bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification of the Trypsin-Dependent Cleavage Activation Site of the Human Metapneumovirus Fusion Protein To Be Trypsin Independent Does Not Increase Replication or Spread in Rodents or Nonhuman Primates
Authors: Biacchesi Stéphane , Pham Quynh N. , Skiadopoulos Mario H. , Murphy Brian R. , Collins Peter L. , Buchholz Ursula J.
Published: May 2006

The contribution of cleavage activation of the fusion F protein of human metapneumovirus (HMPV) to replication and pathogenicity in rodents and nonhuman primates was investigated. Recombinant HMPVs were generated in which the naturally occurring trypsin-dependent cleavage sequence (R-Q-S-R↓) was replaced by each of three sequences whose cleavage in vitro does not depend upon added trypsin. Two of these were multibasic sequences derived from avian metapneumovirus type A (R-R-R-R) or type C (R-K-A-R), with the former containing the consensus furin protease cleavage motif (R-X-R/K-R↓). The third one (R-Q-P-R) was derived from a recently described trypsin independent HMPV isolate (J. H. Schickli, J. Kaur, N. Ulbrandt, R. R. Spaete, and R. S. Tang, J. Virol.
79:
10678-10689, 2005). To preclude the possibility of conferring even greater virulence to this significant human pathogen, the modifications were done in an HMPV variant that was attenuated by the deletion of two of the three envelope glycoproteins, SH and G. Each of the introduced cleavage sequences conferred trypsin independent F cleavage and growth to HMPV in vitro. However, they differed in the efficiency of trypsin independent growth and plaque formation in vitro: R-R-R-R > R-K-A-R > R-Q-P-R > R-Q-S-R. The R-R-R-R mutant was the only one whose growth in vitro was not augmented by added trypsin, indicative of highly efficient trypsin independent cleavage. When inoculated intranasally into hamsters, there was essentially no difference in the magnitude of replication in the upper or lower respiratory tract between the mutants, and virus was not detected in organs outside of the respiratory tract. Evaluation of the most cleavage-efficient mutant, R-R-R-R, in African green monkeys showed that there was no detectable change in the magnitude of replication in the upper and lower respiratory tract or in immunogenicity and protective efficacy against HMPV challenge. These results suggest that cleavage activation is not a major determinant of HMPV virulence.
Double-Stranded RNA Binding May Be a General Plant RNA Viral Strategy To Suppress RNA Silencing
Authors: Mérai Zsuzsanna , Kerényi Zoltán , Kertész Sándor , Magna Melinda , Lakatos Lóránt , Silhavy Dániel
Published: May 2006

In plants, RNA silencing (RNA interference) is an efficient antiviral system, and therefore successful virus infection requires suppression of silencing. Although many viral silencing suppressors have been identified, the molecular basis of silencing suppression is poorly understood. It is proposed that various suppressors inhibit RNA silencing by targeting different steps. However, as double-stranded RNAs (dsRNAs) play key roles in silencing, it was speculated that dsRNA binding might be a general silencing suppression strategy. Indeed, it was shown that the related aureusvirus P14 and tombusvirus P19 suppressors are dsRNA-binding proteins. Interestingly, P14 is a size-independent dsRNA-binding protein, while P19 binds only 21-nucleotide ds-sRNAs (small dsRNAs having 2-nucleotide 3′ overhangs), the specificity determinant of the silencing system. Much evidence supports the idea that P19 inhibits silencing by sequestering silencing-generated viral ds-sRNAs. In this study we wanted to test the hypothesis that dsRNA binding is a general silencing suppression strategy. Here we show that many plant viral silencing suppressors bind dsRNAs.Beet yellows virus PeanutP21,clump virusP15,Barley stripe mosaic virusγB, andTobacco etch virusHC-Pro, like P19, bind ds-sRNAs size-selectively, whileTurnip crinkle virusCP is a size-independent dsRNA-binding protein, which binds long dsRNAs as well as ds-sRNAs. We propose that size-selective ds-sRNA-binding suppressors inhibit silencing by sequestering viral ds-sRNAs, whereas size-independent dsRNA-binding suppressors inactivate silencing by sequestering long dsRNA precursors of viral sRNAs and/or by binding ds-sRNAs. The findings that many unrelated silencing suppressors bind dsRNA suggest that dsRNA binding is a general silencing suppression strategy which has evolved independently many times.
Functional Correlation between a Novel Amino Acid Insertion at Codon 19 in the Protease of Human Immunodeficiency Virus Type 1 and Polymorphism in the p1/p6 Gag Cleavage Site in Drug Resistance and Replication Fitness
Authors: Brann Terrence W. , Dewar Robin L. , Jiang Min-Kan , Shah Akram , Nagashima Kunio , Metcalf Julia A. , Falloon Judith , Lane H. Clifford , Imamichi Tomozumi
Published: May 2006

