bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracardiac Echocardiography during Catheter-Based Ablation of Atrial Fibrillation
Authors: Biermann Jürgen , Bode Christoph , Asbach Stefan
Published: June 2012

Accurate delineation of the variable left atrial anatomy is of utmost importance during anatomically based ablation procedures for atrial fibrillation targeting the pulmonary veins and possibly other structures of the atria. Intracardiac echocardiography allows real-time visualisation of the left atrium and adjacent structures and thus facilitates precise guidance of catheter-based ablation of atrial fibrillation. In patients with abnormal anatomy of the atria and/or the interatrial septum, intracardiac ultrasound might be especially valuable to guide transseptal access. Software algorithms like CARTOSound (Biosense Webster, Diamond Bar, USA) offer the opportunity to reconstruct multiple two-dimensional ultrasound fans generated by intracardiac echocardiography to a three-dimensional object which can be merged to a computed tomography or magnetic resonance imaging reconstruction of the left atrium. Intracardiac ultrasound reduces dwell time of catheters in the left atrium, fluoroscopy, and procedural time and is invaluable concerning early identification of potential adverse events. The application of intracardiac echocardiography has the great capability to improve success rates of catheter-based ablation procedures.
Two‐Dimensional and Axisymmetric Unsteady Flows due to Normally Expanding or Contracting Parallel Plates
Authors: Dinarvand Saeed , Moradi Abed
Published: June 2012

The flow of a viscous incompressible fluid between two parallel plates due to the normal motion of the plates for two cases, the two‐dimensional flow case and the axisymmetric flow case, is investigated. The governing nonlinear equations and their associated boundary conditions are transformed into a highly non‐linear ordinary differential equation. The series solution of the problem is obtained by utilizing the homotopy perturbation method (HPM). Graphical results are presented to investigate the influence of the squeeze number on the velocity, skin friction, and pressure gradient. The validity of our solutions is verified by the numerical results obtained by shooting method, coupled with Runge‐Kutta scheme.
Pharmacogenomic Profiling and Pathway Analyses Identify MAPK-Dependent Migration as an Acute Response to SN38 in p53 Null and p53-Mutant Colorectal Cancer Cells
Authors: Allen Wendy L. , Turkington Richard C. , Stevenson Leanne , Carson Gail , Coyle Vicky M. , Hector Suzanne , Dunne Philip , Van Schaeybroeck Sandra , Longley Daniel B. , Johnston Patrick G.
Published: June 2012

The topoisomerase I inhibitor irinotecan is used to treat advanced colorectal cancer and has been shown to have p53-independent anticancer activity. The aim of this study was to identify the p53-independent signaling mechanisms activated by irinotecan. Transcriptional profiling of isogenic HCT116 p53 wild-type and p53 null cells was carried out following treatment with the active metabolite of irinotecan, SN38. Unsupervised analysis methods showed that p53 status had a highly significant impact on gene expression changes in response to SN38. Pathway analysis indicated that pathways involved in cell motility [adherens junction, focal adhesion, mitogen-activated protein kinase (MAPK), and regulation of the actin cytoskeleton] were significantly activated in p53 null cells, but not p53 wild-type cells, following SN38 treatment. In functional assays, SN38 treatment increased the migratory potential of p53 null and p53-mutant colorectal cancer cell lines, but not p53 wild-type lines. Moreover, p53 null SN38-resistant cells were found to migrate at a faster rate than parental drug-sensitive p53 null cells, whereas p53 wild-type SN38-resistant cells failed to migrate. Notably, cotreatment with inhibitors of the MAPK pathway inhibited the increased migration observed following SN38 treatment in p53 null and p53-mutant cells. Thus, in the absence of wild-type p53, SN38 promotes migration of colorectal cancer cells, and inhibiting MAPK blocks this potentially prometastatic adaptive response to this anticancer drug. Mol Cancer Ther; 11(8); 1724–34. ©2012 AACR.
Sorafenib Inhibits Many Kinase Mutations Associated with Drug-Resistant Gastrointestinal Stromal Tumors
Authors: Heinrich Michael C. , Marino-Enriquez Adrian , Presnell Ajia , Donsky Rachel S. , Griffith Diana J. , McKinley Arin , Patterson Janice , Taguchi Takahiro , Liang Cher-Wei , Fletcher Jonathan A.
Published: June 2012

Sorafenib has substantial clinical activity as third- or fourth-line treatment of imatinib- and sunitinib-resistant gastrointestinal stromal tumors (GIST). Because sorafenib targets both angiogenesis-related kinases (VEGFR) and the pathogenetic kinases found in GIST (KIT or PDGFRA), the molecular basis for sorafenib efficacy in this setting remains unknown. We sought to determine the spectrum of activity of sorafenib against different mutant kinases associated with drug-sensitive and drug-resistant GIST. We compared the activity of imatinib and sorafenib against transiently expressed mutant forms of KIT and PDGFRA, including various secondary mutations that have been identified in imatinib-resistant or sunitinib-resistant GISTs. We also examined these drugs against four GIST cell lines, three of which are imatinib resistant. In our in vitro studies, we determined that sorafenib inhibited imatinib-resistant mutations in exons encoding the ATP/drug-binding pocket and in exons encoding the activation loop, with the exception of substitutions at KIT codon D816 and PDGFRA codon 842. Notably our data indicate that sorafenib is more effective than imatinib or sunitinib for inhibiting the kinase activity of drug-resistant KIT mutants (as assessed by biochemical IC50). We hypothesize that a major determinant of the efficacy of sorafenib for treatment of advanced GIST is the activity of this agent against KIT or PDGFRA-mutant kinases. These results have implications for the further development of treatments for drug-resistant GIST. Mol Cancer Ther; 11(8); 1770–80. ©2012 AACR.
Anisotropic Reinforcement of Acute Anteroapical Infarcts Improves Pump Function
Authors: Fomovsky Gregory M. , Clark Samantha A. , Parker Katherine M. , Ailawadi Gorav , Holmes Jeffrey W.
Published: June 2012

