bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular localization of minicircle DNA in the dinoflagellate Amphidinium massartii
Authors: Owari Satomi , Hayashi Aiko , Ishida Ken‐ichiro
Published: November 2013

Peridinin‐containing dinoflagellates have small circular DNA molecules called minicircle DNAs, each of which encodes one, or occasionally a few, plastid proteins or ribosomal RNA. Dinoflagellate minicircle DNA is composed of two parts: a gene‐coding sequence and a non‐coding sequence that consists of several variable and core regions. The core regions are identical among the minicircle DNAs with different genes within a species or strain. Because such structure is very different from those of well known plastid DNAs, many functional and evolutionary questions have been raised for the minicircle DNAs, and several studies that focus on answering those questions are underway. However, the localization of minicircle DNA is still controversial: several lines of indirect evidence have implied plastid localization, whereas the nuclear localization of minicircle DNA has also been suggested in a species. In order to understand the evolution and function of minicircle DNA, it is important to know its precise localization. In this study, we sequenced two typical minicircle DNAs, one encodes psbA and the other encodes 23S rRNA genes, from an Amphidinium massartii strain (TM16). To determine the subcellular localization of these minicircle DNAs, we performed DNA‐targeted whole cell fluorescence in situ hybridization with A. massartii minicircle DNA‐specific probes and demonstrated that minicircle DNAs were present in plastids. This study provides the first direct evidence for the plastid localization of dinoflagellate minicircle DNAs.
Effects of Connectivity and Regional Dynamics on Restoration of Small Mammal Communities in Midwestern Grasslands
Authors: Mulligan Matthew P. , Schooley Robert L. , Ward Michael P.
Published: November 2013

Grasslands are among the most imperiled North American ecosystems. State Acres for Wildlife Enhancement (SAFE) is a national conservation program that converts agricultural fields into grasslands mainly to improve habitat for high priority wildlife species. To provide a broader assessment of the contribution of the SAFE program to biodiversity in the Midwest region of North America, we evaluated local and landscape constraints to restoration of small mammal communities. We livetrapped small mammals during three summers (2009–2011) on plots that were recently seeded, seeded 1–4 years prior to sampling, or established references (>10 years old). Restoration trajectories for small mammal communities included a shift over time from dominance by the habitat generalist Peromyscus maniculatus (deer mouse) to communities dominated by grassland Microtus species (prairie voles and meadow voles). Vole abundance during the first year following restoration depended on spatial connectivity provided by linear habitats (roadside ditches and grass waterways) within 300 m of the restored grassland. Patch size and seeding type (cool‐season versus warm‐season grasses) were not predictors of early restoration success. In 2011, voles experienced a severe regional decline consistent with multi‐year population cycles. During the crash, most remaining voles occurred on restored SAFE grasslands, but not on established grasslands. This surprising outcome suggests young restoration plots could function as refuges for voles during population declines in agricultural landscapes.
Efficacy of procaterol combined with inhaled budesonide for treatment of cough‐variant asthma
Authors: Bao Wuping , Chen Qin , Lin Yanping , Liu Huiguo , Zhao Guangdong , Chen Zhibin , Zhou Xin
Published: November 2013

Background and objective

Procaterol, a selective, short‐acting beta‐2 adrenoceptor agonist, is effective in treating ‘classical’ asthma, but its efficacy for cough‐variant asthma (CVA) is unknown. We evaluated the efficacy and safety of procaterol combined with budesonide for CVA.

Methods

A prospective, randomized, double‐blind, placebo‐controlled, multicenter trial in China was conducted. One hundred and fifty‐nine patients diagnosed with CVA (aged 18–75 years) were randomly divided into two groups to receive twice daily for 8 weeks, inhaled budesonide 100 μg plus either oral procaterol 25 μg or placebo. Primary and secondary efficacy variables were cough symptom severity scores and Leicester Cough Questionnaire (LCQ) life quality scores. Adverse events were also assessed.

Results

The budesonide/placebo and budesonide/procaterol groups contained 80 and 78 participants (one excluded for later diagnosis of eosinophilic bronchitis), respectively, with similar baseline characteristics. Daily cough score declined during treatment in both groups and was lower in the budesonide/procaterol group at 8 (0.44 vs 0.73) and 10 (0.36 vs 0.69) weeks (P < 0.05). Compared with the budesonide/placebo group, the proportion of patients with a reduction of 3 points or greater (66% vs 42%) and that of patients scoring 0 points (63% vs 51%) was higher in the budesonide/procaterol group for daily cough scores (P < 0.05). At 8 weeks, LCQ score improvement was superior in the budesonide/procaterol group (38.94 ± 19.24 vs 32.71 ± 18.92; P < 0.05).

