bluuebunny/crossref_metadata_2025 huggingface dataset:
Partial Hyperbolic-Tangent Friction Element Based Phenomenological Models for Shape Memory Alloy Pseudoelastic Hysteresis
Authors: Malovrh Brendon , Gandhi Farhan
Published: June 2006

A new mechanism-based phenomenological model, comprising linear and nonlinear springs and a nonlinear friction element, is presented for the pseudoelastic damping behavior of shape memory alloys. The use of a partial hyperbolic tangent friction element (a hybrid of an ideal and hyperbolic tangent friction element) is seen to increase accuracy in simulating experimental hysteresis behavior over earlier models. Comparisons are then made with existing models. Compared to the thermodynamic-based models, the present models have the benefit of not requiring calculation of austenite-martensite phase transformations. Unlike previously developed phenomenological models, the models presented herein have mechanical analogies that provide a strong physical basis, and clear relationships can be established between the unlocking of the friction element and the occurrence of phase transformation. These models are simpler and more intuitive than existing models.
Combustion Synthesis of a Functionally Graded NiTi-TiCx Composite
Authors: Burkes Douglas E. , Moore John J.
Published: June 2006

Combustion synthesis (CS) is an alternative technique for producing advanced materials and is dependent upon a highly exothermic chemical reaction to become self-sustaining after only a short energy pulse is applied to initiate the reaction. A NiTi-TiCx functionally graded material (FGM) was investigated that combines superelastic and shape memory capabilities of NiTi with the high hardness, wear, and corrosion resistance of TiCx. CS was employed to produce a FGM from 100% TiCx ceramic to 100% NiTi intermetallic. Temperature and burning velocity data of the CS reaction were recorded. XRD of the final product layers was conducted to determine phase composition. The combustion temperature, burning velocity, and cooling rate in each layer decreased with increasing NiTi content. Large blowholes were present in the high NiTi content layers as a result of outgassing of volatile species from the reactant powders. XRD analysis revealed the presence of Ni-Ti intermetallics along with a substoichiometric TiC (TiC0.7). Production of a NiTi-TiCx FGM is possible through use of a CS reaction employing the propagating mode (SHS). The material layers were observed as functionally graded in both composition and porosity.
The Effect of Damage on the Viscoelastic Behavior of Human Vertebral Trabecular Bone
Authors: Bredbenner Todd L. , Davy Dwight T.
Published: June 2006

The present study examines the viscoelastic behavior of cancellous bone at low strains and the effects of damage on this viscoelastic behavior. It provides experimental evidence of interaction between stress relaxation behavior and the effect of accumulated damage. The results suggest that damage is at least orthotropic in trabecular bone specimens under uniaxial loading. Simple linear models of viscoelasticity described the time-dependent stress-strain behavior at low strains before and after specimen damage, although better fits of these models were obtained prior to damage. Modeling the observed changes in relaxation times with damage accumulation appears necessary to successfully predict the post-damage viscoelastic response.
A Structural Model for the Flexural Mechanics of Nonwoven Tissue Engineering Scaffolds
Authors: Engelmayr George C. , Sacks Michael S.
Published: June 2006

The development of methods to predict the strength and stiffness of biomaterials used in tissue engineering is critical for load-bearing applications in which the essential functional requirements are primarily mechanical. We previously quantified changes in the effective stiffness (E) of needled nonwoven polyglycolic acid (PGA) and poly-L-lactic acid (PLLA) scaffolds due to tissue formation and scaffold degradation under three-point bending. Toward predicting these changes, we present a structural model for E of a needled nonwoven scaffold in flexure. The model accounted for the number and orientation of fibers within a representative volume element of the scaffold demarcated by the needling process. The spring-like effective stiffness of the curved fibers was calculated using the sinusoidal fiber shapes. Structural and mechanical properties of PGA and PLLA fibers and PGA, PLLA, and 50:50 PGA/PLLA scaffolds were measured and compared with model predictions. To verify the general predictive capability, the predicted dependence of E on fiber diameter was compared with experimental measurements. Needled nonwoven scaffolds were found to exhibit distinct preferred (PD) and cross-preferred (XD) fiber directions, with an E ratio (PD/XD) of ∼3:1. The good agreement between the predicted and experimental dependence of E on fiber diameter (R2=0.987) suggests that the structural model can be used to design scaffolds with E values more similar to native soft tissues. A comparison with previous results for cell-seeded scaffolds (Engelmayr, G. C., Jr., et al., 2005, Biomaterials, 26(2), pp. 175–187) suggests, for the first time, that the primary mechanical effect of collagen deposition is an increase in the number of fiber-fiber bond points yielding effectively stiffer scaffold fibers. This finding indicated that the effects of tissue deposition on needled nonwoven scaffold mechanics do not follow a rule-of-mixtures behavior. These important results underscore the need for structural approaches in modeling the effects of engineered tissue formation on nonwoven scaffolds, and their potential utility in scaffold design.
The Effect of Vortex Formation on Left Ventricular Filling and Mitral
Valve Efficiency
Authors: Pierrakos Olga , Vlachos Pavlos P.
Published: June 2006

