bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary evaluation of therapeutic ion release from Sr-doped zinc-silicate glass ceramics
Authors: Looney Mark , O’Shea Helen , Boyd Daniel
Published: September 2011

Bioactive and degradable porous bioceramics play an important role in many clinical situations. Porosity is essential to the performance of a material that is proposed to be used as an implantable osseous scaffold. Scaffolds provide a three dimensional support and template to osseous integration and vascularization. Combining the porosity of a scaffold with the ability of the scaffold material to deliver therapeutic ions to the site of implantation goes some way towards developing an ideal bone graft. A series of strontium-doped zinc silicate (Ca-Sr-Na-Zn-Si) glass ceramics scaffoldswere developed, whose porosity was measured to be between 93% and 96%, which is advantageous in terms of osseous integration and vascularization. The levels of Zn2+ and Sr2+ detected as a result of degradation of the crystalline phases were found to be 1.4–600 parts per million (ppm) and 0–583 ppm, respectively. The levels detected correlate well with the levels of Sr2+ and Zn2+ions typically associated with clinical benefits, including antibacterial efficacy, osteoblastic differentiation and impaired osteoclastic resorption.
Toward New Avenues in the Treatment of Nonsuicidal Self-Injury
Authors: Bloom Christopher M. , Holly Shareen
Published: September 2011

The treatment of self-injury, or self-destruction of one’s own body tissue, has become a new focus for both researchers and clinicians. Traditionally, the field of self-injury has distinguished between the behaviors exhibited among individuals with a developmental disability (self-injurious behaviors [SIBs]) and those present within a normative population (nonsuicidal self-injury [NSSI]). Despite this distinction, many pharmacotherapies for self-injury have been administered for both populations. The current review begins by summarizing the available efficacy studies investigating common pharmacological interventions in the treatment of self-injury. These studies are organized based on the most empirically supported neurochemical pathways in the development or maintenance of NSSI: endogenous opiods and monoamines. Although significant advances have been made in the field, conclusions based on efficacy studies of the pharmacological interventions used in the treatment of self-injury have been somewhat inconsistent. Finally, the review includes a discussion about potential avenues in the pharmacological treatment of NSSI via animal models of self-injury. Animal models present a unique opportunity to test neurobiological theories of self-injury using a controlled, systematic approach. Clinical considerations are presented as they relate to the available research findings and best practices in the treatment of self-injury.
The Provision of Diabetes-Monitoring Exams to Older Latinos
Authors: Herrera Angelica P. , Smith Matthew Lee , Ory Marcia G. , Rodriguez Hector P. , Warre Ruth , Thompson Wesley K. , Azcue Annette , Romero Jairo A.
Published: September 2011

Objectives: To explore factors associated with the provision of diabetes-monitoring practices among older Latinos with type 2 diabetes. Method: Data from 547 Latinos (≥55 years) were analyzed from the 2007 California Health Interview Survey. Multivariate logistic regression modeled the relationship between health status and sociodemographic factors and the receipt of semiannual HbA1c tests, annual foot exams, and annual retinal exams. Results: The majority of older Latino diabetics received foot exams (87%) and retinal exams (77%), but the provision of semiannual HbA1c tests (30%) was low. Higher English-language proficiency and health insurance coverage were associated with the provision of HbA1c tests and foot exams, but not retinal exams. Insulin therapy was positively associated with semiannual HbA1c testing, but negatively associated with foot exams. Discussion: There are considerable missed opportunities in the provision of diabetes monitoring for older Latinos, particularly those with limited English proficiency, less comprehensive insurance, and noninsulin therapy.
International Service and the Perceived Impacts on Volunteers
Authors: McBride Amanda Moore , Lough Benjamin J. , Sherraden Margaret Sherrard
Published: September 2011

Although international volunteer service is growing in prevalence worldwide, there is little rigorous research about its impacts. This quasi-experimental study assesses the perceived impacts of international service on international volunteers. We focus on four internationally oriented outcome categories: international awareness, intercultural relations, international social capital, and international career intentions. International service provides exposure and immersion to develop these perspectives, relationships, and intentions. Using generalized linear mixed regression modeling, international volunteers ( n = 145) are statistically more likely to report increases between the baseline (1 month before service) and postservice time periods (1 week to 1 month after service) in all outcomes except intercultural relations, as compared to a matched comparison group ( n = 145). Age, race, occupational experience, and previous international experience are also associated with various outcomes. Implications include continued cultural growth, potential mutual impacts of international social capital, and future research on the volunteers and host communities.
Probabilistic approach to mechanism reliability with multi-influencing factors
Authors: Lai X , Duan J
Published: September 2011

The mechanism reliability includes kinematic and dynamic aspects. Both are influenced by probabilistic uncertainties of influential factors, such as dimensional errors, joint clearances, assembling errors, friction coefficients, errors of input driving velocities and external loads, etc. In order to synthetically consider the effect of such factors on the mechanism and efficiently compute its reliability at the same time, a new Monte Carlo simulation method is presented.
Tool path planning based on endpoint build-in optimization in rapid prototyping
Authors: Xiaomao H , Chunsheng Y , Yongjun H
Published: September 2011

