bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin-Converting Enzyme Inhibition Prevents the Release of Monocytes From Their Splenic Reservoir in Mice With Myocardial Infarction
Authors: Leuschner Florian , Panizzi Peter , Chico-Calero Isabel , Lee Won Woo , Ueno Takuya , Cortez-Retamozo Virna , Waterman Peter , Gorbatov Rostic , Marinelli Brett , Iwamoto Yoshiko , Chudnovskiy Aleksey , Figueiredo Jose-Luiz , Sosnovik David E. , Pittet Mikael J. , Swirski Filip K. , Weissleder Ralph , Nahrendorf Matthias
Published: October 2010

Rationale:

Monocytes recruited to ischemic myocardium originate from a reservoir in the spleen, and the release from their splenic niche relies on angiotensin (Ang) II signaling.

Objective:

Because monocytes are centrally involved in tissue repair after ischemia, we hypothesized that early angiotensin-converting enzyme (ACE) inhibitor therapy impacts healing after myocardial infarction partly via effects on monocyte traffic.

Methods and Results:

In a mouse model of permanent coronary ligation, enalapril arrested the release of monocytes from the splenic reservoir and consequently reduced their recruitment into the healing infarct by 45%, as quantified by flow cytometry of digested infarcts. Time-lapse intravital microscopy revealed that enalapril reduces monocyte motility in the spleen. In vitro migration assays and Western blotting showed that this was caused by reduced signaling through the Ang II type 1 receptor. We then studied the long-term consequences of blocked splenic monocyte release in atherosclerotic apolipoprotein (apo)E
−/−
mice, in which infarct healing is impaired because of excessive inflammation in the cardiac wound. Enalapril improved histologic healing biomarkers and reduced inflammation in infarcts measured by FMT-CT (fluorescence molecular tomography in conjunction with x-ray computed tomography) of proteolytic activity. ACE inhibition improved MRI-derived ejection fraction by 14% on day 21, despite initially comparable infarct size. In apoE
−/−
mice, ischemia/reperfusion injury resulted in larger infarct size and enhanced monocyte recruitment and was reversible by enalapril treatment. Splenectomy reproduced antiinflammatory effects of enalapril.

Conclusion:

This study suggests that benefits of early ACE inhibition after myocardial infarction can partially be attributed to its potent antiinflammatory impact on the splenic monocyte reservoir.
Aspirin in Alzheimer’s Disease
Authors: Thoonsen Hanneke , Richard Edo , Bentham Peter , Gray Richard , van Geloven Nan , De Haan Rob J. , Van Gool Willem A. , Nederkoorn Paul J.
Published: October 2010

Background and Purpose—

In a randomized controlled trial in Alzheimer’s disease (AD), we found a higher number of intracerebral hemorrhages (ICHs) in patients randomized to aspirin treatment. Here, we evaluate the literature on the risk of ICH as a complication in patients with AD treated with aspirin.

Methods—

Systematic review and comparison of the occurrence of events over time between the aspirin and control group in each trial using Cox regression analysis. Estimated hazard ratios (HRs) were combined in a pooled HR.

Results—

Two randomized controlled trials on aspirin for AD were found. In the Evaluation of Vascular Care in Alzheimer’s Disease (EVA) trial (conducted in our center), 4.6% of patients in the group receiving a multicomponent treatment that included aspirin had an ICH (3/65; 95% confidence interval [CI], 1.0 to 12.9) versus 0% in the control group (0/58; 95% CI, 0 to 6.2). In the Aspirin in Alzheimer’s Disease (AD2000) trial, these proportions were, respectively, 2.6% (4/156; 95% CI, 0.7 to 6.4) and 0% (0/154; 95% CI, 0 to 2.4). The pooled proportion of ICHs in the aspirin group is 3.2% (7/221; 95% CI, 1.3 to 6.4) versus 0% in the control group (0/212; 95% CI, 0 to 1.7). The pooled HR for an ICH in AD patients using aspirin is 7.63 (95% CI, 0.72 to 81.00;
P
=0.09).

Conclusions—

Although the number of cases in both trials is small, our findings suggest that aspirin use in AD might pose an increased risk of ICH, whereas it has no effect on cognition. If there is an unequivocal cardiovascular indication for aspirin, it should not be withheld in AD patients.
Cerebral Autoregulation in Stroke
Authors: Aries Marcel J.H. , Elting Jan W. , De Keyser Jacques , Kremer Berry P.H. , Vroomen Patrick C.A.J.
Published: October 2010

Background and Purpose—

Cerebral autoregulation may become impaired after stroke. To provide a review of the nature and extent of any autoregulation impairment after stroke and its course over time, a technique allowing repeated bedside measurements with good temporal resolution is required. Transcranial Doppler (TCD) in combination with continuous blood pressure measurements allows noninvasive continuous bedside investigation with high temporal resolution of the dynamic and the steady-state components of cerebral autoregulation. Therefore, this review focuses on all TCD studies on cerebral autoregulation in the setting of documented ischemic stroke.

Methods—

PubMed and EMBASE were searched for studies of stroke, autoregulation, and TCD. Studies were either acute phase (<96 hours after index stroke) or chronic phase (>96 hours after index stroke) autoregulation studies. Quality of studies was studied in a standardized fashion.

