bluuebunny/crossref_metadata_2025 huggingface dataset:
Unsteady Hydrodynamic Forces due to Rotor-Stator Interaction on a Diffuser Pump With Identical Number of Vanes on the Impeller and Diffuser
Authors: Zhang M. , Tsukamoto H.
Published: July 2005

Experimental and computational study was developed for unsteady hydrodynamic forces on a diffuser pump impeller excited by the interaction between the impeller and the vaned diffuser with the same number of vanes as impeller. Unsteady flow calculations are made using commercially available CFD software, CFX-TASCflow, as well as the two-dimensional vortex method. Calculated pressure and fluid forces on the impeller show good agreement with measured ones. It has been demonstrated that the fluid forces on the impeller with the same number of vanes as the vaned diffuser are smaller compared with other combinations of vane numbers. However, the pressure fluctuations are found to be greater than other cases.
Limitations of Richardson Extrapolation and Some Possible Remedies
Authors: Celik Ismail , Li Jun , Hu Gusheng , Shaffer Christian
Published: July 2005

The origin of oscillatory convergence in finite difference methods is investigated. Fairly simple implicit schemes are used to solve the steady one-dimensional convection-diffusion equation with variable coefficients, and possible scenarios are shown that exhibit the oscillatory convergence. Also, a manufactured solution to difference equations is formulated that exhibits desired oscillatory behavior in grid convergence, with a varying formal order of accuracy. This model-error equation is used to statistically assess the performance of several methods of extrapolation. Alternative extrapolation schemes, such as the deferred extrapolation to limit technique, to calculate the coefficients in the Taylor series expansion of the error function are also considered. A new method is proposed that is based on the extrapolation of approximate error, and is shown to be a viable alternative to other methods. This paper elucidates the problem of oscillatory convergence, and brings a new perspective to the problem of estimating discretization error by optimizing the information from a minimum number of calculations.
High-Pass Filtered Eddy-Viscosity Models for Large-Eddy Simulations of Compressible Wall-Bounded Flows
Authors: Stolz Steffen
Published: July 2005

In this contribution we consider large-eddy simulation (LES) using the high-pass filtered (HPF) Smagorinsky model of a spatially developing supersonic turbulent boundary layer at a Mach number of 2.5 and momentum-thickness Reynolds numbers at inflow of ∼4500. The HPF eddy-viscosity models employ high-pass filtered quantities instead of the full velocity field for the computation of the subgrid-scale (SGS) model terms. This approach has been proposed independently by Vreman (Vreman, A. W., 2003, Phys. Fluids, 15, pp. L61–L64) and Stolz et al. (Stolz, S., Schlatter, P., Meyer, D., and Kleiser, L., 2003, in Direct and Large Eddy Simulation V, Kluwer, Dordrecht, pp. 81–88). Different from classical eddy-viscosity models, such as the Smagorinsky model (Smagorinsky, J., 1963, Mon. Weath. Rev, 93, pp. 99–164) or the structure-function model (Métais, O. and Lesieur, M., 1992, J. Fluid Mech., 239, pp. 157–194) which are among the most often employed SGS models for LES, the HPF eddy-viscosity models do need neither van Driest wall damping functions for a correct prediction of the viscous sublayer of wall-bounded turbulent flows nor a dynamic determination of the coefficient. Furthermore, the HPF eddy-viscosity models are formulated locally and three-dimensionally in space. For compressible flows the model is supplemented by a HPF eddy-diffusivity ansatz for the SGS heat flux in the energy equation. Turbulent inflow conditions are generated by a rescaling and recycling technique in which the mean and fluctuating part of the turbulent boundary layer at some distance downstream of inflow is rescaled and reintroduced at the inflow position (Stolz, S. and Adams, N. A., 2003, Phys. Fluids, 15, pp. 2389–2412).
Regulation of X-Chromosome Counting by
Tsix
and
Xite
Sequences
Authors: Lee Jeannie T.
Published: July 2005

In mammals, X-inactivation establishes X-chromosome dosage parity between males and females. How X-chromosome counting regulates this process remains elusive, because neither the hypothesized inactivation “blocking factor” nor the required cis-elements have been defined. Here, a mouse knockout and transgenic analysis identified DNA sequences within the noncoding
Tsix
and
Xite
genes as numerators. Homozygous deficiency of
Tsix
resulted in “chaotic choice” and a variable number of inactive X's, whereas overdosage of
Tsix
/
Xite
inhibited X-inactivation. Thus, counting was affected by specific
Tsix
/
Xite
mutations, suggesting that counting is genetically separable from but molecularly coupled to choice. The mutations affect XX and XY cells differently, demonstrating that counting and choice are regulated not by one “blocking factor,” but by both a “blocking” and a “competence” factor.
We're Not Fred or Wilma
Authors: Bolhuis Johan J.
Published: July 2005

Adapting Minds
. Evolutionary Psychology and the Persistent Quest for Human Nature.
By David J. Buller
. MIT Press, Cambridge, MA, 2005. 564 pp. $34.95, £22.95. ISBN 0-262-02579-5.