Background—

We hypothesize that a therapy that improves left ventricular (LV) pump function early after infarction should decrease the need for compensation through sympathetic activation and dilation, thereby reducing the risk of developing heart failure. The mechanical properties of healing myocardial infarcts are an important determinant of LV function, yet improving function by altering infarct properties has proven unexpectedly difficult. Using a computational model, we recently predicted that stiffening a large anterior infarct anisotropically (in only one direction) would improve LV function, whereas isotropic stiffening, the focus of previous studies and therapies, would not. The goal of this study was to test the novel strategy of anisotropic infarct reinforcement.

Methods and Results—

We tested the effects of anisotropic infarct reinforcement in 10 open-chest dogs with large anteroapical infarcts that depressed LV pump function. We measured regional mechanics, LV volumes, and cardiac output at a range of preloads at baseline, 45 minutes after coronary ligation (ischemia), and 30 minutes later, after surgical reinforcement in the longitudinal direction (anisotropic). Ischemia shifted the end-systolic pressure–volume relationship and cardiac output curves rightward, decreasing cardiac output at matched end-diastolic pressure by 44%. Anisotropic reinforcement significantly improved systolic function without impairing diastolic function, recovering half the deficit in overall LV function.

Conclusions—

We conclude that anisotropic reinforcement is a promising new approach to improving LV function after a large myocardial infarction.
Vascular Medicine in
Circulation
and the
Circulation
Subspecialty Journals
Authors:   The Editors
Published: June 2012

The following articles are being highlighted as part of
Circulation's
Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in
Circulation
and the
Circulation
subspecialty journals. The studies included in this article represent the articles related to vascular medicine that were published in
Circulation
and the
Circulation
subspecialty journals in 2010 and 2011.
Endothelial Cells Are Able to Synthesize and Release Catecholamines Both In Vitro and In Vivo
Authors: Sorriento Daniela , Santulli Gaetano , Del Giudice Carmine , Anastasio Antonio , Trimarco Bruno , Iaccarino Guido
Published: June 2012

Recently it has been demonstrated that catecholamines are produced and used by macrophages and mediate immune response. The aim of this study is to verify whether endothelial cells (ECs), which are of myeloid origin, can produce catecholamines. We demonstrated that genes coding for tyrosine hydroxylase, Dopa decarboxylase, dopamine β hydroxylase (DβH), and phenylethanolamine-
N
-methyl transferase, enzymes involved in the synthesis of catecholamines, are all expressed in basal conditions in bovine aorta ECs, and their expression is enhanced in response to hypoxia. Moreover, hypoxia enhances catecholamine release. To evaluate the signal transduction pathway that regulates catecholamine synthesis in ECs, we overexpressed in bovine aorta ECs either protein kinase A (PKA) or the transcription factor cAMP response element binding, because PKA/cAMP response element binding activation induces tyrosine hydroxylase transcription and activity in response to stress. Both cAMP response element binding and PKA overexpression enhance DβH and phenylethanolamine-
N
-methyl transferase gene expression and catecholamine release, whereas H89, inhibitor of PKA, exerts the opposite effect, evidencing the role of PKA/cAMP response element binding transduction pathway in the regulation of catecholamine release in bovine aorta ECs. We then evaluated by immunohistochemistry the expression of tyrosine hydroxylase, Dopa decarboxylase, DβH, and phenylethanolamine-
N
-methyl transferase in femoral arteries from hindlimbs of C57Bl/6 mice 3 days after removal of the common femoral artery to induce chronic ischemia. Ischemia evokes tyrosine hydroxylase, Dopa decarboxylase, DβH, and phenylethanolamine-
N
-methyl transferase expression in the endothelium. Finally, the pharmacological inhibition of catecholamine release by fusaric acid, an inhibitor of DβH, reduces the ability of ECs to form network-like structures on Matrigel matrix. In conclusion, our study demonstrates for the first time that ECs are able to synthesize and release catecholamines in response to ischemia.
Possible Involvement of Angiotensin-Converting Enzyme 2 and Mas Activation in Inhibitory Effects of Angiotensin II Type 1 Receptor Blockade on Vascular Remodeling
Authors: Iwai Masaru , Nakaoka Hirotomo , Senba Izumi , Kanno Harumi , Moritani Tomozo , Horiuchi Masatsugu
Published: June 2012