Conclusion

Procaterol combined with budesonide was well tolerated and effective at improving cough symptoms and quality of life in patients with CVA.
Risk factors and intervention for chronic obstructive pulmonary disease in China
Authors: Zhou Yumin , Chen Rongchang
Published: November 2013

In China, chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases with a prevalence of 8.2% in the population over 40 years of age. In 2006, it was the third most common cause of death in China accounting for 17.6% of all deaths. Although worldwide smoking is the most common risk factor for COPD, in China, additional important risk factors include environmental tobacco smoke, biomass smoke and post‐pulmonary tuberculosis. Interventions based on mitigating these risk factors have a particularly important role in strategies aimed at preventing COPD in China. Indeed, preliminary research findings have shown that early intervention based on minimizing these risk factors might be a cost‐effective way to prevent COPD in China. Future research should focus on large scale, randomized and controlled prospective studies to address the efficacy, feasibility and health economics of minimizing these important risk factors in China.
Asthma research in China: A five‐year review
Authors: Chen Zhi‐Hua , Wang Ping‐Li , Shen Hua‐Hao
Published: November 2013

Asthma is one of the most common chronic diseases worldwide with increasing morbidity. China has the largest asthmatic population and is one of the countries with the highest asthma mortality. Fortunately, asthma research in China, both clinical and scientific, has developed markedly over the past few years. This has resulted in significant increases in our understanding of Chinese asthma prevalence, risk factors, control status, pathogenesis, and new prevention or treatment strategies. In this review, the major achievements of asthma research in China from 2008 to 2012 are summarized.
On Modelling Early Life Weight Trajectories
Authors: Pizzi Costanza , Cole Tim J. , Corvalan Camila , Silva Isabel dos Santos , Richiardi Lorenzo , De Stavola Bianca L.
Published: November 2013

There is broad recognition that early life growth trajectories can contribute to the study of the onset and development of several health outcomes. We review the random-effects specifications of two models that have been purposely developed to describe anthropometric data and a shape invariant random-effects model recently proposed in the statistical literature. They are compared in terms of their ability to extract salient and biologically meaningful features of growth in infancy and also to represent the data validly. We discuss advantages and limitations in choosing and interpreting each of the models by using longitudinal weight data taken from 0 to 4 years from three contemporary birth cohorts.
Taking an Item‐Level Approach to Measuring Change With the Force and Motion Conceptual Evaluation: An Application of Item Response Theory
Authors: Talbot Robert M.
Published: November 2013

In order to evaluate the effectiveness of curricular or instructional innovations, researchers often attempt to measure change in students' conceptual understanding of the target subject matter. The measurement of change is therefore a critical endeavor. Often, this is accomplished through pre–post testing using an assessment such as a concept inventory, and aggregate test scores are compared from pre to post‐test in order to characterize gains. These comparisons of raw or normalized scores are most often made under the assumptions of Classical Test Theory (CTT). This study argues that measuring change at the item level (rather than the person level) on the Force and Motion Conceptual Evaluation (FMCE) can provide a more detailed insight into the observed change in students' Newtonian thinking. Further, such an approach is more warranted under the assumptions of Item Response Theory (IRT). In comparing item‐level measures of change under CTT and IRT measurement models, it was found that the inferences drawn from each analysis are similar, but those derived from IRT modeling stand on a stronger foundation statistically. Second, the IRT approach leads to analyzing common item groupings which provide further information about change at the item and topic level.
Increasing Equity and Achievement in Fifth Grade Mathematics: The Contribution of Content Exposure
Authors: Ottmar Erin R. , Konold Timothy R. , Berry Robert Q. , Grissmer David W. , Cameron Claire E.
Published: November 2013

This study uses a large nationally representative data set (ECLS‐K) of 5,181 students to examine the extent to which exposure to content and instructional practice contributes to mathematics achievement in fifth grade. Using hierarchical linear modeling, results suggest that more exposure to content beyond numbers and operations (i.e., geometry, algebra, measurement, and data analysis) contribute to student mathematics achievement, but there is no main effect for increased exposure on developing numbers and operations. Two significant interactions between exposure to specific content and racial composition of the classroom emerge. Specifically, as exposure to more diverse content increases, the classroom mathematics achievement gap among students in predominately Caucasian classrooms and those composed predominately of students of color appears to narrow. Findings are discussed with regard to promoting increased opportunities to learn mathematics for students in racially diverse classrooms.
Digital Exclusion Despite Digital Accessibility: Empirical Evidence from an English City
Authors: Bunyan Sabrina , Collins Alan
Published: November 2013

This study provides a high resolution investigation into the socio‐economic determinants of digital exclusion, within a single, densely populated city, where access is less likely to be a barrier to users. It employs data drawn from a representative interview survey of 1,005 households from across the city of Portsmouth, UK. In this study digital exclusion refers to those individuals who do not use the internet either at home, work, place of study or elsewhere. Multivariate statistical analysis identifies those significant factors raising or depressing the probability of being categorised as digitally excluded including, inter alia, age, gender, income, education, disability, tenure, working status, the presence of young people in the household and city neighbourhood districts (‘super groups’).
Spatial Implications of Using Firm Level Quotas to Employ Low Productive Workers
Authors: Edzes Arjen J.E. , Rijnks Richard , van Dijk Jouke
Published: November 2013