Population-based sequence analysis revealed the presence of a variant of human immunodeficiency virus type 1 (HIV-1) containing an insertion of amino acid Ile in the protease gene at codon 19 (19I) and amino acid substitutions in the protease at codons 21 (E21D) and 22 (A22V) along with multiple mutations associated with drug resistance, M46I/P63L/A71V/I84V/I93L, in a patient who had failed protease inhibitor (PI) therapy. Longitudinal analysis revealed that the P63L/A71V/I93L changes were present prior to PI therapy. Polymorphisms in the Gag sequence were only seen in the p1/p6 cleavage site at the P1′ position (Leu to Pro) and the P5′ position (Pro to Leu). To characterize the role of these mutations in drug susceptibility and replication capacity, a chimeric HIV-1 strain containing the 19I/E21D/A22V mutations with the M46I/P63L/A71V/I84V/I93L and p1/p6 mutations was constructed. The chimera displayed high-level resistance to multiple PIs, but not to lopinavir, and grew to 30% of that of the wild type. To determine the relative contribution of each mutation to the phenotypic characteristic of the virus, a series of mutants was constructed using site-directed mutagenesis. A high level of resistance was only seen in mutants containing the 19I/A22V and p1/p6 mutations. The E21D mutation enhanced viral replication. These results suggest that the combination of the 19I/E21D/A22V mutations may emerge and lead to high-level resistance to multiple PIs. The combination of the 19I/A22V mutations may be associated with PI resistance; however, the drug resistance may be caused by the presence of a unique set of mutations in the p1/p6 mutations. The E21D mutation contributes to replication fitness rather than drug resistance.
The Cysteine-Rich Region and Secreted Form of the Attachment G Glycoprotein of Respiratory Syncytial Virus Enhance the Cytotoxic T-Lymphocyte Response despite Lacking Major Histocompatibility Complex Class I-Restricted Epitopes
Authors: Bukreyev Alexander , Serra Maria Elina , Laham Federico R. , Melendi Guillermina A. , Kleeberger Steven R. , Collins Peter L. , Polack Fernando P.
Published: May 2006

The cytotoxic T-lymphocyte (CTL) response is important for the control of viral replication during respiratory syncytial virus (RSV) infection. The attachment glycoprotein (G) of RSV does not encode major histocompatibility complex class I-restricted epitopes in BALB/c mice (H-2d). Furthermore, studies to date have described an absence of significant CTL activity directed against this protein in humans. Therefore, G previously was not considered necessary for the generation of RSV-specific CTL responses. In this study, we demonstrate that, despite lacking H-2d-restricted epitopes, G enhances the generation of an effective CTL response against RSV. Furthermore, we show that this stimulatory effect is independent of virus titers and RSV-induced inflammation; that it is associated primarily with the secreted form of G; and that the effect depends on the cysteine-rich region of G (GCRR), a segment conserved in wild-type isolates worldwide. These findings reveal a novel function for the GCRR with potential implications for the generation of protective cellular responses and vaccine development.
Medians for second-trimester maternal serum markers: geographical differences and variation caused by median multiples-of-median equations
Authors: Vranken G , Reynolds T , Van Nueten J
Published: May 2006

Objectives:To establish gestational age-specific mid-trimester normal medians for the prenatal serum markers α fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3) for a Belgian population by using the Beckman Coulter Access chemiluminiscent immunoassays; to compare these data with data obtained from other geographical regions; to propose regression coefficients for regressed medians and analyse variation induced by different regression equations; to evaluate the effect of formulas used for gestation correction on estimating risk in Down’s syndrome.

Design:Data derived from 862 fresh serum samples from women being screened for Down’s syndrome pregnancy, composed of selected pregnancies deemed to be normal, were examined in a retrospective study. Regressed medians were calculated by using a first-degree logarithmic–linear fit of the raw data. Multiples-of-median (MoM) values estimated by using a simple logarithmic–linear equation were compared with those calculated with higher-degree polynomials chosen with a goodness-of-fit analysis. Model-specific variation was estimated and the effect on risk for Down’s syndrome was evaluated.

Results:Regressed medians (Y) for Access serum markers AFP (IU/ml), HCG (IU/ml) and uE3 (nmol/l) for a Belgian population can be estimated with the equation Y = 10(A+BX)with X = decimal weeks. The best fit was obtained with a third-degree and a second-degree polynomial for AFP and uE3, respectively. Differences between the medians and among the slopes of the geographical populations were found to be significant (analysis of covariance, p<0.001).

Conclusions:Belgian marker medians versus gestational time are found to show a pattern that is similar to that in the literature. The log–linear equation is observed to give a good fit and can be suggested as a tool for calculating median MoM values for Belgian laboratories that use Access biochemical prenatal markers.
Feminism and public health ethics
Authors: Rogers W A
Published: May 2006

This paper sketches an account of public health ethics drawing upon established scholarship in feminist ethics. Health inequities are one of the central problems in public health ethics; a feminist approach leads us to examine not only the connections between gender, disadvantage, and health, but also the distribution of power in the processes of public health, from policy making through to programme delivery. The complexity of public health demands investigation using multiple perspectives and an attention to detail that is capable of identifying the health issues that are important to women, and investigating ways to address these issues. Finally, a feminist account of public health ethics embraces rather than avoids the inescapable political dimensions of public health.
Some perspectives on Chekhov’s short storyA Case History
Authors: Niemi J
Published: May 2006

The Russian writer and physician Anton Chekhov (1860–1904) draws on his clinical experience in many of his stories. One of his later masterpieces entitledA Case History(1898) depicts a physician’s visit to a small industrial community where a wealthy young woman is suffering from diffuse symptoms. The physician, Dr Koryolov, meets the patient and makes a diagnosis. While staying on the estate overnight he also analyses the patient’s relation to her living conditions.
Evaluating a poetry workshop in medical education
Authors: Collett T J , McLachlan J C
Published: May 2006

