bluuebunny/crossref_metadata_2025 huggingface dataset:
A PARAMETERIZED ALGORITHM TO EXPLORE FORMAL CONTEXTS WITH A TAXONOMY
Authors: CELLIER PEGGY , FERRÉ SÉBASTIEN , RIDOUX OLIVIER , DUCASSÉ MIREILLE
Published: April 2008

Formal Concept Analysis (FCA) is a natural framework to learn from examples. Indeed, learning from examples results in sets of frequent concepts whose extent contains mostly these examples. In terms of association rules, the above learning strategy can be seen as searching the premises of rules where the consequence is set. In its most classical setting, FCA considers attributes as a non-ordered set. When attributes of the context are partially ordered to form a taxonomy, Conceptual Scaling allows the taxonomy to be taken into account by producing a context completed with all attributes deduced from the taxonomy. The drawback, however, is that concept intents contain redundant information. In this article, we propose a parameterized algorithm, to learn rules in the presence of a taxonomy. It works on a non-completed context. The taxonomy is taken into account during the computation so as to remove all redundancies from intents. Simply changing one of its operations, this parameterized algorithm can compute various kinds of concept-based rules. We present instantiations of the parameterized algorithm to learn rules as well as to compute the set of frequent concepts.
AN INTELLIGENT USER INTERFACE FOR BROWSING AND SEARCHING MPEG-7 IMAGES USING CONCEPT LATTICES
Authors: DUCROU JON , EKLUND PETER
Published: April 2008

This paper presents the evaluation of a design and architecture for browsing and searching MPEG-7 images. Our approach is novel in that it exploits concept lattices for the representation and navigation of image content. Several concept lattices provide the foundation for the system (called IMAGE-SLEUTH) each representing a different search context, one for image shape, another for color and luminance, and a third for semantic content, namely image browsing based on a metadata ontology. The test collection used for our study is a sub-set of MPEG-7 images created from the popular The Sims 2™ game. The evaluation of the IMAGE-SLEUTH program is based on usability testing among 29 subjects. The results of the study are used to build an improved second generation program – IMAGE-SLEUTH2 – however these results also indicate that image navigation via a concept lattice is a highly successful interface paradigm. Our results provide general insights for interface design using concept lattices that will be of interest to any applied research and development using concept lattices.
ON SUCCINCT REPRESENTATION OF KNOWLEDGE COMMUNITY TAXONOMIES WITH FORMAL CONCEPT ANALYSIS
Authors: ROTH CAMILLE , OBIEDKOV SERGEI , KOURIE DERRICK G.
Published: April 2008

We present an application of formal concept analysis aimed at representing a meaningful structure of knowledge communities in the form of a lattice-based taxonomy. The taxonomy groups together agents (community members) who develop a set of notions. If no constraints are imposed on how it is built, a knowledge community taxonomy may become extremely complex and difficult to analyze. We consider two approaches to building a concise representation, respecting the underlying structural relationships while hiding superfluous information: a pruning strategy based on the notion of concept stability and a representational improvement based on nested line diagrams and "zooming". We illustrate the methods on two examples: a community of embryologists and a community of researchers in complex systems.
ALGORITHMS FOR THE JOIN AND AUTO-INTERSECTION OF MULTI-TAPE WEIGHTED FINITE-STATE MACHINES
Authors: CHAMPARNAUD JEAN-MARC , GUINGNE FRANCK , KEMPE ANDRÉ , NICART FLORENT
Published: April 2008

A weighted finite-state machine with n tapes describes a rational relation on n strings. We recall some basic operations on n-ary rational relations, recast the important join operation in terms of "auto-intersection", and propose restricted algorithms for both operations. If two rational relations are joined on more than one tape, it can unfortunately lead to non-rational relations with undecidable properties. As a consequence, there cannot be a fully general algorithm, able to compile any rational join or auto-intersection. We define a class of triples 〈A,i,j〉 for which we are able to compile the auto-intersection of the machine A w.r.t. tapes i and j. We hope that this class is sufficient for many practical applications.
Neuronal nitric oxide synthase signaling within cardiac myocytes targets phospholamban
Authors: Wang Honglan , Kohr Mark J. , Traynham Christopher J. , Wheeler Debra G. , Janssen Paul M. L. , Ziolo Mark T.
Published: April 2008

Studies have shown that neuronal nitric oxide synthase (nNOS, NOS1) knockout mice (NOS1−/−) have increased or decreased contractility, but consistently have found a slowed rate of intracellular Ca2+ ([Ca2+]i) decline and relengthening. Contraction and [Ca2+]i decline are determined by many factors, one of which is phospholamban (PLB). The purpose of this study is to determine the involvement of PLB in the NOS1-mediated effects. Force-frequency experiments were performed in trabeculae isolated from NOS1−/− and wild-type (WT) mice. We also simultaneously measured Ca2+ transients (Fluo-4) and cell shortening (edge detection) in myocytes isolated from WT, NOS1−/−, and PLB−/− mice. NOS1−/− trabeculae had a blunted force-frequency response and prolonged relaxation. We observed similar effects in myocytes with NOS1 knockout or specific NOS1 inhibition with S-methyl-l-thiocitrulline (SMLT) in WT myocytes (i.e., decreased Ca2+ transient and cell shortening amplitudes and prolonged decline of [Ca2+]i). Alternatively, NOS1 inhibition with SMLT in PLB−/− myocytes had no effect. Acute inhibition of NOS1 with SMLT in WT myocytes also decreased basal PLB serine16 phosphorylation. Furthermore, there was a decreased SR Ca2+ load with NOS1 knockout or inhibition, which is consistent with the negative contractile effects. Perfusion with FeTPPS (peroxynitrite decomposition catalyst) mimicked the effects of NOS1 knockout or inhibition. β-Adrenergic stimulation restored the slowed [Ca2+]i decline in NOS1−/− myocytes, but a blunted contraction remained, suggesting additional protein target(s). In summary, NOS1 inhibition or knockout leads to decreased contraction and slowed [Ca2+]i decline, and this effect is absent in PLB−/− myocytes. Thus NOS1 signaling modulates PLB serine16 phosphorylation, in part, via peroxynitrite.
Bestrophin Cl− channels are highly permeable to HCO3−
Authors: Qu Zhiqiang , Hartzell H. Criss
Published: April 2008

