bluuebunny/crossref_metadata_2025 huggingface dataset:
Cigarette and Tobacco Consumption: Have Anti‐Smoking Policies Made a Difference?
Authors: BARDSLEY PETER , OLEKALNS NILSS
Published: October 2007

The consumption of cigarette and tobacco products in Australia is modelled using the rational addiction theory of Becker and Murphy, augmented by data on advertising, regulatory intervention, and demographic factors. Over the past 35 years, price (including tobacco taxes), real income, and demographic effects explain most of the variation in tobacco consumption. Advertising by tobacco companies has had a relatively small direct effect on consumption. Work‐place smoking bans and health warnings on cigarette packs have had a relatively minor impact, while anti‐smoking advertising and bans on electronic media advertising have had no detectable direct effect.
Cyclical and Competitive Influences on Pricing in Australian Manufacturing
Authors: BLOCH HARRY , OLIVE MICHAEL
Published: October 2007

Dynamic pricing equations are estimated using an error correction model, with data on a panel of 89 Australian manufacturing industries for the 14 years, 1971172 through 1984/85. The overall pattern is consistent with prices approximately following a fixed mark‐up rule in low concentration industries, while the mark‐up factor in high concentration industries is strongly pro‐cyclical. Also, in high concentration industries that are heavily exposed to import competition, the mark‐up factor increases with prices of foreign competing products and with the general price level for domestic manufactures.
The Lags of Monetary Policy
Authors: GRUEN DAVID , ROMALIS JOHN , CHANDRA NAVEEN
Published: October 2007

The length of the transmission lags from monetary pblicy to output has been the subject of much research over the years, but there are serious problems in isolating the lags with any precision. This paper uses a simple model of Australian output to estimate the length of the lags, and then examines how attempts to grapple with the estimation problems might change the results.

We estimate that output growth falls by about one‐third of one per cent in both the first and second years after a one percentage point rise in the short‐term real interest rate, and by about one‐sixth of one per cent in the third year. This implies an average lag of about five or six quarters in monetary policy's impact on output growth. Each of these estimates is, however, subject to considerable uncertainty. We discuss the implications for policy of these relatively long and uncertain lags. Finally, we find no evidence that the average lag from monetary policy to output growth has become any shorter in the 1990s.
The Consumer Tax Equivalent of a Tariff with Imperfect Substitutes
Authors: SALERIAN JOHN , DAVIS LEE , JOMINI PATRICK
Published: October 2007

In estimating the Consumer Tax Equivalent (CTE) and Producer Subsidy Equivalent (PSE) of a tariff, it is often assumed that the imported good is a perfect substitute for the relevant locally made good. However, in evaluating the economy‐wide effects of a change in tariff using general equilibrium models, it is common to assume that the imported good is an imperfect substitute (so‐called Arming‐ton assumption)1 This paper estimates CTE assuming imperfect substitution in order to be consistent with the assumption commonly used in general equilibrium models. It shows how estimates of the CTE and PSE are sensitive to assumptions about the substitution elasticity of demand and the price elasticity of supply for the locally made good.
Colin George Frederick Simkin, 1915–1998
Authors: HOGAN WARREN P.
Published: October 2007

This paper reviews the career of Professor C.G.F. Simkin who was Professor of Economics in the University of Auckland between 1946 and 1969 and then in the University of Sydney from 1969 until his retirement in 1980. H was educated in the University of Otago winning many prizes and scholarships. He had close ties with Sir Karl Popper and Sir John Hicks. His major works included The Instability of a Dependent Economy, The Traditional Trade of Asia and Economics at Large. Asian economies held a great interest.
A Comparative Static Model of the Relationship between Immigration and the Short‐Run Job Prospects of Unemployed Residents
Authors: CHAPMAN BRUCE , COBB‐CLARK DEBORAH
Published: October 2007

A novel theoretical approach is developed to illustrate the consequences of immigration for the probability that unemployed residents gain a job. Through the use of the vacancies to unemployment ratio it is shown that immigration in theory can either increase or decrease unemployed residents' employment probabilities, but that, contrary to populist rhetoric, an increase is more likely the more recessed is the labour market. With reference to feasible Australian values of the parameters of interest, it is demonstrated that in practically all circumstances immigration increases the overall employment prospects of unemployed residents. Even so, the analysis is very short run, and strong conclusions as to what might be happening over the longer term are not appropriate.
Estimates of the Underground Economy in Australia
Authors: BAJADA CHRISTOPHER
Published: October 2007

In an age of tighter government regulation, many individuals and businesses are distorting our notion of the size of the Australian economy by actively participating in the underground economy. The consequences are clear: policy makers have imperfect knowledge on the state of economic affairs. Although there exists considerable international literature on the size of the underground economy, academics and public officials alike appear to have paid little attention to the extent of illicit economic behaviour in Australia. The aim of this paper is to provide the first known time‐series estimate of the size of the Australian underground economy and to illustrate that its existence has implications for the nature of the business cycle in Australia.
Towards a More General Approach to Trade Liberalization
Authors: GRUEN NICHOLAS
Published: October 2007

Despite the frequency with which they have been promoted as a model of development. East Asian trade policies have had little influence on the normative economics of trade reform. In contrast to directly dismantling protection, developing countries have often provided concessional import rights which override existing protection. These instruments include EPZs and duty remission. This paper accommodates these instruments of ‘new trade liberalization’ within a more general understanding of trade liberalization illustrating their similarities and their differences. Both old and new trade liberalization can, on their own, bring about complete free trade. Needless to say, so far, neither has!
Combined Income Taxes and Tax‐Benefit Systems
Authors: EBERT UDO , LAMBERT PETER J.
Published: October 2007