This study aimed at evaluating how doing poetry could affect students’ understanding of medical practice and at assessing the effectiveness of the evaluation method used. Qualitative research was carried out on the experiences of medical students participating in a poetry workshop, followed by some quantitative analysis. The study was conducted at Peninsula Medical School and St Ives, Cornwall, UK, with three medical students, a poet and a pathologist as participants. Data were collected by interviews, observation and web access. “Doing poetry” with a professional poet was found to assist communication between doctors and patients as it enhanced skills of observation, heightened awareness of the effect of language and fostered deep reflection. Poetry was also found to offer an outlet for medics and patients. The voluntary workshop attracted three participants; however, it might have had an effect on the wider student community because the poetry website received 493 hits in four months. Qualitative methods worked well as a tool for evaluation. “Doing poetry for poetry’s sake” seemed to foster the development of skills related to empathy. The opportunity to do poetry should be made available to medical students as part of a wider arts and humanities programme.
Long hours in paid and domestic work and subsequent sickness absence: does control over daily working hours matter?
Authors: Ala-Mursula L , Vahtera J , Kouvonen A , Väänänen A , Linna A , Pentti J , Kivimäki M
Published: May 2006

Objectives:To explore the associations of working hours (paid, domestic, commuting, and total) with sickness absence, and to examine whether these associations vary according to the level of employee control over daily working hours.

Methods:Prospective cohort study among 25 703 full-time public sector employees in 10 towns in Finland. A survey of working hours and control over working hours was carried out in 2000–01. The survey responses were linked with register data on the number of self-certified (⩽3 days) and medically certified (>3 days) sickness absences until the end of 2003. Poisson regression analyses with generalised estimating equations were used to take into account the fact that the employees were nested within work units. Adjustments were made for work and family characteristics and health behaviour. The mean follow-up period was 28.1 (SD 8.1) months.

Results:Long domestic and total working hours were associated with higher rates of medically certified sickness absences among both genders. In contrast, long paid working hours were associated with lower rates of subsequent self-certified sickness absences. Long commuting hours were related to increased rates of sickness absence of both types. Low control over daily working hours predicted medically certified sickness absences for both the women and men and self-certified absences for the men. In combinations, high control over working hours reduced the adverse associations of long domestic and total working hours with medically certified absences.

Conclusions:Employee control over daily working hours may protect health and help workers successfully combine a full-time job with the demands of domestic work.
Fiscal versus social responsibility: how Philip Morris shaped the public funds divestment debate
Authors: Wander N , Malone R E
Published: May 2006

Calls for institutional investors to divest (sell off) tobacco stocks threaten the industry’s share values, publicise its bad behaviour, and label it as a politically unacceptable ally. US tobacco control advocates began urging government investment and pension funds to divest as a matter of responsiblesocialpolicy in 1990. Following the initiation of Medicaid recovery lawsuits in 1994, advocates highlighted the contradictions between state justice departments suing the industry, and state health departments expanding tobacco control programmes, while state treasurers invested in tobacco companies. Philip Morris (PM), the most exposed US company, led the divestment opposition, consistently framing the issue as one of responsiblefiscalpolicy. It insisted that funds had to be managed for the exclusive interest of beneficiaries, not the public at large, and for high share returns above all. This paper uses tobacco industry documents to show how PM sought to frame both the rhetorical contents and the legal contexts of the divestment debate. While tobacco stock divestment was eventually limited to only seven (but highly visible) states, US advocates focused public attention on the issue in at least 18 others plus various local jurisdictions. This added to ongoing, effective campaigns to denormalise and delegitimise the tobacco industry, dividing it from key allies. Divestment as a delegitimisation tool could have both advantages and disadvantages as a tobacco control strategy in other countries.
Decline in respiratory symptoms in service workers five months after a public smoking ban
Authors: Eagan T M L , Hetland J , Aarø L E
Published: May 2006

Objective:To evaluate the effect of a total ban on smoking indoors in restaurants and other hospitality business premises in Norway, on respiratory symptoms among workers in the industry.

Methods:Phone interviews with 1525 employees in the hospitality business were conducted immediately before the enacting of the law. In a follow-up study five months later, 906 of the workers from the baseline sample participated. Questions were asked on demographic variables, passive smoking exposure, personal smoking, attitudes towards the law, and five respiratory symptoms. Change in symptom prevalence was analysed with McNemar’s test and with analysis of variance (ANOVA) for repeated measures.

Results:The prevalence of all five symptoms declined after the ban; for morning cough from 20.6% to 16.2% (p < 0.01); for daytime cough from 23.2% to 20.9%; for phlegm cough from 15.3% to 11.8% (p < 0.05); for dyspnoea from 19.2% to 13.0% (p < 0.01); and for wheezing from 9.0% to 7.8%. ANOVA showed that the largest decline in symptom prevalence was seen among workers who themselves gave up smoking, and subjects with a positive attitude towards the law before it took effect.