Results—

Twenty-three studies met the inclusion criteria. General agreement existed on cerebral autoregulation being impaired, even after minor stroke. Bilateral impairment of autoregulation was documented, particularly after lacunar stroke. Studies showed progressive deterioration of cerebral autoregulation in the first 5 days after stroke and recovery over the next 3 months. Impaired cerebral autoregulation as assessed by TCD was related to neurological deterioration, the necessity for decompressive surgery, and poor outcome. Synthesis of the data of various studies was, however, limited by studies not meeting key methodological criteria for observational studies.

Conclusions—

TCD in combination with continuous blood pressure measurement offers a method with a high temporal resolution feasible for bedside evaluation of cerebral autoregulation in the stroke unit. TCD studies have shown impairment of cerebral autoregulation in various subtypes of ischemic stroke. To improve the synthesis of data from various research groups, there is urgent need for standardization of methodology of TCD studies in cerebral autoregulation.
Testing the Hypothesis that the MJO is a Mixed Rossby–Gravity Wave Packet
Authors: Yang Da , Ingersoll Andrew P.
Published: October 2010

The Madden–Julian oscillation (MJO), also known as the intraseasonal oscillation (ISO), is a planetary-scale mode of variation in the tropical Indian and western Pacific Oceans. Basic questions about the MJO are why it propagates eastward at ∼5 m s−1, why it lasts for intraseasonal time scales, and how it interacts with the fine structure that is embedded in it. This study will test the hypothesis that the MJO is not a wave but a wave packet—the interference pattern produced by a narrow frequency band of mixed Rossby–gravity (MRG) waves. As such, the MJO would propagate with the MRG group velocity, which is eastward at ∼5 m s−1. Simulation with a 3D model shows that MRG waves can be forced independently by relatively short-lived, eastward- and westward-moving disturbances, and the MRG wave packet can last long enough to form the intraseasonal variability. This hypothesis is consistent with the view that the MJO is episodic, with an irregular time interval between events rather than a periodic oscillation. The packet is defined as the horizontally smoothed variance of the MRG wave—the rectified MRG wave, which has features in common with the MJO. The two-dimensional Fourier analysis of the NOAA outgoing longwave radiation (OLR) dataset herein indicates that there is a statistically significant correlation between the MJO amplitude and wave packets of MRG waves but not equatorial Rossby waves or Kelvin waves, which are derived from the Matsuno shallow water theory. However, the biggest absolute value of the correlation coefficient is only 0.21, indicating that the wave packet hypothesis explains only a small fraction of the variance of the MJO in the OLR data.
Polarimetric Phased-Array Radar for Weather Measurement: A Planar or Cylindrical Configuration?
Authors: Zhang Guifu , Doviak Richard J. , Zrnić Dusan S. , Palmer Robert , Lei Lei , Al-Rashid Yasser
Published: October 2010

This paper suggests a cylindrical configuration for agile beam polarimetric phased-array radar (PPAR) for weather surveillance. The most often used array configuration for PAR is a planar array antenna. The planar configuration, however, has significant deficiencies for polarimetric measurements, as well as other limitations, such as increases in beamwidth, decreases of sensitivity, and changes in the polarization basis when the beam scans off its broadside. The cylindrical polarimetric phased-array radar (CPPAR) is proposed to avoid these deficiencies. The CPPAR principle and potential performance are demonstrated through theoretical analysis and simulation. It is shown that the CPPAR has the advantage of a scan-invariant polarization basis, and thus avoids the inherent limitations of the planar PPAR (i.e., PPPAR).
Toward an Uncertainty Budget for a Coastal Ocean Model
Authors: Kim Sangil , Samelson R. M. , Snyder Chris
Published: October 2010

Estimates of three components of an uncertainty budget for a coastal ocean model in a wind-forced regime are made based on numerical simulations. The budget components behave differently in the shelf regime, inshore of the 200-m isobath, and the slope-interior regime, between the 200-m isobath and a fixed longitude (126°W) that is roughly 150 km offshore. The first of the three budget components is an estimate of the uncertainty in the ocean state given only a known history of wind stress forcing, with errors in the wind forcing estimated from differences between operational analyses. It is found that, over the continental shelf, the response to wind forcing is sufficiently strong and deterministic that significant skill in estimating shelf circulation can be achieved with knowledge only of the wind forcing, and no ocean data, for wind fields with these estimated errors. The second involves initial condition error and its influence on uncertainty, including both error growth with time from well-known initial conditions and error decay with time from poorly known initial conditions but with well-known wind forcing. The third component is that of boundary condition error and its influence on the interior solutions, including the dependence of that influence on the specific location along the boundary of the boundary condition error. Boundary condition errors with amplitude comparable to the root-mean-square variability at the boundary lead eventually to errors equal to the root-mean-square variability in the slope-interior regime, and somewhat smaller errors in the shelf regime. Covariance estimates based on differences of the wind-forced solutions from the ensemble mean are not dramatically different from those based on the full fields, and do not show strong state dependence.
Efficient Ensemble Covariance Localization in Variational Data Assimilation
Authors: Bishop Craig H. , Hodyss Daniel , Steinle Peter , Sims Holly , Clayton Adam M. , Lorenc Andrew C. , Barker Dale M. , Buehner Mark
Published: October 2010