We extend the analysis of income tax progression to combined taxes, benefits, and the tax‐benefit system. The overall redistributive impacts of constituent reforms are identified. Our findings point to the importance of interaction effects and demonstrate the dangers of isolated reforms.
The Future of Banking: A Survey
Authors: HOGAN W. P.
Published: October 2007

The paper examines the prospects for banking. After a brief appraisal of the knowledge available at the time of the Wallis Inquiry in 1997, attention is directed to issues associated with asymmetric information and then technology. The former explains predominant influences in banking while the second is devoted to exploring what technological innovation is about and what this means for business operations. Attention then turns to the various functions which can be used to explain and define what banks are about. Most recent empirical evidence is assessed to establish the latest results about banking business. These are then used in conjunction with information and technology to derive a series of themes about future prospects.
Do Selection Criteria Make a Difference?: Visa Category and the Labour Market Status of Immigrants to Australia
Authors: COBB‐CLARK DEBORAH A.
Published: October 2007

This paper assesses the role of selection criteria in the immigrant settlement process. Do skill‐based immigrants have higher participation and employment rates than family‐based immigrants? Does this represent a head start or a persistent labour market advantage? The Longitudinal Survey of Immigrants to Australia is used to address these questions. Generally, migrants selected for their skills have better labour market outcomes. Over time, the relative gap in participation rates increases, while the gap in employment rates decreases. Net of visa category, outcomes are better for native English speakers and for those who visited Australia prior to migration.
Capital Equalization and the Australian States
Authors: PETCHEY JEFFREY , KOSHY GARRY MACDONALD PAUL , SHAPIRO PERRY
Published: October 2007

The Australian Grants Commission has recently considered ways to take account of differences in capital costs across States within the existing fiscal equalization formula. Here we develop a theoretical methodology for estimating differences in the costs of capital faced by the States in the General Government Sector. This methodology is used to generate preliminary estimates of State capital cost ‘disabilities’ from 1962–63 to 1995–96. Finally, we suggest how the methodology and the estimates of capital cost disabilities might be integrated into the Commission's formula to produce a grant distribution which reflects different costs of capital across States.
Savings, Investment, Productivity and Economic Growth of Australia 1861–1990: Some Explorations
Authors: CHAUDHRI D.P. , WILSON E.
Published: October 2007

Policy makers' concerns over sub‐optimal savings rates in Australia mistakenly concentrate on symptoms rather than causes of low rates of growth in investment and productivity. A growth model of a small open economy is used to demonstrate possible interdependencies of these variables which are tested using cointegration and long‐run Granger causality techniques for the periods 1861–1900 and 1949–90. As expected, no direct long‐run relationship is found between savings and investment. However the interactions between investment and productivity growth are found to be complex and evolving, whilst savings appear to be determined residually in the growth process.
Consumption and Income Inequality in Australia
Authors: BARRETT GARRY F. , CROSSLEY THOMAS F. , WORSWICK CHRISTOPHER
Published: October 2007

Consumption may be a more appropriate measure of household well‐being than income or earnings. Using four ABS Household Expenditures Surveys collected between 1975 and 1993, we compare trends in consumption and income inequality among Australian households. We find that consumption is much more equal than income. While there were significant increases in both income and consumption inequality, consumption inequality rose by much less. One interpretation of the results is that some income inequality in Australia reflects transitory fluctuations which households can smooth,‘and that part of the growth in income inequality reflects an increase in these transitory fluctuations.
Deregulation and Subequilibrium in the Australian Dairy Processing Industry
Authors: DOUCOULIAGOS HRISTOS , HONE PHILLIP
Published: October 2007

The Australian dairy processing industry is currently undergoing a program of substantial regulatory reform. In this paper we assess the impact of this deregulation on the production and cost systems of the industry. This is undertaken using a translog restricted cost function, for the period 1969 to 1996, with labour, milk and energy as the variable inputs and capital as the one fixed input. We find that this industry has undergone significant changes in terms of factor demand and cost structures associated with the introduction of new technology.
A Ricardian Model with Endogenous Comparative Advantage and Endogenous Trade Policy Regimes
Authors: LI CHENG WEN , LIU MENG‐CHUN , YANG XIAOKAI
Published: October 2007

This paper develops a Ricardian model with transaction costs and endogenous and exogenous comparative advantages. It shows that the level of division of labour and trade increases as transaction conditions improve. It identifies the conditions for trade negotiations that result in zero tariff rates and the conditions for the coexistence of unilateral tariff protection and unilateral laissez faire policies. The model may explain the policy transformation of some European governments from Mercantilism to laissez faire in the 18th and 19th century and policy changes in developing countries from protection tariff to trade liberalization and tariff negotiation.
On the Exchange Rate as a Nominal Anchor: The Rise and Fall of the Credibility Hypothesis
Authors: TAVLAS GEORGE S.
Published: October 2007

The credibility hypothesis, which was used to support the use of a pegged exchange rate arrangement as a nominal anchor mechanism, is based on restrictive analytical foundations that circumscribe its real world applicability. While all pegged exchange rate arrangements are subject to circumstances that can undermine the sustainability of the peg, exchange rate nominal anchor pegs are especially fragile because such arrangements introduce problems that are endogenous to that particular type of regime. The East Asian crisis is used to demonstrate the fragility of exchange rate nominal anchor pegs, while the case of Australia demonstrates how a floating currency escaped the contagion of the East Asian crisis.
Optimal Schooling Investments and Earnings: An Analysis Using Australian Twins Data
Authors: LEE YEW LIANG
Published: October 2007

