bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatotoxic effects of chloroform extract of Artemisia macivera Linn in rats following intraperitoneal administration of different subchronic doses
Authors: Atawodi SE , Ene AC , Ameh DA
Published: April 2010

The possible hepatotoxic effects of chloroform extract of Artemisia maciverae was evaluated biochemically and histologically using male Swiss albino rats, randomly assigned into four groups of 24 animals each. The groups (control, 50, 100 and 200 mg/kg body weight) were treated for 60 days and then monitored for another 30 days before sacrifice. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin (total and direct), total protein and albumin were assessed colorimetrically, while tissue specimens were subjected to histological examination following standard hematoxyline-eosin staining techniques. After 1 week of treatment, the extract caused statistically significant elevation in levels of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin (total and direct), while there was significant (p < 0.05) decrease in the levels of serum total protein and albumin at the onset of treatment when compared with the control. These abnormalities in the levels of serum biochemical parameters were spontaneously corrected within 2 weeks of treatment. Similarly, histological assessment showed severe hepatic tissue injuries after 1 week, but these organs recovered spontaneously by the second week of treatment. The results indicate that long-term exposure to therapeutic doses of chloroform extract of A maciverae is relatively safe, but high dose exposure may result in hepatocellular injury.
Association of genotoxic effects of arsenic with haematological malignancy in West Bengal
Authors: Paul Sonali , Chakraborty Tulika , Halder Ajanta , Bandopadhyay Debasis , Chaudhuri Utpal , De Madhusnata
Published: April 2010

Arsenic is a naturally occurring metalloid that has been associated with increased incidence of human cancers in certain highly exposed populations. This present work aimed to study whether arsenic plays any role in the increased incidence of blood cancer among residents of West Bengal, India, which is one of the worst arsenic-affected areas of the world. Our study group included both blood cancer patients and age-, sex-matched healthy controls. We studied the arsenic concentration in the hair and nail samples of our study group. We found significantly higher arsenic concentration in the biological tissues of patients, which also correlated with their greater incidence of chromosomal aberrations. Thus, arsenic may act as a predisposing factor for blood cancer.
Relations Between Behavior Problems in Classroom Social and Learning Situations and Peer Social Competence in Head Start and Kindergarten
Authors: Bulotsky- Shearer Rebecca J. , Domínguez Ximena , Bell Elizabeth R. , Rouse Heather L. , Fantuzzo John W.
Published: April 2010

The relations between early emotional and behavioral problems in classroom situations and peer social competence were examined for a representative sample of urban Head Start children. Behavior problems were assessed within the context of routine peer, teacher, and structured learning classroom situations early in the preschool year. Two path models were tested: (a) direct effects of preschool situational problems on peer social competence at the end of preschool and (b) direct and indirect effects of preschool situational problems on peer social competence at the end of kindergarten, accounting for preschool peer social competence and child demographic variables. Early problems in peer and socially mediated learning situations consistently predicted lower peer social competence in preschool and kindergarten. Problems in preschool peer situations directly and indirectly predicted greater disruptive play at the end of kindergarten, and problems in structured learning situations predicted lower interactive play at both time points. Implications for policy and practice are discussed.
Robust Reliability as a Measure of Stability of Controlled Dynamic Systems with Bounded Uncertain Parameters
Authors: Guo Shu-Xiang
Published: April 2010

Based on an appropriate uncertainty description, a new robust reliability method for stability issue of dynamic systems is developed to deal with bounded uncertainties. The presented methods provide necessary and sufficient conditions for quadratic stability and stabilization of uncertain systems and are suitable both for cases where the bounds of uncertain parameters are known and where they are unknown. Using this method, a robust reliability measure of the stability of parametric uncertain systems can be provided, and the maximum robustness bounds of uncertain parameters such that the system can be stable can be obtained. The design of a controller for stabilizing uncertain systems is carried out by solving a robust-reliability-based convex optimization problem. This makes it possible to take both the robustness with respect to uncertainties and the control cost into account simultaneously in the controller design. Moreover, the presented procedures are within the framework of linear matrix inequality and can be implemented conveniently. Two examples are provided to demonstrate the effectiveness and feasibility of the proposed methods. By numerical simulations and compared with existing results, it is shown that increasing conservatism in controller design by traditional methods does not mean increasing reliability, and so it is significant to take the robust reliability into account in the controller design of uncertain systems.
Experimental Implementation on Vibration Mode Control of a Moving 3-PRR Flexible Parallel Manipulator with Multiple PZT Transducers
Authors: Xuping Zhang  , Mills James K. , Cleghorn William L.
Published: April 2010

This paper presents the experimental implementation of active vibration control applied to a moving 3-PRR parallel manipulator with three flexible links. The active vibration control is implemented using three piezoelectric (PZT) transducer pairs applied to one flexible intermediate link based on modal strain rate feedback (MSRF) control. A real-time active vibration control system is developed using two PCs with LabVIEW Real-Time. Modal analyses are conducted, and the results demonstrate that the vibration modes of the intermediate links are dynamically coupled and the vibration frequency components are complicated and closely spaced. Simplified and efficient modal filters are developed to extract modal coordinates in real time, and a second order compensator is used to filter amplified noises and unmodeled high frequency dynamics. A MSRF controller is then designed using an independent mode space control strategy, and is implemented experimentally with the first mode targeted for control. Experimental results demonstrate that the vibration amplitude of the first vibration mode of the intermediate link is significantly reduced using three PZT control pairs. The experimental results using one PZT control pair and two control pairs are provided to justify the use of three PZT control pairs.
Nonlinear Active Vibration Control of Piezoelastic Laminated Plates Considering Interfacial Damage Effects
Authors: Fu Yiming  , Li Sheng  , Jiang Yejie
Published: April 2010

