bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Dividend, Cash Flow, and Earnings Approaches to Equity Valuation*
Authors: PENMAN STEPHEN H. , SOUGIANNIS THEODORE
Published: April 2010

Standard formulas for valuing the equity of going concerns require forecasting payoffs to infinity but practical analysis requires that payoffs be forecasted over finite horizons. This truncation inevitably involves often‐troublesome terminal value calculations. This paper contrasts dividend discount techniques, discounted cash flow analysis, and techniques based on accrual earnings when each is applied with finite‐horizon forecasts. Valuations based on average ex post payoffs over various horizons, with and without terminal value calculations, are compared with ex ante market prices to discover the error introduced by each technique in truncating the horizon. Valuation errors are lower using accrual earnings techniques rather than cash flow and dividend discounting techniques. The accounting features that make a given technique less than ideal for finite horizon analysis are also detailed. Conditions where a given technique requires particularly long forecasting horizons are identified and the performance of the alternative techniques under those conditions is examined.
An Analysis of the Economic Consequences of the Proportionate Liability Rule*
Authors: CHAN DEREK K. , PAE SUIL
Published: April 2010

Major accounting firms in the United States have singled out elimination of joint and several liability as one of the most needed legal reforms in the country. The recent legislation of the Private Securities Litigation Reform Act of 1995 replaced joint and several liability with proportionate liability. This paper develops a simple model to analyze the economic consequences of such a change in the legal environment facing public accountants. In particular, we examine the incentive effects induced by the proportionate liability rule on the auditor's effort and financial statement users' litigation decisions. Our analysis demonstrates that replacing joint and several liability with proportionate liability can decrease the equilibrium audit effort, lawsuit probability, market price of the firm, and audit fee. More important, even though the proportionate liability rule reduces the equilibrium audit effort, we show that it can actually increase social welfare.
Price and Volume Reactions to Public Information Releases: An Experimental Approach Incorporating Traders' Subjective Beliefs*
Authors: GILLETTE ANN B. , STEVENS DOUGLAS E. , WATTS SUSAN G. , WILLIAMS ARLINGTON W.
Published: April 2010

This paper examines how market prices, volume, and traders' dividend expectations respond to public information releases in laboratory markets for a long‐lived financial asset. The objective is to study deviations from the symmetric information risk‐neutral rational expectations (RE) benchmark, which predicts no trade in such settings. The results of a series of double‐auction and call markets are reported in which traders manage a portfolio of cash and asset shares over 15 rounds of trading. A public signal regarding the value of the liquidating dividend is released every third round, and traders' subjective expectations of the liquidating dividend are elicited each round as cash‐motivated forecasts. We find that, despite the public dividend signal, traders' dividend forecasts are heterogeneous. Forecasts and prices both underreact to the public signals, with prices under‐reacting more than forecasts. In general, price changes are not closely associated with public signals, and there is greater excess price volatility in double auctions than in call markets. Forty‐three percent of trades are inconsistent with the trader's forecasts, and inconsistent trades occur more frequently in the double‐auction markets. On average, approximately 10 percent of the outstanding shares are traded in each round, and trading volume is increasing in the mean absolute forecast revision and decreasing in the contemporaneous dispersion in forecasts. These results suggest that differential processing of the public signal and/or speculative trading for short‐term gain may help to explain why symmetric information RE predictions are often not supported in empirical and experimental settings. They also suggest that market reactions to public information releases may be influenced by market microstructure.
How many hosts? Modelling host breadth from field samples
Authors: Vesk Peter A. , McCarthy Michael A. , Moir Melinda L.
Published: April 2010

1. Host‐specificity is important in fundamental and applied studies of biodiversity, but it is difficult to generate definitive data for many species.

2. Here, we present a model framework for estimating the realized host breadth of dependent fauna from samples collected from replicate host individuals. We use Bayesian, Zero‐inflated Poisson regression to model the abundance conditional upon host use – our focal parameter. We illustrate the model using a data set of insects on threatened and non‐threatened plant species from eastern Australia. Estimating co‐extinction risk through threats to host organisms is a key application for the model, requiring assessment of the host‐specificity of biota, whilst incorporating uncertainty.

3. The host breadth model indicated that several insect species had high probability of narrow host breadth, including several species that appeared to only have one host. Furthermore, the model distinguished polyphagous, oligophagous and monophagous insect species. Modification of the model to account for false positives also identified tourist occurrences.

4. The host breadth model can be utilized not only towards focusing conservation actions on the most co‐threatened dependent invertebrate species, but also for other projects involving host‐specificity, such as estimating the number of insects globally, and selecting the most likely candidates for biological control of invasive species. Further uses are likely in various data sets of associations between species.
Residues of intertwining operators for SO*6 as character identities
Authors: Shahidi Freydoon , Spallone Steven
Published: April 2010

