bluuebunny/crossref_metadata_2025 huggingface dataset:
THE TWO TRIBES OF ‘THE ECON’: A STUDY OF ECONOMISTS AND ECONOMIC MEDIA COMMENTARY IN AUSTRALIA
Authors: MILLMOW ALEX , COURVISANOS JERRY
Published: April 2010

This article analyses and speculates upon an interesting but unsettling development within the Australian economic profession. It argues that there is a schism within the profession when it comes to providing economic commentary to the media. We argue that only financial market economist voices dominate in the Australian media when it comes to commentary on current economic issues. This has implications for the acceptance of economic policy since these economists are apt to uphold the interests of their employer. In contrast, academic economists suffer from a lack of recognition and ‘reach’ in the media, which biases the promulgation of economic policy options in the broader community. We present evidence showing that today's generation of academic economists, in contrast to previous generations, is becoming reticent on matters of public policy.
INSTITUTIONAL CHANGE AND ECONOMIC GROWTH: THE EVOLUTION OF WATER RIGHTS IN VICTORIA, AUSTRALIA 1850–1886
Authors: HARRIS EDWYNA
Published: April 2010

This paper provides a preliminary exploration of the role of adaptive efficiency and institutional learning as the basis for long‐run economic growth in Australia by means of an analysis of the institutional changes in water rights between 1850 and 1886 in the colony of Victoria. It is argued that the effects of adaptive efficiency and institutional learning led to the replacement of growth‐hindering institutional arrangements in water supply in favour of growth‐enhancing frameworks that provided the basis for better economic performance over the long‐run. The analysis presents evidence that suggests that in addition to the colonial experience, adaptive efficiency embedded in the inheritance of British culture rather than institutions has played an important role in Australia's economic performance.
TAX REFORM: A DIFFERENT VIEW
Authors: KINGSTON GEOFFREY
Published: April 2010

The mainstream view of tax reformers in Australia is that dropping our top personal tax rate closer to our corporate rate is the best way to use persistent budget surpluses in order to promote national prosperity. Yet the international evidence suggests that dropping our corporate rate would be more effective in lifting output and wages. Prominent tax reformers have tended to go along with recent measures that will shield the elderly from most direct taxation. Further down the track, however, questions will arise about whether the young are bearing an inordinate share of the tax burden.
NATIONAL EXUBERANCE: A NOTE ON THE MELBOURNE CUP EFFECT IN AUSTRALIAN STOCK RETURNS
Authors: WORTHINGTON ANDREW C.
Published: April 2010

This note examines the presence of a Melbourne Cup effect in Australian daily stock returns over the forty‐five years from 3 January 1961 to 30 December 2005. First run in 1861, the Melbourne Cup is Australia's premier horse race and one of the world's leading handicaps. Parametric tests of differences in means and a regression‐based approach are used to test for the effect alongside a conventional day‐of‐the‐week (Tuesday) and month‐of‐the year (November) effects. The results indicate that the mean Melbourne Cup Day return of 0.1916 is significantly higher than the mean return for other Tuesdays in November (−0.2345), Tuesdays in other months of the year (−0.0352), and Monday, Wednesday, Thursday, and Friday returns throughout the year (0.0516). This suggests the exuberance associated with Australia's unofficial national day is translated into irrationally positive market behaviour.
MINIMUM WAGES AND THE ‘WORKING POOR’
Authors: WOODEN MARK , WILKINS ROGER , McGUINNESS SEAMUS
Published: April 2010

This paper uses data from the HILDA Survey to examine whether or not a minimum wage increase can do much to alleviate poverty or reduce earnings inequality. It is concluded that any poverty reducing effects will be modest. Most low‐wage employees are not found living in the poorest households, and among those that are, many combine part‐time work with receipt of a government benefit. It is also concluded that minimum wage increases are likely to be of limited effectiveness in protecting the living standards of the ‘working poor’. This is because the large increases in hourly wages experienced by most low‐wage workers do not always translate into similarly large increases in annual earnings.
WHY DO AUSTRALIAN UNIVERSITIES FARE SO POORLY IN INTERNATIONAL RANKINGS? EVIDENCE FOR ECONOMICS DEPARTMENTS AND SOME HYPOTHESES
Authors: POMFRET RICHARD
Published: April 2010

This paper reviews the literature that ranks universities and economics departments. In international rankings Australian universities fare well, but the most popular (ARWU and THES) measures are biased in ways that favour Australian universities. In international rankings of economics departments by their research performance, Australian universities fare poorly, relative to natural comparators. Several hypotheses can explain this phenomenon: inappropriate measures, low productivity, time spent on non‐research activities, age and cohort effects and lack of resources.
QUANTIFYING BENEFIT ESTIMATES FOR PRUDENTIAL RULE MAKING
Authors: LITTRELL CHARLES , ANASTOPOULOS PHILLIP
Published: April 2010