A new mechanism for quantifying the filling energetics in the left ventricle (LV) and past mechanical heart valves (MHV) is identified and presented. This mechanism is attributed to vortex formation dynamics past MHV leaflets. Recent studies support the conjecture that the natural healthy left ventricle (LV) performs in an optimum, energy-preserving manner by redirecting the flow with high efficiency. Yet to date, no quantitative proof has been presented. The present work provides quantitative results and validation of a theory based on the dynamics of vortex ring formation, which is governed by a critical formation number (FN) that corresponds to the dimensionless time at which the vortex ring has reached its maximum circulation content, in support of this hypothesis. Herein, several parameters (vortex ring circulation, vortex ring energy, critical FN, hydrodynamic efficiencies, vortex ring propagation speed) have been quantified and presented as a means of bridging the physics of vortex formation in the LV. In fact, the diastolic hydrodynamic efficiencies were found to be 60, 41, and 29%, respectively, for the porcine, anti-anatomical, and anatomical valve configurations. This assessment provides quantitative proof of vortex formation, which is dependent of valve design and orientation, being an important flow characteristic and associated to LV energetics. Time resolved digital particle image velocimetry with kilohertz sampling rate was used to study the ejection of fluid into the LV and resolve the spatiotemporal evolution of the flow. The clinical significance of this study is quantifying vortex formation and the critical FN that can potentially serve as a parameter to quantify the LV filling process and the performance of heart valves.
Simulation of Physiological Loading in Total Hip Replacements
Authors: Ramos A. , Fonseca F. , Simões J. A.
Published: June 2006

The determination of biomechanical force systems of implanted femurs to obtain adequate strain measurements has been neglected in many published studies. Due to geometric alterations induced by surgery and those inherent to the design of the prosthesis, the loading system changes because the lever arms are modified. This paper discusses the determination of adequate loading of the implanted femur based on the intact femur-loading configuration. Four reconstructions with Lubinus SPII, Charnley Roundback, Müller Straight and Stanmore prostheses were used in the study. Pseudophysiologic and nonphysiologic implanted system forces were generated and assessed with finite element analysis. Using an equilibrium system of forces composed by the Fx (medially direction) component of the hip contact force and the bending moments Mx (median plane) and My (coronal plane) allowed adequate, pseudo-physiological loading of the implanted femur. We suggest that at least the bending moment at the coronal plane must be restored in the implanted femur-loading configuration.
In Vitro Assessment of a Motion-Based Optimization Method for Locating the Talocrural and Subtalar Joint Axes
Authors: Lewis Gregory S. , Sommer H. J. , Piazza Stephen J.
Published: June 2006

The locations of the joint axes of the ankle complex vary considerably between subjects, yet no noninvasive method with demonstrated accuracy exists for locating these axes. The moments of muscle and ground reaction forces about the joint axes are dependent on axis locations, making knowledge of these locations critical to accurate musculoskeletal modeling of the foot and ankle. The accuracy of a computational optimization method that fits a two-revolute model to measured motion was assessed using computer-generated data, a two-revolute mechanical linkage, and three lower-leg cadaver specimens. Motions were applied to cadaver specimens under axial load while bone-mounted markers attached to the tibia, talus, and calcaneus were tracked using a video-based motion analysis system. Estimates of the talocrural and subtalar axis locations were computed from motions of the calcaneus relative to the tibia using the optimization method. These axes were compared to mean helical axes computed directly from tibia, talus, and calcaneus motions. The optimization method performed well when the motions were computer-generated or measured in the mechanical linkage, with angular differences between optimization and mean helical axes ranging from 1deg to 5deg. In the cadaver specimens, however, these differences exceeded 20deg. Optimization methods that locate the anatomical joint axes of the ankle complex by fitting two revolute joints to measured tibia-calcaneus motions may be limited because of problems arising from non-revolute behavior.
Frequency Response of a Viscoelastic Tensegrity Model: Structural Rearrangement Contribution to Cell Dynamics
Authors: Cañadas Patrick , Wendling-Mansuy Sylvie , Isabey Daniel
Published: June 2006

In an attempt to understand the role of structural rearrangement onto the cell response during imposed cyclic stresses, we simulated numerically the frequency-dependent behavior of a viscoelastic tensegrity structure (VTS model) made of 24 elastic cables and 6 rigid bars. The VTS computational model was based on the nonsmooth contact dynamics (NSCD) method in which the constitutive elements of the tensegrity structure are considered as a set of material points that mutually interact. Low amplitude oscillatory loading conditions were applied and the frequency response of the overall structure was studied in terms of frequency dependence of mechanical properties. The latter were normalized by the homogeneous properties of constitutive elements in order to capture the essential feature of spatial rearrangement. The results reveal a specific frequency-dependent contribution of elastic and viscous effects which is responsible for significant changes in the VTS model dynamical properties. The mechanism behind is related to the variable contribution of spatial rearrangement of VTS elements which is decreased from low to high frequency as dominant effects are transferred from mainly elastic to mainly viscous. More precisely, the elasticity modulus increases with frequency while the viscosity modulus decreases, each evolution corresponding to a specific power-law dependency. The satisfactorily agreement found between present numerical results and the literature data issued from in vitro cell experiments suggests that the frequency-dependent mechanism of spatial rearrangement presently described could play a significant and predictable role during oscillatory cell dynamics.
Squeezing Flows of Vaginal Gel Formulations Relevant to Microbicide Drug Delivery
Authors: Kieweg Sarah L. , Katz David F.
Published: June 2006