In this paper, the coupling of the direct and converse piezoelectric effects of the piezoelectric layers treated as sensor and actuator is considered, and a nonlinear active vibration control model for cross-ply piezoelastic laminated plates containing the damage effect of the intra-layer materials and inter-laminar interfaces is presented. The model is based on the general six-degrees-of-freedom plate theory and Von Karman-type of nonlinear strains. For the interfacial conditions, interfacial shear slip modeling between layers is introduced, which is depicted by three shape functions and interfacial damage variables. By using the Hamilton variation principle and the simple negative velocity feedback control algorithm, the active control of damping is derived to the nonlinear dynamic equations and used to actively control the vibration response of the plate. In numerical examples for simply supported laminated plates, this model is validated by comparison with existing results documented in the literature; the effects of feedback control gain and the location of piezoelectric layers on the vibration control is discussed, and different damage models on the nonlinear vibration response of piezoelectric laminated plate with interfacial imperfections are investigated.
Eigenvalue Assignment via the Lambert W Function for Control of Time-delay Systems
Authors: Yi S. , Nelson P.W. , Ulsoy A.G.
Published: April 2010

In this paper, we consider the problem of feedback controller design via eigenvalue assignment for linear time-invariant systems of linear delay differential equations (DDEs) with a single delay. Unlike ordinary differential equations (ODEs), DDEs have an infinite eigenspectrum, and it is not feasible to assign all closed-loop eigenvalues. However, we can assign a critical subset of them using a solution to linear systems of DDEs in terms of the matrix Lambert W function. The solution has an analytical form expressed in terms of the parameters of the DDE, and is similar to the state transition matrix in linear ODEs. Hence, one can extend controller design methods developed based upon the solution form of systems of ODEs to systems of DDEs, including the design of feedback controllers via eigenvalue assignment. We present such an approach here, illustrate it using some examples, and compare with other existing methods.
Computation of Asymptotic Stability for a Class of Partial Differential Equations with Delay
Authors: Breda D. , Maset S. , Vermiglio R.
Published: April 2010

In this paper the question of asymptotic stability for retarded functional reaction diffusion equations is faced. Due to the infinite dimension of the problem a numerical approach is necessary. Here we propose a technique based on a pseudospectral discretization in time and on a spectral discretization in space of the infinitesimal generator associated to the semigroup of solution operators. Some numerical experiments on a Hutchinson-type equation modeling heat conduction in a rod with spatially variable gain delayed feedback are performed to show the efficiency of the scheme. This work represents a nontrivial extension of previous work of the authors on the computation of asymptotic stability for delay differential equations.
Computer-aided Nonlinear Vehicle-bridge Interaction Analysis
Authors: Li Q. , Xu Y.L. , Wu D.J. , Chen Z.W.
Published: April 2010

The interaction between railway vehicle and bridge is dynamic and nonlinear in nature. This paper aims to develop a computer-aided numerical method for analyzing coupled railway vehicle-bridge systems of nonlinear features. The finite element method is used to establish not only a bridge model (bridge subsystem) but also flexible vehicle models (vehicle subsystem). The connections between the two subsystems are considered through wheel-rail contact models with and without wheel jumps. All the nonlinear forces and concentrated damping forces in the two subsystems and the nonlinear contact forces at their interface are treated as pseudo forces to facilitate nonlinear analysis. The mode superposition method is then applied to the two subsystems, and both non-iterative and iterative computation schemes are utilized to find the best solution. The convergence of iterative computation schemes is investigated with and without wheel jumps. The explicit integration scheme is found to possess higher convergence than other schemes. The applicability and accuracy of the proposed numerical method are finally illustrated through numerical examples and comparisons with previous work.
Developing an Adaptive Controller for a Shape Memory Alloy Walking Assistive Device
Authors: Tarkesh Esfahani Ehsan , Elahinia Mohammad H.
Published: April 2010

The Shape Memory Alloy is a lightweight, compact and biocompatible actuation mechanism which is considered here to replace the current actuation technologies in assistive locomotion devices. This paper is aimed toward the development of an adaptive robust controller to deal with control problems in the actuation of shape memory alloys (SMA). In this research the ankle joint is considered to be actuated by SMA but it can be extended to the other joints as well. To check the performance of the controller, the dynamics of the ankle joint during walking is studied and an SMA manipulator with a similar behavior is used for the experiment. Nonlinear behavior of SMA wires requires nonlinear control techniques for tracking the desired ankle angle. Since the device is subjected to several uncertainties and unmodeled parameters, it is also necessary for the implemented control technique to be robust and adaptive. To this end, the proposed control technique consists of two parts. The first part is an adaptive PID controller which is motivated from a sliding mode control. The control gains are adjusted based on an adaptation mechanism to minimize the sliding condition. The second part of the controller is a supervisory control that guarantees the stability of the system.
Intimate Partner Violence and Maternal Depression During the Perinatal Period: A Longitudinal Investigation of Latinas
Authors: Rodríguez Michael A. , Valentine Jeanette , Ahmed Sawssan R. , Eisenman David P. , Sumner Lekeisha A. , Heilemann MarySue V. , Liu Honghu
Published: April 2010