The potential impact that unobserved ability can have on both schooling and earnings outcomes has been modelled by Ashenfelter and Rouse (1998). This paper applies their model to the Australian Twins Sample. The best estimate of the return to schooling for genetically identical (or MZ) twins is 8.9 per cent. Measurement errors in the schooling data are shown to constitute a more serious problem than the omission of the family effects that impact on ability. Individuals from higher ability families receive a lower marginal benefit from their investment in human capital.
Patents, Innovation and Growth
Authors: CROSBY MARK
Published: October 2007

New growth theories emphasize the role played by innovation in promoting economic growth. Since it is difficult to quantify the amount of innovation undertaken in an economy, there is little available empirical evidence assessing the contribution made by innovation to growth, in contrast to abundant evidence on the role of physical capital accumulation in the growth process. In this paper patent data are used to proxy the amount of innovation undertaken in an economy. The patent data are used to explore two questions. First, how important is innovation to economic growth in Australia, and second, are reductions in innovations sourced in Australia offset by increases in foreign sourced innovations in Australia?
Addictive Consumption under Conditions of Risk
Authors: CLARKE HARRY
Published: October 2007

Addictive consumption involves health and other risks. This paper analyzes how such risks influence steady state consumption and equilibrium addiction. Mortality risks deter addictive consumption provided they are strongly addiction‐dependent. If however risks are addiction‐independent they may increase addictive consumption. Risks, which lead not to death but to large ongoing disutility, also deter addictive consumption provided they are strongly addiction‐dependent. Non‐steady state extensions of these results hold provided large enough disutility is associated with addiction‐dependent risk. Increasing addiction‐dependent risk and reducing addiction‐independent risk promotes the social objective of reducing addictive consumption.
Diminished Returns? Growth and Investment in East Asia
Authors: ROBERTSON PETER E.
Published: October 2007

This paper investigates the investment‐led growth hypothesis for the newly industrialized economies of East Asia. Using numerical simulations and a neoclassical model, it is shown that the revolution in investment rates only explains about 30 per cent of the growth of GDP per worker. In contrast, productivity growth and improvements in labour quality, explain around half the growth of GDP per ‐worker. This reflects the effects of productivity growth on capital accumulation. Contrary to recent growth‐accounting studies, the results suggest that understanding the sources of productivity growth in East Asia will provide the most useful lessons for other developing economies.
It's the Economy Stupid: Macroeconomics and Federal Elections in Australia
Authors: CAMERON LISA , CROSBY MARK
Published: October 2007

In this paper we examine the impact of macroeconomic conditions on Federal electoral performance in 20th‐century Australia. We find that the electorate penalizes a government for high inflation and high unemployment relative to trend. Real GDP growth and real wage growth were not found to have a systematic relationship with incumbent vote share at the Federal level. We also examine the voteshare of the Federal incumbent in three electorates: the safe Liberal seat of Kooyong, the safe Labor seat of Melbourne Pans, and the swinging seat of Latrobe. We find some evidence that unemployment affects electoral outcomes in the swinging seat, but no macroeconomic variables affect outcomes in the safe seats.
Australian Economic Growth: Nonlinearities and International Influences
Authors: HENRY ÓLAN T. , SUMMERS PETER M.
Published: October 2007

This paper considers the extent to which fluctuations in Australian economic growth are affected by domestic and overseas economic performance. We investigate the performance of a range of nonlinear models versus linear models, comparing the models using Bayes factors and posterior odds ratios. The posterior odds ratios favour nonlinear specifications in which fluctuations in economic activity in the US affect Australia's economic performance. Our results suggest that an exogenous negative shock will be more persistent, lead to greater output volatility, and have a greater impact on growth, than a positive shock of equal magnitude.
The Role of Advanced Lipid Testing in Clinical Practice
Authors: Karalis Dean G.
Published: October 2007

The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines recommend assessing an individual's cardiovascular (CV) risk from the Framingham risk score; however, the Framingham risk score may underestimate coronary heart disease (CHD) risk. Current guidelines have identified some emerging lipid risk factors that can be measured by several commercially available advanced cholesterol tests. These emerging lipid risk factors are meant to supplement the Framingham risk score to help the clinician to better assess CV risk. Although advanced lipid testing cannot be recommended for routine screening, it may be of value in individuals with a family history of premature CHD, postmenopausal women, and individuals at intermediate risk for CHD, especially if they are near the boundary of being at high risk. This review examines the role of advanced lipid testing in clinical practice.
In Vitro Monitoring of
Plasmodium falciparum
Drug Resistance in French Guiana: a Synopsis of Continuous Assessment from 1994 to 2005
Authors: Legrand Eric , Volney Béatrice , Meynard Jean-Baptiste , Mercereau-Puijalon Odile , Esterre Philippe
Published: October 2007