We explored the roles of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7), and Mas activation in angiotensin II type 1 receptor blockade-mediated attenuation of vascular remodeling. Vascular injury was induced by polyethylene-cuff placement around the mouse femoral artery. After cuff placement, the mRNA level of both ACE2 and Mas was markedly decreased in wild-type mice, whereas ACE mRNA was not changed. Immunostaining of ACE2 and Mas was observed mainly in the media and was reduced in the injured artery. Administration of angiotensin-(1-7) decreased neointimal formation after cuff placement, whereas administration of [D-Ala(7)] angiotensin-(1-7), a Mas antagonist, increased it. Consistent with these results, we also demonstrated that neointimal formation induced by cuff placement was further increased in ACE2 knockout mice. In angiotensin II type 1a receptor knockout mice, mRNA expression and immunostaining of ACE2 and Mas in the injured artery were greater, with less neointimal formation than in wild-type mice. Increased ACE2 expression in the injured artery was also observed by treatment of wild-type mice with an angiotensin II type 1 receptor blocker, olmesartan. These results suggested that activation of the ACE2-angiotensin-(1-7)-Mas axis is at least partly involved in the beneficial effects of angiotensin II type 1 receptor blockade on vascular remodeling.
Wasps, Termites, and Waspmites: Distinguishing Competence from Performance in Collective Construction
Authors: Bullock Seth , Ladley Dan , Kerby Michael
Published: June 2012

We introduce a distinction between algorithm performance and algorithm competence and argue that bio-inspired computing should characterize the former rather than the latter. To exemplify this, we explore and extend a bio-inspired algorithm for collective construction influenced by paper wasp behavior. Despite its being provably general in its competence, we demonstrate limitations on the algorithm's performance. We explain these limitations, and extend the algorithm to include pheromone-mediated behavior typical of termites. The resulting hybrid waspmite algorithm shares the generality of the original wasp algorithm, but exhibits improved performance and scalability.
Can Capital Account Liberalization Lessen Capital Volatility in a Country with “Original Sin”?
Authors: Park Bokyeong , An Jiyoun
Published: June 2012

The term “original sin” refers to countries that cannot take out foreign loans that are denominated in its own currency. This study investigates how capital account liberalization affects capital flow volatility in countries with and without original sin. Overall, we find that the level of capital openness increases capital flow volatility, and that countries with original sin experience additional volatility in their capital flows. When the data sample is limited to countries with high institutional quality, the difference remains between the two groups—confirming that the different effects of capital openness on volatility should be attributed to differences in the international status of currencies rather than in institutional quality. Emerging economies whose currencies are not internationalized should therefore be more cautious of capital account liberalization.
On the Equivalence of Two Schemes for Convective Momentum Transport
Authors: Romps David M.
Published: June 2012

The Gregory–Kershaw–Inness (GKI) parameterization of convective momentum transport, which has a tunable parameter C, is shown to be identical to a parameterization with no pressure gradient force and a mass flux smaller by a factor of 1 − C. Using cloud-resolving simulations, the transilient matrix for momentum is diagnosed for deep convection in radiative–convective equilibrium. Using this transilient matrix, it is shown that the GKI scheme underestimates the compensating subsidence of momentum by a factor of 1 − C, as predicted. This result is confirmed using a large-eddy simulation.
Thermodynamic Causes for Future Trends in Heavy Precipitation over Europe Based on an Ensemble of Regional Climate Model Simulations
Authors: Radermacher Christine , Tomassini Lorenzo
Published: June 2012

An extreme-value analysis of projected changes in heavy precipitation is carried out for an ensemble of eight high-resolution regional climate model simulations over the European domain. The consideration of several regional climate models that are forced by different global models allows for an assessment of the robustness of the results in terms of intersimulation agreement. The extreme-value statistical method is based on a model that includes time-dependent parameters. Summer and winter are examined separately. This allows for identifying and sharpening the understanding of physical processes inducing the changes in precipitation characteristics. Thermodynamic aspects of changes in heavy precipitation are discussed. Variables that are related to the process of precipitation formation, such as precipitable water and cloud liquid water, are examined. In this context, the scaling of changes in heavy precipitation and other thermodynamic quantities with changes in temperature is explored. The validity of a Clausius–Clapeyron scaling of heavy precipitation is assessed on regional scales. Significant regional and seasonal differences in trends of heavy precipitation and only a limited validity of the Clausius–Clapeyron scaling are found. In winter, enhanced moisture transport and storm-track intensity lead to an increase in heavy precipitation, especially over the northern parts of the European continent. In summer, the increase of precipitable water is less than that required to maintain the same probability for saturation over southern Europe, which results in negative trends of heavy precipitation in these regions.
Local and Remote Climate Impacts from Expansion of Woody Biomass for Bioenergy Feedstock in the Southeastern United States
Authors: Murphy Lisa N. , Riley William J. , Collins William D.
Published: June 2012

Many efforts have been taken to find energy alternatives to reduce anthropogenic influences on climate. Recent studies have shown that using land for bioenergy plantations may be more cost effective and provide a greater potential for CO2 abatement than using land for carbon sequestration. Native southern U.S. pines (i.e., loblolly) have excellent potential as bioenergy feedstocks. However, the land-cover change due to expansion of biofuels may impact climate through biophysical feedbacks. Here, the authors access the local and remote consequences of greater forest management and biofuel feedstock expansion on climate and hydrology using a global climate model, the NCAR Community Climate System Model, version 4 (CCSM4).

