bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparison of Methods for Estimating Reynolds Stress from ADCP Measurements in Wavy Environments
Authors: Kirincich Anthony R. , Rosman Johanna H.
Published: August 2011

Turbulent Reynolds stresses are now routinely estimated from acoustic Doppler current profiler (ADCP) measurements in estuaries and tidal channels using the variance method, yet biases due to surface gravity waves limit its use in the coastal ocean. Recent modifications to this method, including spatially filtering velocities to isolate the turbulence from wave velocities and fitting a cospectral model to the below-wave band cospectra, have been used to remove this bias. Individually, each modification performed well for the published test datasets, but a comparative analysis over the range of conditions in the coastal ocean has not yet been performed. This work uses ADCP velocity measurements from five previously published coastal ocean and estuarine datasets, which span a range of wave and current conditions as well as instrument configurations, to directly compare methods for estimating stresses in the presence of waves. The computed stresses from each were compared to bottom stress estimates from a quadratic drag law and, where available, estimates of wind stress. These comparisons, along with an analysis of the cospectra, indicated that spectral fitting performs well when the wave climate is wide-banded and/or multidirectional as well as when instrument noise is high. In contrast, spatial filtering performs better when waves are narrow-banded, low frequency, and when wave orbital velocities are strong relative to currents. However, as spatial filtering uses vertically separated velocity bins to remove the wave bias, spectral fitting is able to resolve stresses over a larger fraction of the water column.
E4DVar: Coupling an Ensemble Kalman Filter with Four-Dimensional Variational Data Assimilation in a Limited-Area Weather Prediction Model
Authors: Zhang Meng , Zhang Fuqing
Published: August 2011

A hybrid data assimilation approach that couples the ensemble Kalman filter (EnKF) and four-dimensional variational (4DVar) methods is implemented for the first time in a limited-area weather prediction model. In this coupled system, denoted E4DVar, the EnKF and 4DVar systems run in parallel while feeding into each other. The multivariate, flow-dependent background error covariance estimated from the EnKF ensemble is used in the 4DVar minimization and the ensemble mean in the EnKF analysis is replaced by the 4DVar analysis, while updating the analysis perturbations for the next cycle of ensemble forecasts with the EnKF. Therefore, the E4DVar can obtain flow-dependent information from both the explicit covariance matrix derived from ensemble forecasts, as well as implicitly from the 4DVar trajectory. The performance of an E4DVar system is compared with the uncoupled 4DVar and EnKF for a limited-area model by assimilating various conventional observations over the contiguous United States for June 2003. After verifying the forecasts from each analysis against standard sounding observations, it is found that the E4DVar substantially outperforms both the EnKF and 4DVar during this active summer month, which featured several episodes of severe convective weather. On average, the forecasts produced from E4DVar analyses have considerably smaller errors than both of the stand-alone EnKF and 4DVar systems for forecast lead times up to 60 h.
U.S. Landfalling and North Atlantic Hurricanes: Statistical Modeling of Their Frequencies and Ratios
Authors: Villarini Gabriele , Vecchi Gabriel A. , Smith James A.
Published: August 2011

Time series of U.S. landfalling and North Atlantic hurricane counts and their ratios over the period 1878–2008 are modeled using tropical Atlantic sea surface temperature (SST), tropical mean SST, the North Atlantic Oscillation (NAO), and the Southern Oscillation index (SOI). Two SST input datasets are employed to examine the uncertainties in the reconstructed SST data on the modeling results. Because of the likely undercount of recorded hurricanes in the earliest part of the record, both the uncorrected hurricane dataset (HURDAT) and a time series with a recently proposed undercount correction are considered.

Modeling of the count data is performed using a conditional Poisson regression model, in which the rate of occurrence can depend linearly or nonlinearly on the climate indexes. Model selection is performed following a stepwise approach and using two penalty criteria. These results do not allow one to identify a single “best” model because of the different model configurations (different SST data, corrected versus uncorrected datasets, and penalty criteria). Despite the lack of an objectively identified unique final model, the authors recommend a set of models in which the parameter of the Poisson distribution depends linearly on tropical Atlantic and tropical mean SSTs.

Modeling of the fractions of North Atlantic hurricanes making U.S. landfall is performed using a binomial regression model. Similar to the count data, it is not possible to identify a single best model, but different model configurations are obtained depending on the SST data, undercount correction, and penalty criteria These results suggest that these fractions are controlled by local (related to the NAO) and remote (SOI and tropical mean SST) effects.
Logistics node simulator as an enabler for supply chain development: innovative portainer simulator as the assessment tool for human factors in port cranes
Authors: Bruzzone Agostino , Fadda Paolo , Fancello Gianfranco , Massei Marina , Bocca Enrico , Tremori Alberto , Tarone Federico , D'Errico Gianmarco
Published: August 2011

This paper focuses on the development of a new generation of interoperable simulators of micro activities in a logistics node; the proposed example focuses on a real-time full-scope virtual simulator of port activities able to simulate the activities of the whole port by having ships, cranes, trucks and containers interoperating in a federation. The technologies adopted in terms of architecture and installation were very effective in creating a mobile laboratory open to further extension by online interoperation with other simulators and with biomedical devices for assessing human capabilities within this framework. This approach allows us to face the existing challenges in extending the capabilities of a logistics node over their current capabilities limited by technological and human factors.
Democracy and Political Islam in Bangladesh
Authors: Hasan Mubashar
Published: August 2011

