bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Resistance inHaemophilus influenzae
Authors: Tristram Stephen , Jacobs Michael R. , Appelbaum Peter C.
Published: April 2007

Haemophilus influenzaeis a major community-acquired pathogen causing significant morbidity and mortality worldwide. Meningitis and bacteremia due to type b strains occur in areas where the protein-conjugated type b vaccine is not in use, whereas nontypeable strains are major causes of otitis media, sinusitis, acute exacerbations of chronic bronchitis, and pneumonia. Antibiotic resistance in this organism is more diverse and widespread than is commonly appreciated. Intrinsic efflux resistance mechanisms limit the activity of the macrolides, azalides, and ketolides. β-Lactamase production is highly prevalent worldwide and is associated with resistance to ampicillin and amoxicillin. Strains with alterations in penicillin binding proteins, particularly PBP3 (β-lactamase negative ampicillin resistant and β-lactamase positive amoxicillin-clavulanate resistant), are increasing in prevalence, particularly in Japan, with increasing resistance to ampicillin, amoxicillin, amoxicillin-clavulanate, and many cephalosporins, limiting the efficacy of expanded-spectrum cephalosporins against meningitis and of many oral cephalosporins against other diseases. Most strains remain susceptible to the carbapenems, which are not affected by penicillin binding protein changes, and the quinolones. The activity of many oral agents is limited by pharmacokinetics achieved with administration by this route, and the susceptibility of isolates based on pharmacokinetic and pharmacodynamic parameters is reviewed.
Problems in Diagnosing Scabies, a Global Disease in Human and Animal Populations
Authors: Walton Shelley F. , Currie Bart J.
Published: April 2007

Scabies is a worldwide disease and a major public health problem in many developing countries, related primarily to poverty and overcrowding. In remote Aboriginal communities in northern Australia, prevalences of up to 50% among children have been described, despite the availability of effective chemotherapy. Sarcoptic mange is also an important veterinary disease engendering significant morbidity and mortality in wild, domestic, and farmed animals. Scabies is caused by the ectoparasitic miteSarcoptes scabieiburrowing into the host epidermis. Clinical symptoms include intensely itchy lesions that often are a precursor to secondary bacterial pyoderma, septicemia, and, in humans, poststreptococcal glomerulonephritis. Although diagnosed scabies cases can be successfully treated, the rash of the primary infestation takes 4 to 6 weeks to develop, and thus, transmission to others often occurs prior to therapy. In humans, the symptoms of scabies infestations can mimic other dermatological skin diseases, and traditional tests to diagnose scabies are less than 50% accurate. To aid early identification of disease and thus treatment, a simple, cheap, sensitive, and specific test for routine diagnosis of active scabies is essential. Recent developments leading to the expression and purification ofS. scabieirecombinant antigens have identified a number of molecules with diagnostic potential, and current studies include the investigation and assessment of the accuracy of these recombinant proteins in identifying antibodies in individuals with active scabies and in differentiating those with past exposure. Early identification of disease will enable selective treatment of those affected, reduce transmission and the requirement for mass treatment, limit the potential for escalating mite resistance, and provide another means of controlling scabies in populations in areas of endemicity.
Role ofd-Alanylation ofStreptococcus gordoniiLipoteichoic Acid in Innate and Adaptive Immunity
Authors: Chan Karenn G. , Mayer Matt , Davis Elisabeth M. , Halperin Scott A. , Lin Tong-Jun , Lee Song F.
Published: April 2007

In recent years, there has been considerable interest in using the oral commensal gram-positive bacteriumStreptococcus gordoniias a live vaccine vector. The present study investigated the role ofd-alanylation of lipoteichoic acid (LTA) in the interaction ofS. gordoniiwith the host innate and adaptive immune responses. A mutant strain defective ind-alanylation was generated by inactivation of thedltAgene in a recombinant strain ofS. gordonii(PM14) expressing a fragment of the S1 subunit of pertussis toxin. The mutant strain was found to be more susceptible to killing by polymyxin B, nisin, magainin II, and human β defensins than the parent strain. When it was examined for binding to murine bone marrow-derived dendritic cells (DCs), thedltAmutant exhibited 200- to 400-fold less binding than the parent but similar levels of binding were shown for Toll-like receptor 2 (TLR2) knockout DCs and HEp-2 cells. In a mouse oral colonization study, the mutant showed a colonization ability similar to that of the parent and was not able to induce a significant immune response. The mutant induced significantly less interleukin 12p70 (IL-12p70) and IL-10 than the parent from DCs. LTA purified from the bacteria induced tumor necrosis factor-alpha and IL-6 production from wild-type DCs but not from TLR2 knockout DCs, and the mutant LTA induced a significantly smaller amount of these two cytokines. These results show thatd-alanylation of LTA inS. gordoniiplays a role in the interaction with the host immune system by contributing to the relative resistance to host defense peptides and by modulating cytokine production by DCs.
Genome-Wide Identification ofFrancisella tularensisVirulence Determinants
Authors: Su Jingliang , Yang Jun , Zhao Daimin , Kawula Thomas H. , Banas Jeffrey A. , Zhang Jing-Ren
Published: April 2007