Implemented as one arm of the malaria control program in French Guiana in the early 1990s, our laboratory has since established in vitro profiles for parasite drug susceptibility to a panel of eight antimalarials for more than 1,000
Plasmodium falciparum
isolates from infected patients. The quinine-doxycycline combination was introduced in 1995 as the first-line drug treatment against uncomplicated
P. falciparum
malaria, replacing chloroquine, and the first-line drug combination was changed to the artemether-lumefantrine combination in 2002. Resistance to chloroquine declined 5 years after it was dropped in 1995 as the first-line drug, but unlike similar situations in Africa, there was a rapid halt to this decline. Doxycycline susceptibility substantially decreased from 2002 to 2005, suggesting parasite selection under quinine-doxycycline drug pressure. Susceptibility to mefloquine decreased from 1997 onward. Throughout the period from 1994 to 2005, most isolates were sensitive in vitro to quinine, amodiaquine, and atovaquone. Susceptibility to amodiaquine was strongly correlated with that to chloroquine and to a lesser extent with that to mefloquine and halofantrine. Susceptibilities to mefloquine and to halofantrine were also strongly correlated. There were two alerts issued for in vitro artemether resistance in the period from 2002 to 2003 and again in 2005, both of which could be associated with the presence of an S769N polymorphism in the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA)-type
P. falciparum ATPase6
(Pf
ATPase6
) gene. Analysis of susceptibility to lumefantrine, conducted for the first time in 2005, indicates an alarming rate of elevated 50% inhibitory concentrations. In vitro monitoring of parasite drug susceptibility should be pursued to further document the consequences of specific drug policies on the local parasite population and, in particular, to establish profiles of susceptibility to individual components of drug combinations to provide early warning signs of emerging parasite resistance.
Anaerobic NADH-Fumarate Reductase System Is Predominant in the Respiratory Chain of
Echinococcus multilocularis
, Providing a Novel Target for the Chemotherapy of Alveolar Echinococcosis
Authors: Matsumoto Jun , Sakamoto Kimitoshi , Shinjyo Noriko , Kido Yasutoshi , Yamamoto Nao , Yagi Kinpei , Miyoshi Hideto , Nonaka Nariaki , Katakura Ken , Kita Kiyoshi , Oku Yuzaburo
Published: October 2007

Alveolar echinococcosis, which is due to the massive growth of larval
Echinococcus multilocularis
, is a life-threatening parasitic zoonosis distributed widely across the northern hemisphere. Commercially available chemotherapeutic compounds have parasitostatic but not parasitocidal effects. Parasitic organisms use various energy metabolic pathways that differ greatly from those of their hosts and therefore could be promising targets for chemotherapy. The aim of this study was to characterize the mitochondrial respiratory chain of
E. multilocularis
, with the eventual goal of developing novel antiechinococcal compounds. Enzymatic analyses using enriched mitochondrial fractions from
E. multilocularis
protoscoleces revealed that the mitochondria exhibited NADH-fumarate reductase activity as the predominant enzyme activity, suggesting that the mitochondrial respiratory system of the parasite is highly adapted to anaerobic environments. High-performance liquid chromatography-mass spectrometry revealed that the primary quinone of the parasite mitochondria was rhodoquinone-10, which is commonly used as an electron mediator in anaerobic respiration by the NADH-fumarate reductase system of other eukaryotes. This also suggests that the mitochondria of
E. multilocularis
protoscoleces possess an anaerobic respiratory chain in which complex II of the parasite functions as a rhodoquinol-fumarate reductase. Furthermore, in vitro treatment assays using respiratory chain inhibitors against the NADH-quinone reductase activity of mitochondrial complex I demonstrated that they had a potent ability to kill protoscoleces. These results suggest that the mitochondrial respiratory chain of the parasite is a promising target for chemotherapy of alveolar echinococcosis.
Oral Therapy with Amlodipine and Lacidipine, 1,4-Dihydropyridine Derivatives Showing Activity against Experimental Visceral Leishmaniasis
Authors: Palit Partha , Ali Nahid
Published: October 2007

Amlodipine and lacidipine, conventional antihypertensive drugs, inhibited
Leishmania donovani
infection in vitro and in BALB/c mice when administered orally. These 1,4-dihydropyridine derivatives functioned through dose-dependent inhibition of oxygen consumption, triggering caspase 3-like activation-mediated programmed cell death of the parasites.
Mutated Response Regulator
graR
Is Responsible for Phenotypic Conversion of
Staphylococcus aureus
from Heterogeneous Vancomycin-Intermediate Resistance to Vancomycin-Intermediate Resistance
Authors: Neoh Hui-min , Cui Longzhu , Yuzawa Harumi , Takeuchi Fumihiko , Matsuo Miki , Hiramatsu Keiichi
Published: October 2007

Multistep genetic alteration is required for methicillin-resistant
Staphylococcus aureus
(MRSA) to achieve the level of vancomycin resistance of vancomycin-intermediate
S. aureus
(VISA). In the progression of vancomycin resistance, strains with heterogeneous vancomycin resistance, designated hetero-VISA, are observed. In studying the whole-genome sequencing of the representative hetero-VISA strain Mu3 and comparing it with that of closely related MRSA strains Mu50 (VISA) and N315 (vancomycin-susceptible
S. aureus
[VSSA]), we identified a mutation in the response regulator of the
graSR
two-component regulatory system. Introduction of mutated
graR
, designated
graR
*, but not intact
graR
, designated
graRn
, could convert the hetero-VISA phenotype of Mu3 into a VISA phenotype which was comparable to that of Mu50. The same procedure did not appreciably increase the vancomycin resistance of VSSA strain N315, indicating that
graR
* expression was effective only in the physiological milieu of hetero-VISA cell to achieve a VISA phenotype. Interestingly, the overexpression of
graR
* increased the daptomycin MICs in both Mu3 and N315 and decreased the oxacillin MIC in N315.
Results of a Double-Blind, Randomized Trial of Ceftobiprole Treatment of Complicated Skin and Skin Structure Infections Caused by Gram-Positive Bacteria
Authors: Noel Gary J. , Strauss Richard S. , Amsler Karen , Heep Markus , Pypstra Rienk , Solomkin Joseph S.
Published: October 2007