Previous descriptions of how localized ensemble covariances can be incorporated into variational (VAR) data assimilation (DA) schemes provide few clues as to how this might be done in an efficient way. This article serves to remedy this hiatus in the literature by deriving a computationally efficient algorithm for using nonadaptively localized four-dimensional (4D) or three-dimensional (3D) ensemble covariances in variational DA. The algorithm provides computational advantages whenever (i) the localization function is a separable product of a function of the horizontal coordinate and a function of the vertical coordinate, (ii) and/or the localization length scale is much larger than the model grid spacing, (iii) and/or there are many variable types associated with each grid point, (iv) and/or 4D ensemble covariances are employed.
Accuracy of 3D Reconstructions Based on Cone Beam Computed Tomography
Authors: Maret D. , Molinier F. , Braga J. , Peters O.A. , Telmon N. , Treil J. , Inglèse J.M. , Cossié A. , Kahn J.L. , Sixou M.
Published: October 2010

Three-dimensional imaging of teeth will increase its impact in clinical practice if reconstructions are metrically accurate. We hypothesized that, with cone beam computed tomography (CBCT) data, three-dimensional images of teeth can be reconstructed with the same accuracy and precision as with in vitro micro-computed tomography (micro-CT) data acquisition, the current reference standard. We used a sample of CBCT and micro-CT data taken of tooth germs. Volumes obtained with CBCT and micro-CT devices were statistically similar (n = 120, Passing-Bablok regression). Geometric deviations between CBCT and micro-CT three-dimensional surface reconstructions did not show any areas of important and systematic errors. Future investigations with the use of larger samples may also demonstrate that CBCT data will be helpful for a more in-depth study of other aspects of dental morphology—for example, assessing tooth development. With sufficient accuracy for clinical situations, potential future medical applications of such measurements with CBCT are envisaged.
Building a Political Constituency for Urban School Reform
Authors: Warren Mark R.
Published: October 2010

In this article, the author argues that urban school reform falters, in part, because of the lack of an organized political constituency among the stakeholders with the most direct interest in school improvement, that is, parents whose children attend urban schools. The author examines community organizing as a potential strategy to build such a constituency. Drawing primarily on extensive fieldwork research, he constructs a case study of one of the country’s largest community organizing networks, the Texas Industrial Areas Foundation (IAF). He analyzes the network’s Alliance Schools initiative to promote school reform in 120 public schools in districts across the state. This article finds that organizing efforts like the IAF, despite important limitations, are beginning to create an external force for change in district policy as well as to collaborate internally with educators to produce change in the practice of education within schools.
Integrating Behavioral Psychology Services Into Adult Day Programming for Individuals With Dementia
Authors: LeBlanc Linda A.
Published: October 2010

Many individuals with dementia and problem behavior are served in nursing home settings long before health issues necessitate constant medical care. Alternative community-based adult day health care programs allow individuals with dementia to remain in their home with their families at a substantially reduced cost; however, many adult day programs face the same difficulties in managing problem behavior as family members do, leading to premature termination of services. This article describes a multiyear project that integrated behavior analytic services into an adult day program for individuals with dementia and problematic behavior. A comprehensive practicum system was developed to provide assessment and treatment services that allowed consumers with problem behavior to remain successfully served in adult day programming while postponing out-of-home nursing home care.
Thyroid Follicular Lesions Induced by Oral Treatment for 2 Years with 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Dioxin-like Compounds in Female Harlan Sprague-Dawley Rats
Authors: Yoshizawa Katsuhiko , Walker Nigel J. , Nyska Abraham , Kissling Grace E. , Jokinen Micheal P. , Brix Amy E. , Sells Donald M. , Wyde Michael E.
Published: October 2010

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and structurally-similar dioxin-like compounds affect thyroid function and morphology and thyroid hormone metabolism in animals and humans. The National Toxicology Program conducted eight 2-year gavage studies in female Harlan Sprague-Dawley rats to determine the relative potency of chronic toxicity and carcinogenicity of TCDD, 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 2,3′,4,4′,5-pentachlorobiphenyl (PCB118), 2,2′,4,4′,5,5′-hexachloro-biphenyl (PCB153), a tertiary mixture of TCDD/PCB126/PeCDF, and two binary mixtures (PCB126/PCB153 and PCB126/PCB118). Administration of these compounds was associated with increased incidences of thyroid follicular cell hypertrophy, variably observed in the 14-, 31-, and 53-week interim and 2-year sacrifice groups. In all studies, the incidences of follicular cell adenoma and carcinoma were not increased. Decreased levels of serum thyroxine were primarily noted in the 14-or-later -week interim groups of all chemicals. Serum triiodothyronine (T3) levels were increased in the TCDD, PCB126, PeCDF, TCDD/PCB126/PeCDF, and PCB126/PCB153 studies, while decreased levels were noted in the PCB153 and PCB126/PCB118 studies. TCDD, PCB126, PCB126/PCB153, and PCB126/PCB118 increased levels of serum thyroid-stimulating hormone almost in a dose-dependent manner in the 14-week groups. These data suggest that although dioxin-like compounds alter thyroid hormones and increase follicular cell hyperplasia, there is not an increase in thyroid adenoma or carcinoma in female Sprague-Dawley rats.
Medial Patellofemoral Ligament Reconstruction Fixed With a Cylindrical Bone Plug and a Grafted Semitendinosus Tendon at the Original Femoral Site for Recurrent Patellar Dislocation
Authors: Deie Masataka , Ochi Mitsuo , Adachi Nobuo , Shibuya Hayatoshi , Nakamae Atsuo
Published: October 2010