Bestrophin-1 (Best1) is a Cl− channel that is linked to various retinopathies in both humans and dogs. Dysfunction of the Best1 Cl− channel has been proposed to cause retinopathy because of altered Cl− transport across the retinal pigment epithelium (RPE). In addition to Cl−, many Cl− channels also transport HCO3−. Because HCO3− is physiologically important in pH regulation and in fluid and ion transport across the RPE, we measured the permeability and conductance of bestrophins to HCO3− relative to Cl−. Four human bestrophin homologs (hBest1, hBest2, hBest3, and hBest4) and mouse Best2 (mBest2) were expressed in HEK cells, and the relative HCO3− permeability ( PHCO3/ PCl) and conductance ( GHCO3/ GCl) were determined. PHCO3/ PCl was calculated from the change in reversal potential ( Erev) produced by replacing extracellular Cl− with HCO3−. hBest1 was highly permeable to HCO3− ( PHCO3/ PCl = ∼0.44). hBest2, hBest4, and mBest2 had an even higher relative HCO3− permeability ( PHCO3/ PCl = 0.6–0.7). All four bestrophins had HCO3− conductances that were nearly the same as Cl− ( GHCO3/ GCl = 0.9–1.1). Extracellular Na+ did not affect the permeation of hBest1 to HCO3−. At physiological HCO3− concentration, HCO3− was also highly conductive. The hBest1 disease-causing mutations Y85H, R92C, and W93C abolished both Cl− and HCO3− currents equally. The V78C mutation changed PHCO3/ PCl and GHCO3/ GCl of mBest2 channels. These results raise the possibility that disease-causing mutations in hBest1 produce disease by altering HCO3− homeostasis as well as Cl− transport in the retina.
Specific signals involved in the long-term maintenance of radiation-induced fibrogenic differentiation: a role for CCN2 and low concentration of TGF-β1
Authors: Haydont Valérie , Riser Bruce L. , Aigueperse Jocelyne , Vozenin-Brotons Marie-Catherine
Published: April 2008

The fibrogenic differentiation of resident mesenchymal cells is a key parameter in the pathogenesis of radiation fibrosis and is triggered by the profibrotic growth factors transforming growth factor (TGF)-β1 and CCN2. TGF-β1 is considered the primary inducer of fibrogenic differentiation and is thought to control its long-term maintenance, whereas CCN2 is considered secondary effector of TGF-β1. Yet, in long-term established fibrosis like that associated with delayed radiation enteropathy, in situ TGF-β1 deposition is low, whereas CCN2 expression is high. To explore this apparent paradox, cell response to increasing doses of TGF-β1 was investigated in cells modeling initiation and maintenance of fibrosis, i.e., normal and fibrosis-derived smooth muscle cells, respectively. Activation of cell-specific signaling pathways by low TGF-β1 doses was demonstrated with a main activation of the Rho/ROCK pathway in fibrosis-derived cells, whereas the Smad pathway was mainly activated in normal cells. This leads to subsequent and cell-specific regulation of the CCN2 gene. These results suggested a specific profibrotic role of CCN2 in fibrosis-initiated cells. Furthermore, the modulation of CCN2 expression by itself and the combination of TGF-β1 and CCN2 was investigated in fibrosis-derived cells. In fibrosis-initiated cells CCN2 triggered its autoinduction; furthermore, low concentration of TGF-β1-potentiated CCN2 autoinduction. Our findings showed a differential requirement and action of TGF-β1 in the fibrogenic response of normal vs. fibrosis-derived cells. This study defines a novel Rho/ROCK but Smad3-independent mode of TGF-β signaling that may operate during the chronic stages of fibrosis and provides evidence of both specific and combinatorial roles of low TGF-β1 dose and CCN2.
Effect of chronic inhibition of converting enzyme on proximal tubule acidification
Authors: Diaz-Sylvester Paula L. , Fiori Mariana C. , Dieguez Stella M. , Müller Angélica C. , Lopardo Mariano L. , Amorena Carlos E.
Published: April 2008