Ceftobiprole is the first broad-spectrum cephalosporin with activity against methicillin-resistant
Staphylococcus aureus
(MRSA) to be assessed in late-stage clinical trials. As a pivotal step in the clinical development of ceftobiprole, a multicenter, global, randomized, double-blind trial was conducted to compare the efficacy of ceftobiprole to that of vancomycin in patients with complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria. The primary objective was to assess noninferiority on the basis of the cure rates 7 to 14 days after the completion of therapy in patients administered ceftobiprole 500 mg every 12 h or vancomycin 1 g every 12 h. Of 784 patients randomized, 282 receiving ceftobiprole and 277 receiving vancomycin were clinically evaluable. Of these patients, 93.3% treated with ceftobiprole and 93.5% treated with vancomycin were cured (95% confidence interval of difference, −4.4%, 3.9%). The cure rates for patients with MRSA infections were 91.8% (56/61) with ceftobiprole treatment and 90.0% (54/60) with vancomycin treatment (95% confidence interval of difference, −8.4%, 12.1%). At least one adverse event (AE) was reported by 52% of the ceftobiprole-treated patients and 51% of the vancomycin-treated patients. The most common AEs reported by the ceftobiprole-treated patients were nausea (14%) and taste disturbance (8%). Discontinuation of the study drug because of treatment-emergent AEs occurred in 4% (
n
= 17) of the ceftobiprole-treated patients and 6% (
n
= 22) of the vancomycin-treated patients. The results of this trial support the use of ceftobiprole as an effective and well-tolerated treatment option for patients with cSSSIs caused by a spectrum of gram-positive bacteria.
Subinhibitory Concentrations of Azithromycin Decrease Nontypeable
Haemophilus influenzae
Biofilm Formation and Diminish Established Biofilms
Authors: Starner Timothy D. , Shrout Joshua D. , Parsek Matthew R. , Appelbaum Peter C. , Kim GunHee
Published: October 2007

Nontypeable
Haemophilus influenzae
(NTHi) commonly causes otitis media, chronic bronchitis in emphysema, and early airway infections in cystic fibrosis. Long-term, low-dose azithromycin has been shown to improve clinical outcomes in chronic lung diseases, although the mechanism of action remains unclear. The inhibition of bacterial biofilms by azithromycin has been postulated to be one mechanism mediating these effects. We hypothesized that subinhibitory concentrations of azithromycin would affect NTHi biofilm formation. Laboratory strains of NTHi expressing green fluorescent protein and azithromycin-resistant clinical isolates were grown in flow-cell and static-culture biofilm models. Using a range of concentrations of azithromycin and gentamicin, we measured the degree to which these antibiotics inhibited biofilm formation and persistence. Large biofilms formed over 2 to 4 days in a flow cell, displaying complex structures, including towers and channels. Subinhibitory concentrations of azithromycin significantly decreased biomass and maximal thickness in both forming and established NTHi biofilms. In contrast, subinhibitory concentrations of gentamicin had no effect on biofilm formation. Furthermore, established NTHi biofilms became resistant to gentamicin at concentrations far above the MIC. Biofilm formation of highly resistant clinical NTHi isolates (azithromycin MIC of >64 μg/ml) was similarly decreased at subinhibitory azithromycin concentrations. Clinically obtainable azithromycin concentrations inhibited biofilms in all but the most highly resistant isolates. These data show that subinhibitory concentrations of azithromycin have antibiofilm properties, provide mechanistic insights, and supply an additional rationale for the use of azithromycin in chronic biofilm infections involving
H. influenzae
.
Betulinic Acid Derivatives That Target gp120 and Inhibit Multiple Genetic Subtypes of Human Immunodeficiency Virus Type 1
Authors: Lai Weihong , Huang Li , Ho Phong , Li Zhijun , Montefiori David , Chen Chin-Ho
Published: October 2007

Betulinic acid (BA) derivatives can inhibit human immunodeficiency virus type 1 (HIV-1) entry or maturation depending on side chain modifications. While BA derivatives with antimaturation activity have attracted considerable interest, the anti-HIV-1 profile and molecular mechanism of BA derivatives with anti-HIV-1 entry activity (termed BA entry inhibitors) have not been well defined. In this study, we have found that two BA entry inhibitors, IC9564 and A43D, exhibited a broad spectrum of anti-HIV-1 activity. Both compounds inhibited multiple strains of HIV-1 from clades A, B, and C at submicromolar concentrations. Clade C viruses were more sensitive to the compounds than clade A and B viruses. Interestingly, IC9564 at subinhibitory concentrations could alter the antifusion activities of other entry inhibitors. IC9564 was especially potent in increasing the sensitivity of HIV-1
YU2
Env-mediated membrane fusion to the CCR5 inhibitor TAK-779. Results from this study suggest that the V3 loop of gp120 is a critical determinant for the anti-HIV-1 activity of IC9564. IC9564 escape viruses contained mutations near the tip of the V3 loop. Moreover, IC9564 could compete with the binding of V3 monoclonal antibodies 447-52D and 39F. IC9564 also competed with the binding of gp120/CD4 complexes to chemokine receptors. In summary, these results suggest that BA entry inhibitors can potently inhibit a broad spectrum of primary HIV-1 isolates by targeting the V3 loop of gp120.
Increased Macrolide Resistance of
Mycoplasma pneumoniae
in Pediatric Patients with Community-Acquired Pneumonia
Authors: Morozumi Miyuki , Iwata Satoshi , Hasegawa Keiko , Chiba Naoko , Takayanagi Reiko , Matsubara Keita , Nakayama Eiichi , Sunakawa Keisuke , Ubukata Kimiko
Published: October 2007