The author reviews experimental support for the paradigm of evolutionary psychology and finds it wanting.
Mutations of a Residue within the Polyproline-Rich Region of Env Alter the Replication Rate and Level of Cytopathic Effects in Chimeric Avian Retroviral Vectors
Authors: Chang Kevin W. , Barsov Eugene V. , Ferris Andrea L. , Hughes Stephen H.
Published: July 2005

Previous attempts to extend the host range of the avian sarcoma/leukosis virus (ASLV)-based RCASBP vectors produced two viral vectors, RCASBP M2C (4070A) and RCASBP M2C (797-8), which replicate using the amphotropic murine leukemia virus 4070A Env protein (2). Both viruses were adapted to replicate efficiently in the avian cell line DF-1, but RCASBP M2C (4070A) caused extensive cytopathic effects (CPE) in DF-1 cells whereas RCASBP M2C (797-8) induced low levels of CPE. The two viruses differed only at amino acid 242 of the polyproline-rich region in the surface (SU) subunit of the Env protein. In RCASBP M2C (4070A), an isoleucine replaced the wild-type proline residue, whereas a threonine residue was found in RCASBP M2C (797-8). In the present study, we show that other amino acid substitutions at position 242 strongly influence the CPE and replication rate of the chimeric viruses. There was a correlation between the amount of unintegrated linear retroviral DNA present in infected DF-1 cells and the level of CPE. This suggests that there may be a role for superinfection in the CPE. The treatment of RCASBP M2C (4070A)-infected cells with dantrolene, which inhibits the release of calcium from the endoplasmic reticulum (ER), reduced the amount of CPE seen during infection with the highly cytotoxic virus. Dantrolene treatment did not appear to affect virus production, suggesting that Ca2+release from the ER had a role in the CPE caused by these viruses.
Characterization of Neuraminidase-Resistant Mutants Derived from Rotavirus Porcine Strain OSU
Authors: López José Agustín , Maldonado Antonio José , Gerder Marlene , Abanero José , Murgich Juan , Pujol Flor H. , Liprandi Ferdinando , Ludert Juan Ernesto
Published: July 2005

Infection by some rotavirus strains requires the presence of sialic acid on the cell surface, its infectivity being reduced in cells treated with neuraminidase. A neuraminidase treatment-resistant mutant was isolated from the porcine rotavirus strain OSU. In reassortant strains, the neuraminidase-resistant phenotype segregated with the gene coding for VP4. The mutant retained its capacity to bind to sialic acid. The VP4 sequence of the mutant differed from that of the parental OSU strain in an Asp-to-Asn substitution at position 100. Neutralization escape mutants selected from an OSU neuraminidase-sensitive clone by monoclonal antibodies that failed to recognize the neuraminidase-resistant mutant strain carried the same mutation at position 100 and were also neuraminidase resistant. Neuraminidase sensitivity was restored when the mutation at position 100 was compensated for by a second mutation (Gln to Arg) at position 125. Molecular mechanics simulations suggest that the neuraminidase-resistant phenotype associated with mutation of OSU residue 100 from Asp to Asn reflects the conformational changes of the sialic acid cleft that accompany sialic acid binding.
Early Alpha/Beta Interferon Production by Myeloid Dendritic Cells in Response to UV-Inactivated Virus Requires Viral Entry and Interferon Regulatory Factor 3 but Not MyD88
Authors: Hidmark Åsa S. , McInerney Gerald M. , Nordström Eva K. L. , Douagi Iyadh , Werner Kristen M. , Liljeström Peter , Hedestam Gunilla B. Karlsson
Published: July 2005

Alpha/beta interferons (IFN-α/β) are key mediators of innate immunity and important modulators of adaptive immunity. The mechanisms by which IFN-α/β are induced are becoming increasingly well understood. Recent studies showed that Toll-like receptors 7 and 8 expressed by plasmacytoid dendritic cells (pDCs) mediate the endosomal recognition of incoming viral RNA genomes, a process which requires myeloid differentiation factor 88 (MyD88). Here we investigate the requirements for virus-induced IFN-α/β production in cultures of bone marrow-derived murine myeloid DCs (mDCs). Using recombinant Semliki Forest virus blocked at different steps in the viral life cycle, we show that replication-defective virus induced IFN-α/β in mDCs while fusion-defective virus did not induce IFN-α/β. The response to replication-defective virus was largely intact in MyD88
−/−
mDC cultures but was severely reduced in mDC cultures from mice lacking IFN regulatory factor 3. Our observations suggest that mDCs respond to incoming virus via a pathway that differs from the fusion-independent, MyD88-mediated endosomal pathway described for the induction of IFN-α/β in pDCs. We propose that events during or downstream of viral fusion, but prior to replication, can activate IFN-α/β in mDCs. Thus, mDCs may contribute to the antiviral response activated by the immune system at early time points after infection.
Effects of Ebola Virus Glycoproteins on Endothelial Cell Activation and Barrier Function
Authors: Wahl-Jensen Victoria M. , Afanasieva Tatiana A. , Seebach Jochen , Ströher Ute , Feldmann Heinz , Schnittler Hans-Joachim
Published: July 2005