The acute effect of angiotensin-converting enzyme inhibition (ACEi) on proximal convoluted tubule (PCT) function is well documented. However, the effect of chronic treatment is less known. The aim of this work was to evaluate the effect of chronic ACEi on PCT acidification (JHCO3−). Rats received enalapril (10 mg·kg−1·day−1, added to the drinking water) during 3 mo. Micropuncture experiments were performed to measure the effect of chronic ACEi on JHCO3−. Nitric oxide (NO·) synthesis in kidney cortex homogenates was assessed by quantifying the conversion of [14C]-l-arginine to [14C]-l-citrulline. Western blot analysis was performed to determine the abundances of V-H+ATPase and NHE3 isoform of the Na+/H+exchanger in proximal brush-border membrane vesicles (BBMV). Enalapril treatment induced a ∼50% increase in JHCO3−. Luminal perfusion with ethyl-isopropyl amiloride (EIPA) 10−4M or bafilomycin 10−6M decreased JHCO3−by ∼60% and ∼30%, respectively, in both control and enalapril-treated rats. The effect of EIPA and bafilomycin on absolute JHCO3−was larger in enalapril-treated than in control rats. Acute inhibition of NO·synthesis with NG-nitro-l-arginine methyl esther abolished the enalapril-induced increase in JHCO3−. Cortex homogenates from enalapril-treated rats displayed a 46% increase in nitric oxide synthase (NOS) activity compared with those from untreated animals. Enalapril treatment did not affect the abundances of NHE3 and V-H+ATPase in BBMV. Our results suggest that PCT acidification is increased during chronic ACEi probably due to an increase in NO·synthesis, which would stimulate Na+/H+exchange and electrogenic proton transport.
Renal hemodynamic effect of cyclooxygenase 2 inhibition in young men and women with uncomplicated type 1 diabetes mellitus
Authors: Cherney David Z. I. , Scholey James W. , Nasrallah Rania , Dekker Maria G. , Slorach Cameron , Bradley Timothy J. , Hébert Richard L. , Sochett Etienne B. , Miller Judith A.
Published: April 2008

In experimental studies, cyclooxygenase 2 (COX2)-derived vasodilatory prostaglandins play a more prominent role in arterial vasoregulation in females. The gender-dependent effect of COX2 modulation in humans with type 1 diabetes mellitus (DM) is unknown. Accordingly, we examined the renal hemodynamic role of prostaglandins by assessing the response to COX2 inhibition in young men and women with type 1 DM. We also used a graded ANG II infusion to determine whether gender-based differences were mediated by effects of COX2 inhibition on the renin angiotensin system (RAS). We hypothesized that COX2 inhibition would be associated with preferential vasoconstriction in women and would augment their response to ANG II. Baseline renal function and the response to an ANG II infusion were assessed during clamped euglycemia, and again after COX2 inhibition (200 mg celecoxib daily for 14 days) in 12 men and 9 women after 1 wk on a controlled protein and sodium diet. COX2 inhibition was associated with increases in filtration fraction ( P = 0.045) and renal vascular resistance and a decline in renal blood flow ( P = 0.04) in women compared with men. Before COX2 inhibition, women exhibited a decline in glomerular filtration rate in response to ANG II. COX2 inhibition abolished this effect, whereas the response was not altered in men. In summary, COX2 inhibition was associated with hemodynamic effects that differed based on gender. The ANG II response suggests that with uncomplicated type 1 DM, prostaglandins may contribute to RAS-mediated gender differences. Our results are consistent with experimental data suggesting augmented female prostanoid dependence.
Cytoplasmic initiation of cisplatin cytotoxicity
Authors: Yu Fang , Megyesi Judit , Price Peter M.
Published: April 2008

The mechanism of action of cisplatin as a chemotherapeutic agent has been attributed to DNA binding, while its mechanism of action as a nephrotoxin is unresolved. Only ∼1% of intracellular cisplatin interacts with DNA, primarily forming intrastrand cross-linked adducts, and many studies have implicated both nuclear and cytoplasmic causes of cisplatin-induced death in cultured cells. We have demonstrated that cisplatin cytotoxicity depends on cdk2 activity, which is at least partly through the cdk2-E2F1 pathway. The mechanism of the dependency on cdk2, and whether cdk2 activation of E2F1 represents the only cell death pathway involved, is still unclear. Our previous work showed that deletion of the nuclear localization signal from p21WAF1/CIP1, a cdk2 inhibitor, did not alter its protective action against cisplatin cytotoxicity. Active cdk2-cyclin complexes are localized in both the nucleus and cytoplasm, and it was reported that cdk2 translocated to the cytoplasm after an apoptotic stimulus. Herein, we show that cisplatin caused cell death in enucleated mouse kidney proximal tubule cells (TKPTS), which was prevented by cdk2 inhibition. Also, we localized cytoplasmic cdk2 to both the endoplasmic reticulum (ER) and Golgi compartments, and ER stress was blocked by specific cdk2 inhibition. We conclude that cisplatin can induce nuclear independent apoptosis, cisplatin cytotoxicity can be initiated by cytoplasmic events, and cytoplasmic cdk2 plays an important role in apoptosis signaling.
Postnatal Changes in the Inactivation Properties of Voltage-Gated Sodium Channels Contribute to the Mature Firing Pattern of Spinal Motoneurons
Authors: Carlin K. P. , Liu J. , Jordan L. M.
Published: April 2008

Most mammals are born with the necessary spinal circuitry to produce a locomotor-like pattern of neural activity. However, rodents seldom demonstrate weight-supported locomotor behavior until the second or third postnatal week, possibly due to the inability of the neuromuscular system to produce sufficient force during this early postnatal period. As spinal motoneurons mature they are seen to fire an increasing number of action potentials at an increasing rate, which is a necessary component of greater force production. The mechanisms responsible for this enhanced ability of motoneurons are not completely defined. In the present study we assessed the biophysical properties of the developing voltage-gated sodium current to determine their role in the maturing firing pattern. Using dissociated postnatal lumbar motoneurons in short-term culture (18–24 h) we demonstrate that currents recorded from the most mature postnatal age group (P10–P12) were significantly better able to maintain channels in an available state during repetitive stimulation than were the younger age groups (P1–P3, P4–P6, P7–P9). This ability correlated with the ability of channels to recover more quickly and more completely from an inactivated state. These age-related differences were seen in the absence of changes in the voltage dependence of channel gating. Differences in both closed-state inactivation and slow inactivation were also noted between the age groups. The results indicate that changes in the inactivation properties of voltage-gated sodium channels are important for the development of a mature firing pattern in spinal motoneurons.
Models and Measurements of Functional Maps in V1
Authors: Issa Naoum P. , Rosenberg Ari , Husson T. Robert
Published: April 2008

