MGMT/RAD52/RAD54, and cMET/RADD52, respectively. Sensitivity to these and additional genotoxic agents and radiation may also be acquired due to loss of cMET/OGG1, reduced glutathione reductase levels, and a G2-phase block that is a crucial step in the damage response associated with enhancement of drug toxicity. Although the genes controlling mitotic arrest and/or apoptosis in response to low extracellular methionine levels are unknown, it is likely that such control is exerted via the induction/up-regulation of tumor suppressors/growth inhibitor genes, such as TGFB, PTEN, GAS1, EGR3, BTG3, MDA7, and the proteoglycans (LUM, BGN, and DCN), as well as the down-regulation/loss of function of prosurvival genes, such as NFκB, MYC, and ERBB2. Although MDS targets several common genes in tumors, mutational variability among melanomas may decide which metabolic and signal transduction pathways will be activated or shutdown. (Mol Cancer Res 2006;4(8):575–89)
Cyclooxygenase-2 Is Involved in S100A2-Mediated Tumor Suppression in Squamous Cell Carcinoma
Authors: Tsai Wan-Chi , Tsai Sen-Tien , Jin Ying-Tai , Wu Li-Wha
Published: August 2006

S100A2 is considered a putative tumor suppressor due to its loss or down-regulation in several cancer types. However, no mechanism has been described for the tumor suppressor role of S100A2. In this study, ectopic expression of S100A2 in the human malignant squamous cell carcinoma cell line KB resulted in a significant inhibition of proliferation, migration, and invasion. Moreover, S100A2 significantly reduced the number of colonies (≥0.5 mm) formed in semisolid agar and decreased tumor growth and burden in nude mice. cDNA microarray analysis was used to compare mRNA expression profiles of vector- and S100A2-expressing isogenic cells. Among the genes deregulated by S100A2, the expression of cyclooxygenase-2 (COX-2) mRNA was significantly suppressed by S100A2 (2.4-fold). Western blot analysis confirmed that S100A2 reduced the expression of COX-2 protein in stably and transiently transfected KB and RPMI-2650 cells. COX-2 is frequently overexpressed in various types of cancer and plays an important role in tumor progression. Partial restoration of COX-2 expression attenuated the antitumor effect of S100A2 both in vitro and in vivo. Although the interplay between S100A2 and COX-2 remains to be clarified, these findings first showed a potent antitumor role of S100A2 in squamous cell carcinoma partly via reduced expression of COX-2. (Mol Cancer Res 2006;4(8):539–47)
Evolution of the Neurotrophin Signaling System in Invertebrates
Authors: Bothwell Mark
Published: August 2006

Nucleotide sequences encoding orthologs of neurotrophins and their receptors, p75NTR and Trk receptors, have been identified in the sea urchin Strongylocentrotus purpuratus, and the acorn worm, Saccoglossus kowalevskii, whereas the ascidian (sea squirt) species Ciona intestinalis and Ciona savignii appear to lack such orthologs. These results suggest that a functional neurotrophin system was already present at the beginning of deuterostome evolution, but was lost in ascidians. Remarkably, it appears that evolution of a p75NTR ortholog represented one of the earliest events in the expansion of the tumor necrosis factor receptor superfamily.
Formation and Evolution of the Chordate Neurotrophin and Trk Receptor Genes
Authors: Hallböök Finn , Wilson Karen , Thorndyke Mike , Olinski Robert P.
Published: August 2006

Neurotrophins are structurally related neurotrophic polypeptide factors that regulate neuronal differentiation and are essential for neuronal survival, neurite growth and plasticity. It has until very recently been thought that the neurotrophin system appeared with the vertebrate species, but identification of a cephalochordate neurotrophin receptor (Trk), and more recently neurotrophin sequences in several genomes of deuterostome invertebrates, show that the system already existed at the stem of the deuterostome group. Comparative genomics supports the hypothesis that two whole genome duplications produced many of the vertebrate gene families, among those the neurotrophin and Trk families. It remains to be proven to what extent the whole genome duplications have driven macroevolutionary change, but it appears certain that the formation of the multi-gene copy neurotrophin and Trk receptor families at the stem of vertebrates has provided a foundation from which the various functions and pleiotropic effects produced by each of the four extant neurotrophins have evolved.
Tracing the Evolution and Function of the Trk Superfamily of Receptor Tyrosine Kinases
Authors: Sossin Wayne S.
Published: August 2006