Ebola virus causes severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. Vascular instability and dysregulation are disease-decisive symptoms during severe infection. While the transmembrane glycoprotein GP
1,2
has been shown to cause endothelial cell destruction, the role of the soluble glycoproteins in pathogenesis is largely unknown; however, they are hypothesized to be of biological relevance in terms of target cell activation and/or increase of endothelial permeability. Here we show that virus-like particles (VLPs) consisting of the Ebola virus matrix protein VP40 and GP
1,2
were able to activate endothelial cells and induce a decrease in barrier function as determined by impedance spectroscopy and hydraulic conductivity measurements. In contrast, the soluble glycoproteins sGP and Δ-peptide did not activate endothelial cells or change the endothelial barrier function. The VLP-induced decrease in barrier function was further enhanced by the cytokine tumor necrosis factor alpha (TNF-α), which is known to induce a long-lasting decrease in endothelial cell barrier function and is hypothesized to play a key role in Ebola virus pathogenesis. Surprisingly, sGP, but not Δ-peptide, induced a recovery of endothelial barrier function following treatment with TNF-α. Our results demonstrate that Ebola virus GP
1,2
in its particle-associated form mediates endothelial cell activation and a decrease in endothelial cell barrier function. Furthermore, sGP, the major soluble glycoprotein of Ebola virus, seems to possess an anti-inflammatory role by protecting the endothelial cell barrier function.
Phylogeography, Population Dynamics, and Molecular Evolution of European Bat Lyssaviruses
Authors: Davis Patricia L. , Holmes Edward C. , Larrous Florence , Van der Poel Wim H. M. , Tjørnehøj Kirsten , Alonso Wladimir J. , Bourhy Hervé
Published: July 2005

European bat lyssaviruses types 1 and 2 (EBLV-1 and EBLV-2) are widespread in Europe, although little is known of their evolutionary history. We undertook a comprehensive sequence analysis to infer the selection pressures, rates of nucleotide substitution, age of genetic diversity, geographical origin, and population growth rates of EBLV-1. Our study encompassed data from 12 countries collected over a time span of 35 years and focused on the glycoprotein (G) and nucleoprotein (N) genes. We show that although the two subtypes of EBLV-1—EBLV-1a and EBLV-1b—have both grown at a low exponential rate since their introduction into Europe, they have differing population structures and dispersal patterns. Furthermore, there were strong constraints against amino acid change in both EBLV-1 and EBLV-2, as reflected in a low ratio of nonsynonymous to synonymous substitutions per site, particularly in EBLV-1b. Our inferred rate of nucleotide substitution in EBLV-1, approximately 5 × 10−5substitutions per site per year, was also one of the lowest recorded for RNA viruses and implied that the current genetic diversity in the virus arose 500 to 750 years ago. We propose that the slow evolution of EBLVs reflects their distinctive epidemiology in bats, where they occupy a relatively stable fitness peak.
Molecular Epidemiology of Group C Viruses (
Bunyaviridae
,
Orthobunyavirus
) Isolated in the Americas
Authors: Nunes Marcio R. T. , Travassos da Rosa Amelia P. A. , Weaver Scott C. , Tesh Robert B. , Vasconcelos Pedro F. C.
Published: July 2005

To date, no molecular studies on group C viruses (
Bunyaviridae
,
Orthobunyavirus
) have been published. We determined the complete small RNA (SRNA) segment and partial medium RNA segment nucleotide sequences for 13 group C members. The full-length SRNA sequences ranged from 915 to 926 nucleotides in length, and revealed similar organization in comparison with other orthobunyaviruses. Based on the 705 nucleotides of the N gene, group C members were distributed into three major phylogenetic groups, with the exception of
Madrid virus
, which was placed outside of these three groups. Analysis of the
Caraparu virus
strain BeH 5546 revealed that it has an SRNA sequence nearly identical to that of
Oriboca virus
and is a natural reassortant virus. In addition, analysis of 345 nucleotides of the Gn gene for eight group C viruses and for strain BeH 5546 revealed a different phylogenetic topology, suggesting a reassortment pattern among them. These findings represent the first evidence for natural reassortment among the group C viruses, which include several human pathogens. Furthermore, our genetic data corroborate previous relationships determined using serologic assays (complement fixation, hemagglutination inhibition, and neutralization tests) and suggest that a combination of informative molecular, serological, and ecological data is a helpful tool to understand the molecular epidemiology of arboviruses.
Evidence for Frequent Reinfection with Human Immunodeficiency Virus Type 1 of a Different Subtype
Authors: Chohan Bhavna , Lavreys Ludo , Rainwater Stephanie M. J. , Overbaugh Julie
Published: July 2005

A major premise underlying current human immunodeficiency virus type 1 (HIV-1) vaccine approaches is that preexisting HIV-1-specific immunity will block or reduce infection. However, the recent identification of several cases of HIV-1 reinfection suggests that the specific immune response generated for chronic HIV-1 infection may not be adequate to protect against infection by a second HIV-1 strain. It has been unclear, though, whether these individuals are representative of the global epidemic or are rare cases. Here we show that in a population of high-risk women, HIV-1 reinfection occurs almost as commonly as first infections. The study was designed to detect cases of reinfection by HIV-1 of a different subtype and thus captured cases where there was considerable diversity between the first and second strain. In each case, the second virus emerged ∼1 year after the first infection, and in two cases, it emerged when viral levels were high, suggesting that a well-established HIV-1 infection may provide little benefit in terms of immunizing against reinfection, at least by more-divergent HIV-1 variants. Our findings indicate an urgent need for studies of larger cohorts to determine the incidence and timing of both intersubtype and intrasubtype reinfection.
Parenchymal Expression of CD86/B7.2 Contributes to Hepatitis C Virus-Related Liver Injury
Authors: Sun Jiaren , Tumurbaatar Batbayar , Jia Junhui , Diao Hong , Bodola Francis , Lemon Stanley M. , Tang Wendell , Bowen David G. , McCaughan Geoffrey W. , Bertolino Patrick , Chan Teh-Sheng
Published: July 2005