Filling defects, which appear on the tool path ends as the existence of the control precision error of enabling components (laser, nozzle) and movement acceleration and deceleration of moving components, cause serious problems in appearance quality of parts in a number of welding-based rapid prototyping processes such as plasma welding, laser welding, and fused deposition modeling. This paper presents a novel tool path planning algorithm based on endpoint build-in optimization, moving the two path endpoints with filling defects from the part surface into the internal region. Experiments in fused deposition modeling processes show that the algorithm effectively addresses this issue, and is reliable and efficient.
Design and development of a novel redundant and fault-tolerant actuator unit for heavy-duty parallel manipulators
Authors: Zhang J , Gao F , Yu H , Zhao X
Published: September 2011

This paper proposes a novel dual-input/single-output actuator unit, called a redundant and fault-tolerant actuator (RFTA), designed for heavy-load parallel manipulators. After the definitions of redundant and fault tolerance are given, the principle of the proposed RFTA is described using its two working processes. According to the derived kinematics, 12 fault modes caused by two different input velocities are developed and classified, and the physical meanings are represented correspondingly. Mechanical transmitting properties of the proposed RFTA are analysed respectively. On the other hand, RFTA, as a dual-module hot spare architecture to achieve high reliability and safety, with its complete redundant structure can be called Multiple Births Structure (MBS) and is different form the traditional partial redundant structures – Siamesed Births Structure (SBS). The reliability models show that RFTA is more reliable than SBS. Three guidelines – the select guideline, the design guideline, and the operation guideline – are suggested. Those design guidelines are useful to designers and users. A prototype of RFTA and its control system are developed and the relevant experiments are carried out. The experimental results demonstrate that RFTA is able to not only supply double driving force but also tolerate some local faults caused by out-of-syncs. RFTA provides heavy-duty equipment, especially large-scale parallel manipulators, with a new probability in changing their drive mode, from the hydraulic power supply to the motor drive. Furthermore, this paper also demonstrates that RFTA has some potential applicable prospects under heavy-duty environments, such as a large-scale parallel earthquake simulator and an electric press with heavy duty cycles.
Development and validation of a rigid–flexible coupled dynamic valve-train model
Authors: Guo J , Zhang W P , Zou D Q
Published: September 2011

A rigid–flexible coupled dynamics model has been developed to analyse the dynamic behaviour of a pushrod valve-train system of an internal combustion engine. The elastic vibration mechanism of each flexible component is described in a floating reference frame. The mechanical impacts in a valve-train system at the opening and closing events of the valve are affected by the contact stiffness and damping of contact components. The contact force model for the cam–tappet interface was developed based on the elasto-hydrodynamic lubrication theory of finite line conjunction. The finite-difference method is used to solve the rigid–flexible coupled dynamic equations. The algorithm of finite difference and the boundary conditions have been carefully selected to solve the fourth-order Bernoulli–Euler beam equation. Experiments were conducted on a motor-driven valve-train system from a four-cylinder diesel engine. The measured valve displacement, acceleration, and contact forces showed excellent consistency with the predicted results. The rigid–flexible coupled dynamics model has shown improved accuracy compared to the lumped rigid mass system in analysing the dynamic performance of the valve-train system.
Optimization method for powertrain mounting systems with uncertain parameters
Authors: Wu J
Published: September 2011

This paper presents an interval optimization method to improve the design robustness of the decoupling layout and frequency allocation of powertrain mounting systems (PMSs). The effects of the uncertainties or variations of the powertrain inertia properties and design parameters on the optimization results are considered in the optimization process. Generally, it is difficult and costly to determine statistical information with sufficient precision for uncertain parameters, so here interval numbers are used to describe the uncertain parameters and only the bounds of them are required. Robustness indices of interval reliability and interval possibility degree are suggested for characterizing the robustness of PMS decoupling layout and frequency allocation respectively. The interval optimization problem is transformed to an equivalent deterministic one based on the robustness indices. The optimization results of a PMS show that the interval optimization method can significantly increase the robustness of the frequency allocation, especially in vertical and pitch directions. This will decrease the possibility of resonance between the powertrain and other parts, such as the wheel, car body, and frame. In contrast to the deterministic optimization method, although the decoupling ratios obtained by the proposed method decrease slightly, the interval optimization results can meet the decoupling layout requirement from the viewpoint of engineering.
Vortex shedding-free strainers
Authors: Khulief Y , Habib M A , Said S A M , Ben-Mansour R , Badr H M , Anis M , Khalifa A E
Published: September 2011