The authors examine a plausible U.S. Department of Energy (DOE) biofuel feedstock goal by afforesting 50 million acres of C4 grasslands in the southeastern United States with an optimized loblolly plant functional type. Changes in sensible and latent heat fluxes are related to increased surface roughness, reduced bare-ground evaporation, and changes in stomatal conductance. In the coupled simulations, these mechanisms lead to a 1°C cooling, higher atmospheric stability, and a more shallow planetary boundary layer over the southeastern United States during the summer; in winter, a cooling of up to 0.25°C between 40° and 60°N, a weakened Aleutian low, and a wetter Australia occurs. A weakened Aleutian low shifts the North Pacific storm track poleward in the future loblolly scenarios. These local and global impacts suggest that biophysical feedbacks need to be considered when evaluating the benefits of bioenergy feedstock production.
Wind Field Characterization from the Trajectories of Small Balloons
Authors: Wilkerson Thomas D. , Marchant Alan B. , Apedaile Thomas J.
Published: June 2012

This paper reports the development and application of a new wind sensing system, ValidWind. ValidWind consists of small, helium-filled tracer balloons and an instrument that tracks them with high spatial resolution by means of an eye-safe lidar rangefinder and records 3D balloon position as a function of time. Lightweight retroreflectors attached to the balloons enhance the optical range. Balloon tracking is automatic. The data products include horizontal wind speed, wind direction, and vertical shear as functions of time and geolocation. Vertical wind speeds can be inferred from variations of the balloons’ rate of rise given the balance between buoyancy and aerodynamic drag. Applications of ValidWind include characterization of katabatic and ridge-top wind fields and monitoring of windborne aerosol transport. The capability of ValidWind balloons to provide useful profiles of the wind from the ground up to an altitude of 2 km AGL is presented and analyzed.
Evaluation of the Spatial and Temporal Uncertainties Distribution of Daily-Integrated Shortwave Downward Radiation Estimated from Polar-Orbiting Satellite Observation
Authors: Liu Yang , Liu Ronggao
Published: June 2012

The polar-orbiting satellite sensor, which can observe the entire Earth’s surface with good spatial and spectral resolution, is a potential tool for estimation of global downward shortwave radiation (DSR). However, it can only provide a couple of snapshots in one day, which should be extended to daily-integrated DSR in order to drive the ecosystem models. In this paper, the temporal and spatial uncertainties for estimating of daily-integrated DSR from instantaneous measurements of polar-orbiting satellites are evaluated using geostationary Geosynchronous Meteorological Satellite-5 (GMS-5) observations over East Asia. Those overpass times—including 1030, 1200, and 1330 local time (LT), which correspond to Terra/Moderate Resolution Imaging Spectroradiometer (MODIS), Sea-Viewing Wide Field-of-View Sensor (SeaWiFS), and Aqua/MODIS—are evaluated. The combinations of multiobservations are also assessed.

The results show that the daily-integrated DSR from polar-orbiting satellite observations of 1030, 1200, and 1330 underestimate solar radiation by 2.16% (0.46 MJ m−2), 5.44% (1.16 MJ m−2), and 5.54% (1.09 MJ m−2), with an RMSE of 2.05 MJ m−2 (12.92%), 2.50 MJ m−2 (13.33%), and 2.34 MJ m−2 (13.95%) in East Asia with large spatial and seasonal variations. In general, the bias is higher in the southern than in the northern part of East Asia. It is low in January, February, and March, then increases from April and reaches the maximum in June and July, and decreases rapidly to lower than 1.0 MJ m−2 in October. The uncertainties of daily-integrated DSR could be reduced by averaging multiday observations or combining of multitime observations. These uncertainties’ distributions are important for evaluation the usability of daily-integrated DSR from polar-orbiting satellite data and probably can be used for its calibration.
Comparison of Drop Size Distribution Parameter (D0) and Rain Rate from S-Band Dual-Polarized Ground Radar, TRMM Precipitation Radar (PR), and Combined PR–TMI: Two Events from Kwajalein Atoll
Authors: Bringi V. N. , Huang Gwo-Jong , Munchak S. Joseph , Kummerow Christian D. , Marks David A. , Wolff David B.
Published: June 2012

The estimation of the drop size distribution parameter [median volume diameter (D0)] and rain rate (R) from the Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) as well as from combined PR–TRMM Microwave Imager (TMI) algorithms are considered in this study for two TRMM satellite overpasses near the Kwajalein Atoll. An operational dual-polarized S-band radar (KPOL) located in Kwajalein is central as the only TRMM ground validation site for measurement of precipitation over the open ocean. The accuracy of the TRMM PR in retrieving D0 and R is better for precipitation over the ocean based on a more stable surface reference technique for estimating the path-integrated attenuation. Also, combined PR–TMI methods are more accurate over the open ocean because of better knowledge of the surface microwave emissivity. Using Zh (horizontal polarized radar reflectivity) and Zdr (differential reflectivity) data for the two TRMM overpass events over Kwajalein, D0 and R from KPOL are retrieved. Herein, the main objective is to see if the D0 retrieved from either PR or the combined PR–TMI algorithms are in agreement with KPOL-derived values. Also, the variation of D0 versus R is compared for convective rain pixels from KPOL, PR, and PR–TMI. It is shown that the PR–TMI optimal estimation scheme does indeed adjust the D0 in the “correct” direction, on average, from the a priori state if the KPOL data are considered to be the ground truth. This correct adjustment may be considered as evidence of the value added by the TMI brightness temperatures in the combined PR–TMI variational scheme, at least for the two overpass events considered herein.
Near-Term Effects of the Lower Atmosphere in Simulated Northwest Flow Snowfall Forced over the Southern Appalachians
Authors: Miller Douglas K.
Published: June 2012