Hepatitis C virus (HCV) infection is a major global health problem. Hepatic expression of immune costimulatory signaling molecules (e.g., B7) is known to be associated with ongoing liver injury in hepatitis C patients. However, due to the general lack of viral culture systems and adequate animal models, the function of these molecules in disease pathogenesis is poorly understood. To investigate the role of CD86 in HCV-related liver injury, we developed two transgenic mouse lineages with inducible expression of HCV structural proteins and constitutive expression of the costimulatory molecule CD86/B7.2 in the liver. Using a hydrodynamic-based, nonviral delivery protocol, we induced HCV transgene expression in the livers of HCV and CD86 single- and double-transgenic mice. We found that hepatic CD86 expression resulted in increased activation of and cytokine production (e.g., interleukin-2 and gamma interferon) by CD4+T cells and that the retention of these cells was associated with more pronounced necroinflammatory lesions in the liver. Taken together, these data suggest that augmented, parenchymal antigen presentation conferred by hepatocyte CD86 expression alters homeostasis and effector functions of CD4+T cells and contributes to liver injury. This study provides an additional rationale for exploring immunomodulation-based therapies that could reduce disease progression in individuals with chronic HCV infection.
AN APPROACH TO POTENTIAL SCATTERING
Authors: GÖNÜL B. , KOÇAK M.
Published: July 2005

Recently developed time-independent bound-state perturbation theory is extended to treat the scattering domain. The changes in the partial wave phase shifts are derived explicitly and the results are compared with those of other methods.
A FORWARD LOOKING, SINGULAR PERTURBATION APPROACH TO PRICING OPTIONS UNDER MARKET UNCERTAINTY AND TRADING NOISE
Authors: SOBEHART JORGE R.
Published: July 2005

In this article we examine the pricing of options when trading noise and uncertainty in the options markets invalidates the assumption that the price of the option depends solely on the price of the underlying security (or any set of underlying state variables). We show that the introduction of trading noise in the options market affects the call-put parity relationship, and can also contribute to generate implied volatility skews.
VALUATION OF EMPLOYEE RELOAD OPTIONS USING UTILITY MAXIMIZATION APPROACH
Authors: LAU KA WO , KWOK YUE KUEN
Published: July 2005

The reload provision in an employee stock option is an option enhancement that allows the employee to pay the strike upon exercising the stock option using his owned stocks and to receive new "reload" stock options. The usual Black–Scholes risk neutral valuation approach may not be appropriate to be adopted as the pricing vehicle for employee stock options, due to the non-transferability of the ownership of the options and the restriction on short selling of the firm's stocks as hedging strategy. In this paper, we present a general utility maximization framework to price non-tradeable employee stock options with reload provision. The risk aversion of the employee enters into the pricing model through the choice of the utility function. We examine how the value of the reload option to the employee is affected by the number of reloads outstanding, the risk aversion level and personal wealth. In particular, we explore how the reload provision may lower the difference between the cost of granting the option and the private option value and improve the compensation incentive of the option award.
INTERRELATIONSHIPS AMONG INTERNATIONAL STOCK MARKET INDICES: EUROPE, ASIA AND THE AMERICAS
Authors: SHARKASI ADEL , RUSKIN HEATHER J. , CRANE MARTIN
Published: July 2005

In this paper, we investigate the price interdependence between seven international stock markets, namely Irish, UK, Portuguese, US, Brazilian, Japanese and Hong Kong, using a new testing method, based on the wavelet transform to reconstruct the data series, as suggested by Lee [11]. We find evidence of intra-European (Irish, UK and Portuguese) market co-movements with the US market also weakly influencing the Irish market. We also find co-movement between the US and Brazilian markets and similar intra-Asian co-movements (Japanese and Hong Kong). Finally, we conclude that the circle of impact is that of the European markets (Irish, UK and Portuguese) on both American markets (US and Brazilian), with these in turn impacting on the Asian markets (Japanese and Hong Kong) which in turn influence the European markets. In summary, we find evidence for intra-continental relationships and an increase in importance of international spillover effects since the mid 1990s, while the importance of historical transmissions has decreased since the beginning of this century.
GENERALIZED WIENER PROCESS AND KOLMOGOROV'S EQUATION FOR DIFFUSION INDUCED BY NON-GAUSSIAN NOISE SOURCE
Authors: DUBKOV ALEXANDER , SPAGNOLO BERNARDO
Published: July 2005

We show that the increments of generalized Wiener process, useful to describe non-Gaussian white noise sources, have the properties of infinitely divisible random processes. Using functional approach and the new correlation formula for non-Gaussian white noise we derive directly from Langevin equation, with such a random source, the Kolmogorov's equation for Markovian non-Gaussian process. From this equation we obtain the Fokker–Planck equation for nonlinear system driven by white Gaussian noise, the Kolmogorov–Feller equation for discontinuous Markovian processes, and the fractional Fokker–Planck equation for anomalous diffusion. The stationary probability distributions for some simple cases of anomalous diffusion are derived.
Angiotensin II-induced negative inotropy in rat ventricular myocytes: role of reactive oxygen species and p38 MAPK
Authors: Palomeque Julieta , Sapia Luciana , Hajjar Roger J. , Mattiazzi Alicia , Vila Petroff Martín
Published: July 2005