Quantifying monetary benefits for cost‐benefit analysis can be a difficult task and globally few prudential regulators have been able to substantiate economic benefits using quantified estimates. This paper outlines a model the Australian Prudential Regulation Authority (APRA) is developing to quantify the economic benefits associated with incremental changes to prudential regulations. The model initially calculates the default probabilities and loss estimates using data from APRA's existing internal risk rating system and the default probabilities from external ratings agencies. For any proposed regulatory change the model calculates the change in the risk ratings of the portfolio and the change in loss estimates to arrive at an annual benefit estimate for the rule change. This value is subsequently reduced to take into account APRA's existing effectiveness at remediating entities and the benefit estimate is converted to a net present value.
URBAN WATER PRICING: PRACTICAL PERSPECTIVES AND CUSTOMER PREFERENCES
Authors: CRASE LIN , O'KEEFE SUE , DOLLERY BRIAN
Published: April 2010

There is considerable variation between Australian jurisdictions in their approach to urban water and waste‐water pricing. Regardless of the explicit commitments of signatories to the National Water Initiative to ‘best practice pricing’ in 2004, there are no obvious signs that a common and efficient pricing regime is emerging. This paper considers one of the dimensions of urban water tariffs: the split between ‘volumetric’ and ‘access’ charges. Given the practical difficulties of implementing a ‘first‐best’ solution, the preferences of household consumers are explored using choice modelling. Results show that household consumers would prefer a tariff regime that embodies greater emphasis on volumetric charges. This approach would also be more attractive on economic grounds compared to current regimes, with their high access charges and fixed waste‐water tariffs.
RETURNS TO EDUCATION IN AUSTRALIA
Authors: LEIGH ANDREW
Published: April 2010

Using data from the 2001–2005 waves of the Household, Income and Labour Dynamics in Australia survey, and taking account of existing estimates of ability bias and social returns to schooling, I estimate the economic return to various levels of education. Raising high school attainment appears to yield the highest annual benefits, with per‐year gains as high as 30% (depending on the adjustment for ability bias). Some forms of vocational training also appear to boost earnings, with significant gains from Certificate Level III/IV qualifications (for high school dropouts only), and from Diploma and Advanced Diploma qualifications. At the university level, bachelor degrees and postgraduate qualifications are associated with significantly higher earnings, with each year of a bachelor degree raising annual earnings by about 15%. For high schools, slightly less than half the gains are due to increased productivity, with the rest being due to higher levels of participation. For vocational training, about one‐third of the gains are from productivity, and two‐thirds from greater participation. For universities, most of the gains are from productivity. I find some evidence that the productivity benefits of education are higher towards the top of the distribution, but the effects on hours worked are higher towards the bottom of the conditional earnings distribution.
THE REGULATION OF INVESTMENTS
Authors: VALENTINE TOM
Published: April 2010

This paper argues that it is time for an inquiry into the regulation of investment products and markets similar to the Campbell Inquiry which recommended the deregulation of the Australian financial system. First, the present approach based on disclosure requirements and legal sanctions has demonstrably failed, as indicated by continuing losses arising from the collapse of large investment vehicles. Second, there is a need to protect investors because of the large amount of assets they have exposed to investment vehicles, investors' lack of knowledge of the complex products now emerging and the possible systemic effects of the failure of large investment vehicles.
BETWEEN FORCED RESUMPTION AND VOLUNTARY SALE: A MECHANISM FOR THE COLLECTIVE SALE OR TRANSFER OF IRRIGATION WATER
Authors: PINCUS JONATHAN , SHAPIRO PERRY
Published: April 2010

Currently, the legitimate transfer of ownership of an asset occurs either through voluntary means—gift, bequest, sale—or through the use of state power—compulsory acquisition, resumption, eminent domain, court order. In Australia and elsewhere, compulsory acquisition of private property is followed by the payment of compensation, which may be too little or too great. This paper outlines an auction mechanism that is intermediate between the forced resumption of water entitlements and their voluntary sale. To be effective, the mechanism requires there to be competitive bidders in the auction; so the mechanism would work best if there were an end to collusion between public agencies in the water market. The seller would be an irrigation district, which would be compelled by government to engage in the auction. The proceeds of any auction sale would be distributed to the individual irrigators, according to fixed and known fractional shares. However, in contrast with the use of forced resumption, under the Shapiro‐Pincus mechanism no sale would be made unless each individual irrigator receives at least what he or she has nominated as a minimum required payment. This guarantee would be secured through the use of a secret reserve for the auction of the district's water entitlements. The combination of a secret reserve, competitive bidding, and the share mechanism should give individual irrigators a financial incentive to nominate truthfully what each requires as a minimum payment. The mechanism may have other applications, including helping to achieve unanimous agreement within an irrigation district to offer to sell all of the district's entitlements.
SHARED SERVICES IN AUSTRALIAN LOCAL GOVERNMENT: A CASE STUDY OF THE QUEENSLAND LOCAL GOVERNMENT ASSOCIATION MODEL
Authors: DOLLERY BRIAN , HALLAM GREG , WALLIS JOE
Published: April 2010

A host of recent public inquiries into Australian local government have recommended increased use of shared services and resource‐sharing models between groups of local councils. While little is known about the extent and consequences of service sharing, emphasis has been fixed on ‘horizontal’ shared service models between different local councils in the same municipal jurisdictions. However, other models of shared services and resource sharing are possible. This paper considers the Queensland Local Government Association (LGAQ) model as a case study of a resource sharing between all councils in a given system of local government. This form of shared service and resource sharing seems to offer excellent prospects for cost savings and capacity enhancement.
AN APPROACH TO TEACHING MONETARY POLICY SINCE DEREGULATION
Authors: COOMBES TREVOR
Published: April 2010