We show that the residue at s=0 of the standard intertwining operator attached to a supercuspidal representation π⊗χ of the Levi subgroup GL2(F)×E1 of the quasisplit group SO*6(F) defined by a quadratic extension E/F of p-adic fields is proportional to the pairing of the characters of these representations considered on the graph of the norm map of Kottwitz–Shelstad. Here π is self-dual, and the norm is simply that of Hilbert’s theorem 90. The pairing can be carried over to a pairing between the character on E1 and the character on E× defining the representation of GL2(F) when the central character of the representation is quadratic, but non-trivial, through the character identities of Labesse–Langlands. If the quadratic extension defining the representation on GL2(F) is different from E the residue is then zero. On the other hand when the central character is trivial the residue is never zero. The results agree completely with the theory of twisted endoscopy and L-functions and determines fully the reducibility of corresponding induced representations for all s.
Selective blockade of protein kinase B protects the rat and human myocardium against ischaemic injury
Authors: Linares‐Palomino José , Husainy Muhammad A. , Lai Vien K. , Dickenson John M. , Galiñanes Manuel
Published: April 2010

Protein kinase B (PKB/Akt) plays a critical role in cell survival but the investigation of its involvement has been limited by the lack of specific pharmacological agents. In this study, using novel PKB inhibitors (VIII and XI), we investigated the role of PKB in cardioprotection of the rat and human myocardium, the location of PKB in relation to mitoKATP channels and p38 mitogen‐activated protein kinase (p38 MAPK), and whether the manipulation of PKB can overcome the unresponsiveness to protection of the diabetic myocardium. Myocardial slices from rat left ventricle and from the right atrial appendage of patients undergoing elective cardiac surgery were subjected to 90 min ischaemia/120 min reoxygenation at 37°C. Tissue injury was assessed by creatine kinase (CK) released and determination of cell necrosis and apoptosis. The results showed that blockade of PKB activity caused significant reduction of CK release and cell death, a benefit that was as potent as ischaemic preconditioning and could be reproduced by blockade of phosphatidylinositol 3‐kinase (PI‐3K) with wortmannin and LY 294002. The protection was time dependent with maximal benefit seen when PKB and PI‐3K were inhibited before ischaemia or during both ischaemia and reoxygenation. In addition, it was revealed that PKB is located downstream of mitoKATP channels but upstream of p38 MAPK. PKB inhibition induced a similar degree of protection in the human and rat myocardium and, importantly, it reversed the unresponsiveness to protection of the diabetic myocardium. In conclusion, inhibition of PKB plays a critical role in protection of the mammalian myocardium and may represent a clinical target for the reduction of ischaemic injury.
Assessment of Steady-State Metal Cutting Temperature Models Based on Simultaneous Infrared and Thermocouple Data
Authors: Stephenson D. A.
Published: April 2010

Several models for metal cutting temperatures which could be applied in simulation programs have been reported in the literature. Since the temperature predicted by the models are difficult to measure, however, there is not sufficient experimental data to determine which available model is most accurate and whether further theoretical refinement is needed. In this paper calculations from four steady-state cutting temperature models are compared with simultaneous infrared and tool-chip thermocouple temperature measurements from end turning tests on 1018 steel, 2024 aluminum, free machining brass, and gray cast iron tubes. Deformation zone temperatures calculated using the models are compared to source temperatures determined from infrared measurements using a new inverse method. Calculated tool-chip contact temperatures are compared to rake face temperatures measured by the widely used tool-work thermocouple method. The data indicates most models, though quantitatively accurate, overestimate cutting temperatures. Models based on Jaeger’s friction slider solution which include workpiece thermal property variations, however, generally give results accurate to within the reliability of experimentai methods for the materials tested. Loewen and Shaw’s model, recently generalized to three-dimensional cutting by Venuvinod and Lau, seems most accurate over a broad range of workpiece and cutting conditions. No model accurately predicts tool-chip temperatures for cast iron or 2024 aluminum, indicating that further theoretical refinement for discontinuous chip formation is needed.
Adaptive Compensation of Dynamic Characteristics for In-Process Sensors
Authors: Spiewak S. A. , Di Corpo J.
Published: April 2010

Monitoring of machine tools and optimization of manufacturing processes require accurate values of in-process measured mechanical quantities such as force, torque, or displacement. Commercial sensors available today do not provide the required performance, usually due to the very principle of their operation. Periodical tuning of these sensors to match the expected characteristics of their working environment is not a solution, since this environment changes rapidly. A system presented in this paper corrects dynamic characteristics of sensors in a continuous fashion. The implemented on-line algorithm comprises three steps performed repeatedly: (1) identification of parameters in a model of the machining process, in which the particular sensor is used; (2) estimation of parameters in the assumed model of the sensor—this estimation is based on results obtained in step 1; (3) evaluation of parameters of the adaptive filter that compensates the actual dynamic properties of the sensor. The developed algorithm has been implemented as a multi-processor, transputer based system integrated with digital signal processors.
Mechanics of Bar Straightening, Part 2: Straightening in Cross-Roll Straighteners
Authors: Das Talukder N. K. , Singh A. N.
Published: April 2010

An analysis is made of the straightening process of rolled circular bars and tubes, with initial residual curvature in different types of cross-roll straighteners indicating the degree of straightness and throughput speed obtainable from them. Suggestions are made for roll arrangement for higher throughput speed and degree of straightness of the product.
Nonlinear Behavior of Articulated Tower in Random Sea
Authors: Jain A. K. , Datta T. K.
Published: April 2010