Most growth factors and their receptors have been strongly conserved during evolution. In contrast, Trks (Tropomyosin-related kinases) and related receptors in the Trk superfamily, Rors (receptor tyrosine kinase-like orphan receptors), Musks (muscle specific kinases) and Ddrs (discoidin domain receptor family), appear to be ancient, but their function has been lost in multiple lineages and the roles for the receptors have been modified over time. We will trace the evolution of the Trk superfamily and discuss possible conserved functional roles, including a unifying theme of target recognition by growing axons. We present an analogy between the evolution of G-protein-coupled receptors and receptor tyrosine kinases (RTKs), proposing that an important driving force for the divergence of receptors is the ease of divergence of their ligands.
Comparative Analysis of Neurotrophin Receptors and Ligands in Vertebrate Neurons: Tools for Evolutionary Stability or Changes in Neural Circuits?
Authors: von Bartheld Christopher S. , Fritzsch Bernd
Published: August 2006

To better understand the role of multiple neurotrophin ligands and their receptors in vertebrate brain evolution, we examined the distribution of trk neurotrophin receptors in representatives of several vertebrate classes. Trk receptors are largely expressed in homologous neuronal populations among different species/classes of vertebrates. In many neurons, trkB and trkC receptors are co-expressed. TrkB and trkC receptors are primarily found in neurons with more restricted, specialized dendritic and axonal fields that are thought to be involved in discriminative or ‘analytical’ functions. The neurotrophin receptor trkA is expressed predominantly in neurons with larger, overlapping dendritic fields with more heterogeneous connections (‘integrative’ or ‘modulatory’ systems) such as nociceptive and sympathetic autonomic nervous system, locus coeruleus and cholinergic basal forebrain. Surveys of trk receptor expression and function in the peripheral nervous system of different vertebrate classes reveal trends ranging from dependency on a single neurotrophin to a more complex dependency on increasing numbers of neurotrophins and their receptors, for example, in taste and inner ear innervation. Gene deletion studies in mice provide evidence for a complex regulation of neuronal survival of sensory ganglion cells by different neurotrophins. Although expression of neurotrophins and their receptors is predominantly conserved in most circuits, increasing diversity of neurotrophin ligands and their receptors and a more complex dependency of neurons on neurotrophins might have facilitated the formation of at least some new neuronal entities.
Neurotrophic and Gliatrophic Contexts in Drosophila
Authors: Hidalgo Alicia , Learte Anabel R. , McQuilton Peter , Pennack Jenny , Zhu Bangfu
Published: August 2006

Trophic interactions in the vertebrate nervous system enable the adjustment of cell number and axon guidance, targeting and connectivity. Computational analysis of the sequenced Drosophila genome failed to identify some of the main trophic factors, the neuregulins and neurotrophins, as well as many other genes. This provoked speculations that the Drosophila nervous system might not require such regulative interactions. Here we review abundant cellular, genetic and functional data that demonstrate the existence of both neurotrophic and gliatrophic interactions in the Drosophila nervous system. Glial survival is maintained by the epidermal growth factor receptor (EGFR) signaling pathway in response to the ligands Spitz, a transforming growth factor-α (TGF-α) signaling molecule, and Vein, a neuregulin homologue. Cellular and genetic evidence predicts the existence of neuronal trophic factors operating at least in the Drosophila embryo during axon guidance and, in the visual system, during the targeting of retinal axons in the brain.
Evolution of the GDNF Family Ligands and Receptors
Authors: Airaksinen Matti S. , Holm Liisa , Hätinen Tuomas
Published: August 2006

Four different ligand-receptor binding pairs of the GDNF (glial cell line-derived neurotrophic factor) family exist in mammals, and they all signal via the transmembrane RET receptor tyrosine kinase. In addition, GRAL (GDNF Receptor Alpha-Like) protein of unknown function and Gas1 (growth arrest specific 1) have GDNF family receptor (GFR)-like domains. Orthologs of the four GFRα receptors, GRAL and Gas1 are present in all vertebrate classes. In contrast, although bony fishes have orthologs of all four GDNF family ligands (GFLs), one of the ligands, neurturin, is absent in clawed frog and another, persephin, is absent in the chicken genome. Frog GFRα2 has selectively evolved possibly to accommodate GDNF as a ligand. The key role of GDNF and its receptor GFRα1 in enteric nervous system development is conserved from zebrafish to humans. The role of neurturin, signaling via GFRα2, for parasympathetic neuron development is conserved between chicken and mice. The role of artemin and persephin that signal via GFRα3 and GFRα4, respectively, is unknown in non-mammals. The presence of RET- and GFR-like genes in insects suggests that a ProtoGFR and a ProtoRET arose early in the evolution of bilaterian animals, but when the ProtoGFL diverged from existing transforming growth factor (TGFβ)-like proteins remains unclear. The four GFLs and GFRαs were presumably generated by genome duplications at the origin of vertebrates. Loss of neurturin in frog and persephin in chicken suggests functional redundancy in early tetrapods. Functions of non-mammalian GFLs and prechordate RET and GFR-like proteins remain to be explored.
Building Complex Brains – Missing Pieces in an Evolutionary Puzzle
Authors: Jaaro Hanna , Fainzilber Mike
Published: August 2006