Efficacy of topical microbicidal drug delivery formulations against HIV depends in part on their ability to coat, distribute, and be retained on epithelium. Once applied to the vagina, a formulation is distributed by physical forces including: gravity, surface tension, shearing, and normal forces from surrounding tissues, i.e., squeezing forces. The present study focused on vaginal microbicide distribution due to squeezing forces. Mathematical simulations of squeezing flows were compared with squeezing experiments, using model vaginal gel formulations. Our objectives were: (1) to determine if mathematical simulations can accurately describe squeezing flows of vaginal gel formulations; (2) to find the best model and optimized parameter sets to describe these gels; and (3) to examine vaginal coating due to squeezing using the best models and summary parameters for each gel. Squeezing flow experiments revealed large differences in spreadability between formulations, suggesting different coating distributions in vivo. We determined the best squeezing flow models and summary parameters for six test gels of two compositions, cellulose and polyacrylic acid (PAA). We found that for some gels it was preferable to deduce model input parameters directly from squeezing flow experiments. For the cellulose gels, slip conditions in squeezing flow experiments needed to be evaluated. For PAA gels, we found that in the absence of squeezing experiments, rotational viscometry measurements (to determine Herschel-Bulkley parameters) led to reasonably accurate predictions of squeezing flows. Results indicated that yield stresses may be a strong determinant of squeezing flow mechanics. This study serves as a template for further investigations of other gels and determination of which sources of rheological data best characterize potential microbicidal formulations. These mathematical simulations can serve as useful tools for exploring drug delivery parameters, and optimizing formulations, prior to costly clinical trials.
Microbubble Expansion in a Flexible Tube
Authors: Ye Tao , Bull Joseph L.
Published: June 2006

We have utilized a computational model of the expansion of a microbubble in a liquid-filled flexible tube to investigate the potential for acoustic vaporization of perfluorocarbon droplets to damage blood vessels during a novel gas embolotherapy technique for the potential treatment of tumors. This model uses a fixed grid, multi-domain, interface tracking, direct numerical simulation method that treats all interfaces and boundaries as sharp discontinuities for high accuracy. In the current work, we examined effects of initial bubble size on the flows and wall stresses that result from droplet vaporization. The remaining dimensionless parameters that govern the system response (Reynolds, Weber, and Strouhal numbers, initial bubble pressure, and wall stiffness and tension) were selected to model an arteriole. The results for a flexible tube are significantly different from those for a rigid tube. Two major flow regimes occur due to the combined effect of bubble and tube deformation: in flow at the tube ends and out flow near the bubble surface. The flexibility of the tube largely dissipates the extreme pressure that develops in the rigid tube model. Both the magnitude and the overall expansion time of the rapidly changing pressure are greatly reduced in the flexible tube. Smaller initial bubble diameters, relative to the vessel diameter, result in lower wall stresses. This study indicates that wall flexibility can significantly influence the wall stresses that result from acoustic vaporization of intravascular perfluorocarbon droplets, and suggests that acoustic activation of droplets in larger, more flexible vessels may be less likely to damage or rupture vessels than activation in smaller and stiffer vessels.
Simulations of Congenital Septal Defect Closure and Reactivity Testing in Patient-Specific Models of the Pediatric Pulmonary Vasculature: A 3D Numerical Study With Fluid-Structure Interaction
Authors: Hunter Kendall S. , Lanning Craig J. , Chen Shiuh-Yung J. , Zhang Yanhang , Garg Ruchira , Ivy D. Dunbar , Shandas Robin
Published: June 2006

Clinical imaging methods are highly effective in the diagnosis of vascular pathologies, but they do not currently provide enough detail to shed light on the cause or progression of such diseases, and would be hard pressed to foresee the outcome of surgical interventions. Greater detail of and prediction capabilities for vascular hemodynamics and arterial mechanics are obtained here through the coupling of clinical imaging methods with computational techniques. Three-dimensional, patient-specific geometric reconstructions of the pediatric proximal pulmonary vasculature were obtained from x-ray angiogram images and meshed for use with commercial computational software. Two such models from hypertensive patients, one with multiple septal defects, the other who underwent vascular reactivity testing, were each completed with two sets of suitable fluid and structural initial and boundary conditions and used to obtain detailed transient simulations of artery wall motion and hemodynamics in both clinically measured and predicted configurations. The simulation of septal defect closure, in which input flow and proximal vascular stiffness were decreased, exhibited substantial decreases in proximal velocity, wall shear stress (WSS), and pressure in the post-op state. The simulation of vascular reactivity, in which distal vascular resistance and proximal vascular stiffness were decreased, displayed negligible changes in velocity and WSS but a significant drop in proximal pressure in the reactive state. This new patient-specific technique provides much greater detail regarding the function of the pulmonary circuit than can be obtained with current medical imaging methods alone, and holds promise for enabling surgical planning.
Finite-Reynolds-Number Effects in Steady, Three-Dimensional Airway Reopening
Authors: Hazel Andrew L. , Heil Matthias
Published: June 2006