Background: The medial patellofemoral ligament (MPFL) is the most important factor for stabilizing the patella and preventing lateral patellar dislocation. Medial patellofemoral ligament reconstruction is an accepted surgical technique to restore patellofemoral stability after lateral patellar dislocation. The authors recently developed a new anatomical MPFL reconstruction method using a cylindrical bone plug and grafted semitendinosus tendon at the anatomical femoral attachment site to mimic the native MPFL. This study evaluated the new technique for stabilizing recurrent patellar dislocation.

Hypothesis: This new MPFL reconstruction technique will improve knee symptoms and function with excellent clinical results.

Study Design: Case series; Level of evidence, 4.

Method: Thirty-one knees were evaluated from 29 cases of recurrent patellar dislocation that were surgically treated using the anatomical MPFL reconstruction technique. The average patient age was 22.2 years (range, 12-34 years); postsurgery follow-up was 2 to 5 years (average, 3.2 years). The patients were clinically evaluated based on the Kujala score, range of motion, and signs of apprehension. The Merchant view was used to measure congruence and tilting angles.

Results: Of the 31 knees, 30 showed good clinical results after surgery, while 1 patient showed remaining signs of apprehension. The Kujala score improved from an average of 64 points (range, 35-70) initially to an average of 94.5 points (range, 79-100) at the final follow-up. Range of motion improved for all patients, with an average knee extension of 0° ± 2° and knee flexion of 145° ± 3° at final follow-up. No patellar redislocation was reported. Radiological assessment indicated significant improvement to the congruence angle from 13° ± 4° before surgery to −5° ± 5° at the final follow-up, while the tilting angle went from 8° ± 7° before surgery to 7° ± 4° at the final follow-up.

Conclusion: This study demonstrated excellent results using the new procedure for recurrent dislocation of the patella, with instability in only 1 of 31 knees (3.2%).
A Proximal Strengthening Program Improves Pain, Function, and Biomechanics in Women With Patellofemoral Pain Syndrome
Authors: Earl Jennifer E. , Hoch Anne Z.
Published: October 2010

Background: It is hypothesized that patients with patellofemoral pain syndrome (PFPS) have hip and core muscle weakness leading to dynamic malalignment of the lower extremity. Thus, hip strengthening is a common PFPS treatment approach.

Purpose: To determine changes in hip strength, core endurance, lower extremity biomechanics, and patient outcomes after proximally focused rehabilitation for PFPS patients.

Study Design: Case series; Level of evidence, 4.

Methods: Nineteen women (age, 22.68 ± 7.19 years; height, 1.64 ± 0.07 m; mass, 60.2 ± 7.35 kg) with PFPS participated in an 8-week program to strengthen the hip and core muscles and improve dynamic malalignment. Paired t tests were used to compare the dependent variables between prerehabilitation and postrehabilitation. The dependent variables were pain; functional ability; isometric hip abduction and external rotation strength; anterior, lateral, and posterior core endurance; joint range of motion (ROM; rearfoot eversion, knee abduction and internal rotation, and hip adduction and internal rotation); and peak internal joint moments (rearfoot inversion, knee abduction, and hip abduction and external rotation) during the stance phase of running.

Results: Significant improvements in pain, functional ability, lateral core endurance, hip abduction, and hip external rotation strength were observed. There was also a significant reduction in the knee abduction moment during running, although there were no significant changes in joint ROM.

Conclusion: An 8-week rehabilitation program focusing on strengthening and improving neuromuscular control of the hip and core musculature produces positive patient outcomes, improves hip and core muscle strength, and reduces the knee abduction moment, which is associated with developing PFPS.
Evaluation of White Matter Changes in Agyria–Pachygyria Complex Using Diffusion Tensor Imaging
Authors: Kao Yu-Chia , Peng Steven Shinn-Forng , Weng Wen-Chin , Lin Ming-I , Lee Wang-Tso
Published: October 2010

Associated abnormalities of the white matter in patients with agyria–pachygyria complex have rarely been investigated using new imaging modalities like diffusion tensor imaging. The present study evaluated the white matter changes of 9 children with agyria–pachygyria complex using diffusion tensor imaging. Regions of interest were placed in 17 white matter tracts. Compared with normal controls, the axial diffusivity of the genu of the corpus callosum, corticospinal tract, and fornix in patients with agyria–pachygyria complex was decreased. In the subcortical white matter without changes in T2-weighted image, there were significant decreases in fractional anisotropy and axial diffusivity and increases in radial diffusivity, indicating significant alterations of the white matter. Since axial diffusivity and radial diffusivity reflect changes in the axon and myelin, respectively, the findings here indicate disturbance in both axonal and myelin development in agyria–pachygyria complex.
Dramatis personae: enactment and performance in primary school headship
Authors: Rhodes Christopher , Greenway Celia
Published: October 2010