The subject of the periodic vortex shedding behind bluff bodies, which exhibits oscillatory behaviour, is of direct relevance to many practical applications, e.g. pipelines and heat exchangers. Repetitive failures were occurring in associated piping components on the suction of a sales gas compressor. Available experimental investigations indicated the occurrences of vibrations at the predominant frequencies of 1500 and 3000 Hz in the compressor strainer pipes. Hence, this study is aimed at identifying the source of such high vibration levels. The study investigated the flow-induced vibrations in the compressor strainer pipe through numerical simulation of the flow in the pipe including the strainer, as well as structural modal analysis calculations for the strainer at steady-state conditions. Three different geometrical configurations were considered. The first strainer has a truncated-cone geometry with uniform size holes. The second is witch-hat geometry with uniform holes, while the third is a modified witch-hat configuration with non-uniform holes. The results obtained from the frequency analysis of the flow field downstream of strainers with the first two geometries indicated dominant amplitudes at 1500 Hz and appreciable excitations at its second harmonic. However, the results demonstrated that the dominant vibration amplitudes have been appreciably reduced for the third case of the modified witch-hat configuration with non-uniform holes.
Parametric effects in a scramjet engine on the interaction between the air stream and the injection
Authors: Huang W , Ma L , Pourkashanian M , Ingham D B , Luo S-B , Wang Z-G
Published: September 2011

The mixing of fuel and air in supersonic flow plays a significant role in the enhancement of the performance of scramjet engines. In this article, the two-dimensional coupled implicit Reynolds-averaged Navier–Stokes equations and the standard k–ε turbulent model are introduced to investigate the interaction between the supersonic air flow and the helium stream injected into a typical scramjet engine. A range of different angles (30–150°) of both the incoming air stream and the helium injection under various pressure conditions (0.62–1.86 MPa) have been investigated to assess their impact on the mixing. It is shown among the cases studied for different helium injections that an angle of 90° produces the highest mixing efficiency. In the cases with a variable air stream angle, then the situation with a 30° air stream angle can achieve a higher mixing efficiency than other angles. In addition, with a higher pressure of the injection, the air stream and the helium mix better.
Design and testing of a propeller for a two-seater aircraft powered by fuel cells
Authors: Romeo G , Cestino E , Pacino M , Borello F , Correa G
Published: September 2011

This article deals with the design, manufacturing, and testing of a propeller for a general aviation aircraft fuelled by hydrogen. The feasibility of the ENFICA-FC project depended on several key-enabling technologies. In order to minimize the power required from both the batteries and the fuel cell, a highly efficient electrical propulsion system was required, in which all the components would need to yield the highest possible efficiency. The choice of the propeller for this specific aircraft was more difficult, above all because the electric motor was limited as to the torque it could handle. In addition, the propeller would also have to provide the necessary airflow for the motor, electronics, and fuel cell cooling to ensure that the temperature did not exceed the limits imposed by the manufacturer. Although a designer may be aided by modern numerical design and analysis programmes to optimize propellers, structural and manufacturing constraints can influence the final choices. Finally, the calculated performance would always have to be validated with experimental tests. An optimal propeller has been designed and manufactured to be installed on the Rapid 200 FC aeroplane. Static tests on the manufactured two-blade propeller were performed by means of a static test facility. Specific tests have also been performed to check the efficiency of the propeller when installation effects (blockage and scrubbing drag effects) are included and to verify the real efficiency of the propulsion and cooling systems, with the propeller installed in the complete converted aircraft. A good agreement between the theoretical and experimental data was obtained.
Reduced-order observer-based fault estimation design for multiple input–multiple output discrete-time systems
Authors: Zhang K , Staroswiecki M , Jiang B
Published: September 2011

In this paper, the fault-estimation problem for discrete-time systems is considered. A multiconstrained reduced-order fault estimation observer (RFEO) design is proposed to handle the case of abrupt and time-varying faults, and a comparison with full-order fault estimation observer is discussed in detail. Then, by introducing a slack matrix, a new multiconstrained RFEO result is obtained to reduce conservatism generated by the conventional method. Further, the present authors investigate robust RFEO design to cope with external disturbances. Simulation results of an aircraft example illustrate their contributions.
Gradient-based and least-squares-based iterative estimation algorithms for multi-input multi-output systems
Authors: Ding F , Liu Y , Bao B
Published: September 2011

System modelling is important for studying the motion laws of dynamical systems. Parameters of the system models can be estimated through identification methods from measurement data. This paper develops a gradient-based and a least-squares-based iterative estimation algorithms to estimate the parameters for a multi-input multi-output (MIMO) system with coloured auto-regressive moving average (ARMA) noise from input–output data, based on the gradient search and least-squares principles, respectively. The key is to replace the unknown noise terms and residuals contained in the information vector with their corresponding estimates at the previous iteration. The simulation test results indicate that the proposed algorithms are effective.
Sports policy development and implementation in context: Researching and understanding the perceptions of community end-users
Authors: Donaldson Alex , Leggett Susan , Finch Caroline F
Published: September 2011