Northwest flow snowfall (NWFS) impacts the southern Appalachian Mountains after the upper-level trough has departed from the region, when moist northwesterly flow near the ground is lifted after encountering the mountains. Snowfall associated with these events is highly localized and challenging to predict as the clouds generating the accumulation are mesoscale in structure and depend on rapidly varying structures of moisture, instability, and wind in the planetary boundary layer (PBL) and on the relief of the local topography. The purpose of this study is to investigate the near-term impact of heat and moisture fluxes at the ground on the evolution of an NWFS event using several simulations of the Advanced Research core of the Weather Research and Forecasting mesoscale model. Model simulations indicate that convective banding is responsible for the snowfall accumulations in the southern Appalachians during the event and the structure of the banding is sensitive to the vertical positions of maximum wind shear and minimal stability within the PBL. Sensible heat fluxes at the ground upstream of the mountains in the daytime tend to deepen the PBL, reduce cloud water content, and reduce snowfall accumulations. At the same time, however, the daytime sensible heating also increases the overall vapor of the PBL through increased turbulent mixing and the transport of vapor made available to the atmosphere through upward latent heat fluxes at the ground. Latent heat fluxes at the ground upstream of the southern Appalachian Mountains provide a source of moisture that contributes a significant fraction of the overall simulated snowfall accumulations.
Tropical Cyclone Intensity Estimation in the North Atlantic Basin Using an Improved Deviation Angle Variance Technique
Authors: Ritchie Elizabeth A. , Valliere-Kelley Genevieve , Piñeros Miguel F. , Tyo J. Scott
Published: June 2012

This paper describes results from an improvement to the objective deviation angle variance technique to estimate the intensity of tropical cyclones from satellite infrared imagery in the North Atlantic basin. The technique quantifies the level of organization of the infrared cloud signature of a tropical cyclone as an indirect measurement of its maximum wind speed. The major change described here is to use the National Hurricane Center’s best-track database to constrain the technique. Results are shown for the 2004–10 North Atlantic hurricane seasons and include an overall root-mean-square intensity error of 12.9 kt (6.6 m s−1, where 1 kt = 0.514 m s−1) and annual root-mean-square intensity errors ranging from 10.3 to 14.1 kt. A direct comparison between the previous version and the one reported here shows root-mean-square intensity error improvements in all years with a best improvement in 2009 from 17.9 to 10.6 kt and an overall improvement from 14.8 to 12.9 kt. In addition, samples from the 7-yr period are binned based on level of intensity and on the strength of environmental vertical wind shear as extracted from Statistical Hurricane Intensity Prediction Scheme (SHIPS) data. Preliminary results suggest that the deviation angle variance technique performs best at the weakest intensity categories of tropical storm through hurricane category 3, representing 90% of the samples, and then degrades in performance for hurricane categories 4 and 5. For environmental vertical wind shear, there is far less spread in the results with the technique performing better with increasing vertical wind shear.
Managing Diabetes in Patients With Diabetes of Long Duration
Authors: Triplitt Curtis L.
Published: June 2012

Purpose

The purpose of this article is to review clinical issues related to the management of hyperglycemia in older patients with diabetes of long duration.

Conclusion

Older adults represent an extensive proportion of patients with type 2 diabetes. Treatment goals need to be individualized to take into account comorbid conditions, life expectancy, diabetes complications, and the benefits of glycemic control. For both older patients and especially those with chronic renal insufficiency, the most important drug-related adverse effect to avoid is hypoglycemia, and avoidance of any severe hypoglycemia should be paramount. Patients with long duration of diabetes are often treated with insulin. Recent data show that glucagon-like peptide-1 receptor agonists may be used in combination with insulin for patients not achieving glycemic goals, with reductions in the doses of insulin used and with a low risk of hypoglycemia and possible weight loss.
Advantage of Guaraná (Paullinia cupana Mart.) Supplementation on Cadmium-induced Damages in Testis of Adult Wistar Rats
Authors: Leite Rodrigo P. , Predes Fabrícia S. , Monteiro Juliana C. , Freitas Karine M. , Wada Ronaldo S. , Dolder Heidi
Published: June 2012