This article offers insights into the leadership enactment of primary school heads in terms of the dramatis personae or ‘masks of the drama’ they perceive themselves to portray during interactions with staff in their schools. The article draws on the reported identities and performances of ten heads in their day-to-day leadership of staff and reveals perceptions held about the presence of a dominant performance supplemented by a wide variety of sub-performances intended to meet particular circumstances. Heads convey reasons for the performances adopted and report on the real emotional cost involved in the portrayals they give in daily school life. The study begins to reveal implications for the ongoing study and practice of leadership, and in particular headship, within contemporary educational settings both in the United Kingdom and internationally. The article invites reflection upon the preparation and development of individuals seeking or already cast in this exacting role.
Employment and Earnings Growth Among Transition-Age Supplemental Security Income Program Participants
Authors: Berry Hugh G. , Caplan Leslie J.
Published: October 2010

This article examines factors that influence employment and earnings growth for Supplemental Security Income (SSI) beneficiaries who have participated in the Vocational Rehabilitation (VR) program. Using hierarchical linear and nonlinear modeling (HLM), the authors examined the employment status of these individuals 2 years after exiting the VR program by using state-level economic and VR agency factors, as well as such individual-level factors as demographics, disabilities, and service types. HLM also was used to examine earnings growth among SSI beneficiaries who sustained employment for 5 years after exiting VR. Findings showed that SSI participants with mental retardation exhibited the highest odds of employment among other disability groups 2 years after exiting the VR program. College or university training and job placement services decreased the odds of employment, whereas supported employment demonstrated increased odds. For SSI participants with sustained employment, African American VR consumers showed higher earnings when compared to other race groups. Among selected VR services, only college or university training was positively associated with earnings growth over time. The authors discuss these and other state-level findings in the context of prior and future research, practice, and policies.
Understanding emotional transfer in children with autism spectrum disorders
Authors: Begeer Sander , Meerum Terwogt Mark , Rieffe Carolien , Stegge Hedy , Olthof Tjeert , Koot Hans M.
Published: October 2010

The present study examined the understanding of emotional transfer in 11 children with autism, 20 children with PDD-NOS and 31 typically developing children, aged 6 to 12 years. Children were asked about their emotional responses to successive, conflicting emotional situations. All children reported that preceding emotional situations would influence their emotional response towards a successive situation. Children from the typically developing group reported a stronger influence of preceding negative versus positive emotions. However, children with autism reported equal effects of preceding positive and negative emotions, and children with PDD-NOS were relatively unaffected by the preceding emotions. These findings may indicate a scripted understanding of emotions in children with autism in contrast to a more personalized understanding of typically developing children.
Dynamic characteristics of adhesive bonded high strength steel joints
Authors: Zhao H. , Duan X. , Ma M. , Lu L. , Cai Z. , Wang P. C. , Fickes J. D.
Published: October 2010

With an increase in the use of advanced high strength steels in vehicle architectures, materials joining issues have become increasingly important. Among the various joining methods, adhesive bonding is increasingly used in automobile manufacturing. Successful implementation of adhesive bonding to improve structural crashworthiness and reduce vehicle weight requires the knowledge of issues related not only to processing but also to joint performance. In this study, the impact strength of adhesive bonded high strength steel joints is evaluated with the split Hopkinson tension bar (SHTB) technique. The influences of loading speed and thickness of the steels on the shear strength of the joints were examined. Comparative quasi-static lap shear tests were also conducted on a tensile testing machine. Test results showed that strength and energy absorption of bonded steel joints increase with loading speed, and is greatly affected by the thickness of the steels. As the loading rates are increased to 1100 s–1 (i.e. 20 m s–1), bonded 0·75 mm thick DP600 steel shows a 152% increase in strength and an 83% increase in energy absorption when compared to its quasi-static values. Examination of the impact tested specimens showed the failure mode changes from coarse cohesive mode to fine cohesive mode with increasing loading speed. The results from this study will provide the information for a better understanding of impact failure mechanisms of adhesive bonded high strength steels.
Process–microstructure–property correlations in Al–Li AA2199 friction stir welds
Authors: Altenkirch J. , Steuwer A. , Withers P. J.
Published: October 2010

This paper examines the effect of three friction stir welding process parameters on the residual stresses, hardness and distortion for butt welded aluminium–lithium AA2199 alloy, a novel, low density high strength alloy with potential in the aerospace sector. A systematic set of nine trial welds is examined at different tool rotation and traverse speeds as well as tool downforces. The tensile residual stresses (∼50% of parent material yield strength) and the hardness drop in the weld line varied little with any of the friction stir welding process parameters. However, their breadth increased with rotation speed and downforce and decreased with increasing translation speed, which is consistent with increasing heat input. Weld distortion took the form of a saddle with the longitudinal bending distortion correlating strongly with the width of the tensile zone consistent with it being driven by the magnitude of the tensile buckling forces in the weld region.
Energy and force analysis of linear friction welds in medium carbon steel
Authors: Ofem U. U. , Colegrove P. A. , Addison A. , Russell M. J.
Published: October 2010