Motivated by the physiological problem of pulmonary airway reopening, we study the steady propagation of an air finger into a buckled elastic tube, initially filled with viscous fluid. The system is modeled using geometrically non-linear, Kirchhoff-Love shell theory, coupled to the free-surface Navier-Stokes equations. The resulting three-dimensional, fluid-structure-interaction problem is solved numerically by a fully coupled finite element method. Our study focuses on the effects of fluid inertia, which has been neglected in most previous studies. The importance of inertial forces is characterized by the ratio of the Reynolds and capillary numbers, Re∕Ca, a material parameter. Fluid inertia has a significant effect on the system’s behavior, even at relatively small values of Re∕Ca. In particular, compared to the case of zero Reynolds number, fluid inertia causes a significant increase in the pressure required to drive the air finger at a given speed.
Food for Thought: Lower-Than-Expected Crop Yield Stimulation with Rising CO
2
Concentrations
Authors: Long Stephen P. , Ainsworth Elizabeth A. , Leakey Andrew D. B. , Nösberger Josef , Ort Donald R.
Published: June 2006

Model projections suggest that although increased temperature and decreased soil moisture will act to reduce global crop yields by 2050, the direct fertilization effect of rising carbon dioxide concentration ([CO
2
]) will offset these losses. The CO
2
fertilization factors used in models to project future yields were derived from enclosure studies conducted approximately 20 years ago. Free-air concentration enrichment (FACE) technology has now facilitated large-scale trials of the major grain crops at elevated [CO
2
] under fully open-air field conditions. In those trials, elevated [CO
2
] enhanced yield by ∼50% less than in enclosure studies. This casts serious doubt on projections that rising [CO
2
] will fully offset losses due to climate change.
The
Neurospora
Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles
Authors: Pregueiro António M. , Liu Qiuyun , Baker Christopher L. , Dunlap Jay C. , Loros Jennifer J.
Published: June 2006

The clock gene
period-4
(
prd-4
) in
Neurospora
was identified by a single allele displaying shortened circadian period and altered temperature compensation. Positional cloning followed by functional tests show that PRD-4 is an ortholog of mammalian
checkpoint kinase 2
(
Chk2
). Expression of
prd-4
is regulated by the circadian clock and, reciprocally, PRD-4 physically interacts with the clock component FRQ, promoting its phosphorylation. DNA-damaging agents can reset the clock in a manner that depends on time of day, and this resetting is dependent on PRD-4. Thus,
prd-4
, the
Neurospora Chk2
, identifies a molecular link that feeds back conditionally from circadian output to input and the cell cycle.
Comment on "Ancient DNA from the First European Farmers in 7500-Year-Old Neolithic Sites"
Authors: Ammerman Albert J. , Pinhasi Ron , Bánffy Eszter
Published: June 2006

On the basis of analysis of ancient DNA from early European farmers, Haak
et al
. (Reports, 11 November 2005, p. 1016) argued for the Paleolithic ancestry of modern Europeans. We stress that the study is more limited in scope than the authors claim, in part because not all of the skeletal samples date to the time of the Neolithic transition in a given area of Europe.
The Competitive Cost of Antibiotic Resistance in
Mycobacterium tuberculosis
Authors: Gagneux Sebastien , Long Clara Davis , Small Peter M. , Van Tran , Schoolnik Gary K. , Bohannan Brendan J. M.
Published: June 2006

Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of
Mycobacterium tuberculosis
, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates.
Netrins Promote Developmental and Therapeutic Angiogenesis
Authors: Wilson Brent D. , Ii Masaaki , Park Kye Won , Suli Arminda , Sorensen Lise K. , Larrieu-Lahargue Fréderic , Urness Lisa D. , Suh Wonhee , Asai Jun , Kock Gerhardus A.H. , Thorne Tina , Silver Marcy , Thomas Kirk R. , Chien Chi-Bin , Losordo Douglas W. , Li Dean Y.
Published: June 2006

Axonal guidance and vascular patterning share several guidance cues, including proteins in the netrin family. We demonstrate that netrins stimulate proliferation, migration, and tube formation of human endothelial cells in vitro and that this stimulation is independent of known netrin receptors. Suppression of
netrin1a
messenger RNA in zebrafish inhibits vascular sprouting, implying a proangiogenic role for netrins during vertebrate development. We also show that netrins accelerate neovascularization in an in vivo model of ischemia and that they reverse neuropathy and vasculopathy in a diabetic murine model. We propose that the attractive vascular and neural guidance functions of netrins offer a unique therapeutic potential.
Phase Modifiers Promote Efficient Production of Hydroxymethylfurfural from Fructose
Authors: Román-Leshkov Yuriy , Chheda Juben N. , Dumesic James A.
Published: June 2006

Furan derivatives obtained from renewable biomass resources have the potential to serve as substitutes for the petroleum-based building blocks that are currently used in the production of plastics and fine chemicals. We developed a process for the selective dehydration of fructose to 5-hydroxymethylfurfural (HMF) that operates at high fructose concentrations (10 to 50 weight %), achieves high yields (80% HMF selectivity at 90% fructose conversion), and delivers HMF in a separation-friendly solvent. In a two-phase reactor system, fructose is dehydrated in the aqueous phase with the use of an acid catalyst (hydrochloric acid or an acidic ion-exchange resin) with dimethylsulfoxide and/or poly(1-vinyl-2-pyrrolidinone) added to suppress undesired side reactions. The HMF product is continuously extracted into an organic phase (methylisobutylketone) modified with 2-butanol to enhance partitioning from the reactive aqueous solution.
The Ant Odometer: Stepping on Stilts and Stumps
Authors: Wittlinger Matthias , Wehner Rüdiger , Wolf Harald
Published: June 2006