This article examines the deeply contested approaches of ‘political Islam’ towards modern democracy in Bangladesh, the third largest Muslim country in the world, where sharia law is not the source of public law and where a democratic government is in place. Selecting the political manifestos and constitutions of three different influential Islamist parties, the Jamat e Islami Bangladesh, Hizbut Tahrir Bangladesh and Jamatul Mujahedeen Bangladesh, the study examines through discourse analysis why Islamists take such a hostile approach towards democracy. At first sight, Islamists desire the establishment of an alternative governing system, such as the Caliphate, to replace the present parliamentary system of governance in Bangladesh. Islamists also advocate a change of state philosophy from ‘People’s Republic of Bangladesh’ to an ‘Islamic State’, arguing that sharia should be the legal framework of the country. The key finding of this research, however, is that Political Islam in Bangladesh is also perceived as a reaction to globalisation and that this global aspect, in theory and practice, may be more powerful as a reactive agent than local/national politics.
The impact of a migraine attack and its after-effects on perceptual organization, attention, and working memory
Authors: Koppen Hille , Palm-Meinders Inge , Kruit Mark , Lim Vera , Nugroho Aryo , Westhof Iris , Terwindt Gisela , van Buchem Mark , Ferrari Michel , Hommel Bernhard
Published: August 2011

Introduction: Many migraine patients report cognitive complaints during the first hours or days following a migraine attack. The aim of this study was to assess whether and which cognitive (perceptual, attentional, or memory) processes are impaired during the first 48 hours after a migraine attack.

Methods: Three different cognitive tasks (global-local task, the attentional network task, and N-back task) were administered to 16 migraine patients (13 migraine without aura; mean age 58 years, 15 female) and 18 controls (59 years, 15 female), matched on age, gender, and educational level. Tasks were administered at three time points; during the first headache free day following a migraine attack (first session), 24 hours later (second session), and 12 days after the attack (third session).

Results: The attentional network and N-back tasks showed no significant differences between migraineurs and controls. In the global-local task, controls showed faster reaction times to global than to local stimuli, which is the standard global-precedence effect. This effect was absent in the migraineurs in all three sessions, especially if they used prophylaxis.

Conclusion: Migraineurs had no impaired attentional or working-memory functioning in the 2 days after an attack. They did show impairments in the processing of global visual features compared with controls, both between and immediately after an attack.
A Prospective, Comparative, Radiological, and Clinical Study of the Influence of the “Remplissage” Procedure on Shoulder Range of Motion After Stabilization by Arthroscopic Bankart Repair
Authors: Nourissat Geoffroy , Kilinc Alexandre Sahin , Werther Jean Roger , Doursounian Levon
Published: August 2011

Background: Certain failures of arthroscopic Bankart repairs seem to be related to the presence of a Hill-Sachs defect. It has been suggested that Hill-Sachs lesions can be treated by “remplissage” (filling in) of the defect. The effect of this procedure on the mobility of the shoulder is not known.

Purpose: To determine if filling in the Hill-Sachs defect with rotator cuff tendon would modify the range of motion of the operated shoulder.

Study Design: Cohort study; Level of evidence, 2.

Methods: A prospective study of 2 patient populations (arthroscopic Bankart repair alone vs Bankart and remplissage) was undertaken after selecting patients using the Instability Severity Index Score (ISIS). Patients with a Hill-Sachs lesion seen on anteroposterior radiographs had a remplissage procedure if this procedure allowed them to obtain an ISIS lower than 4. The main clinical outcome was the range of motion (external rotation at the side [ER1], external rotation in abduction [ER2], internal rotation [IR], and forward elevation), assessed by the difference between each shoulder at 1 and 2 years’ follow-up. Complications, recurrence, and the Walch-Duplay scores were noted at the same time. Minimum follow-up was 2 years.

Results: No significant statistical difference was noted in the range of motion between each group: ER1, difference of 4° ( P = .22); ER2, difference of 3° ( P = .49); anterior elevation, difference of 5° ( P = .35); and internal rotation, 2 vertebrae ( P = .22). The rate of recurrence was identical in both groups (6.25%). For patients without redislocation, the Walch-Duplay score was excellent (14/17) or good (3/17) in the first group and excellent (12/15) or good (3/15) in the second group. Posterosuperior pain during forceful movements or when tired was noted in one third of patients having undergone remplissage.