Conclusion:A significant decrease in respiratory symptoms among service industry workers was found five months after the enacting of a public smoking ban.
CONDENSATION IN AN ECONOMIC MODEL WITH BRAND COMPETITION
Authors: CASILLAS L. , ESPINOSA F. J. , HUERTA-QUINTANILLA R. , RODRIGUEZ-ACHACH M.
Published: May 2006

We present a linear agent based model on brand competition. Each agent belongs to one of the two brands and interacts with its nearest neighbors. In the process the agent can decide to change to the other brand if the move is beneficial. The numerical simulations show that the systems always condenses into a state when all agents belong to a single brand. We study the condensation times for different parameters of the model and the influence of different mechanisms to avoid condensation, like anti monopoly rules and brand fidelity.
QUANTUM SECURE DIRECT COMMUNICATION WITHOUT USING PERFECT QUANTUM CHANNEL
Authors: WANG JIAN , ZHANG QUAN , TANG CHAOJING
Published: May 2006

Most of the quantum secure direct communication protocol needs a pre-established secure quantum channel. Only after insuring the security of quantum channel, could the sender encode the secret message and send them to the receiver through the secure channel. In this paper, we present a quantum secure direct communication protocol using Einstein-Podolsky-Rosen pairs without insuring the security of quantum channel before transmitting the secret message. Compared with the protocol proposed by Deng et al. [Phys. Rev. A68, 042317 (2003)] and the scheme proposed by Yan et al. [ Euro. Phys. J. B41, 75 (2004)], the present protocol provides higher efficiency.
PROBE THE EFFECTS OF SPLIT SUSY IN RARE B DECAYS
Authors: CHEN CHUAN-HUNG , GENG CHAO-QIANG
Published: May 2006

We study the decays of B→K(*)ℓ+ℓ- in split supersymmetry with R-parity violation. We find that the decay branching ratio of B→Kτ+τ- in the new physics model due to the scalar interactions can be 1.8×10-6 which is about one order of magnitude larger than in the standard model, whereas those of B→Kℓ+ℓ- (ℓ=e and μ) and the K* modes are insensitive to the new physics. On the other hand, the forward–backward asymmetries of B→Kτ+τ- and Kμ+μ-, vanishing in the standard model, can be over 10 and 1%, respectively. In addition, we show that the new interactions will significantly change the forward–backward asymmetry in B→K*τ+τ-.
THE PHANTOM OF THE OPRA
Authors: COLEY A. , HERVIK S. , LATTA J.
Published: May 2006

The Observed Perlmutter-Riess Acceleration (OPRA) implies that the expansion of the Universe is currently increasing and is motivation for the so-called phantom energy models. We consider the dynamics of phantom scalar field models. An important physical time constraint, which can be used to rule out many cosmological models, is obtained from the condition that all forms of energy density, including the field causing OPRA (e.g., the phantom field), must be non-negligible for an extended period, which is conservatively estimated to be of the order of a few Gyr. We find that this physical time constraint cannot be satisfied in conventional phantom cosmological models.
CASCADING SVMS AS A TOOL FOR MEDICAL DIAGNOSIS USING MULTI-CLASS GENE EXPRESSION DATA
Authors: FLAOUNAS ILIAS N. , IAKOVIDIS DIMITRIS K. , MAROULIS DIMITRIS E.
Published: May 2006

In this paper we propose a novel Support Vector Machines-based architecture for medical diagnosis using multi-class gene expression data. It consists of a pre-processing unit and N-1 sequentially ordered blocks capable of classifying N classes in a cascading manner. Each block embodies both a gene selection and a classification module. It offers the flexibility of constructing block-specific gene expression spaces and hypersurfaces for the discrimination of the different classes. The proposed architecture was applied for medical diagnostic tasks including prostate and lung cancer diagnosis. Its performance was evaluated by using a leave-one-out cross validation approach which avoids the bias introduced by the gene selection process. The results show that it provides high accuracy which in most cases exceeds the accuracy achieved by the popular one-vs-one and one-vs-all SVM combination schemes and Nearest-Neighbor classifiers. The cascading SVMs can be successfully applied as a medical diagnostic tool.
NEW SELF-ADAPTIVE PROBABILISTIC NEURAL NETWORKS IN BIOINFORMATIC AND MEDICAL TASKS
Authors: GEORGIOU V. L. , PAVLIDIS N. G. , PARSOPOULOS K. E. , ALEVIZOS PH. D. , VRAHATIS M. N.
Published: May 2006

We propose a self–adaptive probabilistic neural network model, which incorporates optimization algorithms to determine its spread parameters. The performance of the proposed model is investigated on two protein localization problems, as well as on two medical diagnostic tasks. Experimental results are compared with that of feedforward neural networks and support vector machines. Different sampling techniques are used and statistical tests are conducted to calculate the statistical significance of the results.
ON THE CLASSIFICATION OF KIM AND KOSTRIKIN MANIFOLDS
Authors: CAVICCHIOLI ALBERTO , PAOLUZZI LUISA , SPAGGIARI FULVIA
Published: May 2006

We completely classify the topological and geometric structures of some series of closed connected orientable 3-manifolds introduced by Kim and Kostrikin in [20,21] as quotient spaces of certain polyhedral 3-cells by pairwise identifications of their boundary faces. Then we study further classes of closed orientable 3-manifolds arising from similar polyhedral schemata, and describe their topological properties.
ON THE HULL NUMBERS OF TORUS LINKS
Authors: IZMESTIEV IVAN
Published: May 2006

The nth hull of a union of curves in ℝ3 is the set of points with the property: Any plane passing through the point intersects the curves at least 2n times. The hull number of a link L is defined as the minimum number of non-empty hulls a representative of L can have. We show that the hull numbers of torus links is smaller than expected, but still large. In particular, for a torus link of type (p, p) hull number equals [Formula: see text], and in general for the type (p, q) with q > p it is greater than or equal to [Formula: see text].
ON THE CONTRIBUTIONS FROM DILATONIC STRINGS TO THE FLAT BEHAVIOR OF THE ROTATIONAL CURVES IN GALAXIES
Authors: COSTA M. LEINEKER , OLIVEIRA A. L. N. , GUIMARÃES M. E. X.
Published: May 2006