This study assessed the course of perinatal depression among 210 Latinas who were and were not affected by intimate partner violence (IPV) and identified associated psychosocial factors. Peak depression prevalence occurred prenatally among 45.7% of IPV-exposed and 24.6% of non-IPV-exposed Latinas. At each assessment, depression was significantly higher for IPV-exposed compared to non-IPV-exposed mothers. Mastery and social support were associated with lower depression, whereas history of IPV, perceived stress, and avoidant coping behaviors were associated with higher depression. Findings support recommendations for routine depression and IPV screening of Latinas in perinatal clinical settings.
Simulation Analysis of a System to Defeat Maritime Improvised Explosive Devices (MIED) in a US Port
Authors: Paulo Eugene P. , Jimenez Richard , Rowden Bobby , Causee Christopher
Published: April 2010

Although the risk of an attack in a US port could be considered a low-probability event, the importance ports and waterways play in domestic and global commerce demands timely and effective mitigation of the extremely high consequences associated with restrictions to port access should we face maritime improvised explosive devices (MIEDs) in our maritime transit system (MTS). In order to address the immediate response needed to defeat this threat, we used a systems engineering design methodology to define the problem, generated appropriate operational metrics, developed a series of system alternatives, and evaluated the alternatives through modeling and simulation analysis. These alternative systems, denoted as Adaptive Force Packages (AFPs), incorporate existing systems and technologies, emerging systems, and concepts under development that can be incorporated in the long term, while addressing the varying effects of port environments on sensors and neutralization assets.
The Effect of Pre-emptive Flare Deployment on First Generation Man-Portable Air-Defence (MANPAD) Systems
Authors: Jackman James , Richardson Mark , Yuen Peter , James David , Butters Brian , Walmsley Roy , Millwood Nic
Published: April 2010

Early generation Man-Portable Air-Defence (MANPAD) systems pose a significant threat to all types of aircraft. The need to develop successful countermeasures to this threat is ever more important with their worldwide proliferation. In this paper we discuss the use of CounterSim, a missile engagement and countermeasure simulation software tool, to gain a detailed understanding of the factors affecting an engagement outcome. The work starts by analysing simple engagements of a first generation MANPAD against a fast jet with no countermeasures being employed. From this set of base runs individual engagements are chosen to analyse in further detail. At each time interval in the simulation the aircraft and missile velocities are used to calculate a projected point of closest approach. This is then compared with the simulated impact point and the difference is defined as the projected miss distance, Δd. Features of plots of Δd are investigated to gain insights into the potential countermeasure capability. Finally, pre-emptive countermeasures are tested by firing two flares at the start of the simulation and then a timed sequence of flares.
Closure of a Two-Hole Secundum Atrial Septal Defect Through a Transthoracic Atrial Septal Defect Occlusion Device
Authors: Gan Hui-Li , Zhang Chun , Zhang Jian-qun
Published: April 2010

A simple method to close a 2-hole secundum atrial septal defect (ASD) is described. The right atrium was approached through a minithoracotomy. A double-ring purse string suture was made for the introducer shaft of the ASD occlusion device, and another purse string was made for a slim tissue scissors. A slim tissue scissors was introduced to the right atrium, and the bridge of tissue between the 2 holes was cut. The maximum diameter of the neo-ASD was measured. Thus, the ASD occlusion device of appropriate size could be selected and be placed in position.
Challenges in Delayed Repair of Atrioventricular Septal Defects
Authors: Talwar Sachin , Singh Vishal , Chandra Neeti , Marwah Ashutosh , Sharma Rajesh
Published: April 2010

Delayed diagnosis and surgery for atrioventricular septal defects are not uncommon in the developing world. This review details the challenges faced in managing this difficult subset of patients.
Variation in Models of Care Delivery for Children Undergoing Congenital Heart Surgery in the United States
Authors: Burstein Danielle S. , Rossi Anthony F. , Jacobs Jeffrey P. , Checchia Paul A. , Wernovsky Gil , Li Jennifer S. , Pasquali Sara K.
Published: April 2010