The organization of primary visual cortex has been heavily studied for nearly 50 years, and in the last 20 years functional imaging has provided high-resolution maps of its tangential organization. Recently, however, the usefulness of maps like those of orientation and spatial frequency (SF) preference has been called into question because they do not, by themselves, predict how moving images are represented in V1. In this review, we discuss a model for cortical responses (the spatiotemporal filtering model) that specifies the types of cortical maps needed to predict distributed activity within V1. We then review the structure and interrelationships of several of these maps, including those of orientation, SF, and temporal frequency preference. Finally, we discuss tests of the model and the sufficiency of the requisite maps in predicting distributed cortical responses. Although the spatiotemporal filtering model does not account for all responses within V1, it does, with reasonable accuracy, predict population responses to a variety of complex stimuli.
Two Kinds of fMRI Repetition Suppression? Evidence for Dissociable Neural Mechanisms
Authors: Epstein Russell A. , Parker Whitney E. , Feiler Alana M.
Published: April 2008

Repetition suppression (RS) is a reduction of neural response that is often observed when stimuli are presented more than once. Many functional magnetic resonance imaging (fMRI) studies have exploited RS to probe the sensitivity of cortical regions to variations in different stimulus dimensions; however, the neural mechanisms underlying fMRI-RS are not fully understood. Here we test the hypothesis that long-interval (between-trial) and short-interval (within-trial) RS effects are caused by distinct and independent neural mechanisms. Subjects were scanned while viewing visual scenes that were repeated over both long and short intervals. Within the parahippocampal place area (PPA) and other brain regions, suppression effects relating to both long- and short-interval repetition were observed. Critically, two sources of evidence indicated that these effects were engendered by different underlying mechanisms. First, long- and short-interval RS effects were entirely noninteractive even although they were measured within the same set of trials during which subjects performed a constant behavioral task, thus fulfilling the formal requirements for a process dissociation. Second, long- and short-interval RS were differentially sensitive to viewpoint: short-interval RS was only significant when scenes were repeated from the same viewpoint while long-interval RS less viewpoint-dependent. Taken together, these results indicate that long- and short-interval fMRI-RS are mediated by different neural mechanisms that independently modulate the overall fMRI signal. These findings have important implications for understanding the results of studies that use fMRI-RS to explore representational spaces.
Solar System Motions and the Cosmological Constant: A New Approach
Authors: Iorio Lorenzo
Published: April 2008

We use the corrections to the Newton‐Einstein secular
precessions of the longitudes of perihelia of some planets (Mercury, Earth, Mars,
Jupiter, Saturn) of the Solar System, phenomenologically estimated
as solve‐for parameters by the Russian astronomer E. V. Pitjeva in a
global fit of almost one century of data with the EPM2004 ephemerides,
in order to put on the test the expression for the perihelion precession
induced by a uniform cosmological constant Λ in the framework of the
Schwarzschild‐de Sitter (or Kottler) space‐time. We compare such an
extra rate to the estimated corrections to the planetary perihelion precessions
by taking their ratio for different pairs of planets instead of using
one perihelion at a time for each planet separately, as done so far in
literature. The answer is negative, even by further rescaling by
a factor 10 (and even 100 for Saturn) the errors in the estimated extra
precessions of the perihelia released by Pitjeva. Our conclusions hold
also for any other metric perturbation having the same dependence on
the spatial coordinates, as those induced by other general relativistic
cosmological scenarios and by many modified models of gravity. Currently
ongoing and planned interplanetary spacecraft‐based missions
should improve our knowledge of the planets′ orbits allowing for more
stringent constraints.
Gene Tree Labeling Using Nonnegative Matrix Factorization on Biomedical Literature
Authors: Heinrich Kevin E. , Berry Michael W. , Homayouni Ramin
Published: April 2008

Identifying functional groups of genes is a challenging problem for biological applications. Text mining approaches can be used to build hierarchical clusters or trees from the information in the biological literature. In particular, the nonnegative matrix factorization (NMF) is examined as one approach to label hierarchical trees. A generic labeling algorithm as well as an evaluation technique is proposed, and the effects of different NMF parameters with regard to convergence and labeling accuracy are discussed. The primary goals of this study are to provide a qualitative assessment of the NMF and its various parameters and initialization, to provide an automated way to classify biomedical data, and to provide a method for evaluating labeled data assuming a static input tree. As a byproduct, a method for generatinggold standardtrees is proposed.
A Pull‐in Based Test Mechanism for Device Diagnostic and Process Characterization
Authors: Rocha L. A. , Mol L. , Cretu E. , Wolffenbuttel R. F. , Machado da Silva J.
Published: April 2008

A test technique for capacitive MEMS accelerometers and electrostatic microactuators, based on the measurement of pull‐in voltages and resonance frequency, is described. Using this combination of measurements, one can estimate process‐induced variations in the device layout dimensions as well as deviations from nominal value in material properties, which can be used either for testing or device diagnostics purposes. Measurements performed on fabricated devices confirm that the 250 nm overetch observed on SEM images can be correctly estimated using the proposed technique.
A New Hybrid Iterative Algorithm for Fixed-Point Problems, Variational Inequality Problems, and Mixed Equilibrium Problems
Authors: Yao Yonghong , Liou Yeong-Cheng , Yao Jen-Chih
Published: April 2008