Many Western countries struggle with the realisation of an inclusive labour market: a labour market in which everyone can participate and disabled or otherwise vulnerable, disadvantaged and low productive people can take part in the real labour market to the best of their abilities. Following countries like Germany and Austria, the latest Dutch policy proposal is to introduce mandatory quota for employers with more than 25 employees to create job openings for the disabled for 5 per cent of their workforce. A first calculation of possible job openings shows that from a national perspective a mandatory quota seems promising. However, due to differences in the regional economic structure the arrangement will not be sufficient to solve spatial inequalities in regional exclusion of disabled at the level of municipalities nor for larger regions at the NUTS 1 level like the North of the Netherlands. We conclude that more attention should be paid to the spatial variation in impact when the national government decides to decentralise the implementation of national policy measures to municipalities.
Baseline extracellular potassium level as an indicator of the rate of increase of the same on further storage in CPDA‐1 whole blood units: a potential approach to complement FIFO system for prioritisation of blood bags for release from blood‐banks
Authors: Baliarsingh S. , Jaiswal M.
Published: November 2013

Background

Potassium levels in stored blood bags increases as they age. Hyperkalemia in transfused blood has undesirable cardiac effects.

Materials and methods

Within a 19‐month period, baseline and weekly samples from 15 CPDA‐1 whole blood bags were collected till 28 days of storage and analysed for potassium, sodium, uric acid, albumin and whole blood haemoglobin.

Results

One unit increase in baseline (0 day) potassium in extracellular fluid of blood units was associated with the following increases in potassium levels on later days of storage: around two unit increase at 1 week (r2 = 0·50, P < 0·01) of storage; four units increase at 2 weeks (r2 = 0·64, P < 0·001) and 3 weeks (r2 = 0·51, P < 0·01) of storage; six units at 4 weeks (r2 = 0·53, P < 0·01) of storage. Baseline whole blood haemoglobin showed a moderate association with baseline potassium (r2 = 0·36, P < 0·05) and 2‐week potassium (r2 = 0·35, P < 0·05) values.

Conclusion

For CPDA‐1 blood bags (i) low baseline potassium blood bags might be preferred for transfusion in cases demanding a low potassium load and (ii) coordinating the ‘first‐in‐first‐out’ (FIFO) policy with ‘early release of blood‐bags with high initial potassium’ might be helpful in improving the release of suitable blood units from blood‐banks.
Regulation of human platelet aggregation by genetically modified pig endothelial cells and thrombin inhibition
Authors: Iwase Hayato , Ekser Burcin , Hara Hidetaka , Phelps Carol , Ayares David , Cooper David K.C. , Ezzelarab Mohamed B.
Published: November 2013

Background

Coagulation disorders remain barriers to successful pig‐to‐primate organ xenotransplantation. In vitro, we investigated the impact of pig genetic modifications on human platelet aggregation in response to pig aortic endothelial cells (pAEC).

Methods

In comparison to human (h)AEC and wild‐type (WT) pAEC, the expression of human complement‐ (CD46, CD55) or coagulation (thrombomodulin [TBM], endothelial protein C receptor [EPCR]) ‐regulatory proteins on pAEC from WT or α1,3‐galactosyltransferase gene‐knockout (GTKO) pigs was studied by flow cytometry. Using platelet‐aggregometry, human whole blood platelet aggregation was evaluated after co‐incubation with various AEC. Further, the inhibitory effect on aggregation of heparin, low molecular weight heparin, and hirudin was assessed.

Results

Heparin, low molecular weight heparin and hirudin almost completely prevented platelet aggregation induced by WT pAEC. The level of expression of human CD46, CD55, TBM and EPCR on pAEC was comparable to that on hAEC. Platelet aggregation induced by all genetically modified pAEC was significantly less (P < 0.05) than that by WT pAEC (which was 54%). GTKO/CD46/TBM pAEC induced the least platelet aggregation (27%)—a reduction of almost 50%—but this remained significantly greater (P < 0.01) than aggregation induced by hAEC (4%). There was significant positive correlation between reduction of aggregation and TBM or EPCR expression on pAEC (r = 0.89 and r = 0.86, respectively; P < 0.05). Platelet aggregation induced by GTKO/CD46/TBM pAEC in the presence of hirudin (1 IU/ml) was comparable to platelet aggregation induced by hAEC.

Conclusions

Genetic modification of pAEC is associated with significant reduction of human platelet aggregation in vitro. With concomitant thrombin inhibition, platelet aggregation was comparable to that stimulated by hAEC.
Maximal heart rate does not limit cardiovascular capacity in healthy humans: insight from right atrial pacing during maximal exercise
Authors: Munch G. D. W. , Svendsen J. H. , Damsgaard R. , Secher N. H. , González‐Alonso J. , Mortensen S. P.
Published: November 2013

Key points

During high intensity whole‐body exercise, systemic and contracting skeletal muscle O2delivery and uptake () are compromised, but the underlying mechanisms remain unclear.

We evaluated the effect of a ∼20 beats min−1increase in heart rate (HR) by right atrial pacing during incremental cycling and knee‐extensor exercise on cardiac output () and stroke volume (SV).

An increase in HR during both exercise modalities did not alterdue to a proportional decrease in SV.

The lower SV during atrial pacing in the cycling trial was associated with a diminished cardiac filling pressure, but similar arterial pressure.

The results demonstrate that the human heart can achieve a higher HR than observed during maximal exercise, suggesting that HRmaxand myocardial work capacity do not limit cardiac performance in trained human subjects.