The linear friction welding process is rapidly developing into an important manufacturing technology for high quality joining of engineering materials. The energy required for linear friction welding is an important issue due to economic and environmental reasons, but is not currently fully understood. This paper describes a comprehensive evaluation of the energy input during linear friction welding of a medium carbon steel with different process parameters. This calculation is based on an analysis of force and displacement data from the machine, which takes momentum into account. The analysis shows that energy input to the weld is minimised with high frequencies and rubbing velocities; however, there is a considerable amount of energy lost in oscillating the machine tooling under these conditions. Furthermore, analysis of the force indicates that a peak load occurs just before the samples being aligned, which is probably caused by ploughing of the samples during welding.
Control of weld composition when arc welding high strength aluminium alloys using multiple filler wires
Authors: Pickin C. G. , Williams S. W. , Prangnell P. , Derry C. , Lunt M.
Published: October 2010

An experimental method of controlling weld composition when welding Al2024 has been explored. Utilising the tandem process and a cold wire feed unit, two and three commercially available filler wires were mixed in a single weld pool to control composition. Thermodynamic modelling was used to provide optimum weld compositions for the eradication of solidification cracking. Validation showed that by controlling the principal elements, not only was cracking eliminated, the mechanical properties of the weld could be varied. In particular, a composition was identified, which offered adequate joint strength and ductility. Exceeding this composition resulted in a corresponding increase in weld hardness at the expense of joint ductility.
Fatigue strength optimisation of friction stir welded A6005-T5 alloy sheets
Authors: Jung S. P. , Park T. W. , Kim Y. G.
Published: October 2010

In this study, the friction stir welding process is optimised to improve the fatigue strength of the joints of A6005-T5 alloy sheets. The welding speed, rotational speed and tilting angle of the tool tip are chosen as design variables. Fifteen friction stir welding experiments are performed according to the central composite design table. The regression model function is estimated using the response surface analysis method. Using the model function, sensitivity analysis is carried out and the effect of each design variable on the fatigue strength of the joint is discussed. The optimum values of design variables are determined using the sequential quadratic programming algorithm.
Distinct molecular mechanisms responsible for bortezomib-induced death of therapy-resistant versus -sensitive B-NHL cells
Authors: Olejniczak Scott H. , Blickwedehl Jennifer , Belicha-Villanueva Alan , Bangia Naveen , Riaz Wasif , Mavis Cory , Clements James L. , Gibbs John , Hernandez-Ilizaliturri Francisco J. , Czuczman Myron S.
Published: October 2010

Resistance to currently available therapies is a major impediment to the successful treatment of hematological malignancies. Here, we used a model of therapy-resistant B-cell nonHodgkin lymphoma (B-NHL) developed in our laboratory along with primary B-NHL cells to study basic mechanisms of bortezomib activity. In resistant cells and a subset of primary B-NHLs, bortezomib treatment led to stabilization of Bak and subsequent Bak-dependent activation of apoptosis. In contrast to sensitive cells that die strictly by apoptosis, bortezomib was capable of killing resistant cells through activation of apoptosis or caspase-independent mechanism(s) when caspases were pharmacologically inhibited. Our data demonstrate that bortezomib is capable of killing B-NHL cells via multiple mechanisms, regardless of their basal apoptotic potential, and contributes to growing evidence that proteasome inhibitors can act via modulation of B-cell lymphoma 2 (Bcl-2) family proteins. The capacity of bortezomib to act independently of the intrinsic apoptotic threshold of a given B-NHL cell suggests that bortezomib-based therapies could potentially overcome resistance and result in relevant clinical activity in a relapsed/refractory setting.
IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin
Authors: Botto Sara , Streblow Daniel N. , DeFilippis Victor , White Laura , Kreklywich Craig N. , Smith Patricia P. , Caposio Patrizia
Published: October 2010

Human cytomegalovirus (HCMV) is linked to the acceleration of vascular diseases such as atherosclerosis and transplant vasculopathy. One of the hallmarks of these diseases is angiogenesis (AG) and neovessel formation. Endothelial cells (ECs) are an integral part of AG and are sites of HCMV persistence. AG requires multiple synchronous processes that include EC proliferation, migration, and vessel stabilization. Virus-free supernatant (secretome) from HCMV-infected ECs induces AG. To identify factor(s) involved in this process, we performed a human cytokine array. Several cytokines were significantly induced in the HCMV secretomes including interleukin-6 (IL-6), granulocyte macrophage colony-stimulating factor, and IL-8/CXCL8. Using in vitro AG assays, neutralization of IL-6 significantly reduced neovessel formation. Addition of the HCMV secretome to preformed vessels extended neovessel survival, but this effect was blocked by neutralization of IL-6. In these cells, IL-6 prevented apoptosis by blocking caspase-3 and -7 activation through the induction of survivin. Neutralization of IL-6 receptor on ECs abolished the ability of HCMV secretome to increase survivin expression and activated effector caspases. Moreover, survivin shRNA expression induced rapid regression of tubule capillary networks in ECs stimulated with HCMV secretome and activated effector caspases. These observations may explain how CMV accelerates vascular disease despite limited infection in tissues.
PLCγ-activated signalling is essential for TrkB mediated sensory neuron structural plasticity
Authors: Sciarretta Carla , Fritzsch Bernd , Beisel Kirk , Rocha-Sanchez Sonia M , Buniello Annalisa , Horn Jacqueline M , Minichiello Liliana
Published: October 2010