We introduce a new hybrid iterative algorithm for finding a common element of the set of fixed points of an infinite family of nonexpansive mappings, the set of solutions of the variational inequality of a monotone mapping, and the set of solutions of a mixed equilibrium problem. This study, proves a strong convergence theorem by the proposed hybrid iterative algorithm which solves fixed-point problems, variational inequality problems, and mixed equilibrium problems.
On Prime Near‐Rings with Generalized Derivation
Authors: Bell Howard E.
Published: April 2008

Let N be a 3‐prime 2‐torsion‐free zero‐symmetric left near‐ring with multiplicative center Z. We prove that if N admits a nonzero generalized derivation f such that f(N)⊆Z, then N is a commutative ring. We also discuss some related properties.
Identifying Nonstationary Clock Noises in Navigation Systems
Authors: Galleani Lorenzo , Tavella Patrizia
Published: April 2008

The stability of the atomic clocks on board the satellites of a navigation system should
remain constant with time. In reality there are numerous physical phenomena that make the
behavior of the clocks a function of time, and for this reason we have recently introduced the
dynamic Allan variance (DAVAR), a measure of the time‐varying stability of an atomic clock. In
this paper we discuss the dynamic Allan variance for phase and frequency jumps, two common
nonstationarities of atomic clocks. The analysis of both numerical simulations and experimental
data proves that the dynamic Allan variance is an effective way of characterizing nonstationary
behaviors of atomic clocks.
Brucella abortusStrain RB51 Vaccine: Immune Response after Calfhood Vaccination and Field Investigation in Italian Cattle Population
Authors: Tittarelli Manuela , Bonfini Barbara , De Massis Fabrizio , Giovannini Armando , Di Ventura Mauro , Nannini Donatella , Caporale Vincenzo
Published: April 2008

Immune response toBrucella abortusstrain RB51 vaccine was measured in cattle vaccinated at calfhood. After an increase at day 6 post-vaccination (pv), the antibody level recorded in the 10 vaccinated animals remained constant for two months, and then progressively decreased. All vaccinated animals remained negative from day 162 pv to the end of the study (day 300 pv). Only at days 13 and 14 pv the RB51-CFT showed 100% sensitivity (credibility interval (CI) 76.2%–100%). The results indicate that the possibility to use RB51-CFT for the identification of cattle vaccinated at calfhood with RB51 is limited in time. A field investigation was carried out on 26,975 sera collected on regional basis from the Italian cattle population. The study outcomes indicate that in case of RB51-CFT positive results observed in officially Brucellosis-free (OBF) areas and, in any case, when an illegal use of RB51 vaccine is suspected, the use of the RB51-CFT alone is not sufficient to identify all the vaccinated animals. The design of a more sophisticated diagnostic protocol including an epidemiological investigation, the use of RB51-CFT, and the use of the skin test with RB51 as antigen is deemed more appropriate for the identification of RB51 vaccinated animals.
A Scaffold Analysis Tool Using Mate‐Pair Information in Genome Sequencing
Authors: Kim Pan-Gyu , Cho Hwan-Gue , Park Kiejung
Published: April 2008

We have developed a Windows‐based program, ConPath,
as a scaffold analyzer. ConPath constructs scaffolds by ordering and orienting separate sequence contigs by exploiting the mate‐pair information between
contig‐pairs. Our algorithm builds directed graphs from link information and traverses them to find the longest acyclic graphs. Using end read pairs of fixed‐sized mate‐pair libraries,
ConPath determines relative orientations of all contigs,
estimates the gap size of each adjacent contig pair, and reports wrong assembly
information by validating orientations and gap sizes.
We have utilized ConPath in more than 10 microbial genome projects, including
Mannheimia succiniciproducens and Vibro vulnificus,
where we verified contig assembly and identified several erroneous contigs using the four types of error defined in ConPath. Also, ConPath supports some convenient features and viewers that permit investigation of each contig in detail; these include contig viewer, scaffold viewer, edge information list, mate‐pair list, and the printing of complex scaffold structures.
Mouse Mammary Tumor Virus Promoter‐Containing Retroviral Promoter Conversion Vectors for Gene‐Directed Enzyme Prodrug Therapy are Functional In Vitro and In Vivo
Authors: Klein Reinhard , Ruttkowski Bärbel , Schwab Sonja , Peterbauer Thomas , Salmons Brian , Günzburg Walter H. , Hohenadl Christine
Published: April 2008

Gene directed‐enzyme prodrug therapy (GDEPT) is an approach for sensitization of tumor cells to an enzymatically activated, otherwise nontoxic, prodrug. Cytochrome P450 2B1 (CYP2B1) metabolizes the prodrugs cyclophosphamide (CPA) and ifosfamide (IFA) to produce the cytotoxic substances phosphoramide mustard and isophosphoramide mustard as well as the byproduct acrolein. We have constructed a retroviral promoter conversion (ProCon) vector for breast cancer GDEPT. The vector allows expression of CYP2B1 from the mouse mammary tumor virus (MMTV) promoter known to be active in the mammary glands of transgenic animals. It is anticipated to be used for the generation of encapsulated viral vector producing cells which, when placed inside or close to a tumor, will act as suppliers of the therapeutic CYP2B1 protein as well as of the therapeutic vector itself. The generated vector was effectively packaged by virus producing cells and allowed the production of high levels of enzymatically active CYP2B1 in infected cells which sensitized them to killing upon treatment with both IFA and CPA. Determination of the respective IC50 values demonstrated that the effective IFA dose was reduced by sixteen folds. Infection efficiencies in vivo were determined using a reporter gene‐bearing vector in a mammary cancer cell‐derived xenograft tumor mouse model.
Buckling of Imperfect Thin Cylindrical Shell under Lateral Pressure
Authors: Lo Frano R. , Forasassi G.
Published: April 2008