Instead, restrictions in ventricular filling appear to compromise cardiac preload, SV andat exercise intensities close to.

In humans, maximal aerobic power () is associated with a plateau in cardiac output (), but the mechanisms regulating the interplay between maximal heart rate (HRmax) and stroke volume (SV) are unclear. To evaluate the effect of tachycardia and elevations in HRmaxon cardiovascular function and capacity during maximal exercise in healthy humans, 12 young male cyclists performed incremental cycling and one‐legged knee‐extensor exercise (KEE) to exhaustion with and without right atrial pacing to increase HR. During control cycling,and leg blood flow increased up to 85% of maximal workload (WLmax) and remained unchanged until exhaustion. SV initially increased, plateaued and then decreased before exhaustion (P< 0.05) despite an increase in right atrial pressure (RAP) and a tendency (P= 0.056) for a reduction in left ventricular transmural filling pressure (LVFP). Atrial pacing increased HRmaxfrom 184 ± 2 to 206 ± 3 beats min−1(P< 0.05), butremained similar to the control condition at all intensities because of a lower SV and LVFP (P< 0.05). No differences in arterial pressure, peripheral haemodynamics, catecholamines orwere observed, but pacing increased the rate pressure product and RAP (P< 0.05). Atrial pacing had a similar effect on haemodynamics during KEE, except that pacing decreased RAP. In conclusion, the human heart can be paced to a higher HR than observed during maximal exercise, suggesting that HRmaxand myocardial work capacity do not limitin healthy individuals. A limited left ventricular filling and possibly altered contractility reduce SV during atrial pacing, whereas a plateau in LVFP appears to restrictclose to.
Operational Space Inertia for Closed-Chain Robotic Systems
Authors: Jain Abhinandan
Published: November 2013

Operational space modeling and control are important techniques for robot manipulation. A key element of operational space control is the operational space inertia matrix (OSIM). The OSIM matrix represents a mapping between end-effector spatial forces and spatial accelerations and is configuration-dependent. In the case of multiple end-effectors, the OSIM also encapsulates the dynamics cross coupling between the end-effectors. The rich structure of the OSIM for tree systems has been exploited by researchers for analysis and the development of low-order computational algorithms. Extending such techniques to the OSIM for closed-chain robotic systems is the focus of this short paper. We derive explicit analytical expressions for the closed-chain OSIM that reveals its close relationship to an extended tree-system OSIM.
Introducing and Analyzing a Novel Three-Degree-of-Freedom Spatial Tensegrity Mechanism
Authors: Abadi Bahman Nouri Rahmat , Farid Mehrdad , Mahzoon Mojtaba
Published: November 2013

The objective of the present paper is to introduce and analyze a particular spatial mechanism as a modification of the Stewart robot. The three limbs of the Stewart parallel robot are replaced by springs. Three hydraulic actuators control translational motion of the mechanism. Kinematics of the mechanism is studied and its static equations are derived and for a special case where external and gravitational forces are neglected, an analytical solution is presented. Also, the principle of virtual work is employed to derive the equations of motion of the proposed mechanism. Based on the dynamical equations, the motion of the system is simulated.
Influence of the Fastening Modeling on the Vehicle-Track Interaction at Singular Rail Surface Defects
Authors: Zhao Xin , Li Zili , Dollevoet Rolf
Published: November 2013

With up to 12 spring-damper groups distributed in the actual area of a rail pad, different fastening models are developed in this paper to include the nonuniform pressure distribution within a fastening system and model the constraints at the rail bottom more realistically for the purpose of high frequency dynamics between vehicle and track. Applied to a 3D transient FE model of the vehicle-track interaction, influence of the fastening modeling on the high frequency dynamic contact forces at singular rail surface defects (SRSDs) is examined. Two defect models, one is relatively large and the other is small, are employed. Such a work is of practical significance because squats, as a kind of SRSD, have become a wide spread problem. Results show that the fastening modeling plays an important role in the high frequency dynamic contact forces at SRSDs. Supports in the middle of the rail bottom, modeled as spring-damper groups located under rail web, are found to be most important. The less the rail bottom is constrained or supported, the more isolated the sleepers and substructure are from the wheel-rail interaction, and the more kinetic energy is kept in the rail after impact at a SRSD. Rolling speed is also varied to take into account its influence. Finally, based on the results of this work, influence of the service states of the fastening system on growth of relatively small SRSDs is discussed.
Thermophoretic and Nonlinear Convection in Non-Darcy Porous Medium
Authors: Kameswaran P. K. , Sibanda P. , Partha M. K. , Murthy P. V. S. N.
Published: November 2013

In this paper, we study the effects of nonlinear convection and thermophoresis in steady boundary layer flow over a vertical impermeable wall in a non-Darcy porous medium. Both the fluid temperature and the solute concentration are assumed to be nonlinear while at the wall, both the temperature and concentration are maintained at a constant value. A similarity transformation was used to obtain a system of nonlinear ordinary differential equations, which were then solved numerically using the Matlab bvp4c solver. A comparison of the numerical results with previously published results for special cases shows a good agreement. The effects of the nonlinear temperature and concentration parameters on the velocity and heat and mass transfer are shown graphically. A representative sample of the results is presented showing the effects of thermophoresis on the fluid velocity and heat and mass transfer rates. It is found among other results, that the concentration profiles decreased with increasing values of the thermophoretic parameter.
Statistical Shape Modeling and Population Analysis of the Aortic Root of TAVI Patients
Authors: Bosmans Bart , Huysmans Toon , Wirix-Speetjens Roel , Verschueren Peter , Sijbers Jan , Bosmans Johan , Vander Sloten Jos
Published: November 2013