Conclusion: The remplissage technique did not alter the range of motion of the shoulder compared with Bankart procedure alone; however, one third of patients did experience posterosuperior pain.
Handling transient response of a vehicle with a planar suspension system
Authors: Zhu J J , Khajepour A , Esmailzadeh E
Published: August 2011

A novel design of a planar suspension system (PSS) is proposed to overcome the limitation of a conventional vehicle suspension system that cannot sufficiently absorb the vibrations and shocks caused by the road obstacles in the longitudinal direction because of the very stiff longitudinal connections between the chassis and the wheels. The rather stiff longitudinal linkages are replaced by a spring–damper strut. The results of the investigation into the transient handling behaviour of a vehicle with a PSS in three different scenarios are presented. These include a vehicle turning on a bumpy road, a vehicle turning combined with braking, and a lane change manoeuvre combined with acceleration. The results obtained from this study demonstrate that the PSS vehicle can effectively suppress the vibrations and shocks in the longitudinal direction without causing the handling performance to deteriorate. It has been shown that the vehicle-handling behaviour is generally comparable with, and under some conditions even better than, those reported for vehicles with a conventional suspension system.
Development and experimental validation of a new one-dimensional valve boundary condition based on the method of characteristics
Authors: Brejaud P , Higelin P , Charlet A , Chamaillard Y
Published: August 2011

One-dimensional (1D) engine gas dynamic simulations are necessary in order to develop control laws for specific valve systems such as variable valve timing or the pneumatic hybrid engine. The keystone of 1D engine models is the valve boundary condition, where the pressure wave phenomenon into a pipe is created and the in-cylinder mass flowrate is determined. Most commercial or research simulation codes embed the method of characteristics (MOC) constant-pressure valve boundary condition from Benson. This constant-pressure model in its original form provides good results in most cases, but this paper shows that it does not converge for low valve opening and pressure ratio values, for which the characteristic lines become vertical. A solution to this problem cannot be found in the literature. The current paper presents a new MOC-based valve boundary condition that obviates convergence problems. The computational time of the proposed model is evaluated and compared with that of Benson’s model. The new valve boundary condition is validated experimentally on a valve gas dynamics test bench and compared with the original constant-pressure model. The study shows that results obtained with the proposed model are similar to data from both experiments and Benson’s model.
Andrée Viollis: A ‘Grand Reporter’ in the Intellectual Resistance, 1942−1944
Authors: Brunazzi Elizabeth
Published: August 2011

The centrepiece of this article concerns a brochure published clandestinely in December 1943, ‘Le Racisme hitlérien: machine de guerre contre la France’; and republished in 1944 by the Éditions de la Clandestinité, Mouvement National Contre le Racisme, Lyon, under the following notice: ‘Nous rééditons ici, sans rien y changer, une de nos publications clandestines parue en décembre 1943. Nous sommes heureux de faire figurer cette fois le nom de l’auteur, l’écrivain bien connu Andrée Viollis, dont la grande voix courageuse prit dès le début notre parti.’ When Andrée Viollis (1870−1950) takes up her pen as a writer engaged in the Resistance, she does so as a seasoned reporter and former international correspondent for the major Paris daily, Le Petit Parisien, who in the 1920s and 1930s reported on civil war in Afghanistan; Gandhi and the anti-colonial movement for independence in India; the torture of political prisoners by the French colonial government in Vietnam; the rise of fascism in imperialist Japan and the incursion of the Japanese regime into China; and the Spanish Civil War, among other events and subjects. She also published four novels and a biography of Madame de Lafayette, but her reputation rests principally on her career as a reporter and international correspondent. Her reporting is characterised by richness of description, dramatisation of interviews, detailed reconstruction of historical and socio-economic backgrounds; and astute, if not visionary, analysis and interpretation of the international importance of the events she covers.
Unnatural Bedfellows: Sexuality and Otherness in Representations of Germans
Authors: Atack Margaret
Published: August 2011

The aim of this article is to address a number of texts where the ‘otherness’ of the German is in part constructed through sexuality. The mobilisation of sexuality in narratives about Fascism and the Holocaust such as in the film The Night Porter, to underline and intensify oppressive, perverse power relations at the frontiers of life and death, has long been noted, and often deplored. This article will focus rather on representations within French literature. Various studies have identified features in traditional representations of the German which construct this figure as different from and opposed to France and the French: barbarism, militarism and stress on group rather than individual identity describe both a Prussian heritage and its Fascist renewal; a ponderous, organised and bureaucratic psychology is contrasted to French wit, energy and resourcefulness; one could extend the list. However, the importance of intense, often ‘deviant’, sexualities and sexual relationships in representations of Germans has received less attention. Sequestration, incest, homosexuality and ambiguous sexual doubles of various kinds are to be found in texts from the 1940s to the twenty-first century − sexual encounters which are frequently locked into psychosexual dramas with strange or monstrous parental relationships.
Observer-based exponential stabilization of Takagi–Sugeno fuzzy systems with state and input delays
Authors: Chiu C-S , Chiang T-S
Published: August 2011

This paper proposes an exponential stabilization control method for uncertain Takagi–Sugeno fuzzy systems with state and input delays via output feedback. First, a unified memoryless fuzzy observer-based control method is introduced for stabilizing continuous and discrete uncertain time-delay fuzzy systems. Then, the exponential stability conditions are derived and converted to solving linear matrix inequality (LMI) problems. Based on the developed novel LMI algorithms, the controller and observer gains are able to be separately designed even in the presence of modelling uncertainty, state delay, and input delay. In comparison with existing techniques the proposed technique produces controlled states and state estimation errors that are guaranteed to exponentially converge to zero via output feedback. This is a major breakthrough for the control of uncertain systems with both state and input unavailable time-varying delays. Finally, two studies are carried out on continuous and discrete time-delay systems. Numerical simulation and comparison results demonstrate the quality of the obtained performance.
Mindfulness, Spousal Attachment, and Marital Satisfaction: A Mediated Model
Authors: Jones Kendra C. , Welton Sarah R. , Oliver Tanner C. , Thoburn John W.
Published: August 2011

