bluuebunny/crossref_metadata_2025 huggingface dataset:
Issue Definition, Information Processing, and the Politics of Global Warming
Authors: Wood B. Dan , Vedlitz Arnold
Published: June 2007

Past research has proposed various macrolevel theories of issue definition and agenda setting. However, we propose a microlevel theory of issue definition rooted in how individuals process information. We theorize that people process information about policy issues through a filter that emphasizes past assessments, ideology, background, social cues, and the continuing intrusion of new information. Most of these factors lead individual issue definitions toward stability. However, the introduction of an information signal of appropriate magnitude and character can produce punctuations in issue definition by individuals through time. Since the macrolevel definition of an issue is a type of aggregation of individual definitions, understanding how individuals define issues becomes a precursor to understanding issue definition at the system level. In evaluating the theory, we develop and evaluate a survey to study the issue definition process for individuals across multiple issues, and for global warming specifically. The survey also includes two embedded experiments to demonstrate the potential for punctuation in the issue‐definition process for individuals and the system.
Divergence in Diversity? The Dissimilar Effects of Cleavages on Electoral Politics in New Democracies
Authors: Kristín Birnir Jóhanna
Published: June 2007

Recent theory on ethnic identity suggests that it is constructed and highly influenced by contextual factors and group leaders' strategies. Therefore, while the notion that social cleavages stabilize electoral politics is well established, which cleavages matter and why remain open questions. This article argues that in new democracies the effects of diffuse ethnic cleavages on electoral politics diverge depending on the amount of information they provide to their constituency. The information provision, in turn, depends on how well the cleavage lends itself to the formation of ethnic parties. A formal model of voting stability is developed and empirically tested using data on electoral volatility in all new democracies since 1945 and on individual voting in democratizing Bulgaria. The results show that in the sample examined only identity that centers on language jump‐starts party‐system stabilization, while race and religion do nothing to stabilize the vote in early elections.
On the Dynamics of Ethnic Fractionalization
Authors: Campos Nauro F. , Kuzeyev Vitaliy S.
Published: June 2007

Does fractionalization change over (short periods of) time? If so, are there any substantial implications for economic performance? To answer such questions, we construct a new panel data set with measures of ethnic, linguistic, and religious fractionalization for 26 former communist countries covering the period from 1989 to 2002. Our fractionalization measures show that transition economies became more ethnically homogeneous over such a short period of time, although the same did not happen for linguistic and religious diversity. In line with the most recent literature, there seems to be no effect of (exogenous) diversity on macroeconomic performance (that is, on per capita GDP growth). However, we find that dynamic (endogenous) ethnic diversity is negatively related to growth (although this is still not the case for linguistic and religious diversity). These findings are robust to different specifications, polarization measures, and instrument sets as well as to a composite index of ethnic‐linguistic‐religious fractionalization.
The Dictator Game, Fairness and Ethnicity in Postwar Bosnia
Authors: Whitt Sam , Wilson Rick K.
Published: June 2007

This study considers the effects of ethnic violence on norms of fairness. Once violence is a foregone conclusion, will cooperative norms ever (re‐)emerge beyond ethnic boundaries? We use an experiment that measures how fairly individuals in a postconflict setting treat their own ingroup in comparison to the outgroups—in this case, examining the behavior of 681 Muslims, Croats, and Serbs in postwar Bosnia‐Herzegovina. To assess fairness, we use the dictator game wherein subjects decide how to allocate a sum of money between themselves and an anonymous counterpart of varying ethnicity. We find that the effects of ethnicity on decision making are captured by our experiments. Although results indicate preferential ingroup treatment, the incidence and magnitude of outgroup bias is much less than expected. We conclude that norms of fairness across ethnicity are remarkably strong in Bosnia, and we take this to be a positive sign for reconciliation after violent conflict.
Designing and Analyzing Randomized Experiments: Application to a Japanese Election Survey Experiment
Authors: Horiuchi Yusaku , Imai Kosuke , Taniguchi Naoko
Published: June 2007

Randomized experiments are becoming increasingly common in political science. Despite their well‐known advantages over observational studies, randomized experiments are not free from complications. In particular, researchers often cannot force subjects to comply with treatment assignment and to provide the requested information. Furthermore, simple randomization of treatments remains the most commonly used method in the discipline even though more efficient procedures are available. Building on the recent statistical literature, we address these methodological issues by offering general recommendations for designing and analyzing randomized experiments to improve the validity and efficiency of causal inference. We also develop a new statistical methodology to explore causal heterogeneity. The proposed methods are applied to a survey experiment conducted during Japan's 2004 Upper House election, where randomly selected voters were encouraged to obtain policy information from political parties' websites. An R package is publicly available for implementing various methods useful for designing and analyzing randomized experiments.
Bleomycin Treatment for Verrucae
Authors: Price Norman M.
Published: June 2007

Background.

The treatment of verrucae with bleomycin injections has not become a routinely adopted form of therapy in dermatologic practice since its use was originally described in 1980 because of the adverse effects and complications that have been associated with it.

Objectives.

The goal of this study was to demonstrate the results and the incidence of adverse effects from the use of bleomycin in clinical practice in a retrospective study of patients presenting with verrucae and to demonstrate the convenience and ease of the methodology that was used in obtaining these results.

Methods.

Patients' lesions were injected with bleomycin every 3 to 4 weeks until the lesions had been eliminated or the injections were discontinued because of adverse effects or complications.

Results.