The strength of thin shells, under external pressure, is highly dependent by the nature of imperfection. This paper investigates buckling behaviour of imperfect thin cylindrical shells with analytical, numerical, and experimental methods in conditions for which, at present, a complete theoretical analysis was not found in literature. In general, collapse is initiated by yielding, but interaction with geometrical instabilities is meaningful, in that imperfections reduce the load bearing capacity by an amount of engineering significance also when thickness is considerable. The aim of this study was to conduct experiments that are representative of buckling, in the context of NPP applications as, for instance, the IRIS (international reactor innovative and secure) and LWR steam generator (SG) tubes. At Pisa University, a research activity is being carried out on the buckling of thin walled metal specimen, with a test equipment (and the necessary data acquisition facility) as well as numerical models were set up by means FEM code. The experiments were conducted on A-316 test specimens, tubes with and without longitudinal welding. The numerical and experimental results comparison highlighted the influence of different types of imperfections on the buckling loads with a good agreement between the finite-element predictions and the experimental data.
On the Complexity of Electrostatic Suspension Stabilization of Functionalized Silica Nanoparticles for Biotargeting and Imaging Applications
Authors: Bergman Lotta , Rosenholm Jessica , Öst Anna-Brita , Duchanoy Alain , Kankaanpää Pasi , Heino Jyrki , Lindén Mika
Published: April 2008

Different means of attaching streptavidin to surface functionalized silica particles with a diameter of 240 nm were investigated with special focus on suspension stability for electrostatically stabilized suspensions. The influence of two different fluorescent dyes covalently linked to the streptavidin on suspension stability was also studied. The results clearly show that the stability of the suspensions is crucially dependent on all functional groups present on the surface. The surface functions may either directly affect the effective surface charge if the functions contain charged groups, or indirectly by affecting the relative concentration of charged groups on the particle surface. Poly(ethylene imine)‐functionalized silica particles, where the polymer is grown by surface hyperbranching polymerization, are shown to be promising candidates for bioapplications, as the zeta‐potential can remain strongly positive even under biologically relevant conditions.
PPARs and Female Reproduction: Evidence from Genetically Manipulated Mice
Authors: Yang Jichun , Chen Lihong , Zhang Xiaoyan , Zhou Yunfeng , Zhang Dongjuan , Huo Ming , Guan Youfei
Published: April 2008

Peroxisome proliferator‐activated receptors (PPARs) are ligand‐activated nuclear receptors controlling many important physiological processes, including lipid and glucose metabolism, energy homeostasis, inflammation, as well as cell proliferation and differentiation. In the past decade, intensive study of PPARs has shed novel insight into prevention and treatment of dyslipidemia, insulin resistance, and type 2 diabetes. Recently, a large body of research revealed that PPARs are also functionally expressed in reproductive organs and various parts of placenta during pregnancy, which strongly suggests that PPARs might play a critical role in reproduction and development, in addition to their central actions in energy homeostasis. In this review, we summarize recent findings elucidating the role of PPARs in female reproduction, with particular focus on evidence from gene knockout and transgenic animal model study.
Synthesis, Spectroscopic, and Anticancerous Properties
of Mixed Ligand Palladium(II) and Silver(I) Complexes with 4,6-Diamino-5-hydroxy-2-mercaptopyrimidine and 2,2′-Bipyridyl
Authors: Mostafa Sahar I. , Badria Farid A.
Published: April 2008

Synthesis of two new water-soluble mixed ligand [Pd(bpy)(dahmp)]Cl and [Ag(bpy)(Hdahmp)]NO3 complexes (dahmp and Hdahmp are the deprotonated monoanion and the protonated neutral 4,6-diamino-5-hydroxy-2-mercaptopyrimidine, resp.) is reported. The composition of the reported complexes was discussed on the bases of IR, H1 NMR, and mass spectra, as well as conductivity and thermal measurements. The reported complexes display a significant anticancer activity against Ehrlich ascites tumor cells (EACs). The higher activity of these complexes with their higher conductivity values corresponds to their complete ionization in aqueous solution.
Using Inhomogeneous Planar Layers as Impedance Matchers between Two Different Mediums
Authors: Khalaj-Amirhosseini Mohammad
Published: April 2008

A method is proposed to synthesize optimally inhomogeneous planar layers (IPLs) as impedance matchers between two mediums. First, the electric permittivity function of the IPL is expanded in a truncated Fourier series. Then, the optimum values of the coefficients of the series are obtained through an optimization approach. The usefulness of the proposed method is verified using some examples.
Down-Regulation of Class II Phosphoinositide 3-Kinase α Expression below a Critical Threshold Induces Apoptotic Cell Death
Authors: Elis Winfried , Triantafellow Ellen , Wolters Natalie M. , Sian Katie R. , Caponigro Giordano , Borawski Jason , Gaither L. Alex , Murphy Leon O. , Finan Peter M. , MacKeigan Jeffrey P.
Published: April 2008