An iterative frequency domain method for determining the response of articulated towers to first order wave and current induced forces is presented. The application of the method is illustrated with the help of an idealized articulated tower. The iterative method duly considers the nonlinearities produced due to relative velocity squared drag force, large displacement effect, and variable added mass and buoyancy. The proposed method obtains the nonlinear random response in an efficient manner using fast fourier transform techniques. Using the proposed analysis a parametric study is conducted to investigate the response behavior of the tower to wave and current induced forces.
Optimum Design of a Compliant Uniaxial Accelerometer
Authors: Desrochers Simon , Pasini Damiano , Angeles Jorge
Published: April 2010

This work focuses on the multi-objective optimization of a compliant-mechanism accelerometer. The design objective is to maximize the sensitivity of the accelerometer in its sensing direction, while minimizing its sensitivity in all other directions. In addition, this work proposes a novel compliant hinge intended to reduce the stress concentration in compliant mechanisms. The paper starts with a brief description of the new compliant hinge, the Lamé-shaped hinge, followed by the formulation of the aposteriori multi-objective optimization of the compliant accelerometer. By using the normalized constrained method, an even distribution of the Pareto frontier is found. The paper also provides several optimum solutions on a Pareto plot, as well as the CAD model of the selected solution.
Performance Improvement of Weis-Fogh Type Ship’s Propulsion Mechanism Using a Wing Restrained by an Elastic Spring
Authors: Ro Kideok
Published: April 2010

This study was conducted in an attempt to improve the hydrodynamic performance of a Weis-Fogh type ship propulsion mechanism by installing a spring to the wing so that the opening angle of the wing can be changed automatically. With the prototype design, the average thrust coefficient was almost fixed with all velocity ratios; but with the spring type, the thrust coefficient was increased sharply as the velocity ratio increased. The average propulsive efficiency was higher with a bigger opening angle in the prototype but in the spring type design, the one with a smaller spring coefficient had higher efficiency. In the case of velocity ratios over 1.5 where big thrust can be generated, the spring type had more than twice the increase in propulsion efficiency compared with the prototype.
A Regularized Inexact Penalty Decomposition Algorithm for Multidisciplinary Design Optimization Problems With Complementarity Constraints
Authors: Lu Shen , Kim Harrison M.
Published: April 2010

Economic and physical considerations often lead to equilibrium problems in multidisciplinary design optimization (MDO), which can be captured by MDO problems with complementarity constraints (MDO-CC)—a newly emerging class of problem. Due to the ill-posedness associated with the complementarity constraints, many existing MDO methods may have numerical difficulties solving this class of problem. In this paper, we propose a new decomposition algorithm for the MDO-CC based on the regularization technique and inexact penalty decomposition. The algorithm is presented such that existing proofs can be extended, under certain assumptions, to show that it converges to stationary points of the original problem and that it converges locally at a superlinear rate. Numerical computation with an engineering design example and several analytical example problems shows promising results with convergence to the all-in-one solution.
An Examination of Trapped Bubbles for Viscous Drag Reduction on Submerged Surfaces
Authors: Stephani Kelly A. , Goldstein David B.
Published: April 2010

Viscous drag reduction on a submerged surface can be obtained both in the limit of an unbroken gas film coating the solid and in the nanobubble or perhaps microbubble coating regime when an air layer is created with superhydrophobic coatings. We examine an intermediate bubble size regime with a trapped-bubble array (TBA) formed in a tap water environment using electrolysis to grow and maintain bubbles in thousands of millimeter-sized holes on a solid surface. We show that even though surface tension is sufficient to stabilize bubbles in a TBA against hydrostatic and shear forces beneath a turbulent boundary layer, no drag reduction is obtained. Drag measurements were acquired over Reynolds numbers based on plate length ranging from 7.2×104<ReL<3.1×105 using either a force balance for plates mounted in a vertical orientation, or by performing a momentum integral balance using a wake survey for a flat plate mounted in either vertical or horizontal orientation. In that the drag forces were small, emphasis was placed on minimizing experimental uncertainty. For comparison, the flow over a flat plate covered on one side by a large uninterrupted gas film was examined and found to produce large drag reductions of up to 32%.
Development of a Subframe Type Fuel Tank for Passenger Cars
Authors: Lee Un-Koo , Jang Seong Bae , Cheon Seong S.
Published: April 2010

In this paper, a subframe type fuel tank module was proposed and evaluated to increase the vehicle safety and the design flexibility against rear crash of automotive vehicles. In order to minimize the deformation of the fuel tank during rear crash, crash simulations and optimization of design parameters associated with the subframe type fuel tank module were carried out using the robust design method. A rear crash test was conducted with a midsize passenger car, and the measured deformations of the fuel tank showed an excellent agreement with the simulation. It was also found that the optimized design of the subframe type fuel tank reduced the deformation of the fuel tank up to a maximum of 27.5 times, compared with the deformation in the conventional design. The proposed design of fuel tank not only provides the design flexibility but fulfills the requirements of the revised Federal Motor Vehicle Safety Standards Sec. 301.
On the Suppression of Vortex Shedding From Circular Cylinders Using Detached Short Splitter-Plates
Authors: Dehkordi Behzad Ghadiri , Jafari Hamed Houri
Published: April 2010