Ensuring community clubs implement centrally developed sports policy is a challenge for most sports. One hundred and eighty four (70% male, 68% aged 40 to 59 years) community Australian football club representatives (first-aid providers, administrators, parents, coaches, etc.) from across the country provided their perceptions of an Australian Football League-developed sports trainer policy and associated workforce training structure (jointly referred to hereafter as ‘the policy’) via an online survey. This article presents a qualitative analysis of the open-ended questions within the survey using the analytical lens of symbolic interactionism. Respondents generally supported the intent of the policy and identified many potential benefits of the policy, if adopted. They also provided insight into the organization and operation of community sports clubs and stressed that the volunteer intensive nature of community sport needs to be accommodated in the policy to enhance the likelihood of community-level acceptance and implementation. Successful community club implementation of this type of centrally developed micro-level sport policy requires that policy-makers understand and address the implementation context-related perspectives raised in this study.
How Good Are the Data? Feasible Approach to Validation of Metrics of Quality Derived From an Outpatient Electronic Health Record
Authors: Benin Andrea L. , Fenick Ada , Herrin Jeph , Vitkauskas Grace , Chen John , Brandt Cynthia
Published: September 2011

Although electronic health records (EHRs) promise to be efficient resources for measuring metrics of quality, they are not designed for such population-based analyses. Thus, extracting meaningful clinical data from them is not straightforward. To avoid poorly executed measurements, standardized methods to measure and to validate metrics of quality are needed. This study provides and evaluates a use case for a generally applicable approach to validating quality metrics measured electronically from EHR-based data. The authors iteratively refined and validated 4 outpatient quality metrics and classified errors in measurement. Multiple iterations of validation and measurement resulted in high levels of sensitivity and agreement versus the “gold standard” of manual review. In contrast, substantial differences remained for measurement based on coded billing data. Measuring quality metrics using an EHR-based electronic process requires validation to ensure accuracy; approaches to validation such as those described in this study should be used by organizations measuring quality from EHR-based information.
The Influence of Partisanship, Ideology, and the Law on Redistricting Decisions in the Federal Courts
Authors: McKenzie Mark Jonathan
Published: September 2011

Redistricting cases offer a unique opportunity to test the effects of partisan favoritism in judging and to investigate when partisanship might influence decision making distinctly from ideology. How partisan are federal judges? In an analysis of federal district court cases from 1981 to 2007, this study finds that federal judges are neither neutral arbiters nor crass partisans. Instead, judging in redistricting cases can best be described in terms of constrained partisanship. When redistricting law is clear, judges eschew decision making that furthers their party’s interests. However, where legal precedent is ambiguous, partisan favoritism exacts a strong influence on judicial behavior.
Why History (Still) Matters
Authors: Rast Joel
Published: September 2011

Scholarship on path dependence, policy feedback, timing and sequence, and punctuated versus incremental change has fueled new debates and produced new theoretical insights into how time and history factor into political and social outcomes. This work has done much to clarify why history matters in social scientific investigation. However, it appears to have gone largely unnoticed by most contemporary urban political scientists and sociologists, who are far more likely to focus on the present or the recent past than to pursue genuinely historical approaches. This article examines certain causal mechanisms that operate in time and shows how their application to the study of urban settings can enhance what scholars know about urban political processes.
The Collision of Faith and Economic Development in Toronto’s Inner Suburban Industrial Districts
Authors: Hackworth Jason , Stein Kirsten
Published: September 2011

New places of worship have grown dramatically within former industrial areas in recent decades in Toronto. Many have located within areas that are officially protected against the incursion of nonindustrial land users. The protection of these zones, known as “employment districts,” from noncommercial users has become a centerpiece of Toronto’s economic development strategy. This strategy and the massive expansion of places of worship attempting to locate there have created a great deal of legal and political tension. This article explores this story and attempts to relate it to the larger tension between the project of economic development and the forces of religiosity at the urban scale.
Values Engagement in Evaluation
Authors: Hall Jori N. , Ahn Jeehae , Greene Jennifer C.
Published: September 2011

Values-engagement in evaluation involves both describing stakeholder values and prescribing certain values. Describing stakeholder values is common practice in responsive evaluation traditions. Prescribing or advocating particular values is only explicitly part of democratic, culturally responsive, critical, and other openly ideological traditions in evaluation, but we argue that it is implicit in all evaluation approaches and practices. In this article, we discuss various conceptualizations of values-engagement in evaluation. We further present a specific form of values-engaged evaluation that is committed to descriptive and prescriptive valuing, with an emphasis on its prescriptive advancement of the values of inclusion and equity. Examples from field experience illustrate these two countenances and underscore the multiple challenges invoked by intentional engagement with the values dimensions of evaluation. The examples come from evaluations of science, technology, engineering, and mathematics (STEM) educational programs.
Why the concept ‘‘lifestyle diseases’’ should be avoided
Authors: Vallgårda Signild
Published: September 2011

The concept lifestyle disease is used about a number of different diseases such as coronary heart disease, diabetes, lung cancer etc. The concept indicates that people’s behaviours cause the diseases. This is only partly true. All diseases, both so-called lifestyle diseases and infectious diseases, have multiple causes. Singling out only one type of causes, such as is implied in the concept of lifestyle diseases can lead prevention to focus only on changing people s behaviours or lifestyles, and thus to neglect other possibilities to improve health. Mortality due to chronic diseases has increased during the last century and the main cause behind this is the decrease in the mortality in infectious diseases among younger people. More people live long enough to develop the chronic diseases. The concept lifestyle disease gives a too narrow picture of causes death and should be abandoned and give place for a broader understanding of causes and preventive options.
Excision of Extensive Midfoot Pigmented Villonodular Synovitis With Microvascular Anastamosis of Iliac Crest Bone Graft Using External Fixation
Authors: Oloff Lawrence , Miller Kevin
Published: September 2011