Limited data are available regarding contemporary models of care delivery for patients undergoing congenital heart surgery. The purpose of this survey was to evaluate current US practice patterns in this patient population. Cross-sectional evaluation of US centers caring for patients undergoing congenital heart surgery was performed using an Internet-based survey. Data regarding postoperative care were collected and described overall and were compared in centers with a pediatric intensive care unit (PICU) versus dedicated pediatric cardiac intensive care unit (CICU). A total of 94 (77%) of the estimated 122 US centers performing congenital heart surgery participated in the survey. The majority (79%) of centers were affiliated with a university. Approximately half were located in a free-standing children’s hospital and half in a children’s hospital in a hospital. Fifty-five percent provided care in a PICU versus a CICU. A combination of cardiologists and/or critical care physicians made up the largest proportion of physicians primarily responsible for postoperative care. Trainee involvement most often included critical care fellows (53%), pediatric residents (53%), and cardiology fellows (47%). Many centers (76%) also used physician extenders. In centers with a CICU, there was greater involvement of cardiologists and physicians with dual training (cardiology and critical care), fellows versus residents, and physician extenders. Results of this survey demonstrate variation in current models of care delivery used in patients undergoing congenital heart surgery in the United States. Further study is necessary to evaluate the implications of this variability on quality of care and patient outcomes.
Neoaortic Valve Function 10 to 18 Years After Arterial Switch Operation
Authors: Michalak Krzysztof W. , Moll Jadwiga A. , Moll Maciej , Młudzik Katarzyna , Moll Jacek J.
Published: April 2010

Anatomical correction is a procedure of choice for transposition of the great arteries (TGA) in neonates. During surgery, the aorta and pulmonary artery are switched—the native pulmonary valve becomes the neoaortic valve. The fate of this valve remains uncertain. Many reports suggest that its ability to function worsens with time after surgery. Of 519 patients with TGA operated on between 1991 and 2008, 161 met inclusion criteria for this retrospective study and were followed 10 years or more to assess neoaortic valve regurgitation (NeoAR) occurrence and development and to estimate potential risk factors. The subjects were divided into 2 groups: group 1 (simple TGA) and group 2 (TGA + ventricle septal defect). Within the analyzed group, the frequency of significant regurgitation increased from 9% 1 year after the operation to 47% at the most recent follow-up. No severe regurgitation necessitating reoperation was observed. Analysis of potential risk factors revealed that pulmonary/aortic valve diameter discrepancy and nonfacing commissures were associated with increased risk of development of neoaortic insufficiency. NeoAR arises and develops over time after correction of the defect. No hemodynamic repercussions necessitating cardiac surgical interventions were observed. The majority of insufficiencies are detected between 2 and 6 years after surgery. The degree of incompetence is usually mild and increases during follow-up by about 0.5 or 1 degree. The risk factors for NeoAR appearance are pulmonary artery/aortic annulus discrepancy and nonfacing commissures.
Reoperations After Repair of Partial and Complete Atrioventricular Septal Defect
Authors: Stulak John M. , Burkhart Harold M. , Dearani Joseph A.
Published: April 2010

The most common cause of reoperation following repair of atrioventricular septal defect (AVSD) is left atrioventricular valve regurgitation. However, reoperation for subaortic obstruction is required in some, especially after initial repair of partial AVSD. Etiology of reoperation and late outcome were evaluated. Between 1962 and 2007, 146 patients (59 male) underwent reoperation at the authors' institution after prior repair of partial (n = 96) and complete (n = 50) AVSD. Median age at reoperation after repair of partial AVSD was 26 years (range, 10 months to 71 years) and 4.5 years (range, 53 days to 38 years) after repair of complete AVSD. The 3 most common indications for reoperation included left atrioventricular (AV) valve regurgitation in 105 patients, subaortic stenosis in 29, and right AV valve regurgitation in 21. The most common procedures performed included left AV valve repair in 59 (40%) patients, left AV valve replacement in 56 (38%), subaortic fibrous resection/myectomy in 24 (16%), and right AV valve surgery in 19 (13%). Freedom from subsequent reoperation at 10 years was 48% after initial repair of complete AVSD and 84% after initial repair of partial AVSD. During late follow-up, 10-year actuarial survival was 91% and 77% after initial repair of complete and partial AVSD, respectively. The most common indication for reoperation after initial repair of partial or complete AVSD is left AV valve pathology; left ventricular outflow tract obstruction was more common in partial AVSD. Although freedom from subsequent reoperations is higher after initial repair of partial AVSD, these patients have reduced long-term survival when compared with complete AVSD.
Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia
Authors: Maffei Rossana , Martinelli Silvia , Santachiara Rita , Rossi Davide , Guarnotta Carla , Sozzi Elisa , Zucchetto Antonella , Rigolin Gian Matteo , Fiorcari Stefania , Castelli Ilaria , Fontana Marcella , Coluccio Valeria , Leonardi Giovanna , Zucchini Patrizia , Tripodo Claudio , Cuneo Antonio , Gattei Valter , Del Poeta Giovanni , Forconi Francesco , Gaidano Gianluca , Torelli Giuseppe , Marasca Roberto
Published: April 2010