The octapeptide angiotensin II (ANG II) can modulate cardiac contractility and is increased in heart failure, where contractile function is impaired. In rat cardiac myocytes, 1 μM of ANG II produces a negative inotropic effect (NIE) (24.6 ± 5% reduction). However, the subcellular signaling involved in this effect remains elusive. We examined the mechanisms and signaling events involved in the reduction in contractile function induced by the peptide in indo-1-loaded rat cardiomyocytes. The results showed that the NIE of ANG II was not associated with a parallel decrease in the intracellular Ca2+transient, indicating that a decrease in myofilament responsiveness to Ca2+underlies the reduction in contractility. We assessed the role of PKC, tyrosine kinases, reactive oxygen species (ROS), and mitogen-activated protein kinases (MAPKs) in the NIE of the peptide. Pretreatment of cells with the NAD(P)H oxidase inhibitor diphenyleneiodonium chloride or with the superoxide scavenger 4,5-dihydroxy-1,3-benzene-disulfonic acid did not affect the ANG II-induced NIE. Moreover, ANG II-induced ROS production, after 20 min of incubation with the peptide, could not be detected with the use of either the fluorophore 5-(6)-chloromethyl-2′, 7′-dichlorodihydrofluorecein diacetate or lucigenin-enhanced chemiluminescence. In contrast, the ANG II-induced NIE was abrogated by the inhibitors of PKC (calphostin C), tyrosine kinase (genistein), and p38 MAPK (SB-202190). Furthermore, the NIE was significantly exacerbated (60 ± 10% reduction) by p38 MAPK overexpression. These results exclude the participation of ROS in the NIE of the peptide and point to PKC and tyrosine kinase as upstream mediators. Furthermore, they reveal p38 MAPK as the putative effector of the reduction in myofilament responsiveness to Ca2+and the decrease in contractility induced by the peptide.
Protein kinase C and preconditioning: role of the sarcoplasmic reticulum
Authors: Yamamura Ken , Steenbergen Charles , Murphy Elizabeth
Published: July 2005

Activation of protein kinase C (PKC) is cardioprotective, but the mechanism(s) by which PKC mediates protection is not fully understood. Inasmuch as PKC has been well documented to modulate sarcoplasmic reticulum (SR) Ca2+and because altered SR Ca2+handling during ischemia is involved in cardioprotection, we examined the role of PKC-mediated alterations of SR Ca2+in cardioprotection. Using isolated adult rat ventricular myocytes, we found that addition of 1,2-dioctanoyl- sn-glycerol (DOG), to activate PKC under conditions that reduced myocyte death associated with simulated ischemia and reperfusion, also reduced SR Ca2+. Cell death was 57.9 ± 2.9% and 47.3 ± 1.8% in untreated and DOG-treated myocytes, respectively ( P < 0.05). Using fura 2 fluorescence to monitor Ca2+transients and caffeine-releasable SR Ca2+, we examined the effect of DOG on SR Ca2+. Caffeine-releasable SR Ca2+was significantly reduced (by ∼65%) after 10 min of DOG treatment compared with untreated myocytes ( P < 0.05). From our examination of the mechanism by which PKC alters SR Ca2+, we present the novel finding that DOG treatment reduced the phosphorylation of phospholamban (PLB) at Ser16. This effect is mediated by PKC-ε, because a PKC-ε-selective inhibitory peptide blocked the DOG-mediated decrease in phosphorylation of PLB and abolished the DOG-induced reduction in caffeine-releasable SR Ca2+. Using immunoprecipitation, we further demonstrated that DOG increased the association between protein phosphatase 1 and PLB. These data suggest that activated PKC-ε reduces SR Ca2+content through PLB dephosphorylation and that reduced SR Ca2+may be important in cardioprotection.
The endocannabinoid arachidonyl ethanolamide (anandamide) increases pulmonary arterial pressure via cyclooxygenase-2 products in isolated rabbit lungs
Authors: Wahn Hans , Wolf Jürgen , Kram Florian , Frantz Stefan , Wagner Jens A.
Published: July 2005

Several cannabinoids elicit systemic vasodilation, mainly via CB1 cannabinoid and vanilloid receptors. However, effects in the pulmonary circulation are unknown. Using the isolated, ventilated, buffer-perfused rabbit lung, we have shown that the endocannabinoids arachidonyl ethanolamide (anandamide) and 2-arachidonyl glycerol (2-AG) dose-dependently increase pulmonary arterial pressure (+19.9 ± 3.4 mmHg, 5 μM, and +39.5 ± 10.8 mmHg, 0.4 μM, respectively). 2-AG induced lung edema. The CB1 receptor antagonist AM-251 (0.1 and 5 μM) and the VR1 vanilloid receptor antagonist capsazepine (10 μM) failed to reduce anandamide's effects. The metabolically stable anandamide and 2-AG analogs R-methanandamide and noladin ether, Δ9-tetrahydrocannabinol, and the synthetic cannabinoid HU-210, which is no arachidonic acid product, were without effect. The unspecific cyclooxygenase (COX) inhibitor aspirin (100 μM, P < 0.001) and the specific COX-2 inhibitor nimesulide (10 μM, P < 0.01) completely prevented pulmonary hypertension after 5 μM anandamide. COX-2 RNA was detected in rabbit lungs. The synthetic thromboxane receptor antagonist SQ 29,548 was without effect, but the specific EP1 prostanoid receptor antagonist SC-19220 (100 μM) inhibited the pressure increase after anandamide ( P < 0.05). PCR analysis detected fatty acid amidohydrolase (FAAH), an enzyme that degrades endocannabinoids, in rabbit lung tissue. Furthermore, the specific FAAH inhibitor methyl arachidonyl fluorophosphonate (0.1 μM) blocked pressure effects of anandamide ( P < 0.01). Finally, anandamide (99 ± 55 pmol/g) and 2-AG (19.6 ± 8.4 nmol/g) were found in native lungs. We conclude that anandamide increases pulmonary arterial pressure via COX-2 metabolites following enzymatic degradation by FAAH into arachidonic acid products.
Effects of caffeine, verapamil, lithium, and KB-R7943 on mechanics and energetics of rat myocardial bigeminies
Authors: Savio-Galimberti E. , Ponce-Hornos J. E.
Published: July 2005