Flow over a circular cylinder with detached short splitter-plates is numerically simulated in order to assess the suppression of periodic vortex shedding. A finite-volume solver based on the Cartesian-staggered grid is implemented, and the ghost-cell method in conjunction with Great-Source-Term technique is employed in order to enforce directly the no-slip condition on the cylinder boundary. The accuracy of the solver is validated by simulation of the flow around a single circular cylinder. The results are in good agreement with the experimental data reported in the literature. Finally, the flows over a circular cylinder with splitter-plate in its downstream (off and on the centerline) are computed in Re=40 as a nonvortex shedding case and in Re=100 and 150 as cases with vortex shedding effects. The same simulations are also performed for the case where dual splitter-plates are in a parallel arrangement embedded in the downstream of the cylinder. The optimum location of the splitter-plate to achieve maximum reduction in the lift and drag forces is determined.
On Self-Similarity in the Inner Wall Layer of a Turbulent Channel Flow
Authors: Podvin Bérengère , Fraigneau Yann , Jouanguy Julien , Laval J.-P.
Published: April 2010

We use proper orthogonal decomposition (POD) to estimate the flow in the near-wall region based on information from the outer buffer layer. Our goal is to assess how the flow structures in the inner wall region are connected to those further away from the wall, and to investigate the nature of the coupling between the inner and the outer region in the POD framework. Reconstructions are carried out for numerical simulations of a plane channel flow at two different Reynolds numbers. We show that elongated structures with a spanwise wavelength smaller than a critical value tend to be concentrated in the inner layer. The critical wavelength is shown to scale with the inner layer height, and interactions between the inner and the outer layer appear to take place predominantly over a self-similar, height-dependent, range of wavenumbers, in agreement with Townsend’s attached eddy hypothesis. The reconstructed field appears to capture an adequate energy content and to remain correlated with the real field even close to the wall, which reflects the persistence of energetic structures over the extent of the buffer layer.
Review of Hydraulic Roughness Scales in the Fully Rough Regime
Authors: Flack Karen A. , Schultz Michael P.
Published: April 2010

A review of predictive methods used to determine the frictional drag on a rough surface is presented. These methods utilize a wide range of roughness scales, including roughness height, pitch, density, and shape parameters. Most of these scales were developed for regular roughness, limiting their applicability to predict the drag for many engineering flows. A new correlation is proposed to estimate the frictional drag for a surface covered with three-dimensional, irregular roughness in the fully rough regime. The correlation relies solely on a measurement of the surface roughness profile and builds on previous work utilizing moments of the surface statistics. A relationship is given for the equivalent sandgrain roughness height as a function of the root-mean-square roughness height and the skewness of the roughness probability density function. Boundary layer similarity scaling then allows the overall frictional drag coefficient to be determined as a function of the ratio of the equivalent sandgrain roughness height to length of the surface.
Supporting Students in Developing Literacy in Science
Authors: Krajcik Joseph S. , Sutherland LeeAnn M.
Published: April 2010

Reading, writing, and oral communication are critical literacy practices for participation in a
global society. In the context of science inquiry, literacy practices support learners by enabling them to grapple with ideas, share their thoughts, enrich understanding, and solve problems. Here we suggest five instructional and curricular features that can support students in developing literacy in the context of science: (i) linking new ideas to prior knowledge and experiences, (ii) anchoring learning in questions that are meaningful in the lives of students, (iii) connecting multiple representations, (iv) providing opportunities for students to use science ideas, and (v) supporting students’ engagement with the discourses of science. These five features will
promote students’ ability to read, write, and communicate about science so that they can
engage in inquiry throughout their lives.
Using Texts in Science Education: Cognitive Processes and Knowledge Representation
Authors: van den Broek Paul
Published: April 2010

Texts form a powerful tool in teaching concepts and principles in science. How do readers
extract information from a text, and what are the limitations in this process? Central to comprehension of and learning from a text is the construction of a coherent mental representation that integrates the textual information and relevant background knowledge. This representation engenders learning if it expands the reader’s existing knowledge base or if it corrects misconceptions in this knowledge base. The Landscape Model captures the reading process and the influences of reader characteristics (such as working-memory capacity, reading goal, prior knowledge, and inferential skills) and text characteristics (such as content/structure of presented information, processing demands, and textual cues). The model suggests factors that can optimize—or jeopardize—learning science from text.
Academic Language and the Challenge of Reading for Learning About Science
Authors: Snow Catherine E.
Published: April 2010

A major challenge to students learning science is the academic language in which science is written. Academic language is designed to be concise, precise, and authoritative. To achieve these goals, it uses sophisticated words and complex grammatical constructions that can disrupt reading comprehension and block learning. Students need help in learning academic vocabulary and how to process academic language if they are to become independent learners of science.
Mechanism and Kinetics of Spontaneous Nanotube Growth Driven by Screw Dislocations
Authors: Morin Stephen A. , Bierman Matthew J. , Tong Jonathan , Jin Song
Published: April 2010

Nanosynthesis Without a Twist

The synthesis of many nanoscale materials occurs under conditions of changing saturation because generation of product decreases the concentration of reactants.