The clinical relevance of angiopoietin-2 (Ang2) in chronic lymphocytic leukemia (CLL) was previously suggested by the association between high Ang2, and shorter progression-free survival reported in small series of patients. Here, we evaluated Ang2 glycoprotein levels in plasma samples collected from a multicentric cohort of CLL patients (n = 316) using an enzyme-linked immunosorbent assay method, and we investigated its prognostic role in relation to time to first treatment (TTFT) and overall survival. Based on a cutoff equal to 2459 pg/mL, we divided our cohort in 2 subsets (high and low Ang2) composing 100 (31.6%) and 216 (68.4%) patients, respectively. High Ang2 was predictive of reduced TTFT (P < .001) and overall survival (P = .002). Multivariate analysis confirmed that high Ang2 was an independent prognosticator for TTFT (hazard ratio = 1.739; 95% confidence interval, 1.059-2.857; P = .029). Significant associations were found between high Ang2 and advanced Binet stages (P < .001), high β2-microglobulin (P < .001), unmutated variable region of immunoglobulin heavy chain gene status (P < .001), high CD38 and ζ-chain-associated protein kinase 70 expression (P < .001 and P = .003), and intermediate/high cytogenetic risk (P = .005). Moreover, Ang2 added prognostic power to other conventional prognosticators and helped to refine prognosis among CLL subsets with both high and low vascular endothelial growth factor plasma levels. Ang2 plasma level may be a useful independent prognosticator for CLL.
Adenosine A2A receptor agonists and PDE inhibitors: a synergistic multitarget mechanism discovered through systematic combination screening in B-cell malignancies
Authors: Rickles Richard J. , Pierce Laura T. , Giordano Thomas P. , Tam Winnie F. , McMillin Douglas W. , Delmore Jake , Laubach Jacob P. , Borisy Alexis A. , Richardson Paul G. , Lee Margaret S.
Published: April 2010

Using a combination high-throughput screening technology, multiple classes of drugs and targeted agents were identified that synergize with dexamethasone (Dex) in multiple myeloma (MM) cells. Performing combination screening with these enhancers, we discovered an unexpected synergistic interaction between adenosine receptor agonists and phosphodiesterase (PDE) inhibitors that displays substantial activity in a panel of MM and diffuse large B-cell lymphoma (DLBCL) cell lines and tumor cells from MM patients. We have used selective adenosine receptor agonists, antagonists, and PDE inhibitors as well as small interfering RNAs targeting specific molecular isoforms of these proteins to dissect the molecular mechanism of this synergy. The adenosine A2A receptor and PDE2, 3, 4, and 7 are important for activity. Drug combinations induce cyclic AMP (cAMP) accumulation and up-regulate PDE4B. We also observe rigorous mathematical synergy in 3-way combinations containing A2A agonists, PDE inhibitors, and Dex at multiple concentrations and ratios. Taken together, these data suggest that A2A agonist/PDE inhibitor combinations may be attractive as an adjunctive to clinical glucocorticoid containing regiments for patients with MM or DLBCL and confer benefit in both glucocorticoid-sensitive and -resistant populations.
Bacteria in cancer therapy: a novel experimental strategy
Authors: Patyar S , Joshi R , Byrav DS Prasad , Prakash A , Medhi B , Das BK
Published: April 2010

Resistance to conventional anticancer therapies in patients with advanced solid tumors has prompted the need of alternative cancer therapies. Moreover, the success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity to normal tissues. Several decades after Coley's work a variety of natural and genetically modified non-pathogenic bacterial species are being explored as potential antitumor agents, either to provide direct tumoricidal effects or to deliver tumoricidal molecules. Live, attenuated or genetically modified non-pathogenic bacterial species are capable of multiplying selectively in tumors and inhibiting their growth. Due to their selectivity for tumor tissues, these bacteria and their spores also serve as ideal vectors for delivering therapeutic proteins to tumors. Bacterial toxins too have emerged as promising cancer treatment strategy. The most potential and promising strategy is bacteria based gene-directed enzyme prodrug therapy. Although it has shown successful resultsin vivoyet further investigation about the targeting mechanisms of the bacteria are required to make it a complete therapeutic approach in cancer treatment.
Multi-task learning for cross-platform siRNA efficacy prediction: an in-silico study
Authors: Liu Qi , Xu Qian , Zheng Vincent W , Xue Hong , Cao Zhiwei , Yang Qiang
Published: April 2010

Background

Gene silencing using exogenous small interfering RNAs (siRNAs) is now a widespread molecular tool for gene functional study and new-drug target identification. The key mechanism in this technique is to design efficient siRNAs that incorporated into the RNA-induced silencing complexes (RISC) to bind and interact with the mRNA targets to repress their translations to proteins. Although considerable progress has been made in the computational analysis of siRNA binding efficacy, few joint analysis of different RNAi experiments conducted under different experimental scenarios has been done in research so far, while the joint analysis is an important issue in cross-platform siRNA efficacy prediction. A collective analysis of RNAi mechanisms for different datasets and experimental conditions can often provide new clues on the design of potent siRNAs.

Results

An elegant multi-task learning paradigm for cross-platform siRNA efficacy prediction is proposed. Experimental studies were performed on a large dataset of siRNA sequences which encompass several RNAi experiments recently conducted by different research groups. By using our multi-task learning method, the synergy among different experiments is exploited and an efficient multi-task predictor for siRNA efficacy prediction is obtained. The 19 most popular biological features for siRNA according to their jointly importance in multi-task learning were ranked. Furthermore, the hypothesis is validated out that the siRNA binding efficacy on different messenger RNAs(mRNAs) have different conditional distribution, thus the multi-task learning can be conducted by viewing tasks at an "mRNA"-level rather than at the "experiment"-level. Such distribution diversity derived from siRNAs bound to different mRNAs help indicate that the properties of target mRNA have important implications on the siRNA binding efficacy.