Pigmented villonodular synovitis (PVNS) is a relatively rare lesion in the foot and ankle, most commonly involving the ankle joint and atypically, the subtalar and midtarsal joints. It is a benign proliferative disease characterized by an increase in villous or nodular synovium in joints. Resection of the tumor is often indicated in most cases because of the potentially aggressive joint destructive nature of this lesion. This report presents a case of chronic enlarging pervasive midtarsal and metatarsal–cuneiform joint PVNS in a 28-year-old male. This patient had a midtarsal mass that enlarged over a period of 2 years, causing increased pain, deformity, and difficulty with ambulation. Cross-sectional imaging studies identified evidence of erosive disease through much of the midfoot articulations, with biopsy confirming the mass as PVNS. The dimensions of the mass approximated 5.5 cm × 4.1 cm × 2.8 cm. Simple resection was problematic because of the size and multiple joints involved. Amputation was most commonly advised by multiple consultants. The patient preferred attempt at limb salvage. En bloc resection and placement of a revascularized iliac crest bone graft was used to fill the defect. The graft was microvascularly anastamosed and fixated with standard external fixation. Pathologic and histologic specimens from surgical biopsy reconfirmed the diagnosis of PVNS postoperatively. Second-stage arthrodesis was performed when the patient was stable and disease free. The patient was followed postoperatively for 10 years without recurrence and was able to return to full function and partake in moderate athletic activity at last visit. This case describes a retrospective review of the procedure and reconstruction, as well as an overview of current surgical management of PVNS.

Level of Evidence: Therapeutic, Level IV
Tumoral Calcinosis of the Foot
Authors: Sharkey Anne , Bibbo Christopher
Published: September 2011

Tumoral calcinosis is a disorder characterized by deposits of calcium phosphate in the subcutaneous tissues near large joints. While often resembling a neoplasm, the soft tissue deposits of tumoral calcinosis are benign in nature. The deposits can, however, cause significant morbidity to patients due to tissue pressure or impingement. The focus of this case report will include the presentation, radiographic examinations, clinical course, and treatment of a 90-year-old female patient presenting for evaluation of a painful plantar right foot soft tissue mass associated with chronic renal failure and secondary hyperparathyroidism.

Level of Evidence: Therapeutic, Level IV
Management humor
Authors: Wood Robert E. , Beckmann Nadin , Rossiter John R.
Published: September 2011

Should managers deliberately employ humor to persuade and motivate staff? A framework is presented for analyzing the role of humor in managerial communications. The framework includes the presenter, recipient, message, and medium and elaborates cognitive and emotional reactions to humor by recipients. The framework is applied to analyses of the likely impacts of humor in problem solving and creativity. Facilitators and constraints for the effects of humor in managerial communications are discussed.
Sonographic Patterns of Testicular Torsion
Authors: Wu Size , Liu Guangqing , Chen Shuhuan , Guan Ying
Published: September 2011

The objective of this study was to determine the sonographic patterns of the testes in patients with testicular torsion. Clinical data of 46 patients with testicular torsion confirmed by surgical exploration or manual detorsion were reviewed, and sonographic patterns of testicular torsion were categorized according to the sonographic characteristics of the testes, and their relation to the pathologic changes were analyzed. The sonographic appearances of testicular torsion were categorized into six patterns, reflecting pathologic changes of testicular torsion. Sonography of testicular torsion has different patterns, and recognition of these patterns may help the examiner establish a diagnosis and subsequently manage the patient.
Optimized anti–tumor effects of anthracyclines plus Vinca alkaloids using a novel, mechanism-based application schedule
Authors: Ehrhardt Harald , Schrembs David , Moritz Christian , Wachter Franziska , Haldar Subrata , Graubner Ulrike , Nathrath Michaela , Jeremias Irmela
Published: September 2011

Application of anthracyclines and Vinca alkaloids on the same day represents a hallmark of polychemotherapy protocols for hematopoietic malignancies. Here we show, for the first time, that both drugs might act most efficiently if they are applied on different days. Proof-of-concept studies in 18 cell lines revealed that anthracyclines inhibited cell death by Vinca alkaloids in 83% of cell lines. Importantly, in a preclinical mouse model, doxorubicin reduced the anti–tumor effect of vincristine. Both drugs acted in a sequence-dependent manner and the strongest anti–tumor effect was obtained if both drugs were applied on different days. Most notably for clinical relevance, in 34% of 35 fresh primary childhood leukemia cells tested in vitro, doxorubicin reduced the anti–tumor effect of vincristine. As underlying mechanism, doxorubicin activated p53, p53 induced cell-cycle arrest, and cell-cycle arrest disabled inactivation of antiapoptotic Bcl-2 family members by vincristine; therefore, vincristine was unable to activate downstream apoptosis signaling. As molecular proof, antagonism was rescued by knockdown of p53, whereas knockdown of cyclin A inhibited vincristine-induced apoptosis. Our data suggest evaluating anthracyclines and Vinca alkaloids on different days in future trials. Selecting drug combinations based on mechanistic understanding represents a novel conceptional strategy for potent polychemotherapy protocols.
Macrophages prevent human red blood cell reconstitution in immunodeficient mice
Authors: Hu Zheng , Van Rooijen Nico , Yang Yong-Guang
Published: September 2011