Paullinia cupana is an Amazonian bush whose seeds have long been used in folk medicine. However, most of the therapeutic properties attributed to this plant are broad and nonspecific, although an antioxidant activity has been reported.  On the other hand, cadmium is a heavy metal known for increasing free radicals, hence resulting in cellular oxidative damages. This study was designed to evaluate whether Paullinia cupana is able to reduce cadmium-induced morphological impairment in Wistar rat testis. Adult male Wistar rats 110 days old were ip injected with cadmium (1.15 mg/kg BW [body weight]) and subsequently treated with P. cupana during 56 days.  Furthermore, groups receiving either P. cupana extract or cadmium are mentioned. After the treatment period, testis samples were subjected to histological and stereological analyses. Moderate to severe testicular impairments were shown by the animals exposed to cadmium. However, the animals supplemented with P. cupana after cadmium exposure showed a significant decrease in the proportion of damaged seminiferous tubules. Also, P. cupana supplementation was effective in maintaining the number of Leydig cells per testis in the animals exposed to cadmium. In conclusion, P. cupana supplementation was partially efficient in preventing cadmium from damaging the testis of adult Wistar rats.
The preferences of private equity investors in selecting target acquisitions: An international investigation
Authors: Osborne Sarah , Katselas Dean , Chapple Larelle
Published: June 2012

This study investigates the characteristics and attributes that private equity investors prefer when selecting target acquisitions. These characteristics are examined against a matched sample of firms subject to corporate acquisitions via tender/merger offer during 2000–2009, across seven countries: Australia, Canada, the United Kingdom, the USA, France, Germany and Sweden. We show that firm-specific characteristics are more influential in target selection than external or institutional variables. In particular, private equity targets exhibit lower stock volatility and long-term growth prospects, are larger, and have greater abnormal operating income relative to tender/merger offer target firms. Further, private equity bidders exhibit ‘home bias’, implying that familiarity motivates target selection. Institutional factors remain largely insignificant across all tests.
Increased RLS prevalence in children and adolescents with migraine: A case-control study
Authors: Seidel Stefan , Böck Andreas , Schlegel Werner , Kilic Arzu , Wagner Gudrun , Gelbmann Gloria , Hübenthal Almut , Kanbur Incifer , Natriashvili Sofia , Karwautz Andreas , Wöber Christian , Wöber-Bingöl Çiçek
Published: June 2012

Background: Previous studies have reported an increased frequency of restless legs syndrome (RLS) in adult migraine patients. Until now, the frequency of RLS in pediatric patients has not been investigated. We set out to assess the frequency of RLS in children and adolescents with migraine compared to headache-free controls.

Methods: We investigated 111 consecutive patients with a sole diagnosis of migraine with or without aura presenting to the Headache Unit at the Department of Child and Adolescent Psychiatry and 73 headache-free controls for the presence of RLS using a semistructured interview. In addition, we assessed the level of daytime sleepiness by means of the Epworth sleepiness scale (ESS). A second group of headache-free controls was screened for the presence of RLS using an online questionnaire.

Results: The frequency of RLS in migraine patients was significantly higher than in controls (22% vs. 5% ( p < 0.001) and 8% ( p < 0.001)).

Discussion: This is the first study suggesting an association between RLS and migraine in the pediatric population. Future studies are needed to determine the extent of sleep disruption in children and adolescents with migraine and comorbid RLS.
Optimum piezoelectric patch positioning: A strain energy–based finite element approach
Authors: Bachmann Florian , Bergamini Andrea E , Ermanni Paolo
Published: June 2012

For the design of smart composite structures, the placement of piezoelectric patch transducers is a very important issue. For sensing and passive vibration damping applications, the electric charge and the generalized electromechanical coupling coefficient are important parameters. This article presents an approximative but efficient method for the calculation of the generalized coupling coefficient using finite element simulation results. A smart composite turbomachine blade serves as a test structure for the new method. The influence of different laminate integration layers, positions, rotation angles, patch size variations and performance benefits of increased allowable strain is tested with the new procedure. The efficient nature of the method allows for parametric placement studies or even exhaustive search to find the global positioning optimum for the structure under investigation. The proposed method is compared to state-of-the-art procedures for the calculation of the generalized electromechanical coupling factor. The 1:5 scale models of full carbon fabric/epoxy blades were manufactured with structurally integrated piezo modules. Two different piezo placement positions inside the blade were investigated experimentally. The coupling coefficient was determined and compared to the calculated values.
An integrated structural health monitoring approach for crack growth monitoring
Authors: Vanniamparambil Prashanth Abraham , Bartoli Ivan , Hazeli Kavan , Cuadra Jefferson , Schwartz Eric , Saralaya Raghavendra , Kontsos Antonios
Published: June 2012

A novel structural health monitoring approach consisting of guided ultrasonic waves, acoustic emission, and digital image correlation, as well as real-time and postmortem analyses, was implemented to monitor and quantify crack growth in Al 2024 compact tension specimens, designed, and precracked according to ASTM E647-08. Tensile loads were applied according to ASTM E1290-08. Guided ultrasonic waves were generated with pulses centered at three different frequencies and were recorded using piezoelectric transducers. Guided ultrasonic waves were also modeled using finite element wave propagation models. The same transducers were further used for online acoustic emission monitoring. A digital image correlation system continuously monitored the crack growth and provided full-field surface strains. The application of this integrated structural health monitoring approach resulted in reliable damage detection and quantified crack growth measurements. In addition, a novelty detector based on the Mahalanobis distance was implemented in a data fusion scheme to assess the extent of damage. The reported results constitute a proof-of-concept investigation of a novel structural health monitoring approach based on the combination of real-time optical and acoustic nondestructive testing.
Flexural vibration analysis of an automobile water pump bearing-rotor system with a modified transfer matrix method
Authors: Li Zheng-Mei , Zhou Qiong , Tang Jian-Ping , An Qi
Published: June 2012