Conclusions

The knowledge gained from our study provides useful insights on how to analyze various cross-platform RNAi data for uncovering of their complex mechanism.
Allopolyploid speciation and ongoing backcrossing between diploid progenitor and tetraploid progeny lineages in the Achillea millefoliumspecies complex: analyses of single-copy nuclear genes and genomic AFLP
Authors: Ma Jin-Xiu , Li Yan-Nan , Vogl Claus , Ehrendorfer Friedrich , Guo Yan-Ping
Published: April 2010

Background

In the flowering plants, many polyploid species complexes display evolutionary radiation. This could be facilitated by gene flow between otherwise separate evolutionary lineages in contact zones.Achillea collinais a widespread tetraploid species within theAchillea millefoliumpolyploid complex (Asteraceae-Anthemideae). It is morphologically intermediate between the relic diploids,A. setacea-2x in xeric andA. asplenifolia-2x in humid habitats, and often grows in close contact with either of them. By analyzing DNA sequences of two single-copy nuclear genes and the genomic AFLP data, we assess the allopolyploid origin ofA. collina-4x from ancestors corresponding toA. setacea-2x andA. asplenifolia-2x, and the ongoing backcross introgression between these diploid progenitor and tetraploid progeny lineages.

Results

In both the ncpGSand thePgiCgene tree, haplotype sequences of the diploidA. setacea-2x andA. asplenifolia-2x group into two clades corresponding to the two species, though lineage sorting seems incomplete for thePgiCgene. In contrast,A. collina-4x and its suspected backcross plants show homeologous gene copies: sequences from the same tetraploid individual plant are placed in both diploid clades. Semi-congruent splits of an AFLP Neighbor Net link not onlyA. collina-4x to both diploid species, but some 4x individuals in a polymorphic population with mixed ploidy levels toA. setacea-2x on one hand and toA. collina-4x on the other, indicating allopolyploid speciation as well as hybridization across ploidal levels.

Conclusions

The findings of this study clearly demonstrate the hybrid origin ofAchillea collina-4x, the ongoing backcrossing between the diploid progenitor and their tetraploid progeny lineages. Such repeated hybridizations are likely the cause of the great genetic and phenotypic variation and ecological differentiation of the polyploid taxa inAchillea millefoliumagg.
Dissecting grain yield pathways and their interactions with grain dry matter content by a two-step correlation approach with maize seedling transcriptome
Authors: Fu Junjie , Thiemann Alexander , Schrag Tobias A , Melchinger Albrecht E , Scholten Stefan , Frisch Matthias
Published: April 2010

Background

The importance of maize for human and animal nutrition, but also as a source for bio-energy is rapidly increasing. Maize yield is a quantitative trait controlled by many genes with small effects, spread throughout the genome. The precise location of the genes and the identity of the gene networks underlying maize grain yield is unknown. The objective of our study was to contribute to the knowledge of these genes and gene networks by transcription profiling with microarrays.

Results

We assessed the grain yield and grain dry matter content (an indicator for early maturity) of 98 maize hybrids in multi-environment field trials. The gene expression in seedlings of the parental inbred lines, which have four different genetic backgrounds, was assessed with genome-scale oligonucleotide arrays. We identified genes associated with grain yield and grain dry matter content using a newly developed two-step correlation approach and found overlapping gene networks for both traits. The underlying metabolic pathways and biological processes were elucidated. Genes involved in sucrose degradation and glycolysis, as well as genes involved in cell expansion and endocycle were found to be associated with grain yield.

Conclusions

Our results indicate that the capability of providing energy and substrates, as well as expanding the cell at the seedling stage, highly influences the grain yield of hybrids. Knowledge of these genes underlying grain yield in maize can contribute to the development of new high yielding varieties.
Outbreak of leptospirosis among triathlon participants in Germany, 2006
Authors: Brockmann Stefan , Piechotowski Isolde , Bock-Hensley Oswinde , Winter Christian , Oehme Rainer , Zimmermann Stefan , Hartelt Katrin , Luge Enno , Nöckler Karsten , Schneider Thomas , Stark Klaus , Jansen Andreas
Published: April 2010

Background

In August 2006, a case of leptospirosis occurred in an athlete after a triathlon held around Heidelberg and in the Neckar river. In order to study a possible outbreak and to determine risk factors for infection an epidemiological investigation was performed.

Methods

Participants of the triathlon were contacted by e-mail and were asked to fill out a standardized questionnaire. In addition, they were asked to supply a serum sample for laboratory diagnosis of leptospirosis. A confirmed case patient was defined as a clinical case (i.e. fever and at least one additional symptom suggestive for leptospirosis) with at least two of the following tests positive: ELISA IgM, latex agglutination testing, or microscopic agglutination testing. Rainfall and temperature records were obtained.

Results

A total of 142 of 507 triathletes were contacted; among these, five confirmed leptospirosis cases were found. Open wounds were identified as the only significant risk factor for illness (p = 0.02). Heavy rains that preceded the swimming event likely increased leptospiral contamination of the Neckar River.