Francisella tularensisis a gram-negative pathogen that causes life-threatening infections in humans and has potential for use as a biological weapon. The genetic basis of theF. tularensisvirulence is poorly understood. This study screened a total of 3,936 transposon mutants of the live vaccine strain for infection in a mouse model of respiratory tularemia by signature-tagged mutagenesis. We identified 341 mutants attenuated for infection in the lungs. The transposon disruptions were mapped to 95 different genes, virtually all of which are also present in the genomes of otherF. tularensisstrains, including human pathogenicF. tularensisstrain Schu S4. A small subset of these attenuated mutants carried insertions in the genes encoding previously known virulence factors, but the majority of the identified genes have not been previously linked toF. tularensisvirulence. Among these are genes encoding putative membrane proteins, proteins associated with stress responses, metabolic proteins, transporter proteins, and proteins with unknown functions. Several attenuated mutants contained disruptions in a putative capsule locus which partially resembles the poly-γ-glutamate capsule biosynthesis locus ofBacillus anthracis, the anthrax agent. Deletional mutation analysis confirmed that this locus is essential forF. tularensisvirulence.
Length, orientation, and plant host influence the mutation frequency in microsatellites
Authors: Azaiez Aïda , Bouchard Éric F. , Jean Martine , Belzile François J.
Published: April 2007

Microsatellites are simple, tandem DNA repeats that represent unstable regions of the genome. They undergo frequent changes in tract length by base additions or deletions due to DNA polymerase slippage during replication. To characterize factors affecting the frequency of spontaneous mutations occurring in microsatellites in plants, a reporter system was used in Arabidopsis thaliana and tomato ( Lycopersicon esculentum ). The β-glucuronidase (GUS) reporter system was used to measure the mutation frequency in various microsatellites (G7, G10, G13, G16, and C16) in somatic tissues. Our results indicate that this frequency increases with the number of repeats: a G16tract was almost 80-fold more mutable than a G7tract. Furthermore, the frequency of mutations depends on repeat orientation, as G16was 3-fold more mutable than C16. The mutation rate was also found to differ markedly in Arabidopsis and tomato for an identical microsatellite. Indeed, Arabidopsis showed a 5-fold higher mutation frequency than tomato with the same G7reporter construct. Finally, mutation in a G16tract was frequent enough that mutations transmitted germinally to the next generation could be detected at a relatively high frequency.
Cytogenetic analysis of Anaecypris hispanica and its relationship with the paternal ancestor of the diploid-polyploid Squalius alburnoides complex
Authors: Gromicho Marta , Coelho Maria Manuela , Alves Maria Judite , Collares-Pereira Maria João
Published: April 2007

The karyotype of the endangered fish Anaecypris hispanica was revisited using advanced cytogenetic techniques to elucidate its putative relationship with the paternal ancestor of the hybrid complex Squalius alburnoides and to clarify some of the recently described cytogenetic patterns of the complex. The results of chromomycin A3 and Ag staining, as well as fluorescent in situ hybridization with 28S and 5S rDNA and the (TTAGGG)n telomeric probes, were compared with the patterns observed in specimens of the all-male nonhybrid lineage of S. alburnoides complex, which is considered to reconstitute the nuclear genome of the probably extinct paternal ancestor. Several cytogenetic features observed in A. hispanica specimens were indeed shared by S. alburnoides nuclear nonhybrid males, supporting the hypothesis of a close evolutionary link between A. hispanica and the paternal ancestor of the complex. The genomic rearrangements involving 28S rDNA sites previously described in the S. alburnoides complex and in its maternal ancestor ( S. pyrenaicus ) were not detected in A. hispanica; they are, therefore, probably due to mechanisms related to hybridization and polyploidy.
GRAPH ORIENTATION ALGORITHMS TO MINIMIZE THE MAXIMUM OUTDEGREE
Authors: ASAHIRO YUICHI , MIYANO EIJI , ONO HIROTAKA , ZENMYO KOUHEI
Published: April 2007

This paper studies the problem of orienting all edges of a weighted graph such that the maximum weighted outdegree of vertices is minimized. This problem, which has applications in the guard arrangement for example, can be shown to be [Formula: see text]-hard generally. In this paper we first give optimal orientation algorithms which run in polynomial time for the following special cases: (i) the input is an unweighted graph, and (ii) the input graph is a tree. Then, by using those algorithms as sub-procedures, we provide a simple, combinatorial, [Formula: see text]-approximation algorithm for the general case, where wmax and wmin are the maximum and the minimum weights of edges, respectively, and ε is some small positive real number that depends on the input.
ON THE APPROXIMABILITY OF MAXIMUM AND MINIMUM EDGE CLIQUE PARTITION PROBLEMS
Authors: DESSMARK ANDERS , JANSSON JESPER , LINGAS ANDRZEJ , LUNDELL EVA-MARTA , PERSSON MIA
Published: April 2007

We consider the following clustering problems: given an undirected graph, partition its vertices into disjoint clusters such that each cluster forms a clique and the number of edges within the clusters is maximized (Max-ECP), or the number of edges between clusters is minimized (Min-ECP). These problems arise naturally in the DNA clone classification. We investigate the hardness of finding such partitions and provide approximation algorithms. Further, we show that greedy strategies yield constant factor approximations for graph classes for which maximum cliques can be found efficiently.
ON-DEMAND BOUNDED BROADCAST SCHEDULING WITH TIGHT DEADLINES
Authors: POON CHUNG KEUNG , ZHENG FEIFENG , XU YINFENG
Published: April 2007