The mechanisms underlying evolution of complex nervous systems are not well understood. In recent years there have been a number of attempts to correlate specific gene families or evolutionary processes with increased brain complexity in the vertebrate lineage. Candidates for evocation of complexity include genes involved in regulating brain size, such as neurotrophic factors or microcephaly-related genes; or wider evolutionary processes, such as accelerated evolution of brain-expressed genes or enhanced RNA splicing or editing events in primates. An inherent weakness of these studies is that they are correlative by nature, and almost exclusively focused on the mammalian and specifically the primate lineage. Another problem with genomic analyses is that it is difficult to identify functionally similar yet non-homologous molecules such as different families of cysteine-rich neurotrophic factors in different phyla. As long as comprehensive experimental studies of these questions are not feasible, additional perspectives for evolutionary and genomic studies will be very helpful. Cephalopod mollusks represent the most complex nervous systems outside the vertebrate lineage, thus we suggest that genome sequencing of different mollusk models will provide useful insights into the evolution of complex brains.
Familial Risks for Epilepsy among Siblings Based on Hospitalizations in Sweden
Authors: Hemminki Kari , Li Xinjun , Johansson Sven-Erik , Sundquist Kristina , Sundquist Jan
Published: August 2006

Purpose: Epilepsy is a common disabling condition, with high heritability according to twin studies. Characterization of familial risks for common subtypes of epilepsy will advance the search for the heritable causes of these conditions and their underlying mechanisms. We aim at defining familial risks for siblings to be hospitalized because of epilepsy. Methods: A nationwide ad hoc epilepsy database was constructed by linking the Multigeneration Register on 0- to 69-year-old siblings to the Hospital Discharge Register for data on epilepsies covering the years 1987–2001. Standardized risk ratios (SIRs) were calculated for affected sibling pairs by comparing them to those whose siblings had no epilepsy. Results: Among a total of 26,799 hospitalized cases, 598 affected siblings were identified with a familial SIR of 2.35; the SIR was highest at ages 0–4 years (6.82). Infantile spasms showed the highest risk for any subtype (10.45), when a co-sibling was diagnosed with any epilepsy. When both siblings were diagnosed with a concordant (same) subtype of epilepsy, the SIRs were high, i.e. 8.43 for generalized idiopathic epilepsy, 2.56 for partial epilepsy, 24.72 for status epilepticus and 24.39 for other epilepsies. Generalized idiopathic epilepsy was also associated with grand mal (4.06) and other epilepsies (7.61). The numbers of cases were small but concordant diagnoses always showing higher SIRs compared with discordant diagnoses. Conclusions: Within the limits of the present sample size, our results suggest high familial aggregation for certain subtypes of epilepsy for which distinct genetic mechanisms may underlie.
Family History Associated with Improved Functional Outcome following Ischemic Stroke
Authors: Stover Hertzberg Vicki , Weiss Paul , Stern Barney J. , Frankel Michael R.
Published: August 2006

Background: Few studies to date have documented genetic influences on outcomes of hospitalization among patients with acute ischemic stroke. Objective: To assess the influence of the family history of stroke on in-hospital mortality and hospitalization outcome among patients having acute ischemic stroke. Methods: The medical records for 916 consecutive adult patients admitted for acute ischemic stroke during 12/1/2001–2/28/2002 at 34 randomly selected Georgia hospitals were centrally abstracted. The patients were classified as having a positive family history of stroke or not. The two groups were compared on risk factors, comorbidities, admission characteristics, hospital disposition status, and outcome measures. Multivariate logistic regression was used to assess the independent contributions of important variables identified by univariate screening. Results: A positive family history of stroke was significantly associated with a decreased frequency of medical history of coronary artery disease, a decreased frequency of medical history of congestive heart failure, an increased frequency of medical history of hypertension, and younger age among patients with acute ischemic stroke who were 18 years or older. The family history was not associated with in-hospital mortality (odds ratio 1.49, 95% confidence interval 0.79–2.80 for incident cases). The interaction of family history and age was significantly associated with discharge destination and discharge functional status. Conclusions: Preliminary analyses found associations between family history and stroke outcome. The role of a family history of stroke in stroke outcome merits further study.