Morin
et al.

(p.
476
) used a flow reactor to maintain conditions of low supersaturation during the growth of zinc oxide nanotubes and nanowires. Under these conditions, growth of the tubes was controlled by the release of stress, which prevented the torquing of the crystals along their axis. Since growth at different saturation conditions matched predictions, this looks like a promising method to develop rational and controlled synthesis of nanomaterials at large scale and low cost.
Monolithic Carbide-Derived Carbon Films for Micro-Supercapacitors
Authors: Chmiola John , Largeot Celine , Taberna Pierre-Louis , Simon Patrice , Gogotsi Yury
Published: April 2010

Microcapacitors for Manufacture

Capacitors can store small amounts of charge, and as they can charge and discharge quickly, they work well with batteries for recovering power, such as in regenerative braking in hybrid cars. For very small power requirements, capacitors have not been competitive with microbatteries, but using monolithic carbon films to store the charge,

Chmiola
et al.

(p.
480
) demonstrate the feasibility of such applications. The small pores in the carbon films are sufficiently large to allow electrolyte transport and can be made using a processing technique compatible with current chip manufacturing. Such microcapacitors can thus be integrated with electronics to make autonomous sensors or implantable devices.
Unconventional
s
-Wave Superconductivity in Fe(Se,Te)
Authors: Hanaguri T. , Niitaka S. , Kuroki K. , Takagi H.
Published: April 2010

Breaking Convention

The defining characteristics of a superconductor are symmetry of gap function, which tells us something about how pairs of electrons move through the sample, and the strength of that pairing. Together, this information gives us the highest temperature to which the superconductor can remain superconducting. In conventional superconductors the gap function is symmetric, or s-wave, and tends to have low transition temperatures. The newly discovered iron-based superconductors also have
s
-wave symmetry, but the rather high transition temperatures, in addition to other properties, indicate that they are not conventional.

Hanaguri
et al.

(p.
474
; see the Perspective by

Hoffman

) use scanning tunneling microscopy to provide direct experimental confirmation of the unconventional
s
-wave pairing of the superconducting carriers in these materials.
Salmonella
Susceptibility
Authors: Moir Susan , Fauci Anthony S.
Published: April 2010

HIV-infected individuals produce antibodies to
Salmonella
that block the effects of protective antibodies.
Syntheses That Stay Together
Authors: Roberts Jeffrey W.
Published: April 2010

The rate of mRNA translation determines the rate of mRNA synthesis in bacteria through direct coupling of the respective molecular machinery.
Prioritizing Science Education
Authors: Alberts Bruce
Published: April 2010

In this Special Issue on education,
Science
focuses on the connection between learning science in school and the acquisition of language and communication skills, emphasizing the benefits of teaching science and literacy in the same classrooms whenever possible. In the United States, this would be viewed as a radical proposal. Unfortunately, the great majority of Americans are accustomed to science classrooms where students memorize facts about the natural world and, if they are lucky, perform an experiment or two; in language arts classes, students generally read fictional literature and write about it in fossilized formats such as “compare and contrast.”
Along With Power, Questions Flow at Laos's New Dam
Authors: Stone Richard
Published: April 2010

The start-up of one of Southeast Asia's biggest hydropower dams has launched a new round of debate over how much damage the megaproject might inflict on the environment. Critics say that the ecological harm has only just begun.
Pioneering Geophysicist Tackles Newest Challenge
Authors: Kerr Richard A.
Published: April 2010

Marcia McNutt oversees what she likes to call "the nation's only integrated natural science agency," whose remit includes estimating how much natural gas awaits discovery, figuring out why mixed-gender fish are showing up in rivers, and calculating the odds of sleeping volcanoes erupting. McNutt wants to increase the visibility of the venerable U.S. Geological Survey.
Keeping It Local
Authors: Gough Nancy R.
Published: April 2010

Degradation of a growth factor receptor in the distal axon prevents its retrograde delivery and function as a long-distance neurotrophic factor.
Translation Under Stress
Authors: Wong Wei
Published: April 2010

ER stress selectively induces mRNA translation of a p53 isoform.
Notch Protects the Mitochondria
Authors: Gough Nancy R.
Published: April 2010

The Notch intracellular domain appears to serve as a cell survival factor by preventing mitochondrial damage.
Specificity of Induction of the
vanA
and
vanB
Operons in Vancomycin-Resistant Enterococci by Telavancin
Authors: Hill Craig M. , Krause Kevin M. , Lewis Stacey R. , Blais Johanne , Benton Bret M. , Mammen Mathai , Humphrey Patrick P. , Kinana Alfred , Janc James W.
Published: April 2010