We examined the effects of pharmacological alteration of Ca2+sources on mechanical and energetic properties of paired-pulse (“bigeminic”) contractions. The fraction of heat release that is related to pressure development and pressure-independent heat release were measured during isovolumic contractions in arterially perfused rat ventricles. The heat released by regular and bigeminic contractions showed two brief pressure-independent components (H1 and H2) and a pressure-dependent component (H3). We used the ratio of active heat (H′a) to pressure-time integral (PtI) and the ratio of H3 to PtI to estimate the energetic cost of muscle contraction (overall economy) and pressure maintenance (contractile economy), respectively. Neither of these ratios was affected by stimulation pattern. Caffeine (an inhibitor of sarcoplasmic reticulum function) significantly decreased mechanical responses and increased the energetic cost of contraction (Δ = 101 ± 12.6%). Verapamil (an L-type Ca2+channel blocker) decreased pressure maintenance of extrasystolic (Δ = 43.4 ± 3.7%) and postextrasystolic (Δ = 37.5 ± 3.5%) contractions without affecting postextrasystolic potentiation, suggesting that a verapamil-insensitive fraction is responsible for potentiation. The verapamil-insensitive fraction was further studied in the presence of lithium (45 mM) and KB-R7943 (5 μM), inhibitors of the Na+/Ca2+exchanger. Both agents decreased all mechanical responses, including postextrasystolic potentiation (Δ = 67.3 ± 3.3%), without altering overall or contractile economies, suggesting an association of the verapamil-insensitive Ca2+fraction to the sarcolemmal Na+/Ca2+exchanger. The effect of the inhibitors of the Na+/Ca2+exchanger on potentiation suggests an increased participation of extracellular Ca2+(and, thus, a redistribution of the relative participation of the Ca2+pools) during bigeminic contractions in rat myocardium.
Exercise Training Differentially Affects Intrinsic Excitability of Autonomic and Neuroendocrine Neurons in the Hypothalamic Paraventricular Nucleus
Authors: Jackson Keshia , Silva Helaine M. Vieira , Zhang Wenfeng , Michelini Lisete C. , Stern Javier E.
Published: July 2005

Oxytocinergic and vasopressinergic brain stem projections have been shown to play an important role in mediating cardiovascular adjustments during exercise training (ET). The aim of the present work was to determine whether the intrinsic excitability of hypothalamic neurons giving rise to brain stem peptidergic projections is altered as a consequence of ET. Whole cell patch-clamp recordings were obtained from nucleus of the solitarii tract (NTS)-projecting paraventricular nucleus of the hypothalamus (PVN) neurons and from supraoptic nucleus (SON) and PVN magnocellular cells (MNCs), in hypothalamic slices obtained from sedentary (S) and ET rats. Our results indicate that intrinsic excitability of PVN neurons that innervate the NTS (PVN-NTS) is enhanced by ET, resulting in a more efficient input-output function (increase number of evoked actions potentials, steeper frequency/current relationships and slower decaying frequency/time relationships). Changes in input-output function were accompanied by smaller hyperpolarizing afterpotentials (HAPs) and afterhyperpolarizing potentials (AHPs), during and after trains of spikes, respectively. On the other hand, a decreased efficacy in the input-output function was observed in SON/PVN MNCs during ET. Altogether, our results indicate that ET differentially affects the intrinsic excitability of autonomic and neurosecretory SON and PVN neurons. Increased excitability in PVN-NTS neurons may contribute to enhanced release of OT and VP peptides in the dorsal brain stem, and cardiovascular fine-tuning during exercise training.
Oskar Kokoschka and Auguste Forel
Authors: Huf Veronika , O’Neill Desmond
Published: July 2005

In the spring of 1910, Oskar Kokoschka painted a portrait of the eminent Swiss psychiatrist, neuroanatomist, temperance champion, and myrmecologist Auguste Forel. The painting is a remarkable psychological portrait but also appears to predict the strokes and right hemiparesis that affected Forel more than a year later. Although it is possible that Kokoschka shared a gift of psychic prediction with his mother and grandmother, a more likely explanation can be ascribed to a combination of the artist’s acute perception and the presence of subclinical signs of stroke disease.
Learning Only When Necessary: Better Memories of Correlated Patterns in Networks with Bounded Synapses
Authors: Senn Walter , Fusi Stefano
Published: July 2005

Learning in a neuronal network is often thought of as a linear superposition of synaptic modifications induced by individual stimuli. However, since biological synapses are naturally bounded, a linear superposition would cause fast forgetting of previously acquired memories. Here we show that this forgetting can be avoided by introducing additional constraints on the synaptic and neural dynamics. We consider Hebbian plasticity of excitatory synapses. A synapse is modified only if the postsynaptic response does not match the desired output. With this learning rule, the original memory performances with unbounded weights are regained, provided that (1) there is some global inhibition, (2) the learning rate is small, and (3) the neurons can discriminate small differences in the total synaptic input (e.g., by making the neuronal threshold small compared to the total postsynaptic input). We prove in the form of a generalized perceptron convergence theorem that under these constraints, a neuron learns to classify any linearly separable set of patterns, including a wide class of highly correlated random patterns. During the learning process, excitation becomes roughly balanced by inhibition, and the neuron classifies the patterns on the basis of small differences around this balance. The fact that synapses saturate has the additional benefit that nonlinearly separable patterns, such as similar patterns with contradicting outputs, eventually generate a subthreshold response, and therefore silence neurons that cannot provide any information.
Finite State Automata Resulting from Temporal Information Maximization and a Temporal Learning Rule
Authors: Wennekers Thomas , Ay Nihat
Published: July 2005