Background

The vestibular system provides the primary input of our sense of balance and spatial orientation. Dysfunction of the vestibular system can severely affect a person's quality of life. Therefore, understanding the molecular basis of vestibular neuron survival, maintenance, and innervation of the target sensory epithelia is fundamental.

Results

Here we report that a point mutation at the phospholipase Cγ (PLCγ) docking site in the mouse neurotrophin tyrosine kinase receptor TrkB (Ntrk2) specifically impairs fiber guidance inside the vestibular sensory epithelia, but has limited effects on the survival of vestibular sensory neurons and growth of afferent processes toward the sensory epithelia. We also show that expression of the TRPC3 cation calcium channel, whose activity is known to be required for nerve-growth cone guidance induced by brain-derived neurotrophic factor (BDNF), is altered in these animals. In addition, we find that absence of the PLCγ mediated TrkB signalling interferes with the transformation of bouton type afferent terminals of vestibular dendrites into calyces (the largest synaptic contact of dendrites known in the mammalian nervous system) on type I vestibular hair cells; the latter are normally distributed in these mutants as revealed by an unaltered expression pattern of the potassium channel KCNQ4 in these cells.

Conclusions

These results demonstrate a crucial involvement of the TrkB/PLCγ-mediated intracellular signalling in structural aspects of sensory neuron plasticity.
Inheritance and identification of molecular markers associated with a novel dwarfing gene in barley
Authors: Ren Xifeng , Sun Dongfa , Guan Weiwei , Sun Genlou , Li Chengdao
Published: October 2010

Background

Dwarfing genes have widely been used in barley breeding program. More than 30 types of dwarfs or semidwarfs have been reported, but a few has been exploited in barley breeding because pleiotropic effects of dwarfing genes cause some undesired traits. The plant architecture of newly discovered dwarfing germplasm "Huaai 11" consisted of desirable agronomic traits such as shortened stature and early maturity. Genetic factor controlling the plant height in dwarf line Huaai 11 was investigated.

Results

The Huaai 11 was crossed with tall varieties Monker, Mpyt, Zhenongda 3, Zaoshu 3, Advance, Huadamai 1, Huadamai 6, Hyproly and Ris01508. All the F1 plants displayed tall trait. Both tall and dwarf plants appeared in all the F2 populations with a 3:1 segregation ratio, suggesting that dwarfism of Huaai 11 is controlled by a single recessive gene, btwd1. Allelism test indicated that this dwarfing gene in the Huaai 11 is nonallelic with the gene br, uzu, sdw1 and denso. Using a double haploid population derived from a cross of Huadamai 6 and Huaai 11 and SSR markers the novel dwarfing gene was mapped onto the long arm of chromosome 7H, and closely linked to Bmac031 and Bmac167 with genetic distance of 2.2 cM.

Conclusion

Huaai 11 is a new source of dwarf for broadening the genetic base of dwarfism. This dwarf source was controlled by a recessive dwarfing gene btwd1, was mapped onto the long arm of chromosome 7H.
Gene expression profiling in the stress control brain region hypothalamic paraventricular nucleus reveals a novel gene network including Amyloid beta Precursor Protein
Authors: Tsolakidou Amalia , Czibere Ludwig , Pütz Benno , Trümbach Dietrich , Panhuysen Markus , Deussing Jan M , Wurst Wolfgang , Sillaber Inge , Landgraf Rainer , Holsboer Florian , Rein Theo
Published: October 2010

Background

The pivotal role of stress in the precipitation of psychiatric diseases such as depression is generally accepted. This study aims at the identification of genes that are directly or indirectly responding to stress. Inbred mouse strains that had been evidenced to differ in their stress response as well as in their response to antidepressant treatment were chosen for RNA profiling after stress exposure. Gene expression and regulation was determined by microarray analyses and further evaluated by bioinformatics tools including pathway and cluster analyses.

Results

Forced swimming as acute stressor was applied to C57BL/6J and DBA/2J mice and resulted in sets of regulated genes in the paraventricular nucleus of the hypothalamus (PVN), 4 h or 8 h after stress. Although the expression changes between the mouse strains were quite different, they unfolded in phases over time in both strains. Our search for connections between the regulated genes resulted in potential novel signalling pathways in stress. In particular, Guanine nucleotide binding protein, alpha inhibiting 2 (GNAi2) and Amyloid β (A4) precursor protein (APP) were detected as stress-regulated genes, and together with other genes, seem to be integrated into stress-responsive pathways and gene networks in the PVN.