Telavancin is a bactericidal, semisynthetic lipoglycopeptide indicated in the United States for the treatment of complicated skin and skin structure infections caused by susceptible Gram-positive bacteria and is under investigation as a once-daily treatment for nosocomial pneumonia. The related
vanA
and
vanB
gene clusters mediate acquired resistance to glycopeptides in enterococci by remodeling the dipeptide termini of peptidoglycan precursors from
d
-alanyl-
d
-alanine (
d
-Ala-
d
-Ala) to
d
-alanyl-
d
-lactate (
d
-Ala-
d
-Lac). In this study, we assessed the ability of telavancin to induce the expression of
van
genes in VanA- and VanB-type strains of vancomycin-resistant enterococci. Vancomycin, teicoplanin, and telavancin efficiently induced VanX activity in VanA-type strains, while VanX activity in VanB-type isolates was inducible by vancomycin but not by teicoplanin or telavancin. In VanA-type strains treated with vancomycin or telavancin, high levels of
d
-Ala-
d
-Lac-containing pentadepsipeptide were measured, while
d
-Ala-
d
-Ala pentapeptide was present at very low levels or not detected at all. In VanB-type strains, vancomycin but not telavancin induced high levels of pentadepsipeptide, while pentapeptide was not detected. Although vancomycin, teicoplanin, and telavancin induced similar levels of VanX activity in VanA-type strains, these organisms were more sensitive to telavancin, which displayed MIC values that were 32- and 128-fold lower than those of vancomycin and teicoplanin, respectively.
Macrolide and Clindamycin Resistance inStreptococcus milleriGroup Isolates from the Airways of Cystic Fibrosis Patients
Authors: Grinwis Margot E. , Sibley Christopher D. , Parkins Michael D. , Eshaghurshan Christina S. , Rabin Harvey R. , Surette Michael G.
Published: April 2010

Organisms belonging to theStreptococcus millerigroup (SMG) are known for their role in pyogenic infections but have recently been implicated as etiological agents of pulmonary exacerbation in adult patients with cystic fibrosis (CF). The prolonged exposure of CF patients to antibiotics prompted us to investigate the susceptibility profiles of 118 SMG isolates from the airways of CF patients to 12 antibiotics compared to 43 SMG isolates from patients with invasive infections. We found that ∼60% of all isolates failed to grow using the standard medium for disc diffusion, Mueller-Hinton blood agar (MHBA), so we explored the usefulness of brain heart infusion (BHI) agar for susceptibility testing. Zone-of-inhibition comparisons between BHI and MHBA showed strong correlations for six antibiotics, and interpretations were similar for both medium types. For ceftriaxone and cefepime, both groups of isolates were highly susceptible. Tetracycline resistance levels were comparable between the two groups (22% in CF isolates and 17.4% in invasive isolates). However, more than half of the CF isolates were not susceptible to azithromycin, erythromycin, and clindamycin, compared to 11%, 13%, and 6.5% of invasive isolates, respectively. There were 5-fold and 8-fold increased risks of azithromycin and clindamycin resistance, respectively, for the isolates from the airways of CF patients relative to the invasive isolates. Macrolide resistance was strongly linked to chronic azithromycin therapy in CF patients. This study shows that BHI agar is a suitable alternative for antimicrobial susceptibility testing for the SMG and that SMG isolates from the airways of CF patients are more resistant to macrolides and clindamycin than strains isolated from patients with invasive infections.
Rapid Detection and Differentiation of Antibodies to HIV-1 and HIV-2 Using Multivalent Antigens and Magnetic Immunochromatography Testing
Authors: Granade Timothy C. , Workman Shon , Wells Susan K. , Holder Angela N. , Owen S. Michele , Pau Chou-Pong
Published: April 2010

A simplified lateral-flow assay for the detection of antibodies to HIV using magnetic-bead conjugates and multibranched peptides from both HIV-1 and HIV-2 was developed. Magnetic immunochromatography testing (MICT) uses a standard lateral-flow platform that incorporates magnetic-bead conjugates for quantitative measurement of the magnetic field distortion associated with the bound magnetic conjugate (reported as adjusted relative magnetic units [MAR]). The results of the optimized MICT assay were compared to standard enzyme immunoassay (EIA) and Western blotting (WB) results using a blinded 649-member panel of specimens from the United States, Cameroon, and West Africa. The panel was comprised of samples from individuals infected with various HIV-1 subtypes (
n
= 234) or HIV-2 (
n
= 65) and HIV-seronegative specimens (
n
= 350). Additionally, 13 HIV-1 seroconversion panels (total specimens = 85), a worldwide panel containing seven of the major circulating HIV-1 subtypes (
n
= 18), an HIV-2 panel, an HIV-1/HIV-2 mixed panel, and 100 prospective specimens were tested with completely concordant results. Assay reproducibility (observed MAR) for both intra- and interrun testing was excellent, with coefficients of variation of <12%. MICT can provide a rapid, low-cost method of determining HIV antibody status requiring no subjective interpretations.
Cloning and Characterization of the Acidic Ribosomal Protein P2 ofCryptosporidium parvum, a New 17-Kilodalton Antigen
Authors: Priest Jeffrey W. , Kwon James P. , Montgomery Joel M. , Bern Caryn , Moss Delynn M. , Freeman Amanda R. , Jones Cara C. , Arrowood Michael J. , Won Kimberly Y. , Lammie Patrick J. , Gilman Robert H. , Mead Jan R.
Published: April 2010