An animal model supporting human erythropoiesis will be highly valuable for assessing the biologic function of human RBCs under physiologic and disease settings, and for evaluating protocols of in vitro RBC differentiation. Herein, we analyzed human RBC reconstitution in NOD/SCID or NOD/SCID/γc−/− mice that were transplanted with human CD34+ fetal liver cells and fetal thymic tissue. Although a large number of human CD45−CD71+ nucleated immature erythroid cells were detected in the bone marrow, human RBCs were undetectable in the blood of these mice. Human RBCs became detectable in blood after macrophage depletion but disappeared again after withdrawal of treatment. Furthermore, treatment with human erythropoietin and IL-3 significantly increased human RBC reconstitution in macrophage-depleted, but not control, humanized mice. Significantly more rapid rejection of human RBCs than CD47-deficient mouse RBCs indicates that mechanisms other than insufficient CD47-SIRPα signaling are involved in human RBC xenorejection in mice. All considered, our data demonstrate that human RBCs are highly susceptible to rejection by macrophages in immunodeficient mice. Thus, strategies for preventing human RBC rejection by macrophages are required for using immunodeficient mice as an in vivo model to study human erythropoiesis and RBC function.
Human T cells expressing two additional receptors (TETARs) specific for HIV-1 recognize both epitopes
Authors: Hofmann Christian , Höfflin Sandra , Hückelhoven Angela , Bergmann Silke , Harrer Ellen , Schuler Gerold , Dörrie Jan , Schaft Niels , Harrer Thomas
Published: September 2011

Adoptive TCR transfer against rapidly mutating targets, such as HIV-1 or cancer, must counteract corresponding immune escape. Hence, we generated T cells expressing two additional receptors (TETARs) specific for HIV-1 by TCR mRNA electroporation. An HLA-A2–restricted gag-specific TCR and an HLA-B13–restricted nef-specific TCR were chosen. When both TCRs were transfected simultaneously, strong competitive effects occurred that were overcome by replacing the human constant domains of one TCR with murine counterparts and adapting the amounts of TCR-RNA used for transfection. The resulting TETAR responded to both epitopes with cytokine secretion and cytotoxic function. Cell sorting revealed that one individual cell indeed recognized both epitopes. The T cells diminished their reactivity to each epitope after stimulation but sequentially killed targets that presented the gag epitope and then targets that presented the nef epitope, or vice versa. Taken together, TETARs represent a sophisticated tool to study TCR functionality and might be a useful strategy in immunotherapy.
PGE2 promotes angiogenesis through EP4 and PKA Cγ pathway
Authors: Zhang Yushan , Daaka Yehia
Published: September 2011

Inflammation is increasingly recognized as a critical mediator of angiogenesis, and unregulated angiogenic response is involved in human diseases, including cancer. Proinflammatory prostaglandin E2 (PGE2) is secreted by many cell types and plays important roles in the process of angiogenesis via activation of cognate EP1-4 receptors. Here, we provide evidence that PGE2 promotes the in vitro tube formation of human microvascular endothelial cells, ex vivo vessel outgrowth of aortic rings, and actual in vivo angiogenesis. Use of EP subtype-selective agonists and antagonists suggested EP4 mediates the prostaglandin-induced tube formation, and this conclusion was substantiated with small interfering RNA to specifically knockdown the EP4 expression. EP4 couples to Gαs, leading to activation of protein kinase A (PKA). Inhibition of PKA activity or knockdown of PKA catalytic subunit γ with RNAi attenuates the PGE2-induced tube formation. Further, knocking down the expression of Rap1A, HSPB6, or endothelial NO synthase, which serve as PKA-activatable substrates, inhibits the tube formation, whereas knockdown of RhoA or glycogen synthase kinase 3β that are inactivated after phosphorylation by PKA increases the tube formation. These results support the existence of EP4-to-PKA angiogenic signal and provide rationale for use of selective EP4 signal inhibitors as a probable strategy to control pathologic angiogenesis.
Effect of α+-thalassaemia on episodes of fever due to malaria and other causes: a community-based cohort study in Tanzania
Authors: Veenemans Jacobien , Jansen Esther JS , Baidjoe Amrish Y , Mbugi Erasto V , Demir Ayşe Y , Kraaijenhagen Rob J , Savelkoul Huub FJ , Verhoef Hans
Published: September 2011

Background

It is controversial to what degree α+-thalassaemia protects against episodes of uncomplicated malaria and febrile disease due to infections other than Plasmodium.

Methods

In Tanzania, in children aged 6-60 months and height-for-age z-score < -1.5 SD (n = 612), rates of fevers due to malaria and other causes were compared between those with heterozygous or homozygotes α+-thalassaemia and those with a normal genotype, using Cox regression models that accounted for multiple events per child.