The purpose of this study was to investigate the relationships between mindfulness, spousal attachment, and marital satisfaction. The national sample included 104 married adults aged 19–66. Results indicated partial support for the mediating effect of spousal attachment on the relationship between trait mindfulness and marital satisfaction. Although the relationship between trait mindfulness and marital satisfaction demonstrated in the current study is not the first of its kind, these results provide preliminary support for the role of spousal attachment as the mechanism through which trait mindfulness may contribute to greater marital satisfaction. These findings suggest that mindful attunement to one’s partner may promote the activation and growth of neural circuitry associated with safety, security, and positive affect within the romantic relationship, that mindfulness training may have beneficial effects for couples' therapy and relationship enhancement, and that mindfulness training could help foster healthy spousal attachment.
Parent-Led, Therapist-Assisted, First-Line Treatment for Young Children After Trauma
Authors: Salloum Alison , Storch Eric A.
Published: August 2011

Due to the prevalence of childhood posttraumatic stress disorder and barriers to treatment, novel service delivery approaches such as parent-led, therapist-assisted, trauma-focused cognitive behavioral therapy (PTA-TF-CBT) within a stepped care model are needed. This case study presents the treatment of a 4-year-old boy with posttraumatic stress symptoms whose parent led the treatment with therapist assistance and empirically supported materials. Findings from this case study indicated that: (a) PTA-TF-CBT was an acceptable and satisfactory treatment to the parent, (b) therapist time delivering the treatment was limited thereby conserving resources, and (c) clinically significant improvements in child and parent distress were reported posttreatment and at 5 weeks follow-up. Additional research on the feasibility and efficacy of PTA-TF-CBT within a stepped care model is warranted.
Prelude to populism
Authors: DeCanio Samuel , Smidt Corwin D.
Published: August 2011

This article uses underutilized individual-level data to examine who supported two third parties, the Grange and Greenbackers, in the final decades of the nineteenth century. We find that Greenbackers attracted individuals employed in non-agrarian occupations and others who were wealthier compared to major party voters. However, the Grange principally appealed to farmers, indicating third parties that are believed to have appealed to similar constituencies often appealed to different electoral groups. Both the Grange and the Greenbackers appealed to voters lacking strong ethnocultural identifications with either major party.
Design of active vibration control for launcher of multiple launch rocket system
Authors: Zhan Zh-H , Rui X-T , Rong B , Yang F-F , Wang G-P
Published: August 2011

This study deals with analysis and design of active vibration control algorithm for the launcher of multiple launch rocket system (MLRS). The new method proposed is that guidance and control package are equipped on launcher, not rocket, to active control motion of launcher for the first time. It has interesting advantages as follows: (1) active vibration control is more competent, more pliable, and more realizable in engineering compared to passive vibration control. (2) The guidance and control package will not be destroyed. In this study, transfer matrix method of multibody system is used to build the controlled dynamic model of MLRS. This method does not need the global dynamic equations of system and has high computational rate. Independent modal space control method and optimal control theorem are applied to design control law with feedforward and feedback control loops. The modal filters are designed as the state estimator to obtain the modal coordinates and their derivatives. Modal disturbance force observer is designed to obtain modal disturbance force. Pulse-width pulse-frequency (PWPF) modulator is used to modulate the continue control force command into discrete control force in order to avoid high non-linear control action of pulse thruster. The control force provided by pulse thruster and parameters of PWPF are obtained. The numerical results indicate that control law determined by optimal theorem integrated with PWPF modulator achieves good performance in active vibration control of launcher. This study improves the performance of MLRS in resisting impact and provides theoretical support for accurate launch.
When Ethics and Policy Collide
Authors: Hightower Bynum Blake , Klinker JoAnn Franklin
Published: August 2011

This case study explores an ethical dilemma faced by a new junior high school principal. It is appropriate for use in all preparation course work, including the internship. Studies show that novice principal decision making differs from that of experienced principals in moral dilemmas, including following policy versus best interests of the student. Implications for training prospective principals include internal conflict resolution, rational decision-making theory, the role of intuition in decision making, and ethical behavior standards for school administrators.
Suicide From the Perspectives of Older Men Who Experience Depression
Authors: Oliffe John L. , Han Christina S. E. , Ogrodniczuk John S. , Phillips J.Craig , Roy Philippe
Published: August 2011

Depression can be a pathway to older men’s suicide, yet the mechanisms by which this can occur are poorly understood. A qualitative study of 22 older men who self-identified or were formally diagnosed with depression was conducted to describe the connections between masculinity, depression, and suicide. Analyses of individual interviews revealed that cumulative losses around social bonds were central to older men’s depression, apathy for living, and thoughts about suicide. Prominent were men’s self-assessments of failing to fulfill breadwinner roles, judgments that led participants to ruminate on their shortcomings amid recognizing their older age as limiting opportunities for redemption. Stigma featured as a barrier for men acting on their suicidal thoughts, and guilt about the pain their suicide would evoke on family and friends was a strong deterrent for men’s self-harm. Overall, participants’ alignment to masculine ideals influenced both the connectedness and detachment between older men’s depression and suicide.
Ikaros: master of hematopoiesis, agent of leukemia
Authors: Davis Kara L.
Published: August 2011