Since the full institution of deregulation the mechanics of how monetary policy operates has fundamentally changed. No longer can a change in stance be shown as shifts in the exogenously‐determined money supply function in the Keynesian interest framework, because in competitive banking systems the money supply process is fully endogenous. Money endogeneity correctly suggests a reinterpretation of the vertical money supply function. A vertical money supply function drawn against bond yields does not automatically mean exogeneity. Monetary policy is best shown as shifts in the money demand function.
3D Bipedal Model With Holonomic Constraints for the Decoupled Optimal Controller Design of the Biomechanical Sit-to-Stand Maneuver
Authors: Mughal Asif , Iqbal Kamran
Published: April 2010

Human voluntary movements are complex physical phenomena due to the complex control mechanism for coordination of limbs in the presence of physiological constraints. In this study, we propose a nonlinear human bipedal model with thirteen generalized coordinates to model sit-to-stand (STS) transfer. The model has three position based holonomic constraints and at the first stage, we decouple the translational variables (constrained system) from rotational variables (unconstrained systems). The unconstrained rotational degrees consist of seven sagittal and three frontal plane angles, which are controlled through their respective joint torques. We further decouple these angles in sagittal and frontal plane systems for a better control strategy. In this scheme, there are three decoupled controllers working together to stabilize the nonlinear model for a STS maneuver while satisfying the holonomic constraints. We adopt H∞ and H2 controller designs for feedback torques in sagittal and frontal planes, respectively, and provide simulation results to show the improvement in the angular profiles. We further adopt this modeling strategy to study and analyze the neuromuscular disorders by decoupling healthy and neurodeficient extremities. Our study indicates that the decoupling of the bipedal model improves the controllability of the system and produces better angular profiles for a bipedal STS maneuver. This modeling scheme is useful for analysis of neuromuscular disorders and other relevant physiological motor control models.
Mechanical Stimulation Mediates Gene Expression in MC3T3 Osteoblastic Cells Differently in 2D and 3D Environments
Authors: Barron Matthew J. , Tsai Chung-Jui , Donahue Seth W.
Published: April 2010

Successful bone tissue engineering requires the understanding of cellular activity in three-dimensional (3D) architectures and how it compares to two-dimensional (2D) architecture. We developed a perfusion culture system that utilizes fluid flow to mechanically load a cell-seeded 3D scaffold. This study compared the gene expression of osteoblastic cells in 2D and 3D cultures, and the effects of mechanical loading on gene expression in 2D and 3D cultures. MC3T3-E1 osteoblastlike cells were seeded onto 2D glass slides and 3D calcium phosphate scaffolds and cultured statically or mechanically loaded with fluid flow. Gene expression of OPN and FGF-2 was upregulated at 24 h and 48 h in 3D compared with 2D static cultures, while collagen 1 gene expression was downregulated. In addition, while flow increased OPN in 2D culture at 48 h, it decreased both OPN and FGF-2 in 3D culture. In conclusion, gene expression is different between 2D and 3D osteoblast cultures under static conditions. Additionally, osteoblasts respond to shear stress differently in 2D and 3D cultures. Our results highlight the importance of 3D mechanotransduction studies for bone tissue engineering applications.
Residual Stress Around the Cortical Surface in Bovine Femoral Diaphysis
Authors: Yamada Satoshi , Tadano Shigeru
Published: April 2010

Residual stress in living tissue plays an important role in mechanical strength. We have reported that residual stress exists in the bone tissue of a rabbit’s tibiofibula. The purpose of this study is to measure the residual stress around the outer cortical region of bovine femoral diaphysis and to discuss the distribution of the stress. This work proposed the sin2 ψ method of X-ray diffraction to the measurement of residual stresses in bone tissue. In this method, residual stress can be estimated from the variation in the interplanar spacings orientated to a number of directions without the lattice strain in the stress direction. Four-point bending tests of strip specimens taken from bovine femoral diaphysis were carried out during X-ray irradiation in advance. In the proximal, middle, and distal sections of bovine femoral diaphyses, the residual stresses at the cortical surface were measured using characteristic Mo-Kα X-rays. The bending tests of strip specimens with X-ray irradiation showed that the method could reliably estimate residual stresses in the bone tissue. The residual stress of the bone axial direction was larger than that of the circumferential direction. The stresses in the middle part of five diaphyses along the bone axial direction were tensile. The maximum stress was 162 MPa at the lateral position and the minimum was 78 MPa at the posterior position. The residual stress in the bone axial direction varies around the circumferential region. In addition, the bone axial distributions of residual stresses were different in the proximal, middle, and distal sections of the individual femur. Furthermore, it was confirmed that residual stress in the bone tissue was released by the cutting out of the specimen. The residual stresses in bone tissue could be measured by this method. The results show that residual stress in the bone axial direction at the cortical surface in bovine femoral diaphysis is tensile and varies around the circumferential region.
Experimental Study and Numerical Simulation of Propellant Ignition and Combustion for Cased Telescoped Ammunition in Chamber
Authors: Lu Xin , Zhou Yanhuang , Yu Yonggang
Published: April 2010