Cryptosporidiuminfection is commonly observed among children and immunocompromised individuals in developing countries, but large-scale outbreaks of disease among adults have not been reported. In contrast, outbreaks of cryptosporidiosis in the United States and Canada are increasingly common among patients of all ages. Thus, it seems likely that residents of regions whereCryptosporidiumis highly endemic acquire some level of immunity, while residents of the developed world do not. A new immunodominantCryptosporidium parvumantigen in the 15- to 17-kDa size range was identified as theCryptosporidium parvum60S acidic ribosomal protein P2 (CpP2). We developed a recombinant protein-based enzyme-linked immunosorbent assay for serologic population surveillance for antibodies that was 89% sensitive and 92% specific relative to the results of the large-format Western blot assay. The human IgG response is directed almost exclusively toward the highly conserved, carboxy-terminal 15 amino acids of the protein. Although IgG antibody cross-reactivity was documented with sera from patients with acute babesiosis, the development of an anti-CpP2 antibody response in our Peru study population correlated better withCryptosporidiuminfection than with infection by any other parasitic protozoan. In Haiti, the prevalence of antibodies to CpP2 plateaus at 11 to 20 years of age. Because anti-CpP2 IgG antibodies were found only among residents of countries in the developing world whereCryptosporidiuminfection occurs early and often, we propose that this response may be a proxy for the intensity of infection and for acquired immunity.
Construction and Immunological Evaluation of Multivalent Hepatitis B Virus (HBV) Core Virus-Like Particles Carrying HBV and HCV Epitopes
Authors: Sominskaya Irina , Skrastina Dace , Dislers Andris , Vasiljev Denis , Mihailova Marija , Ose Velta , Dreilina Dzidra , Pumpens Paul
Published: April 2010

A multivalent vaccine candidate against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was constructed on the basis of HBV core (HBc) virus-like particles (VLPs) as carriers. Chimeric VLPs that carried a virus-neutralizing HBV pre-S1 epitope corresponding to amino acids (aa) 20 to 47 in the major immunodominant region (MIR) and a highly conserved N-terminal HCV core epitope corresponding to aa 1 to 60 at the C terminus of the truncated HBcΔ protein (N-terminal aa 1 to 144 of full-length HBc) were produced in
Escherichia coli
cells and examined for their antigenicity and immunogenicity. The presence of two different foreign epitopes within the HBc molecule did not interfere with its VLP-forming ability, with the HBV pre-S1 epitope exposed on the surface and the HCV core epitope buried within the VLPs. After immunization of BALB/c mice, specific T-cell activation by both foreign epitopes and a high-titer antibody response against the pre-S1 epitope were found, whereas an antibody response against the HBc carrier was notably suppressed. Both inserted epitopes also induced a specific cytotoxic-T-lymphocyte (CTL) response, as shown by the gamma interferon (IFN-γ) production profile.
Rapid Cytopathic Effects of
Clostridium perfringens
Beta-Toxin on Porcine Endothelial Cells
Authors: Gurtner Corinne , Popescu Francesca , Wyder Marianne , Sutter Esther , Zeeh Friederike , Frey Joachim , von Schubert Conrad , Posthaus Horst
Published: April 2010

Clostridium perfringens
type C isolates cause fatal, segmental necro-hemorrhagic enteritis in animals and humans. Typically, acute intestinal lesions result from extensive mucosal necrosis and hemorrhage in the proximal jejunum. These lesions are frequently accompanied by microvascular thrombosis in affected intestinal segments. In previous studies we demonstrated that there is endothelial localization of
C. perfringens
type C β-toxin (CPB) in acute lesions of necrotizing enteritis. This led us to hypothesize that CPB contributes to vascular necrosis by directly damaging endothelial cells. By performing additional immunohistochemical studies using spontaneously diseased piglets, we confirmed that CPB binds to the endothelial lining of vessels showing early signs of thrombosis. To investigate whether CPB can disrupt the endothelium, we exposed primary porcine aortic endothelial cells to
C. perfringens
type C culture supernatants and recombinant CPB. Both treatments rapidly induced disruption of the actin cytoskeleton, cell border retraction, and cell shrinkage, leading to destruction of the endothelial monolayer
in vitro
. These effects were followed by cell death. Cytopathic and cytotoxic effects were inhibited by neutralization of CPB. Taken together, our results suggest that CPB-induced disruption of endothelial cells may contribute to the pathogenesis of
C. perfringens
type C enteritis.
A
Burkholderia pseudomallei
Δ
purM
Mutant Is Avirulent in Immunocompetent and Immunodeficient Animals: Candidate Strain for Exclusion from Select-Agent Lists
Authors: Propst Katie L. , Mima Takehiko , Choi Kyoung-Hee , Dow Steven W. , Schweizer Herbert P.
Published: April 2010