Members of the phosphoinositide 3-kinase (PI3K) family collectively control multiple cellular responses, including proliferation, growth, chemotaxis, and survival. These diverse effects can partly be attributed to the broad range of downstream effectors being regulated by the products of these lipid kinases, the 3′-phosphoinositides. However, an additional layer of complexity is introduced by the existence of multiple PI3K enzyme isoforms. Much has been learned over the last years on the roles of the classes I and III PI3K members in cellular signaling, but little is known about the isoform-specific tasks done by the class II PI3Ks (C2α, β, and γ). In this study, we used quantitative reverse transcription–PCR and RNA interference in mammalian cells to gain further insight into the function of these lesser studied PI3K enzymes. We find that PI3K-C2α, but not PI3K-C2β, has an important role in controlling cell survival and by using a panel of RNA interference reagents, we were able to determine a critical threshold of PI3K-C2α mRNA levels, below which the apoptotic program is switched on, via the intrinsic cell death pathway. In addition, knockdown of PI3K-C2α to levels that by themselves do not induce apoptosis sensitize cells to the anticancer agent Taxol (paclitaxel). Lastly, we report that lowering the levels of PI3K-C2α in a number of cancer cell lines reduces their proliferation and cell viability, arguing that PI3K inhibitors targeting not only the class Iα isoform but also class IIα may contribute to an effective anticancer strategy. (Mol Cancer Res 2008;6(4):614–23)
Proteolytic Processing of Cut Homeobox 1 by Neutrophil Elastase in the MV4;11 Myeloid Leukemia Cell Line
Authors: Goulet Brigitte , Markovic Yelena , Leduy Lam , Nepveu Alain
Published: April 2008

Proteolytic processing by cathepsin L generates p110 Cut homeobox 1 (CUX1) at the end of the G1 phase, whereas an alternative transcript encodes p75 CUX1. These short CUX1 isoforms were reported to be overexpressed in cancer cells, and transgenic mice overexpressing the p75 isoform were found to develop myeloproliferative disease–like myeloid leukemias. In the present study, we report that the neutrophil elastase can also generate a short CUX1 isoform in the MV4;11 acute myeloid leukemia cell line. Proteolytic processing was so efficient that the full-length CUX1 protein was detected only when cells were maintained in the presence of the specific elastase inhibitor III. In agreement with these findings, higher levels of the processed cyclin E isoforms were also detected in MV4;11 cells. Reappearance of full-length cyclin E and CUX1 could be induced upon the treatment of MV4;11 cells with the differentiation inducer phorbol 12-myristate 13-acetate or, unexpectedly, following overexpression of a short recombinant CUX1 protein. In both cases, the mechanism involved transcriptional repression of the neutrophil elastase gene. This result revealed a negative feedback loop whereby CUX1 shuts down the expression of the protease that cleaves it. Overall, the findings in MV4;11 and other cancer cells suggest that various mechanisms are used in cancer to favor the expression of short CUX1 isoforms. (Mol Cancer Res 2008;6(4):644–53)
Localization of Fas/CD95 into the Lipid Rafts on Down-Modulation of the Phosphatidylinositol 3-Kinase Signaling Pathway
Authors: Bénéteau Marie , Pizon Mathieu , Chaigne-Delalande Benjamin , Daburon Sophie , Moreau Patrick , De Giorgi Francesca , Ichas François , Rebillard Amélie , Dimanche-Boitrel Marie-Thérèse , Taupin Jean-Luc , Moreau Jean-François , Legembre Patrick
Published: April 2008

Activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway is known to protect tumor cells from apoptosis and more specifically from the Fas-mediated apoptotic signal. The antitumoral agent edelfosine sensitizes leukemic cells to death by inducing the redistribution of the apoptotic receptor Fas into plasma membrane subdomains called lipid rafts. Herein, we show that inhibition of the PI3K signal by edelfosine triggers a Fas-mediated apoptotic signal independently of the Fas/FasL interaction. Furthermore, similarly to edelfosine, blockade of the PI3K activity, using specific inhibitors LY294002 and wortmannin, leads to the clustering of Fas whose supramolecular complex is colocalized within the lipid rafts. These findings indicate that the antitumoral agent edelfosine down-modulates the PI3K signal to sensitize tumor cells to death through the redistribution of Fas into large platform of membrane rafts. (Mol Cancer Res 2008;6(4):604–13)
The CpG Island Methylator Phenotype Correlates with Long-Range Epigenetic Silencing in Colorectal Cancer
Authors: Karpinski Pawel , Ramsey David , Grzebieniak Zygmunt , Sasiadek Maria M. , Blin Nikolaus
Published: April 2008

The CpG island methylator phenotype (CIMP), characterized by an exceptionally high frequency of methylation of discrete CpG islands, is observed in 18% to 25% of sporadic colorectal cancers. Another hypermethylation pattern found in colorectal cancers, termed long-range epigenetic silencing, is associated with DNA/histone methylation in three distinct gene clusters at chromosome 2q14.2, showing that DNA hypermethylation can span larger chromosomal domains and lead to the silencing of flanking, unmethylated genes. We investigated whether these two phenotypes are interrelated in colorectal cancers. The CIMP status of 148 sporadic colorectal cancers was determined by methylation-specific PCR. We determined the BRAF V600E mutation by mutant allele–specific PCR amplification. The methylation status of the MLH1 gene and of three CpG islands (EN1, SCTR, and INHBB), corresponding to three distinct clusters along 2q14.2, was determined by methylation-specific PCR. The average number of sites showing methylation in CIMP+ tumors was 2.21, compared with 1.22 for CIMP− individuals, and this difference was highly significant (P = 3.6 × 10−8, Mann-Whitney test). Moreover, all CIMP+ tumors showed hypermethylation of at least one of these loci, in contrast to CIMP− tumors, where 18 (16%) samples remained unmethylated. The mean number of simultaneously hypermethylated CpG islands at 2q14.2 differs significantly between CIMP− and CIMP+ tumors, suggesting varying effects of domain silencing in this region. Given that the number of hypermethylated loci at 2q14.2 likely affects the range of silenced flanking genes, high frequency of simultaneous hypermethylation of three CpG islands (EN1, SCTR, and INHBB) may have potential influence on specific characteristics of CIMP+ colorectal cancers. (Mol Cancer Res 2008;6(4):585–91)
Transcutaneous Electrical Stimulation of Subjective Tinnitus
Authors: Kapkın Osman , Satar Bulent , Yetiser Sertac
Published: April 2008