Desert ants,
Cataglyphis
, navigate in their vast desert habitat by path integration. They continuously integrate directions steered (as determined by their celestial compass) and distances traveled, gauged by as-yet-unknown mechanisms. Here we test the hypothesis that navigating ants measure distances traveled by using some kind of step integrator, or “step counter.” We manipulated the lengths of the legs and, hence, the stride lengths, in freely walking ants. Animals with elongated (“stilts”) or shortened legs (“stumps”) take larger or shorter strides, respectively, and concomitantly misgauge travel distance. Travel distance is overestimated by experimental animals walking on stilts and underestimated by animals walking on stumps.
Ammonia Channel Couples Glutaminase with Transamidase Reactions in GatCAB
Authors: Nakamura Akiyoshi , Yao Min , Chimnaronk Sarin , Sakai Naoki , Tanaka Isao
Published: June 2006

The formation of glutaminyl transfer RNA (Gln-tRNA
Gln
) differs among the three domains of life. Most bacteria employ an indirect pathway to produce Gln-tRNA
Gln
by a heterotrimeric glutamine amidotransferase CAB (GatCAB) that acts on the misacylated Glu-tRNA
Gln
. Here, we describe a series of crystal structures of intact GatCAB from
Staphylococcus aureus
in the apo form and in the complexes with glutamine, asparagine, Mn
2+
, and adenosine triphosphate analog. Two identified catalytic centers for the glutaminase and transamidase reactions are markedly distant but connected by a hydrophilic ammonia channel 30 Å in length. Further, we show that the first U-A base pair in the acceptor stem and the D loop of tRNA
Gln
serve as identity elements essential for discrimination by GatCAB and propose a complete model for the overall concerted reactions to synthesize Gln-tRNA
Gln
.
Redistributing Work in Aging Europe
Authors: Vaupel James W. , Loichinger Elke
Published: June 2006

As Europe ages, the proportion of people who work will decline unless older individuals remain in the labor force. Such reform could be part of a more general redistribution of work. If a greater share of the population worked, then the average number of hours worked per week could be reduced. This could particularly help younger people and increase Europe's low birth rates. The challenges facing Germany, Europe's most populous country, are highlighted, but statistics are also given for five other European countries and, for comparison, the United States. Social science research is needed to provide policy-relevant knowledge about life-course options.
Spin-Wave Lifetimes Throughout the Brillouin Zone
Authors: Bayrakci S. P. , Keller T. , Habicht K. , Keimer B.
Published: June 2006

We used a neutron spin-echo method with microelectron-volt resolution to determine the lifetimes of spin waves in the prototypical antiferromagnet MnF
2
over the entire Brillouin zone. A theory based on the interaction of spin waves (magnons) with longitudinal spin fluctuations provides an excellent, parameter-free description of the data, except at the lowest momenta and temperatures. This is surprising, given the prominence of alternative theories based on magnon-magnon interactions in the literature. The results and technique open up a new avenue for the investigation of fundamental concepts in magnetism. The technique also allows measurement of the lifetimes of other elementary excitations, such as lattice vibrations, throughout the Brillouin zone.
Molecular Recognition in the Selective Oxygenation of Saturated C-H Bonds by a Dimanganese Catalyst
Authors: Das Siddhartha , Incarvito Christopher D. , Crabtree Robert H. , Brudvig Gary W.
Published: June 2006

Although enzymes often incorporate molecular recognition elements to orient substrates selectively, such strategies are rarely achieved by synthetic catalysts. We combined molecular recognition through hydrogen bonding with C-H activation to obtain high-turnover catalytic regioselective functionalization of sp
3
C-H bonds remote from the –COOH recognition group. The catalyst contains a Mn(μ-O)
2
Mn reactive center and a ligand based on Kemp's triacid that directs a –COOH group to anchor the carboxylic acid group of the substrate and thus modify the usual selectivity for oxidation. Control experiments supported the role of hydrogen bonding in orienting the substrate to achieve high selectivity.
Skill Formation and the Economics of Investing in Disadvantaged Children
Authors: Heckman James J.
Published: June 2006

This paper summarizes evidence on the effects of early environments on child, adolescent, and adult achievement. Life cycle skill formation is a dynamic process in which early inputs strongly affect the productivity of later inputs.
A Distinct Small RNA Pathway Silences Selfish Genetic Elements in the Germline
Authors: Vagin Vasily V. , Sigova Alla , Li Chengjian , Seitz Hervé , Gvozdev Vladimir , Zamore Phillip D.
Published: June 2006

In the
Drosophila
germline, repeat-associated small interfering RNAs (rasiRNAs) ensure genomic stability by silencing endogenous selfish genetic elements such as retrotransposons and repetitive sequences. Whereas small interfering RNAs (siRNAs) derive from both the sense and antisense strands of their double-stranded RNA precursors, rasiRNAs arise mainly from the antisense strand. rasiRNA production appears not to require Dicer-1, which makes microRNAs (miRNAs), or Dicer-2, which makes siRNAs, and rasiRNAs lack the 2′,3′ hydroxy termini characteristic of animal siRNA and miRNA. Unlike siRNAs and miRNAs, rasiRNAs function through the Piwi, rather than the Ago, Argonaute protein subfamily. Our data suggest that rasiRNAs protect the fly germline through a silencing mechanism distinct from both the miRNA and RNA interference pathways.
The Perils of Prognostication
Authors: Jost John T.
Published: June 2006

Expert Political Judgment
. How Good Is It?. How Can We Know?.
By Philip E. Tetlock
. Princeton University Press, Princeton, NJ, 2006. 337 pp. $35, £22.95. ISBN 0-691-12302-2. Paper, $19.95, £12.95. ISBN 0-691-12871-5.