Among 380
Mycoplasma pneumoniae
isolates from 3,678 pediatric patients with community-acquired pneumonia, 50 macrolide-resistant strains had an A2063G transition in domain V of the 23S rRNA, whereas 5 had an A2064G transition. These resistant strains increased rapidly from April 2002 to December 2006.
Exposure-Response Analyses of Tigecycline Efficacy in Patients with Complicated Intra-Abdominal Infections
Authors: Passarell J. A. , Meagher A. K. , Liolios K. , Cirincione B. B. , Van Wart S. A. , Babinchak T. , Ellis-Grosse E. J. , Ambrose P. G.
Published: October 2007

Exposure-response analyses were performed to test the microbiological and clinical efficacies of tigecycline in complicated intra-abdominal infections where
Escherichia coli
and
Bacteroides fragilis
are the predominant pathogens. Data from evaluable patients enrolled in three clinical trials were pooled. Patients received intravenous tigecycline (100-mg loading dose followed by 50 mg every 12 h or 50-mg loading dose followed by 25 mg every 12 h). At the test-of-cure visit, microbiological and clinical responses were evaluated. Patients were prospectively classified into cohorts based on infection with a baseline pathogen(s):
E. coli
only (cohort 1), other mono- or polymicrobial
Enterobacteriaceae
(cohort 2), at least one
Enterobacteriaceae
pathogen plus an anaerobe(s) (cohort 3), at least one
Enterobacteriaceae
pathogen plus a gram-positive pathogen(s) (cohort 4), and all other pathogens (cohort 5). The cohorts were prospectively combined to increase sample size. Logistic regression was used to evaluate ratio of steady-state 24-hour area under the concentration-time curve (AUC) to MIC as a response predictor, and classification-and-regression-tree (CART) analyses were utilized to determine AUC/MIC breakpoints. Analysis began with cohorts 1, 2, and 3 pooled, which included 71 patients, with 106 pathogens. The small sample size precluded evaluation of cohorts 1 (34 patients, 35
E. coli
pathogens) and 2 (16 patients, 24
Enterobacteriaceae
). CART analyses identified a significant AUC/MIC breakpoint of 6.96 for microbiological and clinical responses (
P
values of 0.0004 and 0.399, respectively). The continuous AUC/MIC ratio was also borderline predictive of microbiological response (
P
= 0.0568). Cohort 4 (21 patients, 50 pathogens) was evaluated separately; however, an exposure-response relationship was not detected; cohort 5 (31 patients, 60 pathogens) was not evaluated. The prospective approach of creating homogenous populations of pathogens was critical for identifying exposure-response relationships in complicated intra-abdominal infections.
Bile and Unsaturated Fatty Acids Inhibit the Binding of Cholera Toxin andEscherichia coliHeat-Labile Enterotoxin to GM1 Receptor
Authors: Chatterjee Arpita , Chowdhury Rukhsana
Published: October 2007

Cholera toxin (CT) is an archetypal bacterial toxin that binds with a high affinity to the receptor ganglioside GM1 on the intestinal epithelial surface and that causes the severe watery diarrhea characteristic of the disease cholera. Blockage of the interaction of CT with the GM1 receptor is an attractive approach for therapeutic intervention. We report here that crude bile prevents the interaction of CT with GM1 and reduces CT-mediated fluid accumulation in the rabbit intestine. The unsaturated fatty acids detected in crude bile, arachidonic, linoleic, and oleic acids, were found to be the most effective. Crude bile and the unsaturated fatty acids interacted with CT but not GM1 to prevent CT-GM1 binding. Neither crude bile nor the unsaturated fatty acids had any effect on the subunit structure of CT. The binding of CT to unsaturated fatty acids resulted in a shift of the apparent pI of CT from 6.8 to 8.2 and a marked decrease in intrinsic fluorescence. TheKdwas calculated from fluorescence quenching assays. It was demonstrated by the rabbit ileal loop model that practically no fluid accumulated in the intestinal loops when CT was administered together with inhibitory concentrations of linoleic acid. The bile present in the intestine was sufficient to inhibit the activity of up to 300 ng CT. Bile and unsaturated fatty acids also inhibited the binding ofEscherichia coliheat-labile enterotoxin (LT) to GM1, and no fluid accumulation was observed in rabbit ileal loops when LT was administered together with linoleic acid.
Tetracycline-Inducible Expression of Individual Secreted Aspartic Proteases in
Candida albicans
Allows Isoenzyme-Specific Inhibitor Screening
Authors: Staib Peter , Lermann Ulrich , Blaβ-Warmuth Julia , Degel Björn , Würzner Reinhard , Monod Michel , Schirmeister Tanja , Morschhäuser Joachim
Published: October 2007