There were 211 patients in the study, and 224 lesions were treated. After 1 treatment, 47.6% of the lesions were cleared; another 38.8%were cleared after 2 treatments; and another 9.8% were cleared after 3 treatments. In total, 96% of lesions were cleared after 5 treatments. A small number of temporary adverse effects were noted: 3 patients had local chemical cellulitis, 2 patients had formation of sterile abscesses, 1 patient had postinflammatory hyperpigmentation, and 1 patient had localized pain. No local or systemic complications were observed.

Conclusions.

Therapy with intralesional bleomycin is a relatively rapid and convenient form of therapy, compared with other available treatments, from the point of view of both the patient and the physician.
Low serum level of hepatitis B core‐related antigen indicates unlikely reactivation of hepatitis after cessation of lamivudine therapy
Authors: Matsumoto Akihiro , Tanaka Eiji , Minami Masahito , Okanoue Takeshi , Yatsuhashi Hiroshi , Nagaoka Shinya , Suzuki Fumitaka , Kobayashi Mariko , Chayama Kazuaki , Imamura Michio , Yotsuyanagi Hiroshi , Nakaoka Shigeru , Maki Noboru , Kawata Sumio , Kumada Hiromitsu , Iino Shiro , Kiyosawa Kendo
Published: June 2007

Aim:  The clinical significance of hepatitis B virus (HBV) core‐related antigen (HBcrAg) in predicting the reactivation of hepatitis after halting lamivudine administration was analyzed.

Methods:  A total of 34 patients with chronic hepatitis B were enrolled. Lamivudine was administered for at least 6 months before cessation, and reactivation of hepatitis was defined as elevation of alanine aminotransferase levels to more than 80 IU/L within 12 months of cessation.

Results:  In total, 20 (59%) patients experienced hepatitis reactivation. Although concentrations of HBV DNA and HBcrAg in serum did not differ between the two groups of patients at the onset of lamivudine administration, HBcrAg serum levels were significantly higher (P = 0.009) in the reactivation patients (median 4.9, 25–75% range 4.7– 5.9 log unit/mL) than the non‐reactivation patients (median 3.2, 25–75% range <3.0–4.5 log unit/mL) post‐lamivudine treatment. The concentration of HBV DNA did not differ between the two groups (median <3.7, 25–75% range <3.7–<3.7 log copy/mL in the reactivation group vs. median <3.7, 25–75% range <3.7–<3.7 log copy/mL in the non‐ reactivation group). Receiver operating characteristic analysis of HBcrAg concentration showed an area under the curve of 0.764 in predicting patients without reactivation of hepatitis.

Conclusion:  HBcrAg can be a useful marker to identify patients who are not at risk of reactivation of severe hepatitis after discontinuation of lamivudine administration.
Association of Saquinavir Plasma Concentrations with Side Effects but Not with Antiretroviral Outcome in Patients Infected with Protease Inhibitor-Susceptible Human Immunodeficiency Virus Type 1
Authors: Lötsch Jörn , Harder Sebastian , Stürmer Martin , Doerr Hans-Wilhelm , Geisslinger Gerd , Staszewski Schlomo , von Hentig Nils
Published: June 2007

The objective of this study was to identify parameters among saquinavir pharmacokinetics, patients' demographics or comedications, to be addressed for improved personalized therapy. The presence of human immunodeficiency virus type 1 (HIV-1) RNA at therapy week 48 (principal target parameter), CD4 cell count at week 48, infections and side effects during 48 weeks, indicators of liver toxicity and lipid abnormalities at week 48, and a 12-h saquinavir plasma concentration-versus-time profile were assessed in 56 patients receiving saquinavir-ritonavir (1,000 and 100 mg, respectively) twice daily (44 therapy-naïve and 12 antiretrovirally pretreated patients) for association with saquinavir plasma concentrations, demographics, baseline values of target parameters, and coadministered antiretrovirals. Antiretroviral failure was observed in 8 of the 56 patients in whom HIV-1 RNA was detectable at week 48. This therapeutic failure was not associated with individual saquinavir pharmacokinetics. More likely, therapeutic failure was related to incidences interfering with antiretroviral therapy, causing therapy interruptions or incompliance. Weak associations were, however, seen between high maximum saquinavir plasma concentrations and both CD4 counts of ≥200 cells μl−1at week 48 (P= 0.014) and constitutional side effects during 48 weeks (P= 0.002). However, patients with high CD4 counts and constitutional side effects were not identical (P= 0.53). Saquinavir therapeutic drug monitoring in patients infected with protease inhibitor-susceptible HIV-1 taking saquinavir-ritonavir (1,000 and 100 mg, respectively) is not demanded for improving the antiretroviral effect. It may be contemplated in cases with constitutional side effects or low CD4 counts with weak immune responses.
Antiviral and Anti-Inflammatory Effects of Rosmarinic Acid in an Experimental Murine Model of Japanese Encephalitis
Authors: Swarup Vivek , Ghosh Joydeep , Ghosh Soumya , Saxena Amit , Basu Anirban
Published: June 2007

Rosmarinic acid (RA) reduced the mortality of mice infected with Japanese encephalitis virus (JEV). Significant decreases in viral loads (
P
< 0.001) and proinflammatory cytokine levels (
P
< 0.001) were observed in JEV-infected animals treated with RA compared to levels in infected mice without treatment, at 8 to 9 days postinfection.
Pneumococcal LytA Autolysin, a Potent Therapeutic Agent in Experimental Peritonitis-Sepsis Caused by Highly β-Lactam-Resistant
Streptococcus pneumoniae
Authors: Rodríguez-Cerrato Violeta , García Pedro , Huelves Lorena , García Ernesto , del Prado Gema , Gracia Matilde , Ponte Carmen , López Rubens , Soriano Francisco
Published: June 2007