Evaluating predictions from a range of experts, informed laity, and extrapolation of current trends, the author considers how we might recognize good political judgments and strategic forecasts.
Some Frontiers in Social Science
Authors: Butz William P. , Torrey Barbara Boyle
Published: June 2006

The fundamental challenge in the social sciences is moving from complicated correlations to useful prediction. Progress usually reflects an interplay between theory, data, and tools. Six areas of innovation, principally data and tools, are now pushing at the frontiers of these sciences: longitudinal data, laboratory experimentation, improved statistical methods, geographic information tools, biosocial science, and international replication. These innovations are gaining power as they cross disciplinary boundaries, helping to attribute causality to observed relationships, to understand their nature, and thereby to improve the accuracy and usefulness of predictions.
The
Brucella abortus
Cyclic β-1,2-Glucan Virulence Factor Is Substituted with O-Ester-Linked Succinyl Residues
Authors: Roset Mara S. , Ciocchini Andrés E. , Ugalde Rodolfo A. , Iñón de Iannino Nora
Published: June 2006

Brucella
periplasmic cyclic β-1,2-glucan plays an important role during bacterium-host interaction. Nuclear magnetic resonance spectrometry analysis, thin-layer chromatography, and DEAE-Sephadex chromatography were used to characterize
Brucella abortus
cyclic glucan. In the present study, we report that a fraction of
B. abortus
cyclic β-1,2-glucan is substituted with succinyl residues, which confer anionic character on the cyclic β-1,2-glucan. The oligosaccharide backbone is substituted at C-6 positions with an average of two succinyl residues per glucan molecule. This O-ester-linked succinyl residue is the only substituent of
Brucella
cyclic glucan. A
B. abortus
open reading frame (BAB1_1718) homologous to
Rhodobacter sphaeroides
glucan succinyltransferase (OpgC) was identified as the gene encoding the enzyme responsible for cyclic glucan modification. This gene was named
cgm
for
c
yclic
g
lucan
m
odifier and is highly conserved in
Brucella melitensis
and
Brucella suis
. Nucleotide sequencing revealed that
B. abortus cgm
consists of a 1,182-bp open reading frame coding for a predicted membrane protein of 393 amino acid residues (42.7 kDa) 39% identical to
Rhodobacter sphaeroides
succinyltransferase.
cgm
null mutants in
B. abortus
strains 2308 and S19 produced neutral glucans without succinyl residues, confirming the identity of this protein as the cyclic-glucan succinyltransferase enzyme. In this study, we demonstrate that succinyl substituents of cyclic β-1,2-glucan of
B. abortus
are necessary for hypo-osmotic adaptation. On the other hand, intracellular multiplication and mouse spleen colonization are not affected in
cgm
mutants, indicating that cyclic-β-1,2-glucan succinylation is not required for virulence and suggesting that no low-osmotic stress conditions must be overcome during infection.
An Unstable Competence-Induced Protein, CoiA, Promotes Processing of Donor DNA after Uptake during Genetic Transformation inStreptococcus pneumoniae
Authors: Desai Bhushan V. , Morrison Donald A.
Published: June 2006

Natural genetic transformation inStreptococcus pneumoniaeentails transcriptional activation of at least two sets of genes. One set of genes, activated by the competence-specific response regulator ComE, is involved in initiating competence, whereas a second set is activated by the competence-specific alternative sigma factor ComX and functions in DNA uptake and recombination. Here we report an initial characterization of CoiA, a ComX-dependent gene product that is induced during competence and is required for transformation. CoiA is widely conserved among gram-positive bacteria, and in streptococci, the entirecoiAlocus composed of four genes is conserved. By use of immunoblot assay, we show that, similar to its message, CoiA protein is transient, appearing at 10 min and largely disappearing by 30 min post-competence induction. Using complementation analysis, we establish thatcoiAis the only gene of this induced locus needed for transformability. We find no indication of CoiA having a role in regulating competence. Finally, using32P- and3H-labeled donor DNA, we demonstrate that acoiAmutant can internalize normal amounts of donor DNA compared to the wild-type strain but is unable to process it into viable transformants, suggesting a role for CoiA after DNA uptake, either in DNA processing or recombination.
Regulation of theHelicobacter pyloriFe-S Cluster Synthesis Protein NifS by Iron, Oxidative Stress Conditions, and Fur
Authors: Alamuri Praveen , Mehta Nalini , Burk Andrew , Maier Robert J.
Published: June 2006