Discussion

This is the first outbreak of leptospirosis related to a competitive sports event in Germany. Among people with contact to freshwater, the risk of contracting leptospirosis should be considered by health care providers also in temperate countries, particularly in the summer after heavy rains.
Genetic modifiers of Hb E/β0 thalassemia identified by a two-stage genome-wide association study
Authors: Sherva Richard , Sripichai Orapan , Abel Kenneth , Ma Qianli , Whitacre Johanna , Angkachatchai Vach , Makarasara Wattanan , Winichagoon Pranee , Svasti Saovaros , Fucharoen Suthat , Braun Andreas , Farrer Lindsay A
Published: April 2010

Background

Patients with Hb E/β0 thalassemia display remarkable variability in disease severity. To identify genetic modifiers influencing disease severity, we conducted a two-stage genome scan in groups of 207 mild and 305 severe unrelated patients from Thailand with Hb E/β0 thalassemia and normal α-globin genes.

Methods

First, we estimated and compared the allele frequencies of approximately 110,000 gene-based single nucleotide polymorphisms (SNPs) in pooled DNAs from different severity groups. The 756 SNPs that showed reproducible allelic differences at P < 0.02 by pooling were selected for individual genotyping.

Results

After adjustment for age, gender and geographic region, logistic regression models showed 50 SNPs significantly associated with disease severity (P < 0.05) after Bonferroni adjustment for multiple testing. Forty-one SNPs in a large LD block within the β-globin gene cluster had major alleles associated with severe disease. The most significant was bthal_bg200 (odds ratio (OR) = 5.56, P = 2.6 × 10-13). Seven SNPs in two distinct LD blocks within a region centromeric to the β-globin gene cluster that contains many olfactory receptor genes were also associated with disease severity; rs3886223 had the strongest association (OR = 3.03, P = 3.7 × 10-11). Several previously unreported SNPs were also significantly associated with disease severity.

Conclusions

These results suggest that there may be an additional regulatory region centromeric to the β-globin gene cluster that affects disease severity by modulating fetal hemoglobin expression.
Generation of anti-TLR2 intrabody mediating inhibition of macrophage surface TLR2 expression and TLR2-driven cell activation
Authors: Kirschning Carsten J , Dreher Stefan , Maaß Björn , Fichte Sylvia , Schade Jutta , Köster Mario , Noack Andreas , Lindenmaier Werner , Wagner Hermann , Böldicke Thomas
Published: April 2010

Background

Toll-like receptor (TLR) 2 is a component of the innate immune system and senses specific pathogen associated molecular patterns (PAMPs) of both microbial and viral origin. Cell activation via TLR2 and other pattern recognition receptors (PRRs) contributes to sepsis pathology and chronic inflammation both relying on overamplification of an immune response. Intracellular antibodies expressed and retained inside the endoplasmatic reticulum (ER-intrabodies) are applied to block translocation of secreted and cell surface molecules from the ER to the cell surface resulting in functional inhibition of the target protein. Here we describe generation and application of a functional anti-TLR2 ER intrabody (αT2ib) which was generated from an antagonistic monoclonal antibody (mAb) towards human and murine TLR2 (T2.5) to inhibit the function of TLR2. αT2ib is a scFv fragment comprising the variable domain of the heavy chain and the variable domain of the light chain of mAb T2.5 linked together by a synthetic (Gly4Ser)3amino acid sequence.

Results

Coexpression of αT2ib and mouse TLR2 in HEK293 cells led to efficient retention and accumulation of TLR2 inside the ER compartment. Co-immunoprecipitation of human TLR2 with αT2ib indicated interaction of αT2ib with its cognate antigen within cells. αT2ib inhibited NF-κB driven reporter gene activation via TLR2 but not through TLR3, TLR4, or TLR9 if coexpressed in HEK293 cells. Co-transfection of human TLR2 with increasing amounts of the expression plasmid encoding αT2ib into HEK293 cells demonstrated high efficiency of the TLR2-αT2ib interaction. The αT2ib open reading frame was integrated into an adenoviral cosmid vector for production of recombinant adenovirus (AdV)-αT2ib. Transduction with AdVαT2ib specifically inhibited TLR2 surface expression of murine RAW264.7 and primary macrophages derived from bone marrow (BMM). Furthermore, TLR2 activation dependent TNFα mRNA accumulation, as well as TNFα translation and release by macrophages were largely abrogated upon transduction of αT2ib. αT2ib was expressed in BMM and splenocytes over 6 days upon systemic infection with AdVαT2ib. Systemic transduction applying AdVαT2ib rendered immune cells largely non-responsive to tripalmitoyl-peptide challenge. Our results show persistent paralysis of TLR2 activity and thus inhibition of immune activation.

Conclusion

The generated anti-TLR2 scFv intrabody inhibits specifically and very efficiently TLR2 ligand-driven cell activationin vitroandex vivo. This indicates a therapeutic potential of αT2ib in microbial or viral infections.
Factors that affect mass transport from drug eluting stents into the artery wall
Authors: O'Connell Barry M , McGloughlin Tim M , Walsh Michael T
Published: April 2010