Aim: The effect of the transcutaneous application of the electrical stimulus on tinnitus perception has been reviewed in a placebo-controlled, randomized and comparative analysis to eventually determine the outcome of the therapeutic role of the therapy. Method: There are 42 patients who were randomized into 2 groups according to their order of admission. Group A consists of 31 patients who were subjected to transcutaneous electrical stimulation 3 times a week for 1 month. Group B includes 11 patients who had electrical stimulus attachment but where no stimulus was given (placebo group). The stimulator is a custom-made device which generates direct and alternative current in 10–200 Hz frequency. An alternative low-frequency (not >100 Hz) pulsed current was used for tinnitus therapy through a preauricular skin electrode. The amplitude of stimulus ranged between 50 and 2,000 mA. The pulse frequency was 30 Hz. Each session lasted for 25 min for both groups. Statistical analysis was performed. Result: The rate of improvement following the therapy was 42.8% (18/42) in the electrical therapy group and 28.5% (4/14) in the placebo group. Conclusion: Electrical suppression of the tinnitus does not offer a promising outcome for patients with tinnitus in the presented study.
Role of Histamine H3 and H4 Receptors in Mechanical Hyperalgesia following Peripheral Nerve Injury
Authors: Smith Fiona M. , Haskelberg Hila , Tracey David J. , Moalem-Taylor Gila
Published: April 2008

Objective: Histamine is a chemical mediator that acts at four known types of histamine receptors and has been widely implicated in the development of nociception and neuropathic pain. Blocking histamine H1 and H2 receptors has been shown to reduce hyperalgesia following nerve injury, but the role of histamine H3 and H4 receptors in neuropathic pain has not been studied. Here, we used blockers of histamine H3 and H4 receptors to assess their effects on neuropathic pain behavior and mast cell numbers following peripheral nerve injury. In addition, we assessed the effect of activating H4 receptors on neuropathic pain behavior. Methods: Rats were subjected to a partial ligation of the sciatic nerve, a model of neuropathic pain, and were treated either systemically or locally (hindpaw) with the H3/H4 receptor inverse agonist thioperamide, the specific H4 receptor antagonist JNJ 7777120, or the H4 receptor agonist VUF 8430. Measurements of mechanical hyperalgesia were carried out by Randall-Selitto test for 1–3 weeks, and sciatic nerve tissues were analyzed for numbers of intact mast cells by histology at 9 h after surgery. Results: Rats treated with thioperamide or JNJ 7777120 showed significantly enhanced mechanical hyperalgesia after partial ligation of the sciatic nerve. The number of intact mast cells in the injured nerve of these rats was higher than in control rats suggesting reduced mast cell degranulation, but was still significantly lower than in intact nerves. Rats treated with VUF 8430 showed significantly reduced mechanical hyperalgesia. Conclusion: We propose that the increase in mechanical hyperalgesia produced by thioperamide and JNJ 7777120 and the decrease in mechanical hyperalgesia produced by VUF 8430 may represent a direct effect of these agents on mechanospecific primary afferents, or an indirect effect of these agents via injury-induced inflammation.
Harold Wilson, the British Labour Party, and the War in Vietnam
Authors: Vickers Rhiannon
Published: April 2008

When British Prime Minister Harold Wilson urged Lyndon Johnson not to escalate hostilities in Vietnam in 1965, he did so not because he was morally opposed to the war or thought the war was intractable but because he was concerned about the likely impact of U.S. actions on his own domestic power base. Wilson's stance of providing moral but not military support for U.S. policy in Vietnam caused anger and disillusionment among leftwing Labour Party activists and members of Parliament, spurring them to active opposition against Wilson's government. Even so, Wilson managed to prevent a major schism within his government and party over the Vietnam War. His attempts to broker a peace deal between the combatants were largely designed to placate Labour Party activists while raising Wilson's profile as a world statesman. Although the initiatives did not generate any progress toward a ceasefire, they were relatively successful on the domestic front.
“In a Class by Itself”: Cold War Politics and Finland's Position vis-à-vis the United Nations, 1945–1956
Authors: Götz Norbert
Published: April 2008

From the mid-1950s on, the United Nations (UN) provided a forum for Finland to have an international presence despite its status as a neutral country in the Cold War. But until 1955, Finland's bid to join the UN was blocked by the Soviet Union. The inability to gain admission caused some Finns to favor staying outside the UN, a view that gained its widest circulation in the latter half of 1950 after the UN had been invoked to respond to North Korea's attack on South Korea. Nonetheless, although some Finns were concerned that membership in the UN might cause their country to become embroiled in a superpower Cold War conflict against its will, others believed that entry into the UN would confer prestige and legitimacy on Finland and strengthen its position as a sovereign member of the international community. Although Finns realized that the UN would not provide a security guarantee, the organization did help Finland to consolidate its neutral position in the Cold War international system.