Cased telescoped ammunition (CTA) is a kind of charge structure with projectile embedded in the cartridge case. The advantages of CTA, compared with concepts using conventional ammunition, are: (1) reduced charge/ammunition volume, (2) improved performance, and (3) enhanced power and survivabillity of armament. The projectile is placed in the control tube of the cartridge before shooting. After the primer is struck, propellant product gases, generated by the igniter charge burning in the central igniter tube, drive the projectile to move forward along the control tube, and then causing the main propellants around the igniter tube and control tube to burn. Therefore, in the process of interior ballistics, there is a motion of the projectile in the control tube before the projectile engraves the rifles, in contrast with the traditional ammunition. The consistency of this motion has an important influence on the stability of CTA interior ballistic performance. The experiments on the ignition and combustion of propellants and motion of projectile in the control tube are carried out using a high-speed video recording system in this study. The projectile velocity at the entrance of the rifle is obtained from the recorded images. A two-phase flow model of CTA is also established and simulated by using the two-phase flow method and computational fluid dynamics technology. The calculated projectile velocity is in good agreement with the experimental data. The numerical results show that the developed mathematical model gives the correct trend and can provide useful calculated parameters for the structural design of CTA components.
Identification of the
miR-106b
~
25
MicroRNA Cluster as a Proto-Oncogenic
PTEN
-Targeting Intron That Cooperates with Its Host Gene
MCM7
in Transformation
Authors: Poliseno Laura , Salmena Leonardo , Riccardi Luisa , Fornari Alessandro , Song Min Sup , Hobbs Robin M. , Sportoletti Paolo , Varmeh Shorheh , Egia Ainara , Fedele Giuseppe , Rameh Lucia , Loda Massimo , Pandolfi Pier Paolo
Published: April 2010

A microRNA network regulates the tumor suppressor PTEN in prostate cancer.
Localizing Lipids
Authors: Adler Elizabeth M.
Published: April 2010

VEGF-B regulates endothelial fatty acid transport and thereby lipid disposition by stimulating the production of fatty acid transport proteins.
Ligand-Independent ER Activation
Authors: VanHook Annalisa M.
Published: April 2010

cAMP activation of estrogen receptor α requires PKA-mediated phosphorylation of the arginine methyltransferase CARM1.
Arsenic on the Fingers
Authors: Kiberstis Paula A.
Published: April 2010

Arsenic, a drug used clinically for leukemia, binds directly to an oncogenic protein, thereby promoting its degradation.
Not Lost in Space: Trafficking in the Hedgehog Signaling Pathway
Authors: Milenkovic Ljiljana , Scott Matthew P.
Published: April 2010

Protein kinase A orchestrates Hedgehog signaling from the base of the primary cilium.
A Nonazole CYP51 Inhibitor Cures Chagas’ Disease in a Mouse Model of Acute Infection
Authors: Doyle Patricia S. , Chen Chiung-Kuang , Johnston Jonathan B. , Hopkins Stephanie D. , Leung Siegfried S. F. , Jacobson Matthew P. , Engel Juan C. , McKerrow James H. , Podust Larissa M.
Published: April 2010

Chagas’ disease, the leading cause of heart failure in Latin America, is caused by the kinetoplastid protozoan
Trypanosoma cruzi.
The sterols of
T. cruzi
resemble those of fungi, both in composition and in biosynthesis. Azole inhibitors of sterol 14α-demethylase (CYP51) successfully treat fungal infections in humans, and efforts to adapt the success of antifungal azoles posaconazole and ravuconazole as second-use agents for Chagas’ disease are under way. However, to address concerns about the use of azoles for Chagas’ disease, including drug resistance and cost, the rational design of nonazole CYP51 inhibitors can provide promising alternative drug chemotypes. We report the curative effect of the nonazole CYP51 inhibitor LP10 in an acute mouse model of
T. cruzi
infection. Mice treated with an oral dose of 40 mg LP10/kg of body weight twice a day (BID) for 30 days, initiated 24 h postinfection, showed no signs of acute disease and had histologically normal tissues after 6 months. A very stringent test of cure showed that 4/5 mice had negative PCR results for
T. cruzi
, and parasites were amplified by hemoculture in only two treated mice. These results compare favorably with those reported for posaconazole. Electron microscopy and gas chromatography-mass spectrometry (GC-MS) analysis of sterol composition confirmed that treatment with LP10 blocked the 14α-demethylation step and induced breakdown of parasite cell membranes, culminating in severe ultrastructural and morphological alterations and death of the clinically relevant amastigote stage of the parasite.
In Vitro
Activity of Telavancin against a Contemporary Worldwide Collection of
Staphylococcus aureus
Isolates
Authors: Mendes Rodrigo E. , Moet Gary J. , Janechek Mike J. , Jones Ronald N.
Published: April 2010