Transcription of both chromosomal and extrachromosomally introducednifSwas regulated (up-expressed) by oxygen or by supplemental iron conditions. This up-expression was not observed in afurmutant strain background or when an iron chelator was added. Iron-bound Fur (but not apo-Fur) recognized thenifSpromoter, and Fur bound significantly farther upstream (−155 bp to −190 bp and −210 to −240 bp) in the promoter than documentedHelicobacter pyloriFur binding regions. This binding was stronger than Fur recognition of theflgEornapApromoter and includes a Fur recognition sequence common to theH. pylori pfrandsodBupstream areas. Studies of Fur-regulated genes inH. pylorihave indicated that apo-Fur acts as a repressor, but our results demonstrate that iron-bound Fur activates (nifS) transcription.
Mutational Analysis of the Flagellar Rotor Protein FliN: Identification of Surfaces Important for Flagellar Assembly and Switching
Authors: Paul Koushik , Harmon Jacob G. , Blair David F.
Published: June 2006

FliN is a component of the flagellar switch complex in many bacterial species. The crystal structure is known for most of FliN, and a targeted cross-linking study (K. Paul and D. F. Blair, J. Bacteriol. 188:2502-2511, 2006) showed that it is organized in ring-shaped tetramers at the bottom of the basal body C ring. FliN is essential for flagellar assembly and direction switching, but its precise functions have not been defined. Here, we identify functionally important regions on FliN by systematic mutagenesis. Nonconservative mutations were made at positions sampling the surface of the protein, and the effects on flagellar assembly and function were measured. Flagellar assembly was disrupted by mutations in a conserved hydrophobic patch centered on the dimer twofold axis or by mutations on the surface that forms the dimer-dimer interface in the tetramer. The assembly defect in hydrophobic-patch mutants was partially rescued by overexpression of the flagellar export proteins FliH and FliI, and coprecipitation assays demonstrated a binding interaction between FliN and FliH that was weakened by mutations in the hydrophobic patch. Thus, FliN might contribute to export by providing binding sites for FliH or FliH-containing complexes. The region around the hydrophobic patch is also important for switching; certain mutations in or near the patch caused a smooth-swimming chemotaxis defect that in most cases could be partially rescued by overexpression of the clockwise-signaling protein CheY. The results indicate that FliN is more closely involved in switching than has been supposed, possibly contributing to the binding site for CheY on the switch.
Biochemical and Molecular Characterization of a Na
+
-Translocating F
1
F
o
-ATPase from the Thermoalkaliphilic Bacterium
Clostridium paradoxum
Authors: Ferguson Scott A. , Keis Stefanie , Cook Gregory M.
Published: June 2006

Clostridium paradoxum
is an anaerobic thermoalkaliphilic bacterium that grows rapidly at pH 9.8 and 56°C. Under these conditions, growth is sensitive to the F-type ATP synthase inhibitor
N
,
N′
-dicyclohexylcarbodiimide (DCCD), suggesting an important role for this enzyme in the physiology of
C. paradoxum
. The ATP synthase was characterized at the biochemical and molecular levels. The purified enzyme (30-fold purification) displayed the typical subunit pattern for an F
1
F
o
-ATP synthase but also included the presence of a stable oligomeric
c
-ring that could be dissociated by trichloroacetic acid treatment into its monomeric
c
subunits. The purified ATPase was stimulated by sodium ions, and sodium provided protection against inhibition by DCCD that was pH dependent. ATP synthesis in inverted membrane vesicles was driven by an artificially imposed chemical gradient of sodium ions in the presence of a transmembrane electrical potential that was sensitive to monensin. Cloning and sequencing of the
atp
operon revealed the presence of a sodium-binding motif in the membrane-bound
c
subunit (viz., Q
28
, E
61
, and S
62
). On the basis of these properties, the F
1
F
o
-ATP synthase of
C. paradoxum
is a sodium-translocating ATPase that is used to generate an electrochemical gradient of Na
+
that could be used to drive other membrane-bound bioenergetic processes (e.g., solute transport or flagellar rotation). In support of this proposal are the low rates of ATP synthesis catalyzed by the enzyme and the lack of the C-terminal region of the ε subunit that has been shown to be essential for coupled ATP synthesis.
Roles of the Intramolecular Disulfide Bridge in MotX and MotY, the Specific Proteins for Sodium-Driven Motors in
Vibrio
spp
Authors: Yagasaki Jin , Okabe Mayuko , Kurebayashi Rie , Yakushi Toshiharu , Homma Michio
Published: June 2006

The proteins PomA, PomB, MotX, and MotY are essential for the motor function of Na
+
-driven flagella in
Vibrio
spp. Both MotY and MotX have the two cysteine residues (one of which is in a conserved tetrapeptide [CQLV]) that are inferred to form an intramolecular disulfide bond. The cysteine mutants of MotY prevented the formation of an intramolecular disulfide bond, which is presumably important for protein stability. Disruption of the disulfide bridge in MotX by site-directed mutagenesis resulted in increased instability, which did not, however, affect the motility of the cells. These lines of evidence suggest that the intramolecular disulfide bonds are involved in the stability of both proteins, but only MotY requires the intramolecular bridge for proper function.
Limited Role for the DsrA and RprA Regulatory RNAs in
rpoS
Regulation in
Salmonella enterica
Authors: Jones Amy M. , Goodwill Adam , Elliott Thomas
Published: June 2006