The yeast
Candida albicans
possesses a gene family that encodes secreted aspartic proteases (Saps), which are important for the virulence of this human fungal pathogen. Inhibitors of the Saps could therefore be used as novel antimycotic agents for the treatment of
C. albicans
infections. In the present study, we established a bioassay which allows testing of the activity of potential protease inhibitors against specific Sap isoenzymes by their ability to inhibit protease-dependent growth of
C. albicans
. In a medium containing bovine serum albumin (BSA) as the sole source of nitrogen,
C. albicans
specifically expresses the Sap2p isoenzyme, which degrades the BSA and thereby enables the fungus to grow. As the other
SAP
genes are not significantly expressed under these conditions, mutants lacking
SAP2
are unable to utilize BSA as a nitrogen source and cannot grow in such a medium. To investigate whether forced expression of
SAP
genes other than
SAP2
would also allow growth on BSA, we constructed a set of strains expressing each of the 10
SAP
genes from a tetracycline-inducible promoter in a
sap2
Δ mutant background. Expression of Sap1p, Sap2p, Sap3p, Sap4p, Sap5p, Sap6p, Sap8p, and a C-terminally truncated, secreted Sap9p restored the growth of the
sap2
Δ mutant with different efficiencies. This set of strains was then used to test the activities of various aspartic protease inhibitors against specific Sap isoenzymes by monitoring growth on BSA in the presence of the inhibitors. While pepstatin blocked the activity of all of the Saps tested, the human immunodeficiency virus protease inhibitors ritonavir and saquinavir inhibited growth of the strains expressing Sap1p to Sap3p and Sap1p, respectively, but not that of strains expressing other Saps. Therefore, the strain set can be used to test the activity of new protease inhibitors against individual
C. albicans
Sap isoenzymes by their ability to block the growth of the pathogen.
Staphylococcus epidermidis saeR
Is an Effector of Anaerobic Growth and a Mediator of Acute Inflammation
Authors: Handke L. D. , Rogers K. L. , Olson M. E. , Somerville G. A. , Jerrells T. J. , Rupp M. E. , Dunman P. M. , Fey P. D.
Published: October 2007

The
saeRS
two-component regulatory system regulates transcription of multiple virulence factors in
Staphylococcus aureus
. In the present study, we demonstrated that the
saePQRS
region in
Staphylococcus epidermidis
is transcriptionally regulated in a temporal manner and is arranged in a manner similar to that previously described for
S. aureus
. Studies using a mouse foreign body infection model demonstrated that the virulence of strain 1457 and the virulence of a mutant, strain 1457
saeR
, were statistically equivalent. However, histological analyses suggested that the polymorphonuclear neutrophil response at 2 days postinfection was significantly greater in 1457-infected mice than in 1457
saeR
-infected mice, demonstrating that SaeR influences the early, acute phases of infection. Microarray analysis demonstrated that a
saeR
mutation affected the transcription of 65 genes (37 genes were upregulated and 28 genes were downregulated); in particular, 8 genes that facilitate growth under anaerobic conditions were downregulated in 1457
saeR
. Analysis of growth under anaerobic conditions demonstrated that 1457
saeR
had a decreased growth rate compared to 1457. Further metabolic experiments demonstrated that 1457
saeR
had a reduced capacity to utilize nitrate as a terminal electron acceptor and exhibited increased production of lactic acid in comparison to 1457. These data suggest that in
S. epidermidis
SaeR functions to regulate the transition between aerobic growth and anaerobic growth. In addition, when grown anaerobically, 1457
saeR
appeared to compensate for the redox imbalance created by the lack of electron transport-mediated oxidation of NADH to NAD
+
by increasing lactate dehydrogenase activity and the subsequent oxidation of NADH.
Critical Role of RecN in Recombinational DNA Repair and Survival of
Helicobacter pylori
Authors: Wang Ge , Maier Robert J.
Published: October 2007

Homologous recombination is one of the key mechanisms responsible for the repair of DNA double-strand breaks. Recombinational repair normally requires a battery of proteins, each with specific DNA recognition, strand transfer, resolution, or other functions.
Helicobacter pylori
lacks many of the proteins normally involved in the early stage (presynapsis) of recombinational repair, but it has a RecN homologue with an unclear function. A
recN
mutant strain of
H. pylori
was shown to be much more sensitive than its parent to mitomycin C, an agent predominantly causing DNA double-strand breaks. The
recN
strain was unable to survive exposure to either air or acid as well as the parent strain, and air exposure resulted in no viable
recN
cells recovered after 8 h. In oxidative stress conditions (i.e., air exposure), a
recN
strain accumulated significantly more damaged (multiply fragmented) DNA than the parent strain. To assess the DNA recombination abilities of strains, their transformation abilities were compared by separately monitoring transformation using
H. pylori
DNA fragments containing either a site-specific mutation (conferring rifampin resistance) or a large insertion (kanamycin resistance cassette). The transformation frequencies using the two types of DNA donor were 10- and 50-fold lower, respectively, for the
recN
strain than for the wild type, indicating that RecN plays an important role in facilitating DNA recombination. In two separate mouse colonization experiments, the
recN
strain colonized most of the stomachs, but the average number of recovered cells was 10-fold less for the mutant than for the parent strain (a statistically significant difference). Complementation of the
recN
strain by chromosomal insertion of a functional
recN
gene restored both the recombination frequency and mouse colonization ability to the wild-type levels. Thus,
H. pylori
RecN, as a component of DNA recombinational repair, plays a significant role in
H. pylori
survival in vivo.
Mycoplasma gallisepticum
Invades Chicken Erythrocytes during Infection
Authors: Vogl Gunther , Plaickner Astrid , Szathmary Susan , Stipkovits László , Rosengarten Renate , Szostak Michael P.
Published: October 2007