The activity of telavancin and comparators was assessed against a contemporary (2007 and 2008) global collection of 10,000 isolates of
Staphylococcus aureus
. Telavancin was very active against methicillin-susceptible and -resistant
S
.
aureus
(MSSA and MRSA, respectively; MIC
50/90
for both, 0.12/0.25 μg/ml; 100.0% susceptible). This agent was 2-, 4-, and 8-fold more potent than daptomycin (MIC
90
, 0.5 μg/ml), vancomycin or quinupristin-dalfopristin (MIC
90
, 1 μg/ml), and linezolid (MIC
90
, 2 μg/ml) against MRSA, respectively. These data show a potent activity of telavancin tested against a current global collection of
S
.
aureus
.
Intra- and Interlaboratory Performances of Two Commercial Antimicrobial Susceptibility Testing Methods for Bifidobacteria and Nonenterococcal Lactic Acid Bacteria
Authors: Huys Geert , D'Haene Klaas , Cnockaert Margo , Tosi Lorenzo , Danielsen Morten , Flórez Ana Belén , Mättö Jaana , Axelsson Lars , Korhonen Jenni , Mayrhofer Sigrid , Egervärn Maria , Giacomini Mauro , Vandamme Peter
Published: April 2010

In a small-scale harmonization study involving nine laboratories in eight European countries, the intra- and interlaboratory performances of two commercially available systems, i.e., the VetMIC microplate system and Etest, for antimicrobial susceptibility testing of nonenterococcal lactic acid bacteria (NELAB) and bifidobacteria were analyzed. In addition, one laboratory also performed standard broth microdilution as a reference method. MICs of tetracycline, erythromycin, ampicillin, gentamicin, clindamycin, and streptomycin for the type strains of 25 species of NELAB and bifidobacteria and MICs of vancomycin for a selection of relevant taxa were determined. The previously described lactic acid bacterium susceptibility test medium (LSM) and related mixed-medium formulations, all including Iso-Sensitest broth as a basic component, were used as test media. The overall agreement of median MIC ranges ± 1 log
2
dilution determined by the VetMIC and Etest methods with the median MICs determined by the reference method was very good for tetracycline, ampicillin, and streptomycin (92.3 to 100%) but low for erythromycin (19.5 to 30.7%) and clindamycin (50.0 to 80.8%). There was a consensus among the participating laboratories that VetMIC was preferred over Etest because of its lower cost, better growth support, and more uniform criteria for MIC end point reading. With the range for acceptable intralaboratory reproducibility being defined as the median MIC ± 1 log
2
dilution, VetMIC results (with 69.2% of all data sets in the acceptable range) were shown to display greater reproducibility than Etest results (with 58.8% of all data sets in the acceptable range). Also at the interlaboratory level, the proportion of MIC values obtained with VetMIC that belonged to the complete agreement category (60.0%) was higher than the proportion of such values obtained with Etest (47.0%), which indicates a higher degree of interlaboratory reproducibility for the former method. Apart from some agent-specific effects, the majority of VetMIC and Etest replicate data sets were situated within a 1- to 2-log
2
dilution range, suggesting that the two methods can be considered to be equivalent for recognizing resistance phenotypes. This multicenter study has further validated the standard use of LSM and related mixed-medium formulations with commercially available systems and formed the basis for the ongoing development of the ISO 10932/IDF 223 standard for susceptibility testing of NELAB and bifidobacteria.
Azole Resistance Profile of Amino Acid Changes in
Aspergillus fumigatus
CYP51A Based on Protein Homology Modeling
Authors: Snelders Eveline , Karawajczyk Anna , Schaftenaar Gijs , Verweij Paul E. , Melchers Willem J. G.
Published: April 2010

Molecular studies have shown that the majority of azole resistance in
Aspergillus fumigatus
is associated with amino acid substitutions in the
cyp51A
gene. To obtain insight into azole resistance mutations, the
cyp51A
gene of 130 resistant and 76 susceptible
A. fumigatus
isolates was sequenced. Out of 130 azole-resistant isolates, 105 contained a tandem repeat of 34 bp in the promoter region and a leucine-to-histidine substitution in codon 98 (designated TR/L98H). Additionally, in 12 of these TR/L98H resistant isolates, the mutations S297T and F495I were found, and in 1 isolate, the mutation F495I was found. In eight azole-resistant isolates, known azole resistance mutations were detected in codon G54, G138, or M220. In three azole-susceptible isolates, the mutation E130D, L252L, or S400I was found and in 13 azole-susceptible isolates but also in 1 azole-resistant isolate, the mutations F46Y, G98G, M172V, N248T, D255E, L358L, E427K, and C454C were found. All of the nonsynonymous mutations, apart from the mutations in codons G54, G138, and M220 and L98H, were located at the periphery of the protein, as determined by a structural model of the
A. fumigatus
Cyp51A protein, and were predicted neither to interact with azole compounds nor to affect structural integrity. Therefore, this wide diversity of mutations in the
cyp51A
gene in azole-susceptible
A. fumigatus
isolates is not correlated with azole resistance. Based on the Cyp51A protein homology model, the potential correlation of a mutation to azole resistance can be predicted.
In Vitro
Interactions between New Antitubercular Drug Candidates SQ109 and TMC207
Authors: Reddy Venkata M. , Einck Leo , Andries K. , Nacy Carol A.
Published: April 2010