The new transcatheter technique to implant synthetic aortic valves offers a treatment to patients previously considered untreatable. However, the majority of patients suffer from leakage alongside the implant. Using a statistical shape model of the anatomy, a correlation was discovered between leakage and the shape of the sinuses of Valsalva.
Heat Transfer in Porous Graphite Foams
Authors: Thompson Brian E.
Published: November 2013

Measured values of heat transfer and pressure loss are presented for a variety of porous graphite foams in subsonic turbulent airflow. These foams were developed over the last decade to find combinations of high conductivity, porosity, strength, and low density suitable for application to rapid cooling of electronics and to corrosionless heat-exchangers. Measured maxima in the thermal performance that is the ratio of heat transfer to pressure loss, were correlated the pore structure obtained from scanning electron microscopy, to show a linear dependence of thermal performance on the average diameter of interpore windows representative of the cross-sectional area through which cooling air flows. For the same heat transfer, measured pressure losses were reduced by over two orders of magnitude by increasing pore and window diameters. However, the best thermal performance of porous graphite foams that were strong enough for industrial application, had measured pressure losses that were more than an order of magnitude greater than losses in conventional finned heat exchangers.
Effect of Film Formation Method and Annealing on Morphology and Crystal Structure of Poly(L-Lactic Acid) Films
Authors: Hsu Shan-Ting , Lawrence Yao Y.
Published: November 2013

The poly(L-lactic acid) (PLLA) has potential medical usage such as drug delivery since it can degrade into bioabsorbable products in physiological environments, while the degradation is affected by its crystallites. In this paper, the effects of film formation method and annealing on the crystallites formed in PLLA films are investigated. The films are made through solvent casting and spin coating, and subsequent annealing is conducted. The resulting morphology, molecular order, conformation, and intermolecular interaction are examined using optical microscopy, wide-angle X-ray diffraction, and Fourier transform infrared spectroscopy. It is observed that solvent casting produces category 1 spherulites while annealing the spin coated films leads to spherulites of category 2. The crystal structure of the two kinds of films also shows distinct features. The results enable better understanding of the crystallites in PLLA, which is essential for its medical application.
Deburring Effect of Plasma Produced by Nanosecond Laser Ablation
Authors: Zhou Yun , Gao Yibo , Wu Benxin , Tao Sha , Liu Ze
Published: November 2013

This paper presents an interesting nanosecond (ns) laser-induced plasma deburring (LPD) effect (from microchannel sidewalls) discovered by the authors, which has been rarely reported before in the literature. Fast imagining study has been performed on plasma produced by ns laser ablation of the bottom of microchannels. It has been found that the plasma can effectively remove burrs from the sidewall of the channels, while on the other hand microscopic images taken in this study did not show any obvious size or shape change of the channel sidewall after LPD. LPD using a sacrifice plate has also been studied, where the plasma for deburring is generated by laser ablation of the sacrifice plate instead of the workpiece. The observed laser-induced plasma deburring effect has several potential advantages in practical micromanufacturing applications, such as high spatial resolution, noncontact and no tool wear, and less possibility of damaging or overmachining useful microfeatures when removing burrs from them. The fundamental mechanisms for the observed laser-induced plasma deburring effect still require lots of further work to completely understand, which may include mechanical breaking of burrs due to high kinetic energies carried by plasma and the associated shock wave, and/or thermal transport from plasma to burrs that may cause their heating and phase change, or other mechanisms.
Combined Temperature and Force Control for Robotic Friction Stir Welding
Authors: Fehrenbacher Axel , Smith Christopher B. , Duffie Neil A. , Ferrier Nicola J. , Pfefferkorn Frank E. , Zinn Michael R.
Published: November 2013

Use of robotic friction stir welding (FSW) has gained in popularity as robotic systems can accommodate more complex part geometries while providing high applied tool forces required for proper weld formation. However, even the largest robotic FSW systems suffer from high compliance as compared to most custom engineered FSW machines or modified computer numerical control (CNC) mills. The increased compliance of robotic FSW systems can significantly alter the process dynamics such that control of traditional weld parameters, including plunge depth, is more difficult. To address this, closed-loop control of plunge force has been proposed and implemented on a number of systems. However, due to process parameter and condition variations commonly found in a production environment, force control can lead to oscillatory or unstable conditions and can, in extreme cases, cause the tool to plunge through the workpiece. To address the issues associated with robotic force control, the use of simultaneous tool interface temperature control has been proposed. In this paper, we describe the development and evaluation of a closed-loop control system for robotic friction stir welding that simultaneously controls plunge force and tool interface temperature by varying spindle speed and commanded vertical tool position. The controller was implemented on an industrial robotic FSW system. The system is equipped with a custom real-time wireless temperature measurement system and a force dynamometer. In support of controller development, a linear process model has been developed that captures the dynamic relations between the process inputs and outputs. Process validation identification experiments were performed and it was found that the interface temperature is affected by both spindle speed and commanded vertical tool position while axial force is affected primarily by commanded vertical tool position. The combined control system was shown to possess good command tracking and disturbance rejection characteristics. Axial force and interface temperature was successfully maintained during both thermal and geometric disturbances, and thus weld quality can be maintained for a variety of conditions in which each control strategy applied independently could fail. Finally, it was shown through the use of the control process model, that the attainable closed-loop bandwidth is primarily limited by the inherent compliance of the robotic system, as compared to most custom engineered FSW machines, where instrumentation delay is the primary limiting factor. These limitations did not prevent the implementation of the control system, but are merely observations that we were able to work around.
Automotive Application of Vortex Generators in Ground Effect
Authors: van de Wijdeven Trebsijg , Katz Joseph
Published: November 2013