The in vitro and in vivo antipneumococcal activities of the main pneumococcal autolysin (LytA) and Cpl-1, a lysozyme encoded by phage Cp-1, were studied. Intraperitoneal therapy with LytA or high-dose Cpl-1 remarkably reduced peritoneal bacterial counts (>5 log
10
CFU/ml) compared with those for the controls. After intravenous injection, LytA was the most effective treatment.
RSV604, a Novel Inhibitor of Respiratory Syncytial Virus Replication
Authors: Chapman Joanna , Abbott Elizabeth , Alber Dagmar G. , Baxter Robert C. , Bithell Sian K. , Henderson Elisa A. , Carter Malcolm C. , Chambers Phil , Chubb Ann , Cockerill G. Stuart , Collins Peter L. , Dowdell Verity C. L. , Keegan Sally J. , Kelsey Richard D. , Lockyer Michael J. , Luongo Cindy , Najarro Pilar , Pickles Raymond J. , Simmonds Mark , Taylor Debbie , Tyms Stan , Wilson Lara J. , Powell Kenneth L.
Published: June 2007

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections worldwide, yet no effective vaccine or antiviral treatment is available. Here we report the discovery and initial development of RSV604, a novel benzodiazepine with submicromolar anti-RSV activity. It proved to be equipotent against all clinical isolates tested of both the A and B subtypes of the virus. The compound has a low rate of in vitro resistance development. Sequencing revealed that the resistant virus had mutations within the nucleocapsid protein. This is a novel mechanism of action for anti-RSV compounds. In a three-dimensional human airway epithelial cell model, RSV604 was able to pass from the basolateral side of the epithelium effectively to inhibit virus replication after mucosal inoculation. RSV604, which is currently in phase II clinical trials, represents the first in a new class of RSV inhibitors and may have significant potential for the effective treatment of RSV disease.
Update to the Multiplex PCR Strategy for Assignment of
mec
Element Types in
Staphylococcus aureus
Authors: Milheiriço Catarina , Oliveira Duarte C. , de Lencastre Hermínia
Published: June 2007

Staphylococcal cassette chromosome
mec
(SCC
mec
) typing is important for the identification and definition of methicillin-resistant
Staphylococcus aureus
clones, and for routine purposes, multiplex PCR assays are the most adequate for SCC
mec
typing. Here, we describe an update to the multiplex PCR strategy for SCC
mec
typing that we described in 2002 so that SCC
mec
types IV and V may be properly identified.
Distribution of Suramin, an Antitrypanosomal Drug, across the Blood-Brain and Blood-Cerebrospinal Fluid Interfaces in Wild-Type and P-Glycoprotein Transporter-Deficient Mice
Authors: Sanderson Lisa , Khan Adil , Thomas Sarah
Published: June 2007

Although 60 million people are exposed to human African trypanosomiasis, drug companies have not been interested in developing new drugs due to the lack of financial reward. No new drugs will be available for several years. A clearer understanding of the distribution of existing drugs into the brains of sleeping sickness patients is needed if we are to use the treatments that are available more safely and effectively. This proposal addresses this issue by using established animal models. Using in situ brain perfusion and isolated incubated choroid plexus techniques, we investigated the distribution of [3H]suramin into the central nervous systems (CNSs) of male BALB/c, FVB (wild-type), and P-glycoprotein-deficient (Mdr1a/Mdr1b-targeted mutation) mice. There was no difference in the [3H]suramin distributions between the three strains of mice. [3H]suramin had a distribution similar to that of the vascular marker, [14C]sucrose, into the regions of the brain parenchyma that have a blood-brain barrier. However, the association of [3H]suramin with the circumventricular organ samples, including the choroid plexus, was higher than that of [14C]sucrose. The association of [3H]suramin with the choroid plexus was also sensitive to phenylarsine oxide, an inhibitor of endocytosis. The distribution of [3H]suramin to the brain was not affected by the presence of other antitrypanosomal drugs or the P-glycoprotein efflux transporter. Overall, the results confirm that [3H]suramin would be unlikely to treat the second or CNS stage of sleeping sickness.
Predictive Genotypic Algorithm for Virologic Response to Lopinavir-Ritonavir in Protease Inhibitor-Experienced Patients
Authors: King Martin S. , Rode Richard , Cohen-Codar Isabelle , Calvez Vincent , Marcelin Anne-Geneviève , Hanna George J. , Kempf Dale J.
Published: June 2007

Several genotypic resistance algorithms have been proposed for quantitation of the degree of phenotypic resistance to the human immunodeficiency virus (HIV) protease inhibitor (PI) lopinavir (LPV), including the original LPV mutation score. In this study, we retrospectively evaluated 21 codons in HIV protease known to be associated with PI resistance in a large antiretroviral agent-experienced observational patient cohort, “Autorisation Temporaire d'Utilization” (ATU), to assess whether a more optimal algorithm could be derived by using virologic response data from patients treated with LPV in combination with ritonavir (LPV/r). Five of the 11 mutations constituting the LPV mutation score were not associated with a virologic response, while 4 additional mutations not included in this score demonstrated an association. Therefore, the LPV ATU score, which includes mutations at codons 10, 20, 24, 33, 36, 47, 48, 54, 82, and 84, was constructed and shown in two different types of multivariable analyses of the ATU cohort to be a better predictor of the virologic response than the LPV mutation score. The LPV ATU score was also more strongly associated with a virologic response when it was applied to independent clinical trial populations of PI-experienced patients receiving LPV/r. This study provides the basis for a new genotypic resistance algorithm that is useful for predicting the antiviral activities of LPV/r-based regimens in PI-experienced patients. The refined algorithm may be useful in making clinical treatment decisions and in refining genetic and pharmacologic methods for assessing the activity of LPV/r.
Efflux-Related Resistance to Norfloxacin, Dyes, and Biocides in Bloodstream Isolates ofStaphylococcus aureus
Authors: DeMarco Carmen E. , Cushing Laurel A. , Frempong-Manso Emmanuel , Seo Susan M. , Jaravaza Tinevimbo A. A. , Kaatz Glenn W.
Published: June 2007