We investigate an online scheduling problem motivated by pull-based data delivery systems where there is a server keeping a number of pages; and clients requesting the same page can be satisfied simultaneously by one broadcast. We focus on the special case where preemption is allowed but aborted requests can never be satisfied again. The HEU algorithm of Woeginger [10] is proven to be optimal in maximizing the number of satisfied requests when the pages have equal length and the requests have tight deadlines. However, we show that when there are maximum bounds on the number and weight of requests at any time in the system, the HEU algorithm is not optimal. We then propose a modified algorithm, VAR, which is optimal for this case.
FUSING LOOPLESS ALGORITHMS FOR COMBINATORIAL GENERATION
Authors: TAKAOKA TADAO , VIOLICH STEPHEN
Published: April 2007

Some combinatorial generation problems can be broken into subproblems for which loopless algorithms already exist. This article discusses means by which loopless algorithms can be fused to produce a new loopless algorithm that solves the original problem. It demonstrates this method with two new loopless algorithms. The first generates well-formed parenthesis strings containing two different types of parentheses. The second generates multiset permutations in linear space using only arrays; it is simpler and more efficient than the recent algorithm of Korsh & LaFollette.
PARAMETRIZATIONS OF THE DARK ENERGY DENSITY AND SCALAR POTENTIALS
Authors: GUO ZONG-KUAN , OHTA NOBUYOSHI , ZHANG YUAN-ZHONG
Published: April 2007

We develop a theoretical method of constructing the scalar (quintessence or phantom) potential directly from the dimensionless dark energy function X(z), the dark energy density in units of its present value. We apply our method to two parametrizations of the dark energy density, the quiessence-Lambda ansatz and the generalized Chaplygin gas model, and discuss some features of the constructed potentials.
ELECTROWEAK THEORY AND THE NEUTRINO-MASS AND NEUTRINO-OSCILLATION QUESTIONS
Authors: ZIINO G.
Published: April 2007

It is shown that both conjectures of neutrino mass and neutrino oscillation can be made really well-grounded within the Standard Model provided that one adopts a recent new version of the electroweak scheme spontaneously giving also a fundamental explanation for the so-called "maximal parity-violation" effect. A crucial role is played by the prediction of two distinct, scalar and pseudoscalar, replicas of (electron, muon, and tau) lepton numbers that could fully account for an actual non-coincidence between neutrino mass-eigenstates and gauge-eigenstates.
UNIVERSAL NONPERTURBATIVE EFFECTS IN EVENT SHAPES FROM SOFT-COLLINEAR EFFECTIVE THEORY
Authors: LEE CHRISTOPHER
Published: April 2007

Two-jet event shape distributions, traditionally studied in the language of perturbative QCD, can be described naturally in soft-collinear effective theory. In this language, we demonstrate factorization of event shape distributions into perturbatively-calculable hard and jet functions and nonperturbative soft functions, and show how the latter contribute universal shifts to the mean values of various event shape distributions. Violations of universality in shifts of higher moments can give information on correlations of energy flow in soft radiation.
CONTENT CLASSIFICATION AND RECOMMENDATION TECHNIQUES FOR VIEWING ELECTRONIC PROGRAMMING GUIDE ON A PORTABLE DEVICE
Authors: ZHU JINGBO , MA MATTHEW Y. , GUO JINHONG K. , WANG ZHENXING
Published: April 2007

With the merge of digital television (DTV) and the exponential growth of broadcasting network, an overwhelmingly amount of information has been made available to a consumer's home. Therefore, how to provide consumers with the right amount of information becomes a challenging problem. In this paper, we propose an electronic programming guide (EPG) recommender based on natural language processing techniques, more specifically, text classification. This recommender has been implemented as a service on a home network that facilitates the personalized browsing and recommendation of TV programs on a portable remote device. Evaluations of our Maximum Entropy text classifier were performed on multiple categories of TV programs, and a near 80% retrieval rate is achieved using a small set of training data.
WEB SERVICES USER MODEL SERVER PERFORMING DECISION MAKING
Authors: KABASSI KATERINA , VIRVOU MARIA , TSIHRINTZIS GEORGE A.
Published: April 2007

This paper presents a user model server based on Web Services. User model servers are very important because they allow reusability of user modeling reasoning mechanisms which are typically very complex and difficult to construct from scratch. In this paper we show how the potential of interoperability, reusability and component sharing offered by the technology of Web Services have been exploited in the design of a user model server that performs decision making. The reasoning of the user modeling is based on a multi-criteria decision making theory and has been implemented as a Web Service to provide intelligent assistance to users over the Web. Reusability has been shown through the successful application of the user model server into two different applications: an e-mail and a file manager application.
DEFINITION, PROPERTIES AND WAVELET ANALYSIS OF MULTISCALE FRACTIONAL BROWNIAN MOTION
Authors: BARDET JEAN-MARC , BERTRAND PIERRE
Published: April 2007

In some applications, for instance, finance, biomechanics, turbulence or internet traffic, it is relevant to model data with a generalization of a fractional Brownian motion for which the Hurst parameter H is dependent on the frequency. In this contribution, we describe the multiscale fractional Brownian motions which present a parameter H as a piecewise constant function of the frequency. We provide the main properties of these processes: long-memory and smoothness of the paths. Then we propose a statistical method based on wavelet analysis to estimate the different parameters and prove a functional Central Limit Theorem satisfied by the empirical variance of the wavelet coefficients.
FUZZY DATA REPRESENTATION AND QUERYING IN XML DATABASE
Authors: ÜSTÜNKAYA EKİN , YAZICI ADNAN , GEORGE ROY
Published: April 2007