The
in vitro
interactions of two new antitubercular drugs, SQ109 and TMC207, with each other and with rifampin (RIF) were evaluated. The combination of SQ109 with TMC207 (i) improved an already excellent TMC207 MIC for
M. tuberculosis
H37Rv by 4- to 8-fold, (ii) improved the rate of killing of bacteria over the rate of killing by each single drug, and (iii) enhanced the drug postantibiotic effect by 4 h. In no instance did we observe antagonistic activities with the combination of SQ109 and TMC207. Rifampin activates cytochrome P450 genes to reduce the area under the curve (AUC) for TMC207 in humans. The presence of RIF in three-drug combinations did not affect the synergistic activities of SQ109 and TMC207, and SQ109 also dramatically decreased the MIC of RIF. SQ109 was active by itself, and both its activity was improved by and it improved the
in vitro
activities of both RIF and TMC207.
OXA-24 Carbapenemase Gene Flanked by XerC/XerD-Like Recombination Sites in Different Plasmids from Different
Acinetobacter
Species Isolated during a Nosocomial Outbreak
Authors: Merino María , Acosta Joshi , Poza Margarita , Sanz Francisca , Beceiro Alejandro , Chaves Fernando , Bou Germán
Published: April 2010

A clinical strain of
Acinetobacter calcoaceticus
resistant to carbapenems was isolated from a blood culture sample from an inpatient in a hospital in Madrid (Spain) during a large outbreak of infection (affecting more than 300 inpatients), caused by a multidrug-resistant
Acinetobacter baumannii
clone. The carbapenem resistance in both the
A. calcoaceticus
and
A. baumannii
clones was due to a
bla
OXA-24
gene harbored in different plasmids. The plasmids were fully sequenced, revealing the presence of site-specific recombination binding sites putatively involved in mobilization of the
bla
OXA-24
gene. Comparison of plasmids contained in the two strains revealed possible horizontal transmission of resistance genes between the
Acinetobacter
species.
Antimicrobial Activity of a Halocidin-Derived Peptide Resistant to Attacks by Proteases
Authors: Shin Yong Pyo , Park Ho Jin , Shin Seo Hwa , Lee Young Shin , Park Seungmi , Jo Sungho , Lee Yong Ho , Lee In Hee
Published: April 2010

Cationic antimicrobial peptides (AMPs) have attracted a great deal of interest as a promising candidate for a novel class of antibiotics that might effectively treat recalcitrant infections caused by a variety of microbes that are resistant to currently available drugs. However, the AMPs are inherently limited in that they are inevitably susceptible to attacks by proteases generated by human and pathogenic microbes; this vulnerability severely hinders their pharmaceutical use in human therapeutic protocols. In this study, we report that a halocidin-derived AMP, designated HG1, was found to be resistant to proteolytic degradation. As a result of its unique structural features, HG1 proved capable of preserving its antimicrobial activity after incubation with trypsin, chymotrypsin, and human matrix metalloprotease 7 (MMP-7). Additionally, HG1 was observed to exhibit profound antimicrobial activity in the presence of fluid from human skin wounds or proteins extracted from the culture supernatants of
Staphylococcus aureus
and
Pseudomonas aeruginosa
. Greater understanding of the structural motifs of HG1 required for its protease resistance might provide feasible ways to solve the problems intrinsic to the development of an AMP-based antibiotic.
Francisella tularensisΔpyrFMutants Show that Replication in Nonmacrophages Is Sufficient for PathogenesisIn Vivo
Authors: Horzempa Joseph , O'Dee Dawn M. , Shanks Robert M. Q. , Nau Gerard J.
Published: April 2010

The pathogenesis ofFrancisella tularensishas been associated with this bacterium's ability to replicate within macrophages.F. tularensiscan also invade and replicate in a variety of nonphagocytic host cells, including lung and kidney epithelial cells and hepatocytes. As uracil biosynthesis is a central metabolic pathway usually necessary for pathogens, we characterized ΔpyrFmutants of bothF. tularensisLVS and Schu S4 to investigate the role of these mutants in intracellular growth. As expected, these mutant strains were deficient inde novopyrimidine biosynthesis and were resistant to 5-fluoroorotic acid, which is converted to a toxic product by functional PyrF. TheF. tularensisΔpyrFmutants could not replicate in primary human macrophages. The inability to replicate in macrophages suggested that theF. tularensisΔpyrFstrains would be attenuated in animal infection models. Surprisingly, these mutants retained virulence during infection of chicken embryos and in the murine model of pneumonic tularemia. We hypothesized that theF. tularensisΔpyrFstrains may replicate in cells other than macrophages to account for their virulence. In support of this,F. tularensisΔpyrFmutants replicated in HEK-293 cells and normal human fibroblastsin vitro. Moreover, immunofluorescence microscopy showed abundant staining of wild-type and mutant bacteria in nonmacrophage cells in the lungs of infected mice. These findings indicate that replication in nonmacrophages contributes to the pathogenesis ofF. tularensis.
Lactobacillus jensenii
Surface-Associated Proteins Inhibit
Neisseria gonorrhoeae
Adherence to Epithelial Cells
Authors: Spurbeck Rachel R. , Arvidson Cindy Grove
Published: April 2010