Efflux is an important resistance mechanism inStaphylococcus aureus, but its frequency in patients with bacteremia is unknown. Nonreplicate bloodstream isolates were collected over an 8-month period, and MICs of four common efflux pump substrates, with and without the broad-spectrum efflux pump inhibitor reserpine, were determined (n= 232). A reserpine-associated fourfold decrease in MIC was considered indicative of efflux. Strains exhibiting efflux of at least two of the four substrates were identified (“effluxing strains” [n= 114]). For these strains, MICs with or without reserpine for an array of typical substrates and the expression ofmepA,mdeA,norA,norB,norC, andqacA/Bwere determined using quantitative real-time reverse transcription-PCR (qRT-PCR). A fourfold or greater increase in gene expression was considered significant. The most commonly effluxed substrates were ethidium bromide and chlorhexidine (100 and 96% of effluxing strains, respectively). qRT-PCR identified strains overexpressingmepA(5 [4.4%]),mdeA(13 [11.4%]),norA(26 [22.8%]),norB(29 [25.4%]), andnorC(19 [16.7%]); 23 strains overexpressed two or more genes. Mutations probably associated with increased gene expression included a MepR-inactivating substitution andnorApromoter region insertions or deletions. Mutations possibly associated with increased expression of the other analyzed genes were also observed. Effluxing strains comprised 49% of all strains studied (114/232 strains), with nearly half of these overexpressing genes encoding MepA, MdeA, and/or NorABC (54/114 strains). Reduced susceptibility to biocides may contribute to persistence on environmental surfaces, and efflux of drugs such as fluoroquinolones may predispose strains to high-level target-based resistance.
High Prevalence of Metallo-β-Lactamase and 16S rRNA Methylase Coproduction among Imipenem-ResistantPseudomonas aeruginosaIsolates in Brazil
Authors: Doi Yohei , Ghilardi Angela C. R. , Adams Jennifer , de Oliveira Garcia Doroti , Paterson David L.
Published: June 2007

Rates of metallo-β-lactamase and 16S rRNA methylase production were investigated in 51 imipenem-resistantPseudomonas aeruginosaclinical isolates collected from hospitals in São Paulo, Brazil. Of them, 57% and 75% produced SPM-1 and RmtD, respectively. Of note, 51% produced both enzymes, suggesting that their coproduction is already common in this geographic area.
In Vitro Susceptibility to Posaconazole of 1,903 Yeast Isolates Recovered in France from 2003 to 2006 and Tested by the Method of the European Committee on Antimicrobial Susceptibility Testing
Authors: Lortholary Olivier , Dannaoui Eric , Raoux Dorothée , Hoinard Damien , Datry Annick , Paugam André , Poirot Jean-Louis , Lacroix Claire , Dromer Françoise
Published: June 2007

The posaconazole MIC
90
for 1,903 yeast isolates from France was 1 μg/ml (range, ≤0.015 to 8 μg/ml). Ninety percent of isolates with fluconazole MICs of ≥8 μg/ml (
n
= 509) and 90% of those with voriconazole MICs of ≥2 μg/ml (
n
= 80) were inhibited by 2 and 8 μg/ml of posaconazole, respectively.
In Vivo Efficacy and Pharmacokinetics of Voriconazole in an Animal Model of Dermatophytosis
Authors: Saunte D. M. , Simmel F. , Frimodt-Moller N. , Stolle L. B. , Svejgaard E. L. , Haedersdal M. , Kloft C. , Arendrup M. C.
Published: June 2007

The standard treatment for tinea capitis caused byMicrosporumspecies for many years has been oral griseofulvin, which is no longer universally marketed. Voriconazole has been demonstrated to inhibit growth ofMicrosporum canisin vitro. We evaluated the efficacy and tissue pharmacokinetics of oral voriconazole in a guinea pig model of dermatophytosis. Guinea pigs (n= 16) were inoculated withM. canisconidia on razed skin. Voriconazole was dosed orally at 20 mg/kg/day for 12 days (days 3 to 14). The guinea pigs were scored clinically (redness and lesion severity) and mycologically (microscopy and culture) until day 17. Voriconazole concentrations were measured day 14 in blood, skin biopsy specimens, and interstitial fluid obtained by microdialysis in selected animals. Clinically, the voriconazole-treated animals had significantly less redness and lower lesion scores than untreated animals from days 7 and 10, respectively (P< 0.05). Skin scrapings from seven of eight animals in the voriconazole-treated group were microscopy and culture negative in contrast to zero of eight animals from the untreated group at day 14. The colony counts per specimen were significantly higher in samples from untreated animals (mean colony count of 28) than in the voriconazole-treated animals (<1 in the voriconazole group [P< 0.0001]). The voriconazole concentration in microdialysate (unbound) ranged from 0.9 to 2.0 μg/ml and in the skin biopsy specimens total from 9.1 to 35.9 μg/g. In conclusion, orally administered voriconazole leads to skin concentrations greater than the necessary MICs forMicrosporumand was shown to be highly efficacious in an animal model of dermatophytosis. Voriconazole may be a future alternative for treatment of tinea capitis in humans.
Population Pharmacokinetics at Two Dose Levels and Pharmacodynamic Profiling of Flucloxacillin
Authors: Landersdorfer Cornelia B. , Kirkpatrick Carl M. J. , Kinzig-Schippers Martina , Bulitta Jürgen B. , Holzgrabe Ulrike , Drusano George L. , Sörgel Fritz
Published: June 2007