Real-world information including subjective opinions and judgments need imprecise data to be modeled for representation and querying in databases. The Extensible Markup Language (XML) has become a de-facto standard for data modeling and exchange in recent years. Efforts on modeling imprecision and representing such data in XML have not been fully developed. In this paper, an XML based fuzzy data representation and querying system is presented. Complex and imprecise data are represented using a fuzzy extension of XML. The representation forms the basis for a system which enables fuzzy querying on XML documents using XQuery, a XML query language. The system also enables restructuring of XML Schemas through merging of elements of the XML documents. By using this feature of the system, application specific XML Schema and XML documents can be generated from the existing documents.
POLICY AND INSTITUTIONAL REFORMS FOR AN EFFECTIVE EIA SYSTEM IN SUDAN
Authors: ALI OSMAN MIRGHANI MOHAMED
Published: April 2007

Assessing the potential impact of development projects in the Sudan dates back to the study of the Equatorial Nile Project conducted in the last century during the Anglo-Egyptian Condominium. Environmental Impact Assessment (EIA) studies commenced in the early eighties of the last century with the establishment of the Institute of Environmental Studies in the University of Khartoum. The practice gathered momentum with the recent activities in the oil and roads sectors. Although the practice of (EIA) has only recently been legalized by the passing of the Environment Protection Act of 2001, the performance of EIA is often poor due to flaws in legislative, administrative, institutional and procedural frameworks. Effective implementation of the EIA process in the Sudan requires the institutionalization of the process within the legislative, administrative, political and education system in the country. Special emphasis is needed for the federal system of governance. Other issues include accreditation, sectoral regulations, establishing of a National Centre of EIA for advising the government and for training of human capacities. The paper calls for more involvement of stakeholders via effective popular participation in all steps of EIA. The expected influx of foreign investors following the Comprehensive Peace Accord of 2005 and the concentration of oil reserves in the ecologically rich and sensitive regions, call for an urgent improvement in the legislative, institutional and procedural aspects of the process.
AN INDUCTIVE APPROACH TO DETERMINING CAUSALITY IN COMPARATIVE POLITICS: A FUZZY SET ALTERNATIVE
Authors: MORDESON JOHN N. , CLARK TERRY D. , GRIESER ADAM D. , WIERMAN MARK J.
Published: April 2007

Political science typically tests hypotheses by demonstrating correlations between variables. The most commonly employed method for doing so is regression analysis. The approach is essentially crisp, which carries with it a number of questionable assumptions about the data. Political phenomena such as democracy or stability often involve measuring the degree to which a particular observation demonstrates the qualities of the category. A fuzzy set approach better captures the inherent ambiguity in classifying our observations relative to such categories. However, the attempt to establish correlations between fuzzy sets in the social sciences has been plagued by the priority ranking issue. We illustrate the potential that Jeffrey's Rule has to overcome this difficulty.
Evaluation of intramyocellular lipid breakdown during exercise by biochemical assay, NMR spectroscopy, and Oil Red O staining
Authors: De Bock K. , Dresselaers T. , Kiens B. , Richter E. A. , Van Hecke P. , Hespel P.
Published: April 2007

The study compared the net decline of intramyocellular lipids (IMCL) during exercise ( n = 18) measured by biochemical assay (BIO) and Oil Red O (ORO) staining on biopsy samples from vastus lateralis muscle and by1H-MR spectroscopy (MRS) sampled in an 11 × 11 × 18-mm3voxel in the same muscle. IMCL was measured before and after a 2-h cycling bout (∼75% V̇o2 peak). ORO and MRS measurements showed substantial IMCL use during exercise of 31 ± 12 and 47 ± 6% of preexercise IMCL content. In contrast, use of BIO for IMCL determination did not reveal an exercise-induced breakdown of IMCL (2 ± 9%, P = 0.29) in young healthy males. Correlations between different measures of exercise-induced IMCL degradation were low. Coefficients were 0.48 for MRS vs. ORO ( P = 0.07) and were even lower for BIO vs. MRS ( r = 0.38, P = 0.13) or ORO ( r = 0.08, P = 0.78). This study demonstrates that different methods to measure IMCL in human muscles can result in different conclusions with regard to exercise-induced IMCL changes. MRS has the advantage that it is noninvasive, however, not fiber type specific and hampered by an at least 30-min delay in measurements after exercise completion and may overestimate IMCL use. BIO is the only quantitative method but is subject to variation when biopsies have different fiber type composition. However, BIO yields lower IMCL breakdown compared with ORO and MRS. ORO has the major advantage that it is fiber type specific, and it therefore provides information that is not available with the other methods.
Calcium and Arrhythmogenesis
Authors: ter Keurs Henk E. D. J. , Boyden Penelope A.
Published: April 2007