Results

The overall incidence of malaria was 3.0/child-year (1, 572/526 child-years); no differences were found in malaria rates between genotypes (hazard ratios, 95% CI: 0.93, 0.82-1.06 and 0.91, 0.73-1.14 for heterozygotes and homozygotes respectively, adjusted for baseline factors that were predictive for outcome). However, this association strongly depended on age: among children aged 6-17 months, those with α+-thalassaemia experienced episodes more frequently than those with a normal genotype (1.30, 1.02-1.65 and 1.15, 0.80-1.65 for heterozygotes and homozygotes respectively), whereas among their peers aged 18-60 months, α+-thalassaemia protected against malaria (0.80, 0.68-0.95 and 0.78, 0.60-1.03; p-value for interaction 0.001 and 0.10 for hetero- and homozygotes respectively). No effect was observed on non-malarial febrile episodes.

Conclusions

In this population, the association between α+-thalassaemia and malaria depends on age. Our data suggest that protection by α+-thalassaemia is conferred by more efficient acquisition of malaria-specific immunity.
Proteomic analysis of mare follicular fluid during late follicle development
Authors: Fahiminiya Somayyeh , Labas Valérie , Roche Stéphane , Dacheux Jean-Louis , Gérard Nadine
Published: September 2011

Background

Follicular fluid accumulates into the antrum of follicle from the early stage of follicle development. Studies on its components may contribute to a better understanding of the mechanisms underlying follicular development and oocyte quality. With this objective, we performed a proteomic analysis of mare follicular fluid. First, we hypothesized that proteins in follicular fluid may differ from those in the serum, and also may change during follicle development. Second, we used four different approaches of Immunodepletion and one enrichment method, in order to overcome the masking effect of high-abundance proteins present in the follicular fluid, and to identify those present in lower abundance. Finally, we compared our results with previous studies performed in mono-ovulant (human) and poly-ovulant (porcine and canine) species in an attempt to identify common and/or species-specific proteins.

Methods

Follicular fluid samples were collected from ovaries at three different stages of follicle development (early dominant, late dominant and preovulatory). Blood samples were also collected at each time. The proteomic analysis was carried out on crude, depleted and enriched follicular fluid by 2D-PAGE, 1D-PAGE and mass spectrometry.

Results

Total of 459 protein spots were visualized by 2D-PAGE of crude mare follicular fluid, with no difference among the three physiological stages. Thirty proteins were observed as differentially expressed between serum and follicular fluid. Enrichment method was found to be the most powerful method for detection and identification of low-abundance proteins from follicular fluid. Actually, we were able to identify 18 proteins in the crude follicular fluid, and as many as 113 in the enriched follicular fluid. Inhibins and a few other proteins involved in reproduction could only be identified after enrichment of follicular fluid, demonstrating the power of the method used. The comparison of proteins found in mare follicular fluid with proteins previously identified in human, porcine and canine follicular fluids, led to the identification of 12 common proteins and of several species-specific proteins.

Conclusions

This study provides the first description of mare follicular fluid proteome during the late follicle development stages. We identified several proteins from crude, depleted and enriched follicular fluid. Our results demonstrate that the enrichment method, combined with 2D-PAGE and mass spectrometry, can be successfully used to visualize and further identify the low-abundance proteins in the follicular fluid.
Strong convergence of a hybrid method for monotone variational inequalities and fixed point problems
Authors: Yao Yonghong , Liou Yeong-Cheng , Wong Mu-Ming , Yao Jen-Chih
Published: September 2011

In this paper, we suggest a hybrid method for finding a common element of the set of solution of a monotone, Lipschitz-continuous variational inequality problem and the set of common fixed points of an infinite family of nonexpansive mappings. The proposed iterative method combines two well-known methods: extragradient method and CQ method. Under some mild conditions, we prove the strong convergence of the sequences generated by the proposed method.

Mathematics Subject Classification (2000): 47H05; 47H09; 47H10; 47J05; 47J25.
A common fixed point theorem for a commuting family of nonexpansive mappings one of which is multivalued
Authors: Nanan Narawadee , Dhompongsa Sompong
Published: September 2011

Bruck [Pac. J. Math. 53, 59-71 1974 Theorem 1] proved that for a nonempty closed convex subset E of a Banach space X, if E is weakly compact or bounded and separable and suppose that E has both (FPP) and (CFPP), then for any commuting family S of nonexpansive self-mappings of E, the set F(S) of common fixed points of S is a nonempty nonexpansive retract of E. In this paper, we extend the above result when one of its elements in S is multivalued. The result extends previously known results (on common fixed points of a pair of single valued and multivalued commuting mappings) to infinite number of mappings and to a wider class of spaces.