Flucloxacillin is often used for the treatment of serious infections due to sensitive staphylococci. The pharmacokinetic (PK)-pharmacodynamic (PD) breakpoint of flucloxacillin has not been determined by the use of population PK. Targets based on the duration of non-protein-bound concentrations above the MIC (
fT
>MIC
) best correlate with clinical cure rates for beta-lactams. We compared the breakpoints for flucloxacillin between several dosage regimens. In a randomized, two-way crossover study, 10 healthy volunteers received 500 mg and 1,000 mg flucloxacillin as 5-min intravenous infusions. Drug concentrations were determined by high-pressure liquid chromatography. We used the programs WinNonlin for noncompartmental analysis and statistics and NONMEM for population PK and Monte Carlo simulation. We compared the probability of target attainment (PTA) for intermittent- and continuous-dosage regimens based on the targets of
fT
>MIC
s of ≥50% and ≥30% of the dosing interval. The clearance and the volume of distribution were very similar after the administration of 500 mg and 1,000 mg flucloxacillin. We estimated renal and nonrenal clearances of 5.37 liters/h (coefficient of variation, 19%) and 2.73 liters/h (33%). For near maximal killing (target,
fT
>MIC
of ≥50%) flucloxacillin showed a robust (≥90%) PTA up to MICs of 0.75 to 1 mg/liter (PTA of 86% at 1 mg/liter) for a continuous or a prolonged infusion of 6 g/day. Short-term infusions of 6 g/day had a lower breakpoint of 0.25 to 0.375 mg/liter. The flucloxacillin PK was linear for doses of 500 mg and 1,000 mg. Prolonged and continuous infusion at a 66% lower daily dose achieved the same PK-PD breakpoints as short-term infusions. Prolonged infusion and continuous infusion are appealing options for the treatment of serious infections caused by sensitive staphylococci.
Fate of a
Burkholderia pseudomallei
Lipopolysaccharide Mutant in the Mouse Macrophage Cell Line RAW 264.7: Possible Role for the O-Antigenic Polysaccharide Moiety of Lipopolysaccharide in Internalization and Intracellular Survival
Authors: Arjcharoen S. , Wikraiphat C. , Pudla M. , Limposuwan K. , Woods D. E. , Sirisinha S. , Utaisincharoen P.
Published: June 2007

Burkholderia pseudomallei
is a facultative intracellular gram-negative bacterium that can survive and multiply inside macrophages. One of the mechanisms by which
B. pseudomallei
escapes macrophage killing is by interfering with the expression of inducible nitric oxide synthase (iNOS). However, the bacterial components that modulate antimicrobial activity of the macrophage have not been fully elucidated. In the present study, we demonstrated that
B. pseudomallei
strain SRM117, a lipopolysaccharide (LPS) mutant that lacks the O-antigenic polysaccharide moiety, was more susceptible to macrophage killing during the early phase of infection than the parental wild-type strain (1026b). Unlike the wild type, the LPS mutant could readily stimulate Y701-STAT-1 phosphorylation (pY701-STAT-1) and interferon-regulatory factor 1 (IRF-1) expression, both of which are essential transcription factors of iNOS. Neutralizing antibody against beta interferon was able to inhibit the phosphorylation of Y701-STAT-1 and the expression of IRF-1 and iNOS, all of which resulted in an increased rate of intracellular replication. These data suggest that the O-antigenic polysaccharide moiety of
B. pseudomallei
modulates the host cell response, which in turn controls the intracellular fate of
B. pseudomallei
inside macrophages.
Staphylococcus aureus
Biofilm Metabolism and the Influence of Arginine on Polysaccharide Intercellular Adhesin Synthesis, Biofilm Formation, and Pathogenesis
Authors: Zhu Yefei , Weiss Elizabeth C. , Otto Michael , Fey Paul D. , Smeltzer Mark S. , Somerville Greg A.
Published: June 2007

Staphylococcus aureus
and
Staphylococcus epidermidis
are the leading causes of nosocomial infections in the United States and often are associated with biofilms attached to indwelling medical devices. Despite the importance of biofilms, there is very little consensus about the metabolic requirements of
S. aureus
during biofilm growth. To assess the metabolic requirements of
S. aureus
growing in a biofilm, we grew USA200 and USA300 clonal types in biofilm flow cells and measured the extraction and accumulation of metabolites. In spite of the genetic differences, both clonal types extracted glucose and accumulated lactate, acetate, formate, and acetoin, suggesting that glucose was catabolized to pyruvate that was then catabolized via the lactate dehydrogenase, pyruvate formate-lyase, and butanediol pathways. Additionally, both clonal types selectively extracted the same six amino acids (serine, proline, arginine, glutamine, glycine, and threonine) from the culture medium. These data and recent speculation about the importance of arginine in biofilm growth and the function of arginine deiminase in USA300 clones led us to genetically inactivate the sole copy of the arginine deiminase operon by deleting the arginine/ornithine antiporter gene (
arcD
) in the USA200 clonal type and to assess the effect on biofilm development and pathogenesis. Although inactivation of
arcD
did completely inhibit arginine transport and did reduce polysaccharide intercellular adhesin accumulation,
arcD
mutants formed biofilms and achieved cell densities in catheter infection studies that were equivalent to those for isogenic wild-type strains.
Genetic Basis for the New Pneumococcal Serotype, 6C
Authors: Park In Ho , Park Saeyoung , Hollingshead Susan K. , Nahm Moon H.
Published: June 2007