Ikaros is the founding member of a family of zinc finger transcription factors whose function during early hematopoietic development is required for differentiation into the three major hematopoietic lineages. Ikaros deletions have been described in human malignancies, particularly precursor B-cell leukemia. Deletions of this transcription factor appear to mediate leukemogenesis, although the exact mechanism is unclear. This article reviews the structure and function of Ikaros proteins in chromatin remodeling and gene expression as well as the current knowledge of Ikaros deletions in human malignancies. A new proteomic platform, mass cytometry, is introduced which allows measurements of greater than 30 parameters at the single-cell level and should thus provide a greater level of detail to unravel the mechanistic consequences of Ikaros dysfunction in leukemia.
In vivo imaging of the molecular distribution of the VEGF receptor during angiogenesis in a mouse model of ischemia
Authors: Hamada Yoh , Gonda Kohsuke , Takeda Motohiro , Sato Akira , Watanabe Mika , Yambe Tomoyuki , Satomi Susumu , Ohuchi Noriaki
Published: August 2011

Vascular endothelial growth factor (VEGF) plays a critical role in angiogenesis and has been applied to medical therapy. However, because vascular imaging at the molecular level is impossible, the detailed in vivo dynamics of VEGF and its receptor (VEGFR) remain unknown. In this study, to understand the molecular distribution of VEGF and the VEGFR, we prepared ischemic mice with a new surgical method and induced angiogenesis in the gastrocnemius muscle. Then, we made a VEGF-conjugated fluorescence nanoparticle and performed staining of VEGFR-expressing cells with the fluorescent probe, demonstrating the high affinity of the probe for VEGFR. To observe the physiologic molecular distribution of VEGFR, we performed in vivo single-particle imaging of gastrocnemius in the ischemic leg with the fluorescent probe. The results suggested that only a 3-fold difference of VEGFR distribution is involved in the formation of branched vasculature in angiogenesis, although previous ex vivo data showed a 13-fold difference in its distribution, indicating that a method inducing a several-fold local increase of VEGFR concentration may be effective in generating site-specific angiogenesis in ischemic disease. This new in vivo imaging of ischemic mice could make useful contributions to understanding the mechanisms of angiogenesis and to developing a VEGFR-related drug.
Bcr-abl signals to desensitize chronic myeloid leukemia cells to IFNα via accelerating the degradation of its receptor
Authors: Bhattacharya Sabyasachi , Zheng Hui , Tzimas Christos , Carroll Martin , Baker Darren P. , Fuchs Serge Y.
Published: August 2011

Constitutive activity of Bcr-abl fusion protein kinase causes chronic myeloid leukemia (CML). Inhibitors of Bcr-abl such as imatinib mesylate have replaced the cytokine IFNα as the primary treatment for the management of patients with this malignancy. We found that pretreatment of CML cells with imatinib mesylate augments the antigrowth effects of IFNα. Furthermore, introduction of Bcr-abl into non-CML cells inhibits the cellular responses to IFNα. This inhibition is mediated via a mechanism that involves activation of protein kinase D2. The latter promotes an accelerated phosphorylation-dependent degradation of the interferon-α/β receptor 1 chain of the type I interferon receptor, leading to attenuation of IFNα signaling. We discuss the relationship between Bcr-abl activity and IFNα signaling as a molecular basis of the combination of inhibitors of Bcr-abl and IFNα for CML treatment.
Occlusive thrombi arise in mammals but not birds in response to arterial injury: evolutionary insight into human cardiovascular disease
Authors: Schmaier Alec A. , Stalker Timothy J. , Runge Jeffrey J. , Lee Dooyoung , Nagaswami Chandrasekaran , Mericko Patricia , Chen Mei , Cliché Simon , Gariépy Claude , Brass Lawrence F. , Hammer Daniel A. , Weisel John W. , Rosenthal Karen , Kahn Mark L.
Published: August 2011

Mammalian platelets are small, anuclear circulating cells that form tightly adherent, shear-resistant thrombi to prevent blood loss after vessel injury. Platelet thrombi that form in coronary and carotid arteries also underlie common vascular diseases such as myocardial infarction and stroke and are the target of drugs used to treat these diseases. Birds have high-pressure cardiovascular systems like mammals but generate nucleated thrombocytes rather than platelets. Here, we show that avian thrombocytes respond to many of the same activating stimuli as mammalian platelets but are unable to form shear-resistant aggregates ex vivo. Avian thrombocytes are larger than mammalian platelets, spread less efficiently on collagen, and express much lower levels of the α2bβ3 integrin required for aggregate formation, features predicted to make thrombocyte aggregates less resistant than platelets are to the high fluid shear forces of the arterial vasculature. In vivo carotid vessel injury stimulates the formation of occlusive platelet thrombi in mice but not in the size- and flow-matched carotid artery of the Australian budgerigar. These studies indicate that unique physical and molecular features of mammalian platelets enable them to form shear-resistant arterial thrombi, an essential element in the pathogenesis of human cardiovascular diseases.
BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients
Authors: Visani Giuseppe , Malerba Lara , Stefani Pietro Maria , Capria Saveria , Galieni Piero , Gaudio Francesco , Specchia Giorgina , Meloni Giovanna , Gherlinzoni Filippo , Giardini Claudio , Falcioni Sadia , Cuberli Francesca , Gobbi Marco , Sarina Barbara , Santoro Armando , Ferrara Felicetto , Rocchi Marco , Ocio Enrique M. , Caballero Maria Dolores , Isidori Alessandro
Published: August 2011