Vortex generators (VG) are widely used in the aerospace industry, mainly to control boundary layer transition and to delay flow separations. A different type of VG is used on race cars for manipulating the flow over and under the vehicle, mainly to generate downforce (which is needed for better performance). Contrary to the VGs used on airplanes' wings, the VGs discussed here are much taller than the local boundary layer thickness and are not intended to control laminar to turbulent flow transition. Although, the effect of such VGs was studied in the past, not all features of the flow fields were documented. For example, the shape of the vortex wake behind a VG, the wake rollup and the resulting pressure signature is still not well understood. Consequently, this study investigates the above questions by using experimental methods. A generic model with several VGs was tested in a low speed wind tunnel and in addition to the lift and drag the surface pressure distribution and the trailing vortex signature behind the VGs were studied. In order to demonstrate the incremental effect of the vortex wake, airfoil shaped VGs were also tested, mainly to quantify the “blockage effect” between the plate and the ground plane. The effect of rake (vehicle's angle of attack), which was not documented in previous work, was also investigated here. The results of this study provide quantitative information on the expected loads and pressure distribution behind such large-scale VGs; data needed for the successful application of such devices to actual vehicles.
Immersive experimentation in a wave propagation laboratory
Authors: Vasmel Marlies , Robertsson Johan O. A. , van Manen Dirk-Jan , Curtis Andrew
Published: November 2013

A wave propagation laboratory is proposed which enables the study of the interaction of broadband signals with complex materials. A physical experiment is dynamically linked to a numerical simulation in real time through transmitting and recording transducer surfaces surrounding the target. The numerical simulation represents an arbitrarily larger domain, allowing experiments to be performed in a total environment much greater than the laboratory experiment itself. Specific applications include the study of non-linear effects or wave propagation in media where the physics of wave propagation is not well understood such as the effect of fine scale heterogeneity on broadband propagating waves.
Electret microphones with stiff diaphragms
Authors: Hillenbrand J. , Haberzettl S. , Sessler G. M.
Published: November 2013

Electret microphones with stiff plates instead of flexible diaphragms are described. The stiff plate and a backplate, separated by a soft cellular polymer spacer ring, yield a capacitance that is varied by the incoming sound wave; thus a voltage change in the plates is induced. Various such plate microphones were built and characterized. Sensitivities of more than 10 mV/Pa and equivalent noise levels of 23 dB(A) are obtained. An analytical model for the sensitivity of plate microphones was developed. Advantages of the plate microphones are high mechanical robustness, low harmonic distortion, and no risk of membrane collapse.
Opposing Feedbacks on Ras Tune Receptor Tyrosine Kinase Signaling
Authors: Perry Michael , Desplan Claude
Published: November 2013

The identification of Rau reveals how signaling activity that directs neuronal and glial fate is maintained in the
Drosophila
eye.
Chilly Repression Stalls Flowering
Authors: Hines Pamela J.
Published: November 2013

A warm spring favors early flowering by invoking less transcriptional repression by a floral repressor complex.
Protective Effects of Human Lactoferrin during Aggregatibacter actinomycetemcomitans-Induced Bacteremia in Lactoferrin-Deficient Mice
Authors: Velusamy S. K. , Poojary R. , Ardeshna R. , Alabdulmohsen Waad , Fine D. H. , Velliyagounder K.
Published: November 2013