We have recently reported a new pneumococcal serotype (6C), which is closely related to serotype 6A (I. H. Park et al., J. Clin. Microbiol. 45:1225-1233, 2007). To investigate the genetic basis for serotype 6C, we studied the capsule gene loci of 14 6C isolates from three different continents, including one isolated in Alabama 27 years ago. The
wciN
region of all 6C isolates has a 1,029-bp-long sequence that replaces the 1,222-bp-long sequence of the 6A
wciN
region. This recombination event has created a new 1,125-bp-long open reading frame which encodes a product that is also homologous to glycosyl transferases. Flanking this introduced gene is 300 bp upstream and 100 bp downstream with only about 90% homology with 6A and which is identical in all 6C isolates. Transfer of the
wciN
region converts 6A to 6C. Determination of the DNA sequence of the entire capsule gene locus of one 6C isolate showed that the 6C capsule gene locus is almost identical (>98% homologous) to that of 6A except for the
wciN
region. These findings indicate that the 6C capsule type originated more than 27 years ago by a single recombination event in a 6A locus in which 6A
wciN
was replaced by a gene of unknown origin.
nm- andμm-Scale Surface Roughness on Glass with Specific Optical Scattering Characteristics on Demand
Authors: Fouckhardt Henning , Steingoetter Ingo , Brinkmann Matthias , Hagemann Malte , Zarschizky Helmut , Zschiedrich Lin
Published: June 2007

During maskless ion etching of amorphous glass, self-organization can arise in certain etch parameter ranges, which leads to dense-lying dots/cones with typical diameters and heights in the 30–300 nm range. Another phenomenon, which results in cone sizes around 1 μm or more, is self-masking especially in the case of heterogeneous glasses like borosilicate glass as used in this contribution. Thus, a wide range of characteristic sizes and shapes of individual scatterers on the glass surface, jointly acting as a defined roughness, can be achieved resulting in specific optical scattering characteristics. This contribution gives results on borosilicate thin-glass dry etching. Certain surface morphologies are reported together with experimental results on their optical scattering characteristics.
Morphology of Pyramidal Neurons in the Rat Prefrontal Cortex: Lateralized Dendritic Remodeling by Chronic Stress
Authors: Perez-Cruz Claudia , Müller-Keuker Jeanine I. H. , Heilbronner Urs , Fuchs Eberhard , Flügge Gabriele
Published: June 2007

The prefrontal cortex (PFC) plays an important role in the stress response. We filled pyramidal neurons in PFC layer III with neurobiotin and analyzed dendrites in rats submitted to chronic restraint stress and in controls. In the right prelimbic cortex (PL) of controls, apical and distal dendrites were longer than in the left PL. Stress reduced the total length of apical dendrites in right PL and abolished the hemispheric difference. In right infralimbic cortex (IL) of controls, proximal apical dendrites were longer than in left IL, and stress eliminated this hemispheric difference. No hemispheric difference was detected in anterior cingulate cortex (ACx) of controls, but stress reduced apical dendritic length in left ACx. These data demonstrate interhemispheric differences in the morphology of pyramidal neurons in PL and IL of control rats and selective effects of stress on the right hemisphere. In contrast, stress reduced dendritic length in the left ACx.
Urinary Eosinophil Protein X in Children with Atopic Asthma
Authors: Nuijsink M. , Hop W. C. J. , Sterk P. J. , Duiverman E. J. , Hiemstra P. S. , de Jongste J. C.
Published: June 2007

The aim of this study was to investigate the relationship between urinary eosinophil protein X (uEPX) and asthma symptoms, lung function, and other markers of eosinophilic airway inflammation in asthmatic school children.Methods. A cross-sectional study was performed in 180 steroid dependent atopic children with stable moderately severe asthma, who were stable on 200 or 500μg of fluticasone per day. uEPX was measured in a single sample of urine and was normalized for creatinine concentration (uEPX/c). Symptom scores were kept on a diary card.FEV1andPD20methacholine were measured. Sputum induction was performed in 49 andFENOlevels measured in 24 children.Results. We found an inverse correlation between uEPX/c andFEV1(r=−.20,P=.01) and a borderline significant correlation between uEPX/c andPD20methacholine (r=−.15,P=.06). Symptom score,%eosinophils and ECP in induced sputum andFENOlevels did not correlate with uEPX/c.Conclusion. uEPX/c levels did not correlate with established markers of asthma severity and eosinophilic airway inflammation in atopic asthmatic children.
Asymptotics of Some Classes of Higher-Order Difference Equations
Authors: Stevic Stevo
Published: June 2007

We present some methods for finding asymptotics of some classes of nonlinear higher-order difference equations. Among others, we confirm a conjecture posed by S. Stević (2005). Monotonous solutions of the equationyn=A+(yn−k/∑j=1mβjyn−qj)p,n∈ℕ0, wherep,A∈(0,∞),k,m∈ℕ,qj,j∈{1,…,m}, are natural numbers such thatq1<q2<⋯<qm,βj∈(0,+∞),j∈{1,…,m},∑j=1mβj=1, andy−s,y−s+1,…,y−1∈(0,∞), wheres=max{k,qm}, are found. A new inclusion theorem is proved. Also, some open problems and conjectures are posed.
Anxiety from a Phylogenetic Perspective: Is there a Qualitative Difference between Human and Animal Anxiety?
Authors: Belzung Catherine , Philippot Pierre
Published: June 2007