We extend Linkser's Infomax principle for feedforward neural networks to a measure for stochastic interdependence that captures spatial and temporal signal properties in recurrent systems. This measure, stochastic interaction, quantifies the Kullback-Leibler divergence of a Markov chain from a product of split chains for the single unit processes. For unconstrained Markov chains, the maximization of stochastic interaction, also called Temporal Infomax, has been previously shown to result in almost deterministic dynamics. This letter considers Temporal Infomax on constrained Markov chains, where some of the units are clamped to prescribed stochastic processes providing input to the system. Temporal Infomax in that case leads to finite state automata, either completely deterministic or weakly nondeterministic. Transitions between internal states of these systems are almost perfectly predictable given the complete current state and the input, but the activity of each single unit alone is virtually random. The results are demonstrated by means of computer simulations and confirmed analytically. It is furthermore shown numerically that Temporal Infomax leads to a high information flow from the input to internal units and that a simple temporal learning rule can approximately achieve the optimization of temporal interaction. We relate these results to experimental data concerning the correlation dynamics and functional connectivities observed in multiple electrode recordings.
Science, Instruments, and Guilds in Early-Modern Britain
Authors: Stewart Larry
Published: July 2005

The emergence of instrument-making trades in early-modern England tested the power of established guilds. From the seventeenth century, instrument makers were able to exploit growing markets for scientific apparatus and attempted to exploit connections with the Royal Society. Given the growth in both local and international demand, and in new methods of manufacture, instrument makers were frequently able to evade the diminishing power of guilds to police the efforts of the makers.
Overexpression of cathepsin K during silica-induced lung fibrosis and control by TGF-β
Authors: van den Brûle Sybille , Misson Pierre , Bühling Frank , Lison Dominique , Huaux François
Published: July 2005

Background

Lung fibrosis is characterized by tissue remodeling resulting from an imbalance between synthesis and degradation of extracellular organic matrices. To examine whether cathepsin(s) (Cat) are important in the development of pulmonary fibrosis, we assessed the expression of four Cat known for their collagenolytic activity in a model of silica-induced lung fibrosis.

Methods

Different strains of mice were transorally instilled with 2.5 mg crystalline silica or other particles. Cat expression (Cat K, S, L and B) was quantified in lung tissue and isolated pulmonary cells by quantitative RT-PCR.In vitro, we assessed the effect of different cytokines, involved in lung inflammatory and fibrotic responses, on the expression of Cat K by alveolar macrophages and fibroblasts.

Results

In lung tissue, Cat K transcript was the most strongly upregulated in response to silica, and this upregulation was intimately related to the fibrotic process. In mouse strains known for their differential response to silica, we showed that the level of Cat K expression following silica treatment was inversely related to the level of TGF-β expression and the susceptibility of these strains to develop fibrosis. Pulmonary macrophages and fibroblasts were identified as Cat K overproducing cells in the lung of silicotic mice.In vitro, Cat K was downregulated in mouse and human lung fibroblasts by the profibrotic growth factor TGF-β1.

Conclusion

Altogether, these data suggest that while Cat K may contribute to control lung fibrosis, TGF-β appears to limit its overexpression in response to silica particles.
Conjugative plasmid pAW63 brings new insights into the genesis of the Bacillus anthracis virulence plasmid pXO2 and of the Bacillus thuringiensis plasmid pBT9727
Authors: Van der Auwera Géraldine A , Andrup Lars , Mahillon Jacques
Published: July 2005

Background

Bacillus cereus, Bacillus anthracis and Bacillus thuringiensis belong to the genetically close-knit Bacillus cereus sensu lato group, a family of rod-shaped Gram-positive bacteria. pAW63 is the first conjugative plasmid from the B. cereus group to be completely sequenced.

Results

The 71,777 bp nucleotide sequence of pAW63 reveals a modular structure, including a 42 kb tra region encoding homologs of the Type IV secretion systems components VirB11, VirB4 and VirD4, as well as homologs of Gram-positive conjugation genes from Enterococcus, Lactococcus, Listeria, Streptococcus and Staphylococcus species. It also firmly establishes the existence of a common backbone between pAW63, pXO2 from Bacillus anthracis and pBT9727 from the pathogenic Bacillus thuringiensis serovar konkukian strain 97-27. The alignment of these three plasmids highlights the presence of well conserved segments, in contrast to distinct regions of high sequence plasticity. The study of their specific differences has provided a three-point reference framework that can be exploited to formulate solid hypotheses concerning the functionalities and the molecular evolution of these three closely related plasmids. This has provided insight into the chronology of their divergence, and led to the discovery of two Type II introns on pAW63, matching copies of the mobile element IS231 L in different loci of pXO2 and pBT9727, and the identification on pXO2 of a 37 kb pathogenicity island (PAI) containing the anthrax capsule genes.