2000 Mathematics Subject Classification: 47H09; 47H10
Multidetector-row computed tomography of thoracic aortic anomalies in dogs and cats: Patent ductus arteriosus and vascular rings
Authors: Henjes Christiane R , Nolte Ingo , Wefstaedt Patrick
Published: September 2011

Background

Diagnosis of extracardiac intrathoracic vascular anomalies is of clinical importance, but remains challenging. Traditional imaging modalities, such as radiography, echocardiography, and angiography, are inherently limited by the difficulties of a 2-dimensional approach to a 3-dimensional object. We postulated that accurate characterization of malformations of the aorta would benefit from 3-dimensional assessment. Therefore, multidetector-row computed tomography (MDCT) was chosen as a 3-dimensional, new, and noninvasive imaging technique. The purpose of this study was to evaluate patients with 2 common diseases of the intrathoracic aorta, either patent ductus arteriosus or vascular ring anomaly, by contrast-enhanced 64-row computed tomography.

Results

Electrocardiography (ECG)-gated and thoracic nongated MDCT images were reviewed in identified cases of either a patent ductus arteriosus or vascular ring anomaly. Ductal size and morphology were determined in 6 dogs that underwent ECG-gated MDCT. Vascular ring anomalies were characterized in 7 dogs and 3 cats by ECG-gated MDCT or by a nongated thoracic standard protocol.

Cardiac ECG-gated MDCT clearly displayed the morphology, length, and caliber of the patent ductus arteriosus in 6 affected dogs. Persistent right aortic arch was identified in 10 animals, 8 of which showed a coexisting aberrant left subclavian artery. A mild dilation of the proximal portion of the aberrant subclavian artery near its origin of the aorta was present in 4 dogs, and a diverticulum analogous to the human Kommerell's diverticulum was present in 2 cats.

Conclusions

Contrast-enhanced MDCT imaging of thoracic anomalies gives valuable information about the exact aortic arch configuration. Furthermore, MDCT was able to characterize the vascular branching patterns in dogs and cats with a persistent right aortic arch and the morphology and size of the patent ductus arteriosus in affected dogs. This additional information can be of help with regard to improved diagnoses of thoracic anomalies and the planning of surgical interventions.
Decreased expression of B cell related genes in leukocytes of women with Parkinson's disease
Authors: Kedmi Merav , Bar-Shira Anat , Gurevich Tanya , Giladi Nir , Orr-Urtreger Avi
Published: September 2011

Background

Parkinson's disease (PD) is a complex disorder caused by genetic, environmental and age-related factors, and it is more prevalent in men. We aimed to identify differentially expressed genes in peripheral blood leukocytes (PBLs) that might be involved in PD pathogenesis. Transcriptomes of 30 female PD-patients and 29 age- and sex-matched controls were profiled using GeneChip Human Exon 1.0 ST Arrays. Samples were from unrelated Ashkenazi individuals, non-carriers of LRRK2 G2019S or GBA founder mutations.

Results

Differential expression was detected in 115 genes (206 exons), with over-representation of immune response annotations. Thirty genes were related to B cell functions, including the uniquely B cell-expressed IGHM and IGHD, the B cell surface molecules CD19, CD22 and CD79A, and the B cell gene regulator, PAX5. Quantitative-RT-PCR confirmation of these 6 genes in 79 individuals demonstrated decreased expression, mainly in women patients, independent of PD-pharmacotherapy status.

Conclusions

Our results suggest that the down regulation of genes related to B cell activity reflect the involvement of these cells in PD in Ashkenazi individuals and represents a molecular aspect of gender-specificity in PD.
Short-term effect of fenofibrate on C-reactive protein: A meta-analysis of randomized controlled trials
Authors: Ye Jiatao , Kiage James N , Arnett Donna K , Bartolucci Alfred A , Kabagambe Edmond K
Published: September 2011

Background

C-reactive protein (CRP) is positively associated with risk for cardiovascular disease and all-cause mortality. Some but not all randomized and non-randomized clinical trials found significant associations between fenofibrate therapy and CRP but the direction and magnitude of the association varied across studies. The duration of treatment, patient populations and sample sizes varied greatly, and most short-term studies (i.e., ≤ 12 weeks) had fewer than 50 patients. In this study we meta-analyzed randomized clinical trials to determine the short-term effect of fenofibrate on CRP.

Methods

Two reviewers independently searched PubMed and other online databases for short-term randomized clinical trials that reported CRP concentrations before and after fenofibrate treatment. Of the 81 studies examined, 14 studies with 540 patients were found eligible. Data for the change in CRP and corresponding measures of dispersion were extracted for use in the meta-analysis.

Results

The weighted mean CRP concentrations before and after fenofibrate therapy were 2.15 mg/L and 1.53 mg/L (-28.8% change), respectively. Inverse-variance weighted random effects meta-analysis revealed that short-term fenofibrate treatment significantly lowers CRP by 0.58 mg/L (95% CI: 0.36-0.80). There was significant heterogeneity between studies (Q statistic = 64.5, P< 0.0001, I2 = 79.8%). There was no evidence of publication bias and sensitivity analysis revealed that omitting any of the 14 studies did not lead to a different conclusion from the overall meta-analysis result.

Conclusion

Short-term treatment with fenofibrate significantly lowers CRP concentration. Randomized trials that will recruit patients based with high baseline CRP concentrations and with change in CRP as a primary outcome are needed.