The loading, elastic deformation and hydrodynamic film effect at each rolling element–raceway contact of automobile water pump bearing are analyzed. Based on this analysis, the total radial stiffness, angular stiffness and radial damping of the two rolling element rows are modelled. These stiffness and damping are taken into the transfer matrix to evaluate the lateral vibration characteristics of a rotor-automobile water pump bearing system. The natural frequencies, mode shapes and unbalance responses of the system are calculated. The effects of the pulley and fan unbalances on the system response under different spindle speeds are studied. The calculation results show that the unbalance response of the system can be reduced by fixing the pulley and fan with the initial phase difference between their unbalances to be 180°, and by increasing the pulley unbalance appropriately when keeping the fan unbalance constant.
Reduced-Intensity Modified Constraint-Induced Movement Therapy Versus Conventional Therapy for Upper Extremity Rehabilitation After Stroke
Authors: Smania Nicola , Gandolfi Marialuisa , Paolucci Stefano , Iosa Marco , Ianes Patrizia , Recchia Serena , Giovanzana Chiara , Molteni Franco , Avesani Renato , Di Paolo Pietro , Zaccala Massimo , Agostini Michela , Tassorelli Cristina , Fiaschi Antonio , Primon Daniela , Ceravolo Maria Grazia , Farina Simona
Published: June 2012

Background. Constraint-induced movement therapy (CIMT) is a rehabilitation approach for arm paresis consisting of an intensive schedule of treatment (6 h/d). The high demand of resources for CIMT is a critical issue for its implementation in the Italian health system. Objective. To compare the effects of a reduced-intensity modified CIMT (mCIMT) program that included splinting the unaffected arm for 12 hours daily with the effects of a conventional rehabilitation program for arm paresis in patients with stroke. Methods. Sixty-six participants with hemiparesis (3-24 months poststroke) who could extend the wrist and several fingers at least 10° were randomly assigned to mCIMT or conventional rehabilitation. Each group underwent 10 (2 h/d) treatment sessions (5 d/wk for 2 weeks). Patients were assessed with the Wolf Motor Function Test (WMFT-FA and WMFT-T), the Motor Activity Log (MAL-AOU and MAL-QOM), and the Ashworth Scale before and after treatment and 3 months later. Results. Between-groups analysis showed that the mCIMT group overall had greater improvement than the control group in terms of the WMFT-FA ( P = .010), MAL-AOU ( P < .001), and MAL-QOM ( P < .001). Differences between groups were significant both after treatment ( P < .01) and at the 3-month follow-up ( P < .01), although 40% of participants did not complete the 3-month assessment. Furthermore, the mCIMT group showed a greater decrease of Ashworth Scale score than the control group at 3 months ( P = .021). Conclusion. Two hours of CIMT may be more effective than conventional rehabilitation in improving motor function and use of the paretic arm in patients with chronic stroke.
Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis
Authors: Goldring Mary B.
Published: June 2012

Chondrogenesis occurs as a result of mesenchymal cell condensation and chondroprogenitor cell differentiation. Following chondrogenesis, the chondrocytes remain as resting cells to form the articular cartilage or undergo proliferation, terminal differentiation to chondrocyte hypertrophy, and apoptosis in a process termed endochondral ossification, whereby the hypertrophic cartilage is replaced by bone. Human adult articular cartilage is a complex tissue of matrix proteins that varies from superficial to deep layers and from loaded to unloaded zones. A major challenge to efforts to repair cartilage by stem cell-based and other tissue-engineering strategies is the inability of the resident chondrocytes to lay down a new matrix with the same properties as it had when it was formed during development. Thus, understanding and comparing the mechanisms of cartilage remodeling during development, osteoarthritis (OA), and aging may lead to more effective strategies for preventing cartilage damage and promoting repair. The pivotal proteinase that marks OA progression is matrix metalloproteinase 13 (MMP-13), the major type II collagen-degrading collagenase, which is regulated by both stress and inflammatory signals. We and other investigators have found that there are common mediators of these processes in human OA cartilage. We also observe temporal and spatial expression of these mediators in early through late stages of OA in mouse models and are analyzing the consequences of knockout or transgenic overexpression of critical genes. Since the chondrocytes in adult human cartilage are normally quiescent and maintain the matrix in a low turnover state, understanding how they undergo phenotypic modulation and promote matrix destruction and abnormal repair in OA may to lead to identification of critical targets for therapy to block cartilage damage and promote effective cartilage repair.
Application of vibroacoustic signals to evaluate tools profile changes in friction stir welding on AA 1050 H24 alloy
Authors: Fernández J Blanco , Roca A Sánchez , Fals H Carvajal , Macías E Jiménez , de la Parte M Pérez
Published: June 2012