Triggered activity in cardiac muscle and intracellular Ca2+have been linked in the past. However, today not only are there a number of cellular proteins that show clear Ca2+dependence but also there are a number of arrhythmias whose mechanism appears to be linked to Ca2+-dependent processes. Thus we present a systematic review of the mechanisms of Ca2+transport (forward excitation-contraction coupling) in the ventricular cell as well as what is known for other cardiac cell types. Second, we review the molecular nature of the proteins that are involved in this process as well as the functional consequences of both normal and abnormal Ca2+cycling (e.g., Ca2+waves). Finally, we review what we understand to be the role of Ca2+cycling in various forms of arrhythmias, that is, those associated with inherited mutations and those that are acquired and resulting from reentrant excitation and/or abnormal impulse generation (e.g., triggered activity). Further solving the nature of these intricate and dynamic interactions promises to be an important area of research for a better recognition and understanding of the nature of Ca2+and arrhythmias. Our solutions will provide a more complete understanding of the molecular basis for the targeted control of cellular calcium in the treatment and prevention of such.
Restoration of Barrier Function in Injured Intestinal Mucosa
Authors: Blikslager Anthony T. , Moeser Adam J. , Gookin Jody L. , Jones Samuel L. , Odle Jack
Published: April 2007

Mucosal repair is a complex event that immediately follows acute injury induced by ischemia and noxious luminal contents such as bile. In the small intestine, villous contraction is the initial phase of repair and is initiated by myofibroblasts that reside immediately beneath the epithelial basement membrane. Subsequent events include crawling of healthy epithelium adjacent to the wound, referred to as restitution. This is a highly regulated event involving signaling via basement membrane integrins by molecules such as focal adhesion kinase and growth factors. Interestingly, however, ex vivo studies of mammalian small intestine have revealed the importance of closure of the interepithelial tight junctions and the paracellular space. The critical role of tight junction closure is underscored by the prominent contribution of the paracellular space to measures of barrier function such as transepithelial electrical resistance. Additional roles are played by subepithelial cell populations, including neutrophils, related to their role in innate immunity. The net result of reparative mechanisms is remarkably rapid closure of mucosal wounds in mammalian tissues to prevent the onset of sepsis.
Arrhythmogenic Ion-Channel Remodeling in the Heart: Heart Failure, Myocardial Infarction, and Atrial Fibrillation
Authors: Nattel Stanley , Maguy Ange , Le Bouter Sabrina , Yeh Yung-Hsin
Published: April 2007

Rhythmic and effective cardiac contraction depends on appropriately timed generation and spread of cardiac electrical activity. The basic cellular unit of such activity is the action potential, which is shaped by specialized proteins (channels and transporters) that control the movement of ions across cardiac cell membranes in a highly regulated fashion. Cardiac disease modifies the operation of ion channels and transporters in a way that promotes the occurrence of cardiac rhythm disturbances, a process called “arrhythmogenic remodeling.” Arrhythmogenic remodeling involves alterations in ion channel and transporter expression, regulation and association with important protein partners, and has important pathophysiological implications that contribute in major ways to cardiac morbidity and mortality. We review the changes in ion channel and transporter properties associated with three important clinical and experimental paradigms: congestive heart failure, myocardial infarction, and atrial fibrillation. We pay particular attention to K+, Na+, and Ca2+channels; Ca2+transporters; connexins; and hyperpolarization-activated nonselective cation channels and discuss the mechanisms through which changes in ion handling processes lead to cardiac arrhythmias. We highlight areas of future investigation, as well as important opportunities for improved therapeutic approaches that are being opened by an improved understanding of the mechanisms of arrhythmogenic remodeling.
MDM2 Splice Variants Predominantly Localize to the Nucleoplasm Mediated by a COOH-Terminal Nuclear Localization Signal
Authors: Schuster Katja , Fan Liying , Harris Linda C.
Published: April 2007

Of the >40 alternative and aberrant splice variants of MDM2 that have been described to date, the majority has lost both the well-characterized nuclear localization signal (NLS1) and the nuclear export signal (NES) sequence. Because cellular localization of proteins provides insight regarding their potential function, we determined the localization of three different MDM2 splice variants. The splice variants chosen were the common variants MDM2-A and MDM2-B. In addition, MDM2-FB26 was chosen because it is one of the few variants described that contains the complete p53-binding site. All three splice variants predominantly localized to the nucleus. Nuclear localization of MDM2-A and MDM2-B was controlled by a previously uncharacterized nuclear localization signal (NLS2), whereas nucleoplasmic localization of MDM2-FB26 was mediated by NLS1. p53 and full-length MDM2 colocalized with the splice variants in the nucleus. MDM2-A and MDM2-B both contain a COOH-terminal RING finger domain, and interaction with full-length MDM2 through this domain was confirmed. MDM2-FB26 was the only splice variant evaluated that contained a p53-binding domain; however, interaction between MDM2-FB26 and p53 could not be shown. p14ARF did not colocalize with the splice variants and was predominantly expressed within the nucleoli. In summary, nuclear localization signals responsible for the nucleoplasmic distribution of MDM2 splice variants have been characterized. Colocalization and interaction of MDM2-A and MDM2-B with full-length MDM2 in the nucleus have important physiologic consequences, for example, deregulation of p53 activity. (Mol Cancer Res 2007;5(4):403–12)
Inhibitor of DNA Binding 1 Activates Vascular Endothelial Growth Factor through Enhancing the Stability and Activity of Hypoxia-Inducible Factor-1α
Authors: Kim Hyun-Jun , Chung Heekyoung , Yoo Young-Gun , Kim Hwan , Lee Jeong-Yeon , Lee Mi-Ock , Kong Gu
Published: April 2007