High numbers of lactobacilli in the vaginal tract have been correlated with a decreased risk of infection by the sexually transmitted pathogen
Neisseria gonorrhoeae
. We have previously shown that
Lactobacillus jensenii
, one of the most prevalent microorganisms in the healthy human vaginal tract, can inhibit gonococcal adherence to epithelial cells in culture. Here we examined the role of the epithelial cells and the components of
L. jensenii
involved in the inhibition of gonococcal adherence.
L. jensenii
inhibited the adherence of gonococci to glutaraldehyde-fixed epithelial cells like it inhibited the adherence of gonococci to live epithelial cells, suggesting that the epithelial cells do not need to be metabolically active for the inhibition to occur. In addition, methanol-fixed
L. jensenii
inhibited gonococcal adherence to live epithelial cells, indicating that
L. jensenii
uses a constitutive component to inhibit gonococcal interactions with epithelial cells. Proteinase K treatment of methanol-fixed lactobacilli eliminated the inhibitory effect, suggesting that the inhibitory component contains protein. Released surface components (RSC) isolated from
L. jensenii
were found to contain at least two inhibitory components, both of which are protease sensitive. Using anion-exchange and size exclusion chromatography, an inhibitory protein which exhibits significant similarity to the enzyme enolase was isolated. A recombinant His
6
-tagged version of this protein was subsequently produced and shown to inhibit gonococcal adherence to epithelial cells in a dose-dependent manner.
Rickettsia rickettsiiInfection of Human Macrovascular and Microvascular Endothelial Cells Reveals Activation of Both Common and Cell Type-Specific Host Response Mechanisms
Authors: Rydkina Elena , Turpin Loel C. , Sahni Sanjeev K.
Published: April 2010

Although inflammation and altered barrier functions of the vasculature, due predominantly to the infection of endothelial cell lining of small and medium-sized blood vessels, represent salient pathological features of human rickettsioses, the interactions between pathogenic rickettsiae and microvascular endothelial cells remain poorly understood. We have investigated the activation of nuclear transcription factor-kappa B (NF-κB) and p38 mitogen-activated protein (MAP) kinase, expression of heme oxygenase 1 (HO-1) and cyclooxygenase 2 (COX-2), and secretion of chemokines and prostaglandins afterRickettsia rickettsiiinfection of human cerebral, dermal, and pulmonary microvascular endothelial cells in comparison with pulmonary artery cells of macrovascular origin. NF-κB and p38 kinase activation and increased HO-1 mRNA expression were clearly evident in all cell types, along with relatively similar susceptibility toR. rickettsiiinfectionin vitrobut considerable variations in the intensities/kinetics of the aforementioned host responses. As expected, the overall activation profiles of macrovascular endothelial cells derived from human pulmonary artery and umbilical vein were nearly identical. Interestingly, cerebral endothelial cells displayed a marked refractoriness in chemokine production and secretion, while all other cell types secreted various levels of interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) in response to infection. A unique feature of all microvascular endothelial cells was the lack of induced COX-2 expression and resultant inability to secrete prostaglandin E2afterR. rickettsiiinfection. Comparative evaluation thus yields the first experimental evidence for the activation of both common and unique cell type-specific host response mechanisms in macrovascular and microvascular endothelial cells infected withR. rickettsii, a prototypical species known to cause Rocky Mountain spotted fever in humans.
Timing of defoliation and its effect on bud development, starch reserves, and sap sugar concentration in sugar maple
Authors: Gregory Robert A. , Wargo Philip M.
Published: April 2010

Sapling sugar maple (Acersaccharum Marsh.) trees were defoliated artificially at 10-day intervals beginning May 27 and ending August 5, 1981. Refoliation, terminal bud and shoot development, and xylem starch and sap sugar concentration were observed in defoliated and control trees. All defoliated trees refoliated, but decreasingly with later defoliation. Defoliation caused an acceleration in the rate of primordia initiation in terminal shoot apices. After early season defoliations, the developing buds in the axils of the removed leaves abscissed, but axillary and terminal buds on the refoliated terminal shoots survived through winter. In late season defoliation, most buds of refoliated shoots did not survive and the next year's growth depended on axillary buds formed prior to defoliation. Thus, when progressing from early to late defoliations, the next year's shoot growth depended decreasingly on the last-formed and increasingly on the first-formed portions of the previous year's shoot. Early October starch concentration in xylem decreased with later defoliation and was nearly absent in shoots and roots of trees defoliated in late July. There was not, however, a corresponding decrease in sap sugar concentration. Mortality occurred only in late defoliated trees and was associated with starch depletion.
Effects of dwarf mistletoe on the response of young Douglas-fir to thinning
Authors: Knutson Donald , Tinnin Robert
Published: April 2010

Four sites from two forests were examined to determine the effect of various levels of infection by Arceuthobiumdouglasii on the growth of Pseudotsugamenziesii in precommercially thinned stands. We found less than 1% mortality among the trees that we examined. Changes in level of infection did occur; we estimate that changes to levels of infection sufficient to cause significant reductions in diameter growth occurred among 19% of the infected trees that we studied. Height growth was significantly reduced in both forests, while diameter growth was reduced by infection in one forest. Trees of lower infection rating (dwarf mistletoe rating 0–2) showed a significant increase in radial growth following thinning in both forests, while more heavily infected trees (dwarf mistletoe rating 5 and 6) did not. Trees that were heavily infected and had spike tops consistently showed significant reductions in diameter growth in both forests.
Effects of ambient ozone on the productivity of Populustremuloides Michx. grown under field conditions
Authors: Wang Deane , Karnosky David F. , Bormann F. Herbert
Published: April 2010