We analyze the flat behavior of the rotational curves in some galaxies in the framework of a dilatonic, current-carrying string. We determine the expression of the tangential velocity of test objects following a stable circular equatorial orbit in this space–time.
AN EXACT SELF-SIMILAR SOLUTION FOR AN EXPANDING BALL OF RADIATION
Authors: PONCE DE LEON J. , WESSON P. S.
Published: May 2006

We give an exact solution of the 5D Einstein equations which in 4D can be interpreted as a spherically symmetric dissipative distribution of matter, with heat flux, whose effective density and pressure are nonstatic, nonuniform, and satisfy the equation of state of radiation. The matter satisfies the usual energy and thermodynamic conditions. The energy density and temperature are related by the Stefan–Boltzmann law. The solution admits a homothetic Killing vector in 5D, which induces the existence of self-similar symmetry in 4D, where the line element as well as the dimensionless matter quantities are invariant under a simple "scaling" group.
MAXIMUM MASS OF A CLASS OF COLD COMPACT STARS
Authors: SHARMA R. , KARMAKAR S. , MUKHERJEE S.
Published: May 2006

We calculate the maximum mass of the class of compact stars described by the Vaidya–Tikekar27 model. The model permits a simple method of systematically fixing bounds on the maximum possible mass of cold compact stars with a given value of radius or central density or surface density. The relevant equations of state are also determined. Although simple, the model is capable of describing the general features of the recently observed very compact stars. For the calculation, no prior knowledge of the equation of state (EOS) is required. This is in contrast to earlier calculations for maximum mass which were done by choosing first the relevant EOSs and using those to solve the TOV equation with appropriate boundary conditions. The bounds obtained by us are comparable and, in some cases, more restrictive than the earlier results.
HIGHER-ORDER QUASILINEAR PARABOLIC EQUATIONS WITH SINGULAR INITIAL DATA
Authors: GALAKTIONOV V. A. , SHISHKOV A. E.
Published: May 2006

As a basic model, we study the 2mth-order quasilinear parabolic equation of diffusion-absorption type [Formula: see text] where Δm,pis the 2mth-order p-Laplacian [Formula: see text].

We consider the Cauchy problem in RN× R+with arbitrary singular initial data u0≠ 0 such that u0(x) = 0 for any x ≠ 0. We prove that, in the most delicate case p = q and [Formula: see text], this Cauchy problem admits the unique trivial solution u(·, t) = 0 for t > 0. For λ < λ0, such nontrivial very singular solutions are known to exist for some semilinear higher-order models. This extends the well-known result by Brezis and Friedman established in 1983 for the semilinear heat equation with p = q = m = 1.
AN ISOPERIMETRIC INEQUALITY WITH REMAINDER TERM
Authors: TAKAHASHI FUTOSHI
Published: May 2006

We prove a version of the isoperimetric inequality for mappings with remainder term. Let S = (32π)1/3and Q(u) = ∫R2u · ux1∧ ux2dx for a mapping u : R2→ R3in a function space [Formula: see text] defined below. Let [Formula: see text] be a set of functions in [Formula: see text] for which we have equality in the classical isoperimetric inequality S|Q(u)|2/3≤ ∫R2|∇u|2dx. We show that for some positive constant C > 0, [Formula: see text] holds for any [Formula: see text]. Here, [Formula: see text] denotes the distance of u from [Formula: see text] in [Formula: see text].
CONTINUITY OF THE VOLUME OF SIMPLICES IN CLASSICAL GEOMETRY
Authors: LUO FENG
Published: May 2006

It is proved that the volume of spherical or hyperbolic simplices, when considered as a function of the dihedral angles, can be extended continuously to degenerated simplices. This verifies affirmatively a conjecture of John Minor.
VISUALIZATION OF THE SYMPATHY INTERACTION BETWEEN ARTICLES AND THE READER
Authors: INAMI MAYUMI , IWASAKI HARUMI , MOROHOSHI NORIKO , KATAOKA ISAO , SAITO YOSHIFURU , TSUCHIYA HIROSHI , HORII KIYOSHI
Published: May 2006

The author's peculiarity in Ekuni's short story Duke is visualized in the reader-story fusion world by analyzing the conversation; the inner, direct and indirect speeches. Voices and sounds as conversations and onomatopoeias play an interesting role in her story world. Structures of expression in conversation in her two books are visualized by wavelet multiresolution analysis. In this study, the visualization of Duke is compared with that of Rakka-suru Yugata. As a result, the author's peculiarity and literary genre differences are extracted.
APPLICATION OF WAVELET MULTIRESOLUTION ANALYSIS TO JET FLOW ISSUING FROM ROTATING CIRCULAR PIPE WITH INCLINED SECTION
Authors: NAKASHIMA MASAHIRO , RINOSHIKA AKIRA (HUI LI) , TABATA TAKAHIDE , NOZAKI TSUTOMU
Published: May 2006

The flow feature of the jet issuing from the circular pipe with the rotating inclined section has been investigated by the methods of flow visualization and image processing. It has been found that the jet diffusion is affected by the inclined angle and the rotating speed. The coherent structure of the jet has also been studied by using wavelet multiresolution analysis. The multiscale turbulent structures were visualized and the core and edge of the vortex were identified at different broad scales.
IDENTIFICATION OF ROTATING PRESSURE WAVES IN A CENTRIFUGAL COMPRESSOR DIFFUSER BY MEANS OF THE WAVELET CROSS-CORRELATION
Authors: HORODKO LONGIN
Published: May 2006