This paper presents a study to evaluate the effect of the tool profile on friction stir welding (FSW) process in the aluminium AA 1050, using vibroacoustic signals. The vibroacoustic signals in Z and Y directions have been acquired by the AE instrument NI USB-9234. The characterisation in time and frequency domains and the statistical analysis of vibroacoustical signal have been carried out in order to correlate them with the design of two different tools. Statistical and temporal parameters of discomposed vibroacoustical signals using wavelet transform have been used for filtering vibration signal to eliminate the noise of the FSW machine and the extraction features of them. The analysis has confirmed that the vibroacoustical signals were significantly affected by changes in the tool profiles. Finally, it has been demonstrated that signals generated by this process can be effectively used to characterise the changes on tool design.
Mouse hematopoietic cell–targeted STAT3 deletion: stem/progenitor cell defects, mitochondrial dysfunction, ROS overproduction, and a rapid aging–like phenotype
Authors: Mantel Charlie , Messina-Graham Steven , Moh Akira , Cooper Scott , Hangoc Giao , Fu Xin-Yuan , Broxmeyer Hal E.
Published: June 2012

Nuclear transcription factor Stat3 is important for proper regulation of hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) proliferation, survival, and cytokine signaling responses. A new, noncanonical role for Stat3 in mitochondrial function has been discovered recently. However, there is little information on the role(s) of mitochondrial Stat3 in HSC/HPC function, especially potential effects of Stat3/mitochondrial dysregulation in human diseases. We investigated hematopoietic cell–targeted deletion of the STAT3 gene in HSCs/HPCs with a focus on mitochondrial function. We found that STAT3−/− mice, which have a very shortened lifespan, dysfunctional/dysregulated mitochondrial function and excessive reactive oxygen species production in HSCs/HPCs that coincides with pronounced defects in function. These animals have a blood phenotype with similarities to premature aging and to human diseases of myelodysplastic syndrome and myeloproliferative neoplasms such as erythroid dysplasia, anemia, excessive myeloproliferation, and lymphomyeloid ratio shifts. We show herein that the lifespan of STAT3−/− animals is lengthened by treatment with a reactive oxygen species scavenger, which lessened the severity of the blood phenotype. These data suggest a need for more detailed studies of role(s) of Stat3 in HSC/HPC mitochondrial function in human diseases and raise the idea that mitochondrial Stat3 could be used as a potential therapeutic target.
Ly6G ligation blocks recruitment of neutrophils via a β2-integrin–dependent mechanism
Authors: Wang Jun-Xia , Bair Angela M. , King Sandra L. , Shnayder Ruslan , Huang Ya-Fang , Shieh Chi-Chang , Soberman Roy J. , Fuhlbrigge Robert C. , Nigrovic Peter A.
Published: June 2012

Ly6G is a glycosylphosphatidylinositol (GPI)–anchored protein of unknown function that is commonly targeted to induce experimental neutrophil depletion in mice. In the present study, we found that doses of anti-Ly6G Abs too low to produce sustained neutropenia remained capable of inhibiting experimental arthritis, leaving joint tissues free of infiltrating neutrophils. Thioglycollate-stimulated peritonitis was also attenuated. No alteration in neutrophil apoptosis was observed, implicating impaired recruitment. Indeed, Ly6G ligation abrogated neutrophil migration toward LTB4 and other chemoattractants in a transwell system. Exploring the basis for this blockade, we identified colocalization of Ly6G and β2-integrins by confocal microscopy and confirmed close association by both coimmunoprecipitation and fluorescence lifetime imaging microscopy. Anti-Ly6G Ab impaired surface expression of β2-integrins in LTB4-stimulated neutrophils and mimicked CD11a blockade in inhibiting both ICAM-1 binding and firm adhesion to activated endothelium under flow conditions. Correspondingly, migration of β2-integrin–deficient neutrophils was no longer inhibited by anti-Ly6G. These results demonstrate that experimental targeting of Ly6G has functional effects on the neutrophil population and identify a previously unappreciated role for Ly6G as a modulator of neutrophil migration to sites of inflammation via a β2-integrin–dependent mechanism.
High-content live-cell imaging assay used to establish mechanism of trastuzumab emtansine (T-DM1)–mediated inhibition of platelet production
Authors: Thon Jonathan N. , Devine Matthew T. , Jurak Begonja Antonija , Tibbitts Jay , Italiano Joseph E.
Published: June 2012

Proplatelet production represents a terminal stage of megakaryocyte development during which long, branching processes composed of platelet-sized swellings are extended and released into the surrounding culture. Whereas the cytoskeletal mechanics driving these transformations have been the focus of many studies, significant limitations in our ability to quantify the rate and extent of proplatelet production have restricted the field to qualitative analyses of a limited number of cells over short intervals. A novel high-content, quantitative, live-cell imaging assay using the IncuCyte system (Essen BioScience) was therefore developed to measure the rate and extent of megakaryocyte maturation and proplatelet production under live culture conditions for extended periods of time. As proof of concept, we used this system in the present study to establish a mechanism by which trastuzumab emtansine (T-DM1), an Ab-drug conjugate currently in clinical development for cancer, affects platelet production. High-content analysis of primary cell cultures revealed that T-DM1 is taken up by mouse megakaryocytes, inhibits megakaryocyte differentiation, and disrupts proplatelet formation by inducing abnormal tubulin organization and suppressing microtubule dynamic instability. Defining the pathways by which therapeutics such as T-DM1 affect megakaryocyte differentiation and proplatelet production may yield strategies to manage drug-induced thrombocytopenias.