Field experiments were conducted at a rural site in Millbrook, NY, to measure effects of ambient ozone on saplings of Populustremuloides Michx. Over a 3–year period, four clones representing a range of pollutant sensitivities were exposed to charcoal-filtered and ambient air in open-top chambers. Ambient ozone significantly reduced (12–24%) aboveground dry-matter production and modified tree morphology, root/shoot ratios, and rates of leaf senescence. For two clones, biomass was reduced without visible foliar symptoms. This response raises the possibility of widespread, asymptomatic depression of forest productivity under ambient air pollutant conditions.
Modeling the long-term effects of disturbances on forest succession, Olympic Peninsula, Washington
Authors: Dale Virginia H. , Hemstrom Miles , Franklin Jerry
Published: April 2010

A model of forest development has been adapted for the Pacific Northwest. The regeneration, growth, and death of individual trees are tracked for simulated 0.2 ha plots and tree attributes are aggregated to provide stand measures. The model includes the influence of temperature, soil moisture, light tolerance, and competition on tree growth. Long-term simulations for Douglas-fir dominated forests on the western Olympic Peninsula show that the stand is eventually dominated by western hemlock with silver fir being codominant. Even after 1200 years of subsequent stand development, silver fir fails to replace western hemlock indicating that this is a self-replicating and stable community. Fire, windthrows, insect disturbance, and clear-cut logging followed by replanting are incorporated into the model as single-event disturbances to a 500-year-old forest. For those cases where large Douglas-fir survive the disturbance, stand biomass and leaf area patterns are not significantly impacted until the death of the last large Douglas-fir. The projections were all carried out to the time when the forest is dominated by western hemlock and silver fir. At that time, the differential effect of the earlier disturbance is not apparent from the forest composition, biomass, or leaf area patterns except for the insect disturbance. Following the removal of all Douglas-fir by an insect, leaf area fluctuates regularly with a period of 600 years.
Starch reserves in Piceaabies in relation to defence reaction against a bark beetle transmitted blue-stain fungus, Ceratocystispolonica
Authors: Christiansen Erik , Ericsson Anders
Published: April 2010

Coniferous trees resist invasion of their phloem and xylem by microorganisms through an induced defence reaction; resin-filled reaction zones are formed around the infections to stop the intrusion. The efficacy of the reaction is supposedly dependent on an ample supply of carbohydrates. Two hypotheses were formulated: (i) phloem starch reserves are consumed by the defence reaction; (ii) trees low in phloem starch are vulnerable to infection. To test the hypotheses, stem sections of Piceaabies trees were mass inoculated with a pathogenic blue-stain fungus, Ceratoscystispolonica, associated with the spruce bark beetle Ipstypographus. Stem starch concentration was manipulated through girdling. Mass inoculation lead to a significant decrease in phloem starch concentration. Starch reserves of single trees were not correlated to their resistance to infection. Translocation capacity of the phloem is suggested critical for the defence reaction.
Effects of salal understory removal on photosynthetic rate and stomatal conductance of young Douglas-fir trees
Authors: Price D. T. , Black T. A. , Kelliher F. M.
Published: April 2010

The effects of salal (Gaultheriashallon Pursh.) understory removal on the growth of thinned 32-year-old Douglas-fir (Pseudotsugamenziesii (Mirb.) Franco) trees were determined in a stand subject to growing season soil water deficits. Four pairs of similar trees were selected and the understory was completely removed from around one of each pair, the root zones of which were both isolated using plastic sheeting buried to bedrock. Photosynthesis, stomatal conductance, soil water potential and canopy microclimate were measured intensively in one pair on 4 clear days during an extended dry period in June 1982. Basal area increment of the four pairs of trees was measured over three growing seasons. To determine the effect of soil water potential on tree photosynthesis, the same variables were intensively measured over 3 consecutive days in late August 1982 for another tree initially subjected to a soil water potential of approximately −1.6 MPa, but irrigated to approximately −0.02 MPa between the 1st and 2nd days. Solar irradiance decreased markedly between the 2nd and 3rd days, thereby creating a unique data set. Findings were as follows: (i) removal of understory significantly increased rates of photosynthesis in the trees, both diurnally and seasonally, (ii) photosynthesis was not generally limited by stomatal conductance unless vapour pressure deficit was high and photon flux density was saturating, and (iii) tree growth response to salal removal was due to higher soil water potential, which increased both photosynthetic capacity and stomatal conductance.
Fractal analysis of leaf shapes
Authors: Vlcek J. , Cheung E.
Published: April 2010

An application of fractal mathematics to the analysis of leaf shapes is presented. Six leaves randomly selected from nine tree species were used in the study. A video imaging method together with microcomputer-based image processing was used to generate leaf outlines. A fractal analysis program was written to calculate the fractal dimensions of the leaves. Recalling a leaf outline from a diskette and specifying both the starting position on it (e.g., the beginning of the petiole) and six step lengths (explained later), the program then generates the fractal dimension according to the theory described. The results show that the fractal dimension is sensitive to leaf shape variations within a species. For example, two types of ginkgo leaves (one with and one without a notch in the middle of the leaf outline) showed distinctly different fractal values. Similar sensitivity to shape change was observed among the leaves of white oak, red oak, and sugar maple where such variables as width to length ratio and the degree of jaggedness of the leaf caused a departure of the fractal value from the average.