RpoS, the sigma factor of enteric bacteria that responds to stress and stationary phase, is subject to complex regulation acting at multiple levels, including transcription, translation, and proteolysis. Increased translation of
rpoS
mRNA during growth at low temperature, after osmotic challenge, or with a constitutively activated Rcs phosphorelay depends on two
trans
-acting small regulatory RNAs (sRNAs) in
Escherichia coli
. The DsrA and RprA sRNAs are both highly conserved in
Salmonella enterica
, as is their target, an inhibitory antisense element within the
rpoS
untranslated leader. Analysis of
dsrA
and
rprA
deletion mutants indicates that while the increased translation of RpoS in response to osmotic challenge is conserved in
S. enterica
, dependence on these two sRNA regulators is much reduced. Furthermore, low-temperature growth or constitutive RcsC activation had only modest effects on RpoS expression, and these increases were, respectively, independent of
dsrA
or
rprA
function. This lack of conservation of sRNA function suggests surprising flexibility in RpoS regulation.
GlcNAc-6P Levels Modulate the Expression of Curli Fibers byEscherichia coli
Authors: Barnhart Michelle M. , Lynem Jaclyn , Chapman Matthew R.
Published: June 2006

Curli are extracellular surface fibers that are produced by many members of theEnterobacteriaceaeand contribute to biofilm formation. The environmental cues that promote biofilm formation are poorly understood. We found that deletion of theN-acetylglucosamine-6-phosphate (GlcNAc-6P) deacetylase gene,nagA, resulted in decreased transcription from the curli-specific promoterscsgBAandcsgDEFGand a corresponding decrease in curli production inEscherichia coli. nagAis in an operon that containsnagB,nagC,nagD, andnagE, whose products are required for utilization of GlcNAc as a carbon source. NagC is a repressor of thenagBACDandnagEgenes in the absence of intracellular GlcNAc-6P. We found thatnagCmutants were also defective in curli production. Growth of a wild-type strain on media containing additional GlcNAc reduced curli gene transcription to a level similar to the level observed whennagAwas deleted. The defect in curli production innagAornagCmutants was alleviated by deletion of the GlcNAc transporter gene,nagE. Curli-producing ΔnagAsuppressor mutants whose cells were unable to take up GlcNAc were isolated. These results suggest that elevated levels of intracellular GlcNAc-6P signal cells to down-regulate curli gene expression.
Osmotic Upshift Transiently Inhibits Uptake via ABC Transporters in Gram-Negative Bacteria
Authors: Fox M. A. , White J. P. , Hosie A. H. F. , Lodwig E. M. , Poole P. S.
Published: June 2006

ATP-binding cassette transporters from several rhizobia and
Salmonella enterica
serovar Typhimurium, but not secondarily coupled systems, were inhibited by high concentrations (100 to 500 mM) of various osmolytes, an effect reversed by the removal of the osmolyte. ABC systems were also inactivated in isolated pea bacteroids, probably due to the obligatory use of high-osmolarity isolation media. Measurement of nutrient cycling in isolated pea bacteroids is impeded by this effect.
Autoregulation of the MisR/MisS Two-Component Signal Transduction System inNeisseria meningitidis
Authors: Tzeng Yih-Ling , Zhou Xiaoliu , Bao Shaojia , Zhao Shuming , Noble Corie , Stephens David S.
Published: June 2006

Two-component regulatory systems are involved in processes important for bacterial pathogenesis. The proposedmisR/misS(orphoP/phoQ) system is one of four two-component systems of the obligate human pathogenNeisseria meningitidis. Inactivation of this system results in loss of phosphorylation of the lipooligosaccharide inner core and causes attenuation in a mouse model of meningococcal infection. MisR and the cytoplasmic domain of MisS were purified as His6and maltose binding protein fusion proteins, respectively. The MisS fusion was shown to be autophosphorylated in the presence of ATP, and the phosphoryl group was subsequently transferred to MisR. The phosphotransfer reaction was halted with a MisR/D52A mutation, while a MisS/H246A mutation prevented autophosphorylation. Specific interaction of phosphorylated MisR (MisR∼P) and MisR with themisRpromoter was demonstrated by gel mobility shift assays, where MisR∼P exhibited higher affinity than did the nonphosphorylated protein. The transcriptional start site of themisRSoperon was mapped, and DNase I protection assays revealed that MisR interacted with a 15-bp region upstream of the transcriptional start site that shared no similarity to binding motifs of other two-component systems. Transcriptional reporter studies suggested that MisR phosphorylation is critical for the autoinduction of themisRSoperon. Limited Mg2+concentration failed to induce expression of themisRSoperon, which is the only operon now proven to be under the direct control of the MisRS two-component system. Thus, these results indicate that the meningococcal MisRS system constitutes a functional signal transduction circuit and that both components are critical in the autoregulation of their expression.
Peptidoglycan Structure Analysis of
Lactococcus lactis
Reveals the Presence of an
l
,
d
-Carboxypeptidase Involved in Peptidoglycan Maturation
Authors: Courtin Pascal , Miranda Guy , Guillot Alain , Wessner Françoise , Mézange Christine , Domakova Elena , Kulakauskas Saulius , Chapot-Chartier Marie-Pierre
Published: June 2006

Detailed structural analysis of
Lactococcus lactis
peptidoglycan was achieved by identification of its constituent muropeptides separated by reverse phase high-performance liquid chromatography. Modification of the classical elution buffer allowed direct and sensitive analysis of the purified muropeptides by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The structures of 45 muropeptides were assigned for
L. lactis
strain MG1363. Analysis of the muropeptide composition of an MG1363
dacB
mutant showed that the
dacB
-encoded protein has
l
,
d
-carboxypeptidase activity and is involved in peptidoglycan maturation.