We designed a phase 1-2 study to evaluate the safety and the efficacy of increasing doses of bendamustine (160 mg/m2, 180 mg/m2, and 200 mg/m2 given on days −7 and −6) coupled with fixed doses of etoposide, cytarabine, and melphalan (BeEAM regimen) as the conditioning regimen to autologous stem cell transplantation for resistant/relapsed lymphoma patients. Forty-three patients (median age, 47 years) with non-Hodgkin (n = 28) or Hodgkin (n = 15) lymphoma were consecutively treated. Nine patients entered the phase 1 study; no patients experienced a dose-limiting toxicity. Thirty-four additional patients were then treated in the phase 2. A median number of 6 × 106 CD34+ cells/kg (range, 2.4-15.5) were reinfused. All patients engrafted, with a median time to absolute neutrophil count > 0.5 × 109/L of 10 days. The 100-day transplantation-related mortality was 0%. After a median follow-up of 18 months, 35 of 43 patients (81%) are in complete remission, whereas 6 of 43 relapsed and 2 of 43 did not respond. Disease type (non-Hodgkin lymphomas vs Hodgkin disease) and disease status at transplantation (chemosensitive vs chemoresistant) significantly influenced DFS (P = .01; P = .007). Remarkably, 4 of 43 (9%) patients achieved the first complete remission after receiving the high-dose therapy with autologous stem cell transplantation. In conclusion, the new BeEAM regimen is safe and effective for heavily pretreated lymphoma patients. The study was registered at European Medicines Agency (EudraCT number 2008-002736-15).
Interleukin-17A induces glucocorticoid insensitivity in human bronchial epithelial cells
Authors: Zijlstra G.J. , ten Hacken N.H.T. , Hoffmann R.F. , van Oosterhout A.J.M. , Heijink I.H.
Published: August 2011

A subset of asthma patients suffer from glucocorticoid (GC) insensitivity. T-helper cell type 17 cells have an emerging role in GC insensitivity, although the mechanisms are still poorly understood.

We investigated whether interleukin (IL)-17A induces GC insensitivity in airway epithelium by studying its effects on responsiveness of tumour necrosis factor (TNF)-α-induced IL-8 production to budesonide in human bronchial epithelial 16HBE cells. We unravelled the underlying mechanism by the use of specific pathway inhibitors, reporter and overexpression constructs and a histone deacetylase (HDAC) activity assay.

We demonstrated that IL-17A-induced IL-8 production is normally sensitive to GCs, while IL-17A pre-treatment significantly reduced the sensitivity of TNF-α-induced IL-8 production to budesonide. IL-17A activated the p38, extracellular signal-related kinase (ERK) and phosphoinositide-3-kinase (PI3K) pathways, and the latter appeared to be involved in IL-17A-induced GC insensitivity. Furthermore, IL-17A reduced HDAC activity, and overexpression of HDAC2 reversed IL-17A-induced GC insensitivity. In contrast, IL-17A did not affect budesonide-induced transcriptional activity of the GC receptor, suggesting that IL-17A does not impair the actions of the ligated GC receptor.

In conclusion, we have shown for the first time that IL-17A induces GC insensitivity in airway epithelium, which is probably mediated by PI3K activation and subsequent reduction of HDAC2 activity. Thus, blockade of IL-17A or downstream signalling molecule PI3K may offer new strategies for therapeutic intervention in GC-insensitive asthma.
Bosentan inhibits cigarette smoke-induced endothelin receptor expression in pulmonary arteries
Authors: Milara J. , Gabarda E. , Juan G. , Ortiz J.L. , Guijarro R. , Martorell M. , Morcillo E.J. , Cortijo J.
Published: August 2011

The endothelin (ET) system contributes to lung vascular tension and remodelling in smokers and chronic obstructive pulmonary disease (COPD) patients.

This study examined the effect of cigarette smoke (CS) on ET receptor A (ETA) and B (ETB) expression in human pulmonary artery smooth muscle cells (HPASMCs) and human small intrapulmonary arteries, as well as their functional consequences.

CS extract (CSE) increased ETAand ETBexpression in HPASMCs and small intrapulmonary arteries, which was attenuated by bosentan, the ETAantagonist BQ123 and the ETBantagonist BQ788, and by blocking ET-1 with a monoclonal antibody against ET-1, suggesting a feed-forward mechanism mediated by ET-1 release. ET receptor (ETR) antagonism attenuated the CSE-induced HPASMC proliferation. Furthermore, CSE exposure increased the acute ET-1-induced small intrapulmonary artery contraction, which was attenuated by bosentan, BQ123 and BQ788. Pulmonary arteries from smokers and COPD patients showed a higher expression of ETAand ETBthan those of nonsmoker patients.