Rotating stall is usually the first symptom of approaching compressor instability. It consists of zones of a turbulent flow, which rotate slower than the compressor impeller. The wavelet cross-correlation function was applied to detect rotating objects, whereas the continuous wavelet transform was used to identify different phases of the compressor operation. These methods of signal analysis enabled the identification of rotating pressure waves that appear during all phases of operation. Some of them have several times shorter wavelength than these manifested by the rotating stall. What is more, rotating pressure waves, though very weak, appear also during the stable compressor operation.
Association study of CRP gene polymorphisms with serum CRP level and cardiovascular risk in the NHLBI Family Heart Study
Authors: Wang Qingwei , Hunt Steven C. , Xu Qin , Chen Yuqing E. , Province Michael A. , Eckfeldt John H. , Pankow James S. , Song Qing
Published: May 2006

Recent epidemiological studies have indicated that baseline C-reactive protein (CRP) levels may have value in prediction of cardiovascular risk. Using six tag single-nucleotide polymorphisms (SNPs) selected from our complete list of SNPs on the CRP gene, we investigated the association of CRP genotypes with plasma CRP levels and cardiovascular risk in the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study cohort (1,296 Caucasians, 48.5% male, 54.7 ± 12.8 yr old). There was a significant trend toward association of CRP haplotypes with CRP levels ( P = 0.045). SNP analysis indicated a highly significant association of SNP −757 (rs3093059, P = 0.0004) and SNP −286 (rs3091244, P = 0.0065) and a borderline association of SNP −7180 (rs1341665, P = 0.06) with CRP levels. Neither CRP haplotypes nor individual SNP genotypes were associated with intima-media thickness of the common carotid or internal carotid artery or the bifurcation of the carotid arteries. These results indicated a strong impact of local SNPs of the CRP gene on plasma CRP levels, but there was no direct evidence that these genetically controlled CRP elevations by local CRP SNPs contributed to cardiovascular disease phenotypes.
Impaired defense of core temperature in aged humans during mild cold stress
Authors: DeGroot David W. , Kenney W. Larry
Published: May 2006

Aged humans often exhibit an impaired defense of core temperature during cold stress. However, research documenting this response has typically used small subject samples and strong cold stimuli. The purpose of this study was to determine the responses of young and older subjects, matched for anthropometric characteristics, during mild cold stress. Thirty-six young (YS; 23 ± 1 years, range 18–30) and 46 older (OS; 71 ± 1 years, range 65–89) subjects underwent a slow transient cold air exposure from a thermoneutral baseline, during which esophageal (Tes) and mean skin temperatures (Tsk), O2 consumption, and skin blood flow (SkBF; laser-Doppler flowmetry) were measured. Cold exposure was terminated at the onset of visible sustained shivering. Net metabolic heat production (Mnet), heat debt, predicted change in midregion temperature (ΔTmid), and tissue insulation (It) were calculated. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial pressure and expressed as percent change from baseline (ΔCVC%base). There were no baseline group differences for Tes, but OS Mnet was lower (OS: 38.0 ± 1.1; YS: 41.9 ± 1.1 W · m−2, P < 0.05). Tes was well maintained in YS but fell progressively in OS ( P < 0.01 for all timepoints after 35 min). The skin vasoconstrictor response to mild cold stress was attenuated in OS (42 ± 3 vs. 53 ± 4 ΔCVC%base, P < 0.01). There were no group differences for Tsk or It, while Mnet remained lower in OS ( P < 0.05). The ΔTmid did not account for the drop in Tes in OS. Healthy aged humans failed to maintain Tes; however, the mechanisms underlying this response are not clear.
A novel method to determine lean body water using localized skin biopsies: correlation between lean skin water and lean body water in an overhydration model
Authors: Campbell S. E. , Ostrowski R. , Hoarau C. , Durr N. , Debreczeny M. P.
Published: May 2006

To determine the relationship between total body water (TBW) fraction and local water content measured in the skin (SW) this study assessed eight anesthetized piglets in an overhydration model. TBW was assessed by deuterium oxide dilution and body mass measurements taken throughout the experiments, and by whole body carcass analysis at the end of each experiment. Additionally, extracellular water and plasma volume were assessed using bromide dilution and Evan's blue dilution, respectively. SW was assessed by tissue biopsies taken at 60-min intervals throughout the experiment. Lean body water (LBW) fraction and lean skin water (LSW) fraction were assessed by extracting the fat from the carcass and biopsy samples. A correlation does exist between TBW fraction and SW fraction with r2= 0.58 ( P < 0.05); however, the strongest correlation occurred between the LBW fraction and LSW fraction with r2= 0.87 ( P < 0.05) and an SE of prediction of 0.77%. These data demonstrate that LSW gives an accurate and precise estimate of LBW and could therefore be used to determine the hydration index in appropriate research settings.
Supraspinal fatigue does not explain the sex difference in muscle fatigue of maximal contractions
Authors: Hunter Sandra K. , Butler Jane E. , Todd Gabrielle , Gandevia Simon C. , Taylor Janet L.
Published: May 2006