Aggregatibacter actinomycetemcomitans
, a periodontopathogen, has been associated with several systemic diseases. Herein, we report the protective effect of human lactoferrin (hLF) during
A. actinomycetemcomitans
bacteremia in lactoferrin knockout (LFKO
−/−
) mice. The prophylactic, concurrent, and therapeutic intravenous (i.v.) administrations of hLF significantly cleared the bacteria from blood and organs. Nevertheless, all modes of hLF administration significantly decreased the concentrations of serum proinflammatory cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, and IL-12p70. Additionally, hLF administration significantly decreased hepatic and splenic proinflammatory cytokine expression levels compared to those in the non-hLF-treated group. Furthermore, administration of hLF decreased the serum C-reactive protein level, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) gene expression levels in liver and spleen. hLF treatment has also resulted in a 6-fold decrease in spleen weight with the migration of typical inflammatory cells in infected mice as a result of decreased inflammatory response. These results reveal that hLF protects against
A. actinomycetemcomitans
bacteremia, as indicated by rapid bacterial clearance and decreased host proinflammatory mediators.
Five-Year Retrospective Italian Multicenter Study of Visceral Leishmaniasis Treatment
Authors: Di Masi Francesco , Ursini Tamara , Iannece Maria Donata , Chianura Leonardo , Baldasso Francesco , Foti Giuseppe , Di Gregorio Pietro , Casabianca Angelo , Storaci Nunzio , Nigro Luciano , Colomba Claudia , Marazzi Maria Grazia , Todaro Giovanni , Tordini Giacinta , Zanelli Giacomo , Cenderello Giovanni , Acone Nicola , Polilli Ennio , Migliore Simona , Almi Paolo , Pizzigallo Eligio , Sagnelli Evangelista , Mazzotta Francesco , Russo Rosario , Manzoli Lamberto , Parruti Giustino
Published: November 2013

The treatment of visceral leishmaniasis (VL) is poorly standardized in Italy in spite of the existing evidence. All consecutive patients with VL admitted at 15 Italian centers as inpatients or outpatients between January 2004 and December 2008 were retrospectively considered; outcome data at 1 year after treatment were obtained for all but 1 patient. Demographic characteristics, underlying diseases, diagnostic procedures, treatment regimens and outcomes, as well as side effects were recorded. A confirmed diagnosis of VL was reported for 166 patients: 120 (72.3%) immunocompetent, 21 (12.6%) patients with immune deficiencies other than HIV infection, and 25 (15.1%) coinfected with HIV. Liposomal amphotericin B (L-AmB) was the drug almost universally used for treatment, administered to 153 (92.2%) patients. Thirty-seven different regimens, including L-AmB were used. The mean doses were 29.4 ± 7.9 mg/kg in immunocompetent patients, 32.9 ± 8.6 mg/kg in patients with non-HIV-related immunodeficiencies, and 40.8 ± 6.7 mg/kg in HIV-infected patients (
P
< 0.001). The mean numbers of infusion days were 7.8 ± 3.1 in immunocompetent patients, 9.6 ± 3.9 in non-HIV-immunodeficient patients, and 12.0 ± 3.4 in HIV-infected patients (
P
< 0.001). Mild and reversible adverse events were observed in 12.2% of cases. Responsive patients were 154 (93.3%). Successes were 98.4% among immunocompetent patients, 90.5% among non-HIV-immunodeficient patients, and 72.0% among HIV-infected patients. Among predictors of primary response to treatment, HIV infection and age held independent associations in the final multivariate models, whereas the doses and duration of L-AmB treatment were not significantly associated. Longer treatments and higher doses of L-AmB were not able to significantly modify treatment outcomes either in the immunocompetent or in the immunocompromised population.
Investigation of the Functional Role of P-Glycoprotein in Limiting the Oral Bioavailability of Lumefantrine
Authors: Wahajuddin  , Raju Kanumuri S. R. , Singh Sheelendra P. , Taneja Isha
Published: November 2013

In the quest to explore the reason for the low and variable bioavailability of lumefantrine, we investigated the possible role of P-glycoprotein (P-gp) in lumefantrine intestinal absorption. An
in situ
single-pass intestinal perfusion study in rats with the P-gp inhibitor verapamil or quinidine and an ATPase assay with human P-gp membranes indicated that lumefantrine is a substrate of P-gp which limits its intestinal absorption. To confirm these findings, an
in vivo
pharmacokinetic study was performed in rats. The oral administration of verapamil (10 mg/kg of body weight) along with lumefantrine caused a significant increase in its bioavailability with a concomitant decrease in clearance. The increase in bioavailability of lumefantrine could be due to inhibition of P-gp and/or cytochrome P450 3A in the intestine/liver by verapamil. However, in a rat intestinal microsomal stability study, lumefantrine was found to be resistant to oxidative metabolism. Further, an
in situ
permeation study clearly showed a significant role of P-gp in limiting the oral absorption of lumefantrine. Thus, the increase in lumefantrine bioavailability with verapamil is attributed in part to the P-gp-inhibitory ability of verapamil. In conclusion, lumefantrine is a substrate of P-gp, and active efflux by P-gp across the intestine partly contributed to the low/variable bioavailability of lumefantrine.
Application of DNA Chip Scanning Technology for Automatic Detection of Chlamydia trachomatis and Chlamydia pneumoniae Inclusions
Authors: Bogdanov Anita , Endrész Valeria , Urbán Szabolcs , Lantos Ildikó , Deák Judit , Burián Katalin , Önder Kamil , Ayaydin Ferhan , Balázs Péter , Virok Dezső P.
Published: November 2013