Inhibitor of DNA binding 1 (Id-1) has been implicated in tumor angiogenesis by regulating the expression of vascular endothelial growth factor (VEGF), but its molecular mechanism has not been fully understood. Here, we show the cross talk between Id-1 and hypoxia-inducible factor-1α (HIF-1α), that Id-1 induces VEGF by enhancing the stability and activity of HIF-1α in human endothelial and breast cancer cells. Although both the transcript and proteins levels of VEGF were induced by Id-1, only the protein expression of HIF-1α was induced without transcriptional changes in both human umbilical endothelial cells and MCF7 breast cancer cells. Such induction of the HIF-1α protein did not require de novo protein synthesis but was dependent on the active extracellular response kinase (ERK) pathway. In addition, stability of the HIF-1α protein was enhanced in part by the reduced association of the HIF-1α protein with von Hippel-Lindau protein in the presence of Id-1. Furthermore, Id-1 enhanced nuclear translocation and the transcriptional activity of HIF-1α. Transcriptional activation of HIF-1–dependent promoters was dependent on the active ERK pathway, and the association of HIF-1α protein with cyclic AMP-responsive element binding protein was enhanced by Id-1. Finally, Id-1 induced tube formation in human umbilical endothelial cells, which also required active ERK signaling. In conclusion, we provide the molecular mechanism of the cross talk between HIF-1α and Id-1, which may play a critical role in tumor angiogenesis. (Mol Cancer Res 2007;5(4):321–9)
Adherence to Statin Therapy Under Drug Cost Sharing in Patients With and Without Acute Myocardial Infarction
Authors: Schneeweiss Sebastian , Patrick Amanda R. , Maclure Malcolm , Dormuth Colin R. , Glynn Robert J.
Published: April 2007

Background—

As medication spending grows, Medicare Part D will need to adapt its coverage policies according to emerging evidence from a variety of insurance policies. We sought to evaluate the consequences of copayment and coinsurance policies on the initiation of statin therapy after acute myocardial infarction and adherence to therapy in statin initiators using a natural experiment of all British Columbia residents aged 66 years and older.

Methods and Results—

Three consecutive cohorts that included all patients who began statin therapy during full drug coverage (2001), coverage with a $10 or $25 copay (2002), and coverage with a 25% coinsurance benefit (2003–2004) were followed up with linked healthcare utilization data (n=51 561). Follow-up of cohorts was 9 months after each policy change. Adherence to statin therapy was defined as ≥80% of days covered. Relative to full-coverage policies, adherence to new statin therapy was significantly reduced, from 55.8% to 50.5%, under a fixed copayment policy (−5.4% points; 95% CI, −6.4% to −4.4%) and the subsequent coinsurance policy (−5.4% points; 95% CI, −6.3% to −4.4%). An uninterrupted increase in the proportion of patients initiating statin therapy after an acute myocardial infarction (1.7% points per quarter) was observed over the study period, similar to a Pennsylvania control population with full coverage. Sudden changes to full out-of-pocket spending, similar to Medicare’s Part D “doughnut hole,” almost doubled the risk of stopping statins (adjusted odds ratio, 1.94, 95% CI, 1.82 to 2.08).

Conclusions—

Fixed patient copayment and coinsurance policies have negative effects on adherence to statin lipid-lowering drug therapy but not on their initiation after myocardial infarction.
Instability in the Diagnosis of Metabolic Syndrome in Adolescents
Authors: Goodman Elizabeth , Daniels Stephen R. , Meigs James B. , Dolan Lawrence M.
Published: April 2007

Background—

Factor analyses suggest that the structure underlying metabolic syndrome is similar in adolescents and adults. However, adolescence is a period of intense physiological change, and therefore stability of the underlying metabolic structure and clinical categorization based on metabolic risk is uncertain.

Methods and Results—

We analyzed data from 1098 participants in the Princeton School District Study, a school-based study begun in 2001–2002, who were followed up for 3 years. We performed factor analyses of 8 metabolic risks at baseline and follow-up to assess stability of factor patterns and clinical categorization of metabolic syndrome. Metabolic syndrome was defined using the current American Heart Association/National Heart, Lung, and Blood Institute definition for adults (AHA), a modified AHA definition used in prior pediatric metabolic syndrome studies (pediatric AHA), and the International Diabetes Federation (IDF) guidelines. We found that factor structures were essentially identical at both time points. However, clinical categorization was not stable. Approximately half of adolescents with baseline metabolic syndrome lost the diagnosis at follow-up regardless of the definitions used: pediatric AHA=56% (95% confidence interval [CI], 42% to 69%), AHA=49% (95% CI, 32% to 66%), IDF=53% (95% CI, 38% to 68%). In addition to loss of the diagnosis, new cases were identified. Cumulative incidence rates were as follows: pediatric AHA=3.8% (95% CI, 2.8% to 5.2%); AHA=4.4% (95% CI, 3.3% to 5.9%); IDF=5.2% (95% CI, 4.0% to 6.8%).

Conclusions—

During adolescence, metabolic risk factor clustering is consistent. However, marked instability exists in the categorical diagnosis of metabolic syndrome. This instability, which includes both gain and loss of the diagnosis, suggests that the syndrome has reduced clinical utility in adolescence and that metabolic syndrome–specific pharmacotherapy for youth may be premature.
Identifying Heart Failure Patients at High Risk for Near-Term Cardiovascular Events With Serial Health Status Assessments
Authors: Kosiborod Mikhail , Soto Gabriel E. , Jones Philip G. , Krumholz Harlan M. , Weintraub William S. , Deedwania Prakash , Spertus John A.
Published: April 2007

Background—

Identification of heart failure outpatients at increased risk for clinical deterioration remains a critical challenge, with few tools currently available to assist clinicians. We tested whether serial health status assessments with the Kansas City Cardiomyopathy Questionnaire (KCCQ) can identify patients at increased risk for mortality and hospitalization.