Conclusion

The complete sequence determination of pAW63 has led to a functional map of the plasmid yielding insights into its conjugative apparatus, which includes T4SS-like components, as well as its resemblance to other large plasmids of Gram-positive bacteria. Of particular interest is the extensive homology shared between pAW63 and pXO2, the second virulence plasmid of B. anthracis, as well as pBT9727 from the pathogenic strain B. thuringiensis serovar konkukian strain 97-27.
Heart rate variability in non-apneic snorers and controls before and after continuous positive airway pressure
Authors: Gates Gregory J , Mateika Susan E , Mateika Jason H
Published: July 2005

Background

We hypothesized that sympathetic nervous system activity (SNSA) is increased and parasympathetic nervous system activity (PNSA) is decreased during non-rapid eye movement (NREM) sleep in non-apneic, otherwise healthy, snoring individuals compared to control. Moreover, we hypothesized that these alterations in snoring individuals would be more evident during non-snoring than snoring when compared to control.

Methods

To test these hypotheses, heart rate variability was used to measure PNSA and SNSA in 11 normotensive non-apneic snorers and 12 control subjects before and 7-days after adapting to nasal continuous positive airway pressure (nCPAP).

Results

Our results showed that SNSA was increased and PNSA was decreased in non-apneic snorers during NREM compared to control. However, these changes were only evident during the study in which snoring was eliminated with nCPAP. Conversely, during periods of snoring SNSA and PNSA were similar to measures obtained from the control group. Additionally, within the control group, SNSA and PNSA did not vary before and after nCPAP application.

Conclusion

Our findings suggest that long-lasting alterations in autonomic function may exist in snoring subjects that are otherwise healthy. Moreover, we speculate that because of competing inputs (i.e. inhibitory versus excitatory inputs) to the autonomic nervous system during snoring, the full impact of snoring on autonomic function is most evident during non-snoring periods.
Brands, costs and registration status of antimalarial drugs in the Kenyan retail sector
Authors: Amin Abdinasir A , Snow Robert W
Published: July 2005

Background

Although an important source of treatment for fevers, little is known about the structure of the retail sector in Africa with regard to antimalarial drugs. This study aimed to assess the range, costs, sources and registration of antimalarial drugs in the Kenyan retail sector.

Methods

In 2002, antimalarial drug registration and trade prices were established by triangulating national registration lists, government gazettes and trade price indices. Data on registration status and trade prices were compared with similar data generated through a retail audit undertaken among 880 randomly sampled retailers in four districts of Kenya.

Results

Two hundred and eighteen antimalarial drugs were in circulation in Kenya in 2002. These included 65 "sulfur"-pyrimethamine (sulfadoxine-pyrimethamine and sulfalene-pyrimethamine (SP), the first-line recommended drug in 2002) and 33 amodiaquine (AQ, the second-line recommended drug) preparations. Only half of SP and AQ products were registered with the Pharmacy and Poisons Board. Of SP and AQ brands at district level, 40% and 44% were officially within legal registration requirements. 29% of retailers at district level stocked SP and 95% stocked AQ. The retail price of adult doses of SP and AQ were on average 0.38 and 0.76 US dollars, 100% and 347% higher than trade prices from manufacturers and importers. Artemether-lumefantrine, the newly announced first-line recommended antimalarial drug in 2004, was found in less than 1% of all retail outlets at a median cost of 7.6 US dollars.

Conclusion

There is a need to ensure that all antimalarial drugs are registered with the Pharmacy and Poisons Board to facilitate a more stringent post-marketing surveillance system to ensure drugs are safe and of good quality post-registration.
Electrical properties of iron-sand columns: Implications for induced polarization investigation and performance monitoring of iron-wall barriers
Authors: Slater Lee D. , Choi Jaeyoung , Wu Yuxin
Published: July 2005

We investigate the electrical response (0.1–1000 Hz) of reactive iron barriers by making measurements on zero valent iron ([Formula: see text])-sand columns under the following conditions: (1) variable [Formula: see text] surface area (0.1–100% by volume [Formula: see text] under constant electrolyte chemistry; (2) variable electrolyte activity (0.01–1 mol/liter), valence (mono trivalent), and pH under constant [Formula: see text]-sand composition; and (3) forced precipitation of iron hydroxides and iron carbonates on the [Formula: see text] surface. We model the measurements in terms of conduction magnitude, polarization magnitude, and polarization relaxation time. Our key findings are: (a) Polarization magnitude exhibits a linear relation to the surface area of [Formula: see text], whereas conduction magnitude is only weakly dependent on the [Formula: see text] concentration below 30% by volume [Formula: see text]. (b) Polarization magnitude shows a power law relation to electrolyte activity, with exponents decreasing from 0.9 for monovalent solutions to 0.7 for trivalent solutions. (c) The relaxation time parameter depends on activity and valence in a manner that is partly consistent with the variation in double layer thickness predicted from theory. (d) pH exerts minor control on the electrical parameters. (e) Polarization magnitude and relaxation time both increase as a result of precipitation induced on the surface of [Formula: see text]. Our results show that induced polarization parameters systematically change in response to changes in the [Formula: see text]-electrolyte interfacial chemistry.
The MIT Geophysical Analysis Group (GAG): 1954 and beyond
Authors: Treitel Sven
Published: July 2005

The MIT Geophysical Analysis Group (GAG) laid the groundwork for the so-called “digital revolution” in exploration seismology. Enders Robinson traces in this issue GAG's history from its earliest days till 1954; here, the story continues with GAG's subsequent evolution until its end in 1957. But that was just the beginning — during the 1960s and 1970s, the new digital technology spread throughout the oil and service industries worldwide, making it possible to develop progressively more sophisticated seismic processing and imaging algorithms that permanently changed the landscape of geophysical exploration.