Recently, it was demonstrated using in vitro assays that the avian pathogen
Mycoplasma gallisepticum
is able to invade nonphagocytic cells. It was also shown that this mycoplasma can survive and multiply intracellularly for at least 48 h and that this cell invasion capacity contributes to the systemic spread of
M. gallisepticum
from the respiratory tract to the inner organs. Using the gentamicin invasion assay and a differential immunofluorescence technique combined with confocal laser scanning microscopy, we were able to demonstrate in in vitro experiments that
M. gallisepticum
is also capable of invading sheep and chicken erythrocytes. The frequencies of invasion of three well-defined
M. gallisepticum
strains were examined over a period of 24 h, and a significant increase in invasiveness occurred after 8 h of infection. In addition, blood samples derived from chickens experimentally infected via the aerosol route with the virulent strain
M. gallisepticum
R
low
were analyzed. Surprisingly,
M. gallisepticum
R
low
was detected in the bloodstream of infected chickens by nested PCR, as well as by differential immunofluorescence and interference contrast microscopy that showed that mycoplasmas were not only on the surface but also inside chicken erythrocytes. This finding provides novel insight into the pathomechanism of
M. gallisepticum
and may have implications for the development of preventive strategies.
Mycoplasma pneumoniae-Derived Lipopeptides Induce Acute Inflammatory Responses in the Lungs of Mice
Authors: Shimizu Takashi , Kida Yutaka , Kuwano Koichi
Published: October 2007

The pathogenesis ofMycoplasma pneumoniaeinfection is considered to be in part attributable to excessive immune responses. In this study, we investigated whether synthetic lipopeptides of subunit b of F0F1-type ATPase (F0F1-ATPase), NF-κB-activating lipoprotein 1 (N-ALP1), and N-ALP2 (named FAM20, sN-ALP1, and sN-ALP2, respectively) derived fromM. pneumoniaeinduce cytokine and chemokine production and leukocyte infiltration in vivo. Intranasal administration of FAM20 and sN-ALP2 induced infiltration of leukocyte cells and production of chemokines and cytokines in bronchoalveolar lavage fluid, but sN-ALP1 failed to do so. The activity of FAM20 was notably higher than that of sN-ALP2. FAM20 and sN-ALP2 induced tumor necrosis factor alpha (TNF-α) through Toll-like receptor 2 in mouse peritoneal macrophages. Moreover, in the range of low concentrations of lipopeptides, FAM20 showed relatively high activity of inducing TNF-α in mouse peritoneal macrophages compared to synthetic lipopeptides such as MALP-2 and FSL-1, derived fromMycoplasma fermentansandMycoplasma salivarium, respectively. These findings indicate that the F0F1-ATPase might be a key molecule in inducing cytokines and chemokines contributing to inflammatory responses duringM. pneumoniaeinfection in vivo.
Lipoteichoic Acid Is Important in Innate Immune Responses to Gram-Positive Bacteria
Authors: Seo Ho Seong , Michalek Suzanne M. , Nahm Moon H.
Published: October 2007

To define the role of lipoteichoic acid (LTA) in innate immunity to gram-positive bacteria, we investigated the production of tumor necrosis factor alpha (TNF-α) by macrophages stimulated with gram-positive bacterial culture supernatants (GPCSs) after their LTA was removed or inactivated. GPCSs were obtained from three gram-positive species (pneumococci, staphylococci, and group B streptococci) during the exponential growth phase (designated early GPCSs) or at the senescent stage (designated late GPCSs). LTA was removed using an anti-LTA antibody or was inactivated by alkaline hydrolysis or platelet-activating factor acetylhydrolase (PAF-AH) treatment. Both early and late GPCSs from the three gram-positive bacteria stimulated macrophages to produce TNF-α primarily via Toll-like receptor 2 (TLR2), although late pneumococcal supernatant could stimulate macrophages via TLR4 as well. Following LTA inactivation by both methods, early GPCS lost about 85 to 100% of its activity and late GPCS lost about 50 to 90%. Both early and late culture supernatants fromEscherichia colicould be inactivated by alkali hydrolysis but not by PAF-AH. In addition, removal of LTA from an early staphylococcal culture supernatant with a monoclonal antibody reduced about 70 to 85% of its potency. Reconstitution of inactivated early GPCS with a highly purified LTA restored its inflammatory activity, but the restored GPCS had higher activity than the pure LTA alone. These findings indicate that LTA is the primary TLR2 ligand in the early phase of gram-positive bacterial infection and remains a major ligand in the late phase when another TLR2 and TLR4 ligand(s) appears. In addition, our findings suggest that another gram-positive bacterial factor(s) synergizes with LTA in inducing inflammatory responses.
COMPARISON OF HYDRODYNAMICAL AND EXPERIMENTAL ESTIMATES OF ELLIPTICAL FLOW
Authors: ANDRADE R. , GRASSI F. , HAMA Y. , KODAMA T. , SOCOLOWSKI O.
Published: October 2007

Elliptic flow is easy to compute in hydrodynamics. However experimentally it is obtained in an indirect way. The question we address in this paper (using the hydrodynamical code NeXSPheRIO) is how comparable are these two approaches. We find that there is a disagreement between both methods of 15–30% for η = 0 and 30% for p⊥ = 0.5 GeV .