Methods and Results—

We evaluated 1358 patients with heart failure after an acute myocardial infarction in the Eplerenone’s Neurohormonal Efficacy and Survival Study, a multicenter randomized trial that included serial KCCQ assessments. Cox proportional-hazards models were used to examine whether changes in KCCQ scores during successive outpatient visits were independently associated with all-cause mortality and cardiovascular mortality or hospitalization. Change in KCCQ (ΔKCCQ) was linearly associated with all-cause mortality (hazard ratio [HR], for each 5-point decrease in ΔKCCQ, 1.11; 95% CI, 1.04 to 1.19) and the combined outcome of cardiovascular mortality or hospitalization (HR for each 5-point decrease in ΔKCCQ, 1.12; 95% CI 1.07 to 1.18). In Kaplan-Meier survival analysis, all-cause mortality among patients with ΔKCCQ of ≤−10, >−10 to <10, and >10 points was 26%, 16%, and 13%, respectively (
P
=0.008). After multivariable adjustment, the linear relationship between ΔKCCQ and both all-cause mortality and combined cardiovascular death and hospitalization persisted (HR, 1.09; 95% CI, 1.00 to 1.18; and HR, 1.11; 95% CI, 1.05 to 1.17 for each 5-point decrease in ΔKCCQ, respectively).

Conclusions—

In heart failure outpatients, serial health status assessments with the KCCQ can identify high-risk patients and may prove useful in directing the frequency of follow-up and the intensity of treatment.
Analysis of the ENSO Cycle in the NCEP Coupled Forecast Model
Authors: Zhang Qin , Kumar Arun , Xue Yan , Wang Wanqiu , Jin Fei-Fei
Published: April 2007

Simulations from the National Centers for Environmental Prediction (NCEP) coupled model are analyzed to document and understand the behavior of the evolution of the El Niño–Southern Oscillation (ENSO) cycle. The analysis is of importance for two reasons: 1) the coupled model used in this study is also used operationally to provide model-based forecast guidance on a seasonal time scale, and therefore, an understanding of the ENSO mechanism in this particular coupled system could also lead to an understanding of possible biases in SST predictions; and 2) multiple theories for ENSO evolution have been proposed, and coupled model simulations are a useful test bed for understanding the relative importance of different ENSO mechanisms.

The analyses of coupled model simulations show that during the ENSO evolution the net surface heat flux acts as a damping mechanism for the mixed-layer temperature anomalies, and positive contribution from the advection terms to the ENSO evolution is dominated by the linear advective processes. The subsurface temperature–SST feedback, referred to as thermocline feedback in some theoretical literature, is found to be the primary positive feedback, whereas the advective feedback by anomalous zonal currents and the thermocline feedback are the primary sources responsible for the ENSO phase transition in the model simulation. The basic mechanisms for the model-simulated ENSO cycle are thus, to a large extent, consistent with those highlighted in the recharge oscillator. The atmospheric anticyclone (cyclone) over the western equatorial northern Pacific accompanied by a warm (cold) phase of the ENSO, as well as the oceanic Rossby waves outside of 15°S–15°N and the equatorial higher-order baroclinic modes, all appear to play minor roles in the model ENSO cycles.
ENSO’s Impact on Regional U.S. Hurricane Activity
Authors: Smith Shawn R. , Brolley Justin , O’Brien James J. , Tartaglione Carissa A.
Published: April 2007

Regional variations in North Atlantic hurricane landfall frequency along the U.S. coastline are examined in relation to the phase of El Niño–Southern Oscillation (ENSO). ENSO warm (cold) phases are known to reduce (increase) hurricane activity in the North Atlantic basin as a whole. Using best-track data from the U.S. National Hurricane Center, regional analysis reveals that ENSO cold-phase landfall frequencies are only slightly larger than neutral-phase landfall frequencies along the Florida and Gulf coasts. However, for the East Coast, from Georgia to Maine, a significant decrease in landfall frequency occurs during the neutral ENSO phase as compared to the cold phase. Along the East Coast, two or more major (category 3 or above) hurricanes never made landfall in the observational record (1900–2004) during a single hurricane season classified as an ENSO neutral or warm phase.
Kaniyalar old and new
Authors: Karashima Noboru , Subbarayalu Y.
Published: April 2007

There are two twelfth-century Chola inscriptions recording the royal orders concerning public auctions of land and prohibition of land purchase in the lower Kaveri valley. By analysing these two and other related inscriptions* of the twelfth and thirteenth centuries, the authors clarify the politico-economic conditions of the Chola state, which caused the emergence of big-scale landholders from among the military and other privileged people towards the latter half of Chola rule. These big landholders carved out chiefdoms for themselves in some localities, and finally brought about the demise of the Chola state, preparing the region for the emergence of a feudal state formation in the fourteenth century and after.
A language for music
Authors: Subramanian Lakshmi
Published: April 2007