Young women are less fatigable than young men for maximal and submaximal contractions, but the contribution of supraspinal fatigue to the sex difference is not known. This study used cortical stimulation to compare the magnitude of supraspinal fatigue during sustained isometric maximal voluntary contractions (MVCs) performed with the elbow flexor muscles of young men and women. Eight women (25.6 ± 3.6 yr, mean ± SD) and 9 men (25.4 ± 3.8 yr) performed six sustained MVCs (22-s duration each, separated by 10 s). Before the fatiguing contractions, the men were stronger than the women (75.9 ± 9.2 vs. 42.7 ± 8.0 N·m; P < 0.05) in control MVCs. Voluntary activation measured with cortical stimulation before fatigue was similar for the men and women during the final control MVC (95.7 ± 3.0 vs. 93.3 ± 3.6%; P > 0.05) and at the start of the fatiguing task ( P > 0.05). By the end of the six sustained fatiguing MVCs, the men exhibited greater absolute and relative reductions in torque (65 ± 3% of initial MVC) than the women (52 ± 9%; P < 0.05). The increments in torque (superimposed twitch) generated by motor cortex stimulation during each 22-s maximal effort increased with fatigue ( P < 0.05). Superimposed twitches were similar for men and women throughout the fatiguing task (5.5 ± 4.1 vs. 7.3 ± 4.7%; P > 0.05), as well as in the last sustained contraction (7.8 ± 5.9 vs. 10.5 ± 5.5%) and in brief recovery MVCs. Voluntary activation determined using an estimated control twitch was similar for the men and women at the start of the sustained maximal contractions (91.4 ± 7.4 vs. 90.4 ± 6.8%, n = 13) and end of the sixth contraction (77.2 ± 13.3% vs. 73.1 ± 19.6%, n = 10). The increase in the area of the motor-evoked potential and duration of the silent period did not differ for men and women during the fatiguing task. However, estimated resting twitch amplitude and the peak rates of muscle relaxation showed greater relative reductions at the end of the fatiguing task for the men than the women. These results indicate that the sex difference in fatigue of the elbow flexor muscles is not explained by a difference in supraspinal fatigue in men and women but is largely due to a sex difference of mechanisms located within the elbow flexor muscles.
Repeated static contractions increase mitochondrial vulnerability toward oxidative stress in human skeletal muscle
Authors: Sahlin Kent , Nielsen Jens Steen , Mogensen Martin , Tonkonogi Michail
Published: May 2006

Repeated static contractions (RSC) induce large fluctuations in tissue oxygen tension and increase the generation of reactive oxygen species (ROS). This study investigated the effect of RSC on muscle contractility, mitochondrial respiratory function, and in vitro sarcoplasmic reticulum (SR) Ca2+kinetics in human muscle. Ten male subjects performed five bouts of static knee extension with 10-min rest in between. Each bout of RSC (target torque 66% of maximal voluntary contraction torque) was maintained to fatigue. Muscle biopsies were taken preexercise and 0.3 and 24 h postexercise from vastus lateralis. Mitochondria were isolated and respiratory function measured after incubation with H2O2(HPX) or control medium (Con). Mitochondrial function was not affected by RSC during Con. However, RSC exacerbated mitochondrial dysfunction during HPX, resulting in decreased respiratory control index, decreased mitochondrial efficiency (phosphorylated ADP-to-oxygen consumed ratio), and increased noncoupled respiration (HPX/Con post- vs. preexercise). SR Ca2+uptake rate was lower 0.3 vs. 24 h postexercise, whereas SR Ca2+release rate was unchanged. RSC resulted in long-lasting changes in muscle contractility, including reduced maximal torque, low-frequency fatigue, and faster torque relaxation. It is concluded that RSC increases mitochondrial vulnerability toward ROS, reduces SR Ca2+uptake rate, and causes low-frequency fatigue. Although conclusive evidence is lacking, we suggest that these changes are related to increased formation of ROS during RSC.
The frequency of alternate muscle activity is associated with the attenuation in muscle fatigue
Authors: Kouzaki Motoki , Shinohara Minoru
Published: May 2006

Alternate muscle activity between synergist muscles has been demonstrated during low-level sustained contractions [≤5% of maximal voluntary contraction (MVC) force]. To determine the functional significance of the alternate muscle activity, the association between the frequency of alternate muscle activity during a low-level sustained knee extension and the reduction in knee extension MVC force was studied. Forty-one healthy subjects performed a sustained knee extension at 2.5% MVC force for 1 h. Before and after the sustained knee extension, MVC force was measured. The surface electromyogram was recorded from the rectus femoris (RF), vastus lateralis (VL), and vastus medialis (VM) muscles. The frequency of alternate muscle activity for RF-VL, RF-VM, and VL-VM pairs was determined during the sustained contraction. The frequency of alternate muscle activity ranged from 4 to 11 times/h for RF-VL (7.0 ± 2.0 times/h) and RF-VM (7.0 ± 1.9 times/h) pairs, but it was only 0 to 2 times/h for the VL-VM pair (0.5 ± 0.7 times/h). MVC force after the sustained contraction decreased by 14% ( P < 0.01) from 573.6 ± 145.2 N to 483.3 ± 130.5 N. The amount of reduction in MVC force was negatively correlated with the frequency of alternate muscle activity for the RF-VL and RF-VM pairs ( P < 0.001 and r = 0.65 for both) but not for the VL-VM pair. The results demonstrate that subjects with more frequent alternate muscle activity experience less muscle fatigue. We conclude that the alternate muscle activity between synergist muscles attenuates muscle fatigue.
Chemotherapy-induced epidermal growth factor receptor activation determines response to combined gefitinib/chemotherapy treatment in non–small cell lung cancer cells
Authors: Van Schaeybroeck Sandra , Kyula Joan , Kelly Donal M. , Karaiskou-McCaul Anthi , Stokesberry Susan A. , Van Cutsem Eric , Longley Daniel B. , Johnston Patrick G.
Published: May 2006