These results show a novel mechanism by which ETR blockade attenuates CS-induced ETR overexpression and, subsequently, small intrapulmonary artery tension. These data may be of potential value to explain therapeutic effects of bosentan in some forms of disproportionate pulmonary hypertension in COPD patients.
Surgical implications of the new IASLC/ATS/ERS adenocarcinoma classification
Authors: Van Schil P.E. , Asamura H. , Rusch V.W. , Mitsudomi T. , Tsuboi M. , Brambilla E. , Travis W.D.
Published: August 2011

A new adenocarcinoma classification was recently introduced by a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS). A distinction is made between pre-invasive lesions, and minimally invasive and invasive adenocarcinoma. The confusing term “bronchioloalveolar carcinoma” is not used any more and new subcategories include adenocarcinomain situand minimally invasive adenocarcinoma.

Due to a renewed interest in screen-detected nodules and early-stage lung cancers of <2 cm, this classification also has profound implications for thoracic surgeons.

In this article, surgical topics are discussed: the role of a minimally invasive approach, especially video-assisted thoracic surgery, limited resection for early-stage lung cancer, the extent of lymph node dissection, the accuracy of intraoperative frozen section analysis, management of multiple lung nodules and prognostic factors in operated patients. Specific key issues are presented based on the current evidence and areas of surgical uncertainty are defined providing a basis for further studies.

Thoracic surgeons will play a major role in the application and global introduction of this new adenocarcinoma classification. The remaining controversies regarding the precise diagnosis and management of early-stage lesions will have to be resolved by multidisciplinary and international collaboration.
Resistin-like molecule-β is a human airway remodelling mediator
Authors: Fang C. , Meng Q. , Wu H. , Eid G. , Zhang G. , Zhang X. , Yang S. , Huang K. , Lee T.H. , Corrigan C.J. , Ying S.
Published: August 2011

Though implicated in vascular remodelling, a role for the resistin-like molecule (RELM)-β in human airway remodelling remains unexplored. We hypothesised that RELM-β expression is increased in the airways of asthmatics and regulates airways epithelial cell function.

Expression of RELM-β in the bronchial mucosa and its concentrations in bronchoalveolar lavage (BAL) fluid from asthmatics and controls were measured by immunohistochemistry and ELISA, respectively. Proliferation assays, Western blotting, ELISA and real-time PCR were employed to detect effects of RELM-β on airways epithelial cells.

RELM-β expression was increased in the bronchial mucosa and BAL fluid of asthmatics compared with controls. In the asthmatics, the numbers of mucosal RELM-β+ cells correlated inversely with forced expiratory volume in 1 s (r=-0.531, p=0.016), while the numbers of epithelial RELM-β+ cells correlated positively with those of mucin (MUC)5AC+ cells.In vitro, interleukin-13 enhanced RELM-β expression by primary human airways epithelial cells, while RELM-β itself acted on these cells to induce proliferation, expression of MUC5AC, extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK)-phosphatidylinositol 3-kinase (PI3K)/Akt phosphorylation and elevated expression of transforming growth factor-β2, epidermal growth factor and vascular endothelial growth factor.

RELM-β has the potential to contribute to airway remodelling in diseases such as asthma by acting on epithelial cells to increase proliferation, mucin and growth factor production, at least partlyviaERK/MAPK-PI3K/Akt signalling pathways.
New tools in pulmonary rehabilitation
Authors: Wijkstra P.J. , Wempe J.B.
Published: August 2011

In patients with more severe chronic obstructive pulmonary disease (COPD), the benefits of rehabilitation might not be clear and, therefore, new treatment options have been developed to increase the benefits of rehabilitation. This review provides an overview of new approaches being developed as an addition to exercise training. In turn, the benefits of adding ventilatory support, oxygen, anabolics or neuromuscular stimulation to a rehabilitation programme will be discussed. While positive benefits for a number of these approaches have been found, many questions remain unsolved. Therefore, at present, we cannot recommend these new tools as part of the routine management of patients with COPD who start a rehabilitation programme.
Surfactant protein C G100S mutation causes familial pulmonary fibrosis in Japanese kindred
Authors: Ono S. , Tanaka T. , Ishida M. , Kinoshita A. , Fukuoka J. , Takaki M. , Sakamoto N. , Ishimatsu Y. , Kohno S. , Hayashi T. , Senba M. , Yasunami M. , Kubo Y. , Yoshida L.M. , Kubo H. , Ariyoshi K. , Yoshiura K. , Morimoto K.
Published: August 2011

Several mutations in the surfactant protein C (SP-C) gene (SFTPC) have been reported as causing familial pulmonary fibrosis (FPF). However, the genetic background and clinical features of FPF are still not fully understood.

We identified one Japanese kindred, in which at least six individuals over three generations were diagnosed with pulmonary fibrosis. We examined the patients radiologically and histopathologically and sequenced theirSFTPCandABCA3genes. We also established a cell line stably expressing the mutant gene.

All the patients had similar radiological and histopathological characteristics. Their histopathological pattern was that of usual interstitial pneumonia, showing numerous fibroblastic foci even in areas without abnormal radiological findings on chest high-resolution computed tomography. No child had respiratory symptoms in the kindred. Sequencing ofSFTPCshowed a novel heterozygous mutation, c.298G>A (G100S), in the BRICHOS domain of proSP-C, which co-segregated with the disease. However, in theABCA3gene, no mutation was found.In vitroexpression of the mutant gene revealed that several endoplasmic reticulum stress-related proteins were strongly expressed.