This article takes a closer look at the Tamil Music Movement of the 1940s that contested the basis of the classical music tradition reconstituted by the Madras Music Academy. In espousing the cause of Tamil songs, the movement attempted to articulate a parallel conception of classicism that related to the song texts and to the singing voice, but which failed to break out of the discursive model that the Academy had set up for classical music. This article looks at the pre-history of Tamil Isai, and at how critical changes in the sociology of performance produced a new conception of classicism in both language and music.
Purifying the nation
Authors: Hardiman David
Published: April 2007

This article examines the impact of the Arya Samaj in Gujarat from 1895 to 1930. Although the founder of this body, Dayanand Saraswati, was from Gujarat, it initially proved less popular there than in the Punjab. The first important Arya Samajists in Gujarat were Punjabis, brought there by Sayajirao Gaekwad of Baroda to carry out educational work amongst untouchables. The Arya Samaj only became a mass organisation in Gujarat after a wave of conversions to Christianity in central Gujarat by untouchables, with Arya Samajists starting orphanages to ‘save’ orphans from the clutches of the Christian missionaries. The movement then made considerable headway in Gujarat. The main followers were from the urban middle classes, higher farming castes, and the gentry of the Koli caste. Each had their own reasons for embracing the organisation, ranging from a desire for higher social status, to religious reform, to building caste unity, and as a means, in the case of the Koli gentry, to ‘reconvert’ Kolis who had adopted Islam in medieval times. The movement lost its momentum after Gandhi arrived on the political scene, and many erstwhile Arya Samajists embraced the Gandhian movement. When the Gandhian movement itself flagged after 1922, there was an upsurge in communal antagonism in Gujarat in which Arya Samajists played a provocative role. A riot in Godhra in 1928 is examined.
Job Satisfaction and Psychological Well-Being as Nonadditive Predictors of Workplace Turnover
Authors: Wright Thomas A. , Bonett Douglas G.
Published: April 2007

Data from a 2-year field study were used to examine the relationships among psychological well-being, job satisfaction, and employee job performance with employee turnover. Using a sample of 112 managers employed at a large organization on the West Coast of the United States, and controlling for employee age, gender, ethnicity, and job performance, well-being and job satisfaction were found to predict turnover in a nonadditive manner. As expected, well-being was found to moderate the relation between job satisfaction and job separation, such that job satisfaction was most strongly (and negatively) related to turnover when well-being was low.
Fifty years of scientific and technical information policy in France (1955—2005)
Authors: Cacaly Serge , Le Coadic Yves-François
Published: April 2007

Over the last fifty years, French public authorities have played a major role in developing a policy for scientific and technical information (STI) in France. Four distinct periods can be identified. During the first, from 1955 to 1973, policy was dominated by de Gaulle's concern to combat American hegemony and, since that time, STI policy has always been considered a part of French global politics. The second period from 1973 to 1982 saw the construction of the national STI infrastructure which was followed by a focus on content and database coordination up to 1993. Since that date, France's policy has been marked by the deregulation of telecommunications and the privatization of public services. The question addressed in this paper concerns the current role of public authorities in preparing French society for active participation in the knowledge society.
Lost in translation: contributions of editors to the meanings of text
Authors: Hartley James , Branthwaite Alan , Ganier Frank , Heurley Laurent
Published: April 2007

Background. Authors of scientific articles in one language are often required to provide abstracts of their papers in a second language, and they use a variety of ways to achieve this. Aims. The aims of our studies were (i) to assess the effects of using native English speakers to improve non-native speakers' translations of their abstracts, and (ii) to explore the variations in edits produced by different native speakers. Methods. In Study 1, a French abstract was translated into English by two French authors. Each of these English abstracts was then edited by two native speakers of English (leading to four abstracts altogether). Textual and stylistic analyses were made of these four abstracts. In Study 2, over 200 academics rated these four abstracts on a series of semantic-differential scales to see how readers judged each abstract and what discriminations they made between them. Results. Study 1 showed how the two English editors imposed their own particular styles of writing on to the anglicized French abstracts, and how each changed the meaning in different ways. Study 2 showed that readers did in fact evaluate these pairs of English abstracts differently, indicating that the two English editors wrote in recognizably different `voices', whilst ostensibly carrying out the same task. Comparing the results of Study 1 (using textual analyses) with those of Study 2 (using readers' judgements), it appeared that improving readability and changing style were independent skills, and each had differing effects on meaning and understanding. Conclusions . These data suggest that there are benefits from using native English speakers to edit translated abstracts, but that there will never be a `one-to-one' translation from one language to another, and that different measures may reveal different effects.
Employing log metrics to evaluate search behaviour and success: case study BBC search engine
Authors: Huntington Paul , Nicholas David , Jamali Hamid R.
Published: April 2007

This paper argues that metrics can be generated from search transactional web logs that can help evaluate search engine effectiveness. Search logs from the BBC website were analysed and metrics extracted. Two search metrics — the time lapse between searches and the number of searches in a session — were developed to see whether they could measure search success or satisfaction. In all, 4 million search statements by 900,000 users were evaluated. The BBC search engine possessed a number of functional attributes which sought to improve retrieval and these were subjected to the two metrics to help determine how successful they were in practice. There was some evidence to support the proposition that the search outcome metrics did indeed indicate the effectiveness of engine functionality. The authors argue that this result is significant in that the identification of search outcome metrics will pave the way for assessing the effectiveness of site specific search engines and a greater understanding of the effectiveness of search engine functionality.