Burkholderia pseudomallei
causes the disease melioidosis in humans and is classified as a category B select agent. Research utilizing this pathogen is highly regulated in the United States, and even basic studies must be conducted in biosafety level 3 (BSL-3) facilities. There is currently no attenuated
B. pseudomallei
strain available that is excluded from select-agent regulations and can be safely handled at BSL-2 facilities. To address this need, we created Bp82 and Bp190, which are Δ
purM
derivatives of
B. pseudomallei
strains 1026b and K96243 that are deficient in adenine and thiamine biosynthesis but replication competent
in vitro
in rich medium. A series of animal challenge studies was conducted to ensure that these strains were fully attenuated. Whereas the parental strains 1026b and K96243 and the complemented mutants Bp410 and Bp454 were virulent in BALB/c mice following intranasal inoculation, the Δ
purM
mutants Bp82 and Bp190 were avirulent even when they were administered at doses 4 logs higher than the doses used for the parental strains. Animals challenged with high doses of the Δ
purM
mutants rapidly cleared the bacterium from tissues (lung, liver, and spleen) and remained free of culturable bacteria for the duration of the experiments (up to 60 days postinfection). Moreover, highly susceptible 129/SvEv mice and immune incompetent mice (IFN-γ
−/−
, SCID) were resistant to challenges with Δ
purM
mutant Bp82. This strain was also avirulent in the Syrian hamster challenge model. We concluded that Δ
purM
mutant Bp82 is fully attenuated and safe for use under BSL-2 laboratory conditions and thus is a candidate for exclusion from the select-agent list.
Afa/Dr-Expressing, Diffusely AdheringEscherichia coliStrain C1845 Triggers F1845 Fimbria-Dependent Phosphatidylserine Externalization on Neutrophil-Like Differentiated PLB-985 Cells through an Apoptosis-Independent Mechanism
Authors: Sémiramoth Nicolas , Gleizes Aude , Turbica Isabelle , Sandré Catherine , Marin-Esteban Viviana , Gorges Roseline , Servin Alain , Chollet-Martin Sylvie
Published: April 2010

The enterovirulentEscherichia colistrains potentially involved in inflammatory bowel diseases include diffusely adherent strains expressing Afa/Dr fimbriae (Afa/Dr DAEC). We have previously observed type 1 pilus-mediated interleukin-8 (IL-8) hyperproduction in infected neutrophils. As pathogen induction of host cell death programs and clearance of apoptotic infected cells are crucial for innate immune system homeostasis and host integrity, we examined modulation of neutrophil cell death by Afa/Dr DAEC. Using the human PLB-985 cell line differentiated into fully mature neutrophils, we found that the wild-type enterovirulentE. colistrain C1845 and the recombinant strain DH5α/pF1845 (expressing the fimbrial adhesin F1845) similarly induced time-dependent phosphatidylserine (PS) externalization, suggesting a major specific role of this virulence factor. Using small interfering RNA (siRNA) decay-accelerating factor (DAF)-transfected PLB-985 cells, we then showed that this PS externalization was triggered in part by glycosylphosphatidylinositol (GPI)-anchored DAF receptor engagement (leading to tyrosine kinase and protein kinase C activation) and that it required cytoskeleton and lipid raft architectural integrity. PS externalization under these conditions was not dependent on caspases, mitochondria, lysosomes, or reactive oxygen or nitrogen species. F1845-mediated PS externalization was sufficient to enable macrophage engulfment of infected differentiated PLB-985 cells. These findings provide new insights into the neutrophil response to Afa/Dr DAEC infection and highlight a new role for F1845 fimbriae. Interestingly, although apoptosis pathways were not engaged, C1845-infected PLB-985 cells displayed enhanced removal by macrophages, a process that may participate in the resolution of Afa/Dr DAEC infection and related inflammation.
Autoinducer-2 and QseC Control Biofilm Formation and
In Vivo
Virulence of
Aggregatibacter actinomycetemcomitans
Authors: Novak Elizabeth A. , Shao HanJuan , Daep Carlo Amorin , Demuth Donald R.
Published: April 2010

Biofilm formation by the periodontal pathogen
Aggregatibacter actinomycetemcomitans
is dependent upon autoinducer-2 (AI-2)-mediated quorum sensing. However, the components that link the detection of the AI-2 signal to downstream gene expression have not been determined. One potential regulator is the QseBC two-component system, which is part of the AI-2-dependent response pathway that controls biofilm formation in
Escherichia coli
. Here we show that the expression of QseBC in
A. actinomycetemcomitans
is induced by AI-2 and that induction requires the AI-2 receptors, LsrB and/or RbsB. Additionally, inactivation of
qseC
resulted in reduced biofilm growth. Since the ability to grow in biofilms is essential for
A. actinomycetemcomitans
virulence, strains that were deficient in QseC or the AI-2 receptors were examined in an
in vivo
mouse model of periodontitis. The Δ
qseC
mutant induced significantly less alveolar bone resorption than the wild-type strain (
P
< 0.02). Bone loss in animals infected with the Δ
qseC
strain was similar to that in sham-infected animals. The Δ
lsrB
, Δ
rbsB
, and Δ
lsrB
Δ
rbsB
strains also induced significantly less alveolar bone resorption than the wild type (
P
< 0.03,
P
< 0.02, and
P
< 0.01, respectively). However, bone loss induced by a Δ
luxS
strain was indistinguishable from that induced by the wild type, suggesting that AI-2 produced by indigenous microflora in the murine oral cavity may complement the Δ
luxS
mutation. Together, these results suggest that the QseBC two-component system is part of the AI-2 regulon and may link the detection of AI-2 to the regulation of downstream cellular processes that are involved in biofilm formation and virulence of
A. actinomycetemcomitans
.