The mutation increases endoplasmic reticulum stress and induces apoptotic cell death compared with wild-type SP-C in alveolar type II cells, supporting the significance of this mutation in the pathogenesis of pulmonary fibrosis.
Primary lung adenocarcinoma: characteristics by smoking habit and sex
Authors: Nagy-Mignotte H. , Guillem P. , Vesin A. , Toffart A.C. , Colonna M. , Bonneterre V. , Brichon P.Y. , Brambilla C. , Brambilla E. , Lantuejoul S. , Timsit J.F. , Moro-Sibilot D.
Published: August 2011

The incidence of adenocarcinoma is increasing, particularly among females. We sought to assess the role of tobacco consumption in clinical presentation according to sex.

In this retrospective study, 848 patients diagnosed between 1997 and 2006 at Grenoble University Hospital (Grenoble, France) were stratified into four groups according to smoking habits.

Differences between sexes and two contrasting female profiles emerged. Female current smokers were younger than female never-smokers (median 51versus69 yrs; p<0.001), more often had surgery (62.7%versus39%; p=0.01) and had a median (95% CI) estimated survival of 26.2 (18.1–49.2)versus15.1 (12.8–22.2) months (p=0.002). Both groups had similar survival when taking treatment into account. Among males, smoking did not influence presentation. Male current smokers were older than female current smokers (median 59 yrs; p<0.001) and fewer had surgery (48.8%; p=0.015), although the percentage of stage IIIb–IV disease was similar (53% and 46%; nonsignificant) and they had a poorer estimated survival of 14.3 (13.0–18.5) months (p=0.0024). Males smoked more than females (median 41versus30 pack-yrs; p<0.001). Quitting smoking delayed age at diagnosis by 11 yrs for females (p=0.0035) and 8 yrs for males (p<0.001).

Our results support the hypothesis that carcinogenesis differs between males and females, and between female smokers and never-smokers.
Clara cells drive eosinophil accumulation in allergic asthma
Authors: Sonar S.S. , Ehmke M. , Marsh L.M. , Dietze J. , Dudda J.C. , Conrad M.L. , Renz H. , Nockher W.A.
Published: August 2011

Development of allergic asthma is a complex process involving immune, neuronal and tissue cells. In the lung, Clara cells represent a major part of the “immunomodulatory barrier” of the airway epithelium.

To understand the contribution of these cells to the inflammatory outcome of asthma, disease development was assessed using an adjuvant-free ovalbumin model. Mice were sensitised with subcutaneous injections of 10 μg endotoxin-free ovalbumin in conjunction with naphthalene-induced Clara cell depletion.

Clara epithelial cell depletion in the lung strongly reduced eosinophil influx, which correlated with decreased eotaxin levels and, moreover, diminished the T-helper cell type 2 inflammatory response, including interleukin (IL)-4, IL-5 and IL-13. In contrast, airway hyperresponsiveness was increased. Further investigation revealed Clara cells as the principal source of eotaxin in the lung.

These findings are the first to show that Clara airway epithelial cells substantially contribute to the infiltration of eotaxin-responsive CCR3+ immune cells and augment the allergic immune response in the lung. The present study identifies Clara cells as a potential therapeutic target in inflammatory lung diseases such as allergic asthma.
Cloning and expression profiling of the VLDLR gene associated with egg performance in duck (Anas platyrhynchos)
Authors: Wang Cui , Li Shi-jun , Yu Wen-hua , Xin Qing-wu , Li Chuang , Feng Yan-ping , Peng Xiu-li , Gong Yan-zhang
Published: August 2011

Background

The very low density lipoprotein receptor gene (VLDLR), a member of the low density lipoprotein receptor (LDLR) gene family, plays a crucial role in the synthesis of yolk protein precursors in oviparous species. Differential splicing of this gene has been reported in human, rabbit and rat. In chicken, studies showed that the VLDLR protein on the oocyte surface mediates the uptake of yolk protein precursors into growing oocytes. However, information on the VLDLR gene in duck is still scarce.

Methods

Full-length duck VLDLR cDNA was obtained by comparative cloning and rapid amplification of cDNA ends (RACE). Tissue expression patterns were analysed by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR). Association between the different genotypes and egg performance traits was investigated with the general linear model (GLM) procedure of the SAS® software package.

Results

In duck, two VLDLR transcripts were identified, one transcript (variant-a) containing an O-linked sugar domain and the other (variant-b) not containing this sugar domain. These transcripts share ~70 to 90% identity with their counterparts in other species. A phylogenetic tree based on amino acid sequences showed that duck VLDLR proteins were closely related with those of chicken and zebra finch. The two duck VLDLR transcripts are differentially expressed i.e. VLDLR-a is mainly expressed in muscle tissue and VLDLR-b in reproductive organs. We have localized the duck VLDLR gene on chromosome Z. An association analysis using two completely linked SNP sites (T/C at position 2025 bp of the ORF and G/A in intron 13) and records from two generations demonstrated that the duck VLDLR gene was significantly associated with egg production (P < 0.01), age of first egg (P < 0.01) and body weight of first egg (P < 0.05).

Conclusions

Duck and chicken VLDLR genes probably perform similar function in the development of growing oocytes and deposition of yolk lipoprotein. Therefore, VLDLR could be a candidate gene for duck egg performance and be used as a genetic marker to improve egg performance in ducks.