A phylogenetic approach to anxiety is proposed. The different facets of human anxiety and their presence at different levels of the phylum are examined. All organisms, including unicellular such as protozoan, can display a specific reaction to danger. The mechanisms enabling the appraisal of harmful stimuli are fully present in insects. In higher invertebrates, fear is associated with a specific physiological response. In mammals, anxiety is accompanied by specific cognitive responses. The expression of emotions diversifies in higher vertebrates, only primates displaying facial expressions. Finally, autonoetic consciousness, a feature essential for human anxiety, appears only in great apes. This evolutive feature parallels the progress in the complexity of the logistic systems supporting it (e.g., the vegetative and central nervous systems). The ability to assess one's coping potential, the diversification of the anxiety responses, and autonoetic consciousness seem relevant markers in a phylogenetic perspective.
Pan-European Sarcoma Trials: Moving Forward in a Climate of Increasing Economic and Regulatory Pressure
Authors: Carrle Dorothe , Dantonello Tobias , Bielack Stefan S.
Published: June 2007

Advances in sarcoma treatment are largely based on investigator-initiated, multicentric and interdisciplinary clinical trials. The EU's Good Clinical Practice Directive 2001/20/EC, effective since 2004, was meant to harmonize the conditions for clinical trials across Europe, but, instead, the challenge of initiating and running multinational, noncommercial clinical trials has become greater than ever. Institutions participating in existing noncommercial Pan-European studies are struggling to cope with increased administrative and financial burdens, and few new studies are initiated any more. The aim of a conference entitled “Pan-European Sarcoma Trials: Moving Forward in a Climate of Increasing Economic and Regulatory Pressure,” held in Stuttgart, Germany, 30 November–2 December 2006 as part of the European Science Foundation's ECT-program, was not only to provide an overview of currently active and planned multinational studies on osteo-, Ewing's, and soft tissue sarcoma, but also to draw on areas of synergy between various established sarcoma groups in Europe to define plausible survival strategies for collaborative, interdisciplinary, patient-oriented research.
Microinfusion of Pituitary Adenylate Cyclase-Activating Polypeptide into the Central Nucleus of Amygdala of the Rat Produces a Shift from an Active to Passive Mode of Coping in the Shock-Probe Fear/Defensive Burying Test
Authors: Legradi Gabor , Das Mahasweta , Giunta Brian , Hirani Khemraj , Mitchell E. Alice , Diamond David M.
Published: June 2007

High concentrations of pituitary adenylate cyclase-activating polypeptide (PACAP) nerve fibers are present in the central nucleus of amygdala (CeA), a brain region implicated in the control of fear-related behavior. This study evaluated PACAPergic modulation of fear responses at the CeA in male Sprague-Dawley rats. PACAP (50–100   pmol) microinfusion via intra-CeA cannulae produced increases in immobility and time the rats spent withdrawn into a corner opposite to the electrified probe compared to controls in the shock-probe fear/defensive burying test. Shock-probe burying and exploration, numbers of shocks received, locomotion distance, and velocity were all reduced by intra-CeA PACAP injection. Further, intra-CeA PACAP effects were manifested only when the animals were challenged by shock, as intra-CeA PACAP injections did not cause significant changes in the behaviors of unshocked rats. Thus, intra-CeA administration of PACAP produces a distinct reorganization of stress-coping behaviors from active (burying) to passive modes, such as withdrawal and immobility. These findings are potentially significant toward enhancing our understanding of the involvement of PACAP and the CeA in the neural basis of fear and anxiety.
Comparison of Regression and Artificial Neural Network Models for Surface Roughness Prediction with the Cutting Parameters in CNC Turning
Authors: Nalbant Muammer , Gokkaya Hasan , Toktaş İhsan
Published: June 2007

Surface roughness, an indicator of surface quality, is one of the most specified customer requirements in machining of parts. In this study, the experimental results corresponding to the effects of different insert nose radii of cutting tools (0.4, 0.8, 1.2 mm), various depth of cuts (0.75, 1.25, 1.75, 2.25, 2.75 mm), and different feedrates (100, 130, 160, 190, 220 mm/min) on the surface quality of the AISI 1030 steel workpieces have been investigated using multiple regression analysis and artificial neural networks (ANN). Regression analysis and neural network-based models used for the prediction of surface roughness were compared for various cutting conditions in turning. The data set obtained from the measurements of surface roughness was employed to and tests the neural network model. The trained neural network models were used in predicting surface roughness for cutting conditions. A comparison of neural network models with regression model was carried out. Coefficient of determination was 0.98 in multiple regression model. The scaled conjugate gradient (SCG) model with 9 neurons in hidden layer has produced absolute fraction of variance(R2)values of 0.999 for the training data, and 0.998 for the test data. Predictive neural network model showed better predictions than various regression models for surface roughness. However, both methods can be used for the prediction of surface roughness in turning.
The Localization of Protein Kinase Cδ in Different Subcellular Sites Affects Its Proapoptotic and Antiapoptotic Functions and the Activation of Distinct Downstream Signaling Pathways
Authors: Gomel Ruth , Xiang Cunli , Finniss Susan , Lee Hae Kyung , Lu Wei , Okhrimenko Hana , Brodie Chaya
Published: June 2007