Activating epidermal growth factor receptor (EGFR) mutations have been linked with sensitivity to gefitinib and erlotinib; however, there are no established predictive markers for response to the combination of EGFR inhibitors with standard chemotherapy in non–small cell lung cancer (NSCLC) patients. In this study, we characterized a panel of human EGFR wild-type and mutant NSCLC cells for their sensitivity to gefitinib alone and in combination with cisplatin or Taxol. Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet cell viability assays. Cell cycle distribution was measured by flow cytometry. EGFR expression was measured by flow cytometry, real-time PCR, and Western blotting. EGFR/Her2/Akt and extracellular signal-regulated kinase 1/2 (Erk1/2) phosphorylation were measured by Western blotting. Two of nine EGFR wild type and one of two EGFR mutant NSCLC cells were sensitive to gefitinib, and this was associated with a decrease in phospho (p)–Akt and pErk1/2 following gefitinib exposure. There was no correlation between constitutive EGFR expression or activity and sensitivity to gefitinib nor was there a correlation between Her2/Akt and Erk1/2 activity and gefitinib sensitivity. However, in cells displaying a synergistic interaction between gefitinib and chemotherapy (cisplatin or Taxol), a dose-dependent increase in pEGFR was observed following chemotherapy exposure. In contrast, in cells where no change or a decrease in pEGFR following drug treatment was observed, we found an antagonistic or (at best) an additive interaction between the two compounds. Furthermore, the nature of this interaction was not dependent on the presence of a mutant EGFR. These novel findings suggest that modulation of EGFR activity following drug treatment determines response to gefitinib in combination with chemotherapy in NSCLC cells. [Mol Cancer Ther 2006;5(5):1154–65]
Aspirin reduces the outcome of anticancer therapy in Meth A–bearing mice through activation of AKT-glycogen synthase kinase signaling
Authors: di Palma Antonella , Matarese Giuseppe , Leone Vincenza , Di Matola Tiziana , Acquaviva Fabio , Acquaviva Angela Maria , Ricchi Paolo
Published: May 2006

Aspirin displays, at millimolar concentrations, several mechanisms independent from its ability to inhibit cyclooxygenases. Occasionally, the mechanisms displayed in vitro have been clearly related to an effect of clinical relevance in vivo. An expanding literature has been focusing on the cytoprotective effect of aspirin in neurodegenerative disorders and the activation of AKT pathway in neuroprotection and induction of resistance to anticancer drugs. In this work, we tested the ability of aspirin to activate the AKT survival pathway in methylcholanthrene-induced fibrosarcoma cells (Meth A) transplanted into BALB/c nude mice and the clinical effect of aspirin cotreatment during etoposide (VP-16)–based anticancer therapy. We found that cotreatment with aspirin reduced VP-16-induced apoptosis and activated AKT in vitro and in vivo. In Meth A–bearing mice, aspirin administration also activated glycogen synthase kinase-3 and reduced the activity and the efficacy of anticancer therapy in VP-16 cotreated animals. Our data suggest that the antiapoptotic effect of aspirin operates in vivo through the activation of AKT-glycogen synthase kinase pathway causing a decrease in the outcome of VP-16-based therapy. These findings could have clinical relevance in treatment of human malignancies. [Mol Cancer Ther 2006;5(5):1318–24]
Detection of histone deacetylase inhibition by noninvasive magnetic resonance spectroscopy
Authors: Sankaranarayanapillai Madhuri , Tong William P. , Maxwell David S. , Pal Ashutosh , Pang Jihai , Bornmann William G. , Gelovani Juri G. , Ronen Sabrina M.
Published: May 2006

Histone deacetylase (HDAC) inhibitors are new and promising antineoplastic agents. Current methods for monitoring early response rely on invasive biopsies or indirect blood-derived markers. Our goal was to develop a magnetic resonance spectroscopy (MRS)–based method to detect HDAC inhibition. The fluorinated lysine derivative Boc-Lys-(Tfa)-OH (BLT) was investigated as a 19F MRS molecular marker of HDAC activity together with 31P MRS of endogenous metabolites. In silico modeling of the BLT-HDAC interaction and in vitro MRS studies of BLT cleavage by HDAC confirmed BLT as a HDAC substrate. BLT did not affect cell viability or HDAC activity in PC3 prostate cancer cells. PC3 cells were treated, in the presence of BLT, with the HDAC inhibitor p-fluoro-suberoylanilide hydroxamic acid (FSAHA) over the range of 0 to 10 μmol/L, and HDAC activity and MRS spectra were monitored. Following FSAHA treatment, HDAC activity dropped, reaching 53% of control at 10 μmol/L FSAHA. In parallel, a steady increase in intracellular BLT from 14 to 32 fmol/cell was observed. BLT levels negatively correlated with HDAC activity consistent with higher levels of uncleaved BLT in cells with inhibited HDAC. Phosphocholine, detected by 31P MRS, increased from 7 to 16 fmol/cell following treatment with FSAHA and also negatively correlated with HDAC activity. Increased phosphocholine is probably due to heat shock protein 90 inhibition as indicated by depletion of client proteins. In summary, 19F MRS of BLT, combined with 31P MRS, can be used to monitor HDAC activity in cells. In principle, this could be applied in vivo to noninvasively monitor HDAC activity. [Mol Cancer Ther 2006;5(5):1325–34]