Coronary artery disease can be treated by implanting a stent into the blocked region of an artery, thus enabling blood perfusion to distal vessels. Minimally invasive procedures of this nature often result in damage to the arterial tissue culminating in the re-blocking of the vessel. In an effort to alleviate this phenomenon, known as restenosis, drug eluting stents were developed. They are similar in composition to a bare metal stent but encompass a coating with therapeutic agents designed to reduce the overly aggressive healing response that contributes to restenosis. There are many variables that can influence the effectiveness of these therapeutic drugs being transported from the stent coating to and within the artery wall, many of which have been analysed and documented by researchers. However, the physical deformation of the artery substructure due to stent expansion, and its influence on a drugs ability to diffuse evenly within the artery wall have been lacking in published work to date. The paper highlights previous approaches adopted by researchers and proposes the addition of porous artery wall deformation to increase model accuracy.
Labelling of live cells using fluorescent aptamers: binding reversal with DNA nucleases
Authors: Terazono Hideyuki , Anzai Yu , Soloviev Mikhail , Yasuda Kenji
Published: April 2010

A reversible cell labelling method has been developed for non-destructive and non-invasive cell labelling and purification. Our method uses high affinity single strand DNA (ssDNA) aptamers against surface exposed target molecules on cells. The aptamers are subsequently removed from the cell surface using DNase nuclease treatment. We exemplified our method by labelling human acute lymphoblastic leukemia cells with Qdot-ssDNA aptamers, and restoring them to the label-free condition by treatment with Benzonase. Binding of the fluorescent-aptamers to the cells was evaluated by measuring fluorescence intensity and was further confirmed using flow cytometry. Removal of the aptamers can be achieved in ~10 min by the DNase nuclease digestion. Incubation of cells with aptamers or with the nucleases results in no apparent damage to the cells and does not affect their growth rates. The latter were equivalent to the rates measured for the untreated cells. Our method provides an alternative to traditional antibody-based techniques and could be especially suitable for non-invasive reversible cell labelling and cell separations where maintaining native cell activity is needed.
Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury
Authors: Wang Ying , Li Yansong , Dalle Lucca Shawn L , Simovic Milomir , Tsokos George C , Dalle Lucca Jurandir J
Published: April 2010

Background

Activated complement system is known to mediate neuroinflammation and neurodegeneration following exposure to hypoxic-ischemic insults. Therefore, inhibition of the complement activation cascade may represent a potential therapeutic strategy for the management of ischemic brain injury. Decay-accelerating factor (DAF, also known as CD55) inhibits complement activation by suppressing the function of C3/C5 convertases, thereby limiting local generation or deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured neuronal cells subjected to sodium cyanide (NaCN)-induced hypoxia from degeneration and apoptosis.

Methods

Cultured primary cortical neurons from embryonic Sprague-Dawley rats were assigned one of four groups: control, DAF treatment alone, hypoxic, or hypoxic treated with DAF. Hypoxic cultures were exposed to NaCN for 1 hour, rinsed, followed by 24 hour exposure to 200 ng/ml of recombinant human DAF in normal medium. Human DAF was used in the present study and it has been shown to effectively regulate complement activation in rats. Neuronal cell function, morphology and viability were investigated by measuring plateau depolarization potential, counting the number dendritic spines, and observing TUNEL and MTT assays. Complement C3, C3a, C3a receptor (R) production, C3a-C3aR interaction and MAC formation were assessed along with the generation of activated caspase-9, activated caspase-3, and activated Src.

Results

When compared to controls, hypoxic cells had fewer dendritic spines, reduced plateau depolarization accompanied by increased apoptotic activity and accumulation of MAC, as well as up-regulation of C3, C3a and C3aR, enhancement of C3a-C3aR engagement, and elevated caspase and Src activity. Treatment of hypoxic cells with 200 ng/ml of recombinant human DAF resulted in attenuation of neuronal apoptosis and exerted significant protection against neuronal dendritic spine loss and plateau depolarization reduction. Furthermore, treatment with DAF resulted in decreased accumulation of C3a, MAC, C3a-C3aR interaction, caspase-9, activated caspase-3, and pTyr416-Src (activated Src) tyrosine kinase.

Conclusion

DAF was found to reduce neuronal cell death and apoptosis in NaCN induced hypoxia. This effect is attributed to the ability of DAF to limit complement activation and inhibit the activity of Src and caspases 9 and 3. This study supports the inhibiting of complement as a neuroprotective strategy against CNS ischemia/reperfusion injury.
CNAReporter: a GenePattern pipeline for the generation of clinical reports of genomic alterations
Authors: Kotliarov Yuri , Bozdag Serdar , Cheng Hangjiong , Wuchty Stefan , Zenklusen Jean-Claude , Fine Howard A
Published: April 2010

Background

Genomic copy number alterations are widely associated with a broad range of human tumors and offer the potential to be used as a diagnostic tool. Especially in the emerging era of personalized medicine medical informatics tools that allow the fast visualization and analysis of genomic alterations of a patient's genomic profile for diagnostic and potential treatment purposes increasingly gain importance.

Results

We developed CNAReporter, a software tool that allows users to visualize SNP-specific data obtained from Affymetrix arrays and generate PDF-reports as output. We combined standard algorithms for the analysis of chromosomal alterations, utilizing the widely applied GenePattern framework. As an example, we show genome analyses of two patients with distinctly different CNA profiles using the tool.

Conclusions

Glioma subtypes, characterized by different genomic alterations, are often treated differently but can be difficult to differentiate pathologically. CNAReporter offers a user-friendly way to visualize and analyse genomic changes of any given tumor genomic profile, thereby leading to an accurate diagnosis and patient-specific treatment.