Protein kinase Cδ (PKCδ) regulates cell apoptosis and survival in diverse cellular systems. PKCδ translocates to different subcellular sites in response to apoptotic stimuli; however, the role of its subcellular localization in its proapoptotic and antiapoptotic functions is just beginning to be understood. Here, we used a PKCδ constitutively active mutant targeted to the cytosol, nucleus, mitochondria, and endoplasmic reticulum (ER) and examined whether the subcellular localization of PKCδ affects its apoptotic and survival functions. PKCδ-Cyto, PKCδ-Mito, and PKCδ-Nuc induced cell apoptosis, whereas no apoptosis was observed with the PKCδ-ER. PKCδ-Cyto and PKCδ-Mito underwent cleavage, whereas no cleavage was observed in the PKCδ-Nuc and PKCδ-ER. Similarly, caspase-3 activity was increased in cells overexpressing PKCδ-Cyto and PKCδ-Mito. In contrast to the apoptotic effects of the PKCδ-Cyto, PKCδ-Mito, and PKCδ-Nuc, the PKCδ-ER protected the cells from tumor necrosis factor–related apoptosis-inducing ligand–induced and etoposide-induced apoptosis. Moreover, overexpression of a PKCδ kinase-dead mutant targeted to the ER abrogated the protective effect of the endogenous PKCδ and increased tumor necrosis factor–related apoptosis-inducing ligand–induced apoptosis. The localization of PKCδ differentially affected the activation of downstream signaling pathways. PKCδ-Cyto increased the phosphorylation of p38 and decreased the phosphorylation of AKT and the expression of X-linked inhibitor of apoptosis protein, whereas PKCδ-Nuc increased c-Jun NH2-terminal kinase phosphorylation. Moreover, p38 phosphorylation and the decrease in X-linked inhibitor of apoptosis protein expression played a role in the apoptotic effect of PKCδ-Cyto, whereas c-Jun NH2-terminal kinase activation mediated the apoptotic effect of PKCδ-Nuc. Our results indicate that the subcellular localization of PKCδ plays important roles in its proapoptotic and antiapoptotic functions and in the activation of downstream signaling pathways. (Mol Cancer Res 2007;5(6):627–39)
Association of Carotid Artery Intima-Media Thickness, Plaques, and C-Reactive Protein With Future Cardiovascular Disease and All-Cause Mortality
Authors: Cao Jie J. , Arnold Alice M. , Manolio Teri A. , Polak Joseph F. , Psaty Bruce M. , Hirsch Calvin H. , Kuller Lewis H. , Cushman Mary
Published: June 2007

Background—

Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction.

Methods and Results—

Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged ≥65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (>3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72% (95% CI, 1.46 to 2.01) increased risk for CVD death and a 52% (95% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54% for CVD death and 79% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the
c
statistic.

Conclusions—

In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.
Negative Inotropy of the Gastric Proton Pump Inhibitor Pantoprazole in Myocardium From Humans and Rabbits
Authors: Schillinger Wolfgang , Teucher Nils , Sossalla Samuel , Kettlewell Sarah , Werner Carola , Raddatz Dirk , Elgner Andreas , Tenderich Gero , Pieske Burkert , Ramadori Giuliano , Schöndube Friedrich A. , Kögler Harald , Kockskämper Jens , Maier Lars S. , Schwörer Harald , Smith Godfrey L. , Hasenfuss Gerd
Published: June 2007

Background—

Proton pump inhibitors are used extensively for acid-related gastrointestinal diseases. Their effect on cardiac contractility has not been assessed directly.

Methods and Results—

Under physiological conditions (37°C, pH 7.35, 1.25 mmol/L Ca
2+
), there was a dose-dependent decrease in contractile force in ventricular trabeculae isolated from end-stage failing human hearts superfused with pantoprazole. The concentration leading to 50% maximal response was 17.3±1.3 μg/mL. Similar observations were made in trabeculae from human atria, normal rabbit ventricles, and isolated rabbit ventricular myocytes. Real-time polymerase chain reaction demonstrated the expression of gastric H
+
/K
+
–adenosine triphosphatase in human and rabbit myocardium. However, measurements with BCECF-loaded rabbit trabeculae did not reveal any significant pantoprazole-dependent changes of pH
i
. Ca
2+
transients recorded from field-stimulated fluo 3–loaded myocytes (F/F
0
) were significantly depressed by 10.4±2.1% at 40 μg/mL. Intracellular Ca
2+
fluxes were assessed in fura 2–loaded, voltage-clamped rabbit ventricular myocytes. Pantoprazole (40 μg/mL) caused an increase in diastolic [Ca
2+
]
i
by 33±12%, but peak systolic [Ca
2+
]
i
was unchanged, resulting in a decreased Ca
2+
transient amplitude by 25±8%. The amplitude of the L-type Ca
2+
current (
I
Ca,L
) was reduced by 35±5%, and sarcoplasmic reticulum Ca
2+
content was reduced by 18±6%. Measurements of oxalate-supported sarcoplasmic reticulum Ca
2+
uptake in permeabilized cardiomyocytes indicated that pantoprazole decreased Ca
2+
sensitivity (K
d
) of sarcoplasmic reticulum Ca
2+
adenosine triphosphatase: control, K
d
=358±15 nmol/L; 40 μg/mL pantoprazole, K
d
=395±12 nmol/L (
P
<0.05). Pantoprazole also acted on cardiac myofilaments to reduced Ca
2+
-activated force.

Conclusions—

Pantoprazole depresses cardiac contractility in vitro by depression of Ca
2+
signaling and myofilament activity. In view of the extensive use of this agent, the effects should be evaluated in vivo.