Chlamydiae are obligate intracellular bacteria that propagate in the inclusion, a specific niche inside the host cell. The standard method for counting chlamydiae is immunofluorescent staining and manual counting of chlamydial inclusions. High- or medium-throughput estimation of the reduction in chlamydial inclusions should be the basis of testing antichlamydial compounds and other drugs that positively or negatively influence chlamydial growth, yet low-throughput manual counting is the common approach. To overcome the time-consuming and subjective manual counting, we developed an automatic inclusion-counting system based on a commercially available DNA chip scanner. Fluorescently labeled inclusions are detected by the scanner, and the image is processed by ChlamyCount, a custom plug-in of the ImageJ software environment. ChlamyCount was able to measure the inclusion counts over a 1-log-unit dynamic range with a high correlation to the theoretical counts. ChlamyCount was capable of accurately determining the MICs of the novel antimicrobial compound PCC00213 and the already known antichlamydial antibiotics moxifloxacin and tetracycline. ChlamyCount was also able to measure the chlamydial growth-altering effect of drugs that influence host-bacterium interaction, such as gamma interferon, DEAE-dextran, and cycloheximide. ChlamyCount is an easily adaptable system for testing antichlamydial antimicrobials and other compounds that influence
Chlamydia
-host interactions.
A Reference Laboratory Experience of Clinically Achievable Voriconazole, Posaconazole, and Itraconazole Concentrations within the Bloodstream and Cerebral Spinal Fluid
Authors: Wiederhold Nathan P. , Pennick Gennethel J. , Dorsey Sheryl A. , Furmaga Wieslaw , Lewis James S. , Patterson Thomas F. , Sutton Deanna A. , Fothergill Annette W.
Published: November 2013

Interest in antifungal therapeutic-drug monitoring has increased due to studies demonstrating associations between concentrations and outcomes. We reviewed the antifungal drug concentration database at our institution to gain a better understanding of achievable triazole drug levels. Antifungal concentrations were measured by high-performance liquid chromatography (HPLC), ultraperformance liquid chromatography and single-quadrupole mass spectrometry (UPLC/MS), or a bioassay. For this study, only confirmed human bloodstream (serum or plasma) and cerebral spinal fluid (CSF) concentrations of voriconazole, posaconazole, and itraconazole were analyzed. The largest numbers of bloodstream and CSF samples were found for voriconazole (14,370 and 173, respectively). Voriconazole bloodstream concentrations within the range of 1 to 5.5 μg/ml represented 50.6% of samples. Levels below the lower limit of quantification (0.2 μg/ml) were observed in 14.6% of samples, and 10.4% of samples had levels of ≥5.5 μg/ml. CSF voriconazole levels ranged from undetectable to 15.3 μg/ml and were <0.2 μg/ml in 11% of samples. Posaconazole bloodstream concentrations were ≥0.7 and ≥1.25 μg/ml in 41.6% and 18.9% of samples, respectively. Posaconazole was detected in only 4 of 22 CSF samples (undetectable to 0.56 μg/ml). Itraconazole levels, as measured by UPLC/MS, were ≥0.5 μg/ml in 43.3% and were undetectable in 33.9% of bloodstream samples. In contrast, when measured by a bioassay, itraconazole/hydroxyitraconazole bloodstream concentrations were ≥1.0 μg/ml in 72.9% of samples and were undetectable in 18% of samples. These results indicate that there is marked variability in bloodstream concentrations achieved with these three azoles. In addition, many levels within the bloodstream for each azole and for voriconazole and posaconazole in the CSF were undetectable or below thresholds associated with efficacy.
Biological Cost of Different Mechanisms of Colistin Resistance and Their Impact on Virulence in Acinetobacter baumannii
Authors: Beceiro Alejandro , Moreno Antonio , Fernández Nathalie , Vallejo Juán A. , Aranda Jesús , Adler Ben , Harper Marina , Boyce John D. , Bou Germán
Published: November 2013

Two mechanisms of resistance to colistin have been described in
Acinetobacter baumannii
. One involves complete loss of lipopolysaccharide (LPS), resulting from mutations in
lpxA
,
lpxC
, or
lpxD
, and the second is associated with phosphoethanolamine addition to LPS, mediated through mutations in
pmrAB
. In order to assess the clinical impacts of both resistance mechanisms,
A. baumannii
ATCC 19606 and its isogenic derivatives, AL1851 Δ
lpxA
, AL1852 Δ
lpxD
, AL1842 Δ
lpxC
, and ATCC 19606
pmrB
, were analyzed for
in vitro
growth rate,
in vitro
and
in vivo
competitive growth, infection of A549 respiratory alveolar epithelial cells, virulence in the
Caenorhabditis elegans
model, and virulence in a systemic mouse infection model. The
in vitro
growth rate of the
lpx
mutants was clearly diminished; furthermore,
in vitro
and
in vivo
competitive-growth experiments revealed a reduction in fitness for both mutant types. Infection of A549 cells with ATCC 19606 or the
pmrB
mutant resulted in greater loss of viability than with
lpx
mutants. Finally, the
lpx
mutants were highly attenuated in both the
C. elegans
and mouse infection models, while the
pmrB
mutant was attenuated only in the
C. elegans
model. In summary, while colistin resistance in
A. baumannii
confers a clear selective advantage in the presence of colistin treatment, it causes a noticeable cost in terms of overall fitness and virulence, with a more striking reduction associated with LPS loss than with phosphoethanolamine addition. Therefore, we hypothesize that colistin resistance mediated by changes in
pmrAB
will be more likely to arise in clinical settings in patients treated with colistin.