Conclusions

This search for stress-regulated genes in the PVN revealed its impact on interesting genes (GNAi2 and APP) and a novel gene network. In particular the expression of APP in the PVN that is governing stress hormone balance, is of great interest. The reported neuroprotective role of this molecule in the CNS supports the idea that a short acute stress can elicit positive adaptational effects in the brain.
The longitudinal association of common susceptibility variants for type 2 diabetes and obesity with fasting glucose level and BMI
Authors: Webster Rebecca J , Warrington Nicole M , Beilby John P , Frayling Timothy M , Palmer Lyle J
Published: October 2010

Background

Variation in the effects of genetic variants on physiological traits over time or with age may alter the trajectories of these traits. However, few studies have investigated this possibility for variants associated with type 2 diabetes or obesity, and these show little consensus. We aimed to characterise the possible longitudinal associations of common diabetes-susceptibility variants in the KCNJ11, PPARG, TCF7L2, IGF2BP2, CDKAL1, SLC30A8 and HHEX gene loci, with fasting glucose level; and of an obesity-associated variant in the FTO gene, with body mass index (BMI).

Methods

The study analysed data from the Busselton Health Study (n = 4,554). Cross-sectional association analyses included family data and used the total association test. Longitudinal association analyses of unrelated participant data (n = 2,864) used linear mixed-effects models.

Results

In cross-sectional analyses, we observed associations of the T allele at the IGF2BP2 single nucleotide polymorphism (SNP) rs4402960 with raised fasting glucose (p = 0.045), and the A allele at the FTO SNP rs9939609 with raised BMI (p = 0.003). Longitudinal analyses showed no significant associations between SNPs and changes in fasting glucose or BMI in the same individuals, either over mean follow-up times of 18.7 and 21.8 years respectively, or with age during adulthood.

Conclusions

There was no indication that the effects of common type 2 diabetes variants on fasting glucose varied with age during adulthood or over time.
A novel envelope mediated post entry restriction of murine leukaemia virus in human cells is Ref1/TRIM5α independent
Authors: Oliveira Nidia MM , Trikha Roochi , McKnight Áine
Published: October 2010

Background

'Intrinsic' resistance to retroviral infection was first recognised with the Friend virus susceptibility gene (Fv1), which determines susceptibility to murine leukaemia virus (MLV) infection in different murine species. Similarly, the tripartite motif (TRIM) family of proteins determine lentiviral restriction in a primate host-species specific manner. For example rhesus TRIM5α (rhTRIM5α) can potently restrict HIV-1 infection while human TRIM5α (huTRIM5α) only has a mild effect on SIVmac and HIV-1 infectivity (Lv1). Human TRIM5α is able to restrict MLV-N virus replication, but is ineffective against MLV-B or MLV-NB virus infection. Lv2 restriction of some HIV-2 viruses is seen in human cells. Like Lv1, Lv2 is a post-entry restriction factor, whose viral determinants have been mapped to the viral capsid (CA). Unlike Lv1, however, Lv2 is determined by envelope (Env) in addition to CA. Here we present evidence of a novel Env determined post entry restriction to infection in human cells of pseudotyped MLV-B and MLV-NB cores.

Results

We generated retroviral vectors pseudotyped with various gamma and lentiviral Envs on MLV-B and -NB CAs containing a green fluorescent protein (GFP) reporter. Flow cytometry was used to determine transduction efficiencies in NP2/CD4/CXCR4 (glioma cell line stably transduced with the HIV receptors) and HeLa/CD4 cell lines. The HeLa/CD4 cell line restricted both MLV CAs in an Env dependent manner, compared to NP2/CD4/CXCR4 cells. Quantitative polymerase chain reaction (QT-PCR) analysis of reverse transcription (RT) transcripts demonstrates that this restriction occurs at a post entry and RT level. siRNA knockdown of huTRIM5α ruled out a direct role for this cellular component in mediating this restriction. We describe a previously unobserved Env determined restriction of MLV-B and MLV-NB CAs in HeLa/CD4 cells when pseudotyped with HIV-2 and RD114 Envs, but not gibbon ape leukaemia virus (GALV), HIV-1 or Amphotrophic (Ampho) Envs.

Conclusions

Our data further demonstrate the variability of Env and CA mediated susceptibility to post entry host cell restriction. We discuss the relevance of these findings in light of the growing evidence supporting the complexities involved in innate host immunity to retroviral infection.
Financing the Millennium Development Goals for health and beyond: sustaining the 'Big Push'
Authors: Ooms Gorik , Stuckler David , Basu Sanjay , McKee Martin
Published: October 2010

Many of the Millennium Development Goals are not being achieved in the world's poorest countries, yet only five years remain until the target date. The financing of these Goals is not merely insufficient; current evidence indicates that the temporary nature of the financing, as well as challenges to coordinating its delivery and directing it to the most needy recipients, hinder achievement of the Goals in countries that may benefit most. Traditional approaches to providing development assistance for health have not been able to address both prevalent and emergent public health challenges captured in the Goals; these challenges demand sustained forms of financial redistribution through a coordinated mechanism. A global social health protection fund is proposed to address recurring failures in the modern aid distribution mechanism. Such a Fund could use established and effective strategies for aid delivery to mitigate many financial problems currently undermining the Millennium Development Goals initiative.