bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Immune Markers in Non–Small Cell Lung Cancer
Authors: Suzuki Kei , Kachala Stefan S. , Kadota Kyuichi , Shen Ronglai , Mo Qianxing , Beer David G. , Rusch Valerie W. , Travis William D. , Adusumilli Prasad S. 
Published: June 2011

Abstract
Tumor-associated immune responses have polarized effects in regulating tumor growth. Although a clear association has been shown between the tumor immune response and clinical outcome in colorectal and ovarian cancers, the role of immune markers for stratifying prognosis in non–small cell lung cancer (NSCLC) is less defined. Herein, we review the prognostic significance of published immune markers in the tumor microenvironment and peripheral blood of NSCLC patients. To identify prognostic immune genes, we reviewed all published gene-profiling studies in NSCLC and delineated the significance of immune genes by doing subanalysis on the microarray database of the NIH Director's Challenge study. This first comprehensive review of prognostic immune markers provides a foundation for further investigating immune responses in NSCLC. Clin Cancer Res; 17(16); 5247–56. ©2011 AACR.
Cdc42 Controls Vascular Network Assembly Through Protein Kinase Cι During Embryonic Vasculogenesis
Authors: Qi Yanmei , Liu Jie , Wu Xunwei , Brakebusch Cord , Leitges Michael , Han Yaling , Corbett Siobhan A. , Lowry Stephen F. , Graham Alan M. , Li Shaohua 
Published: June 2011

Objective—
The goal of this study was to determine the role of Cdc42 in embryonic vasculogenesis and the underlying mechanisms.

Methods and Results—
By using genetically modified mouse embryonic stem (ES) cells, we demonstrate that ablation of the Rho GTPase Cdc42 blocks vascular network assembly during embryoid body (EB) vasculogenesis without affecting endothelial lineage differentiation. Reexpression of Cdc42 in mutant EBs rescues the mutant phenotype, establishing an essential role for Cdc42 in vasculogenesis. Chimeric analysis revealed that the vascular phenotype is caused by inactivation of Cdc42 in endothelial cells rather than surrounding cells. Endothelial cells isolated from Cdc42-null EBs are defective in directional migration and network assembly. In addition, activation of atypical protein kinase Cι (PKCι) is abolished in Cdc42-null endothelial cells, and PKCι ablation phenocopies the vascular abnormalities of the Cdc42-null EBs. Moreover, the inhibitory phosphorylation of glycogen synthase kinase-3β (GSK-3β) at Ser9 depends on Cdc42 and PKCι, and expression of kinase-dead GSK-3β in Cdc42-null EBs promotes the formation of linear endothelial segments without branches. These results suggest that PKCι and GSK-3β are downstream effectors of Cdc42 during vascular morphogenesis.

Conclusion—
Cdc42 controls vascular network assembly but not endothelial lineage differentiation by activating PKCι during embryonic vasculogenesis.
Quantification of Monthly Mean Regional-Scale Albedo of Marine Stratiform Clouds in Satellite Observations and GCMs
Authors: Bender Frida A.-M. , Charlson Robert J. , Ekman Annica M. L. , Leahy Louise V. 
Published: June 2011

AbstractPlanetary albedo—the reflectivity for solar radiation—is of singular importance in determining the amount of solar energy taken in by the Earth–atmosphere system. Modeling albedo, and specifically cloud albedo, correctly is crucial for realistic climate simulations. A method is presented herein by which regional cloud albedo can be quantified from the relation between total albedo and cloud fraction, which in observations is found to be approximately linear on a monthly mean scale. This analysis is based primarily on the combination of cloud fraction data from the Moderate Resolution Imaging Spectroradiometer (MODIS) and albedo data from the Clouds and the Earth’s Radiant Energy System (CERES), but the results presented are also supported by the combination of cloud fraction and proxy albedo data from satelliteborne lidar [Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO)]. These data are measured and derived completely independently from the CERES–MODIS data. Applied to low-level marine stratiform clouds in three regions (off the coasts of South America, Africa, and North America), the analysis reveals regionally uniform monthly mean cloud albedos, indicating that the variation in cloud shortwave radiative properties is small on this scale. A coherent picture of low “effective” cloud albedo emerges, in the range from 0.35 to 0.42, on the basis of data from CERES and MODIS. In its simplicity, the method presented appears to be useful as a diagnostic tool and as a constraint on climate models. To demonstrate this, the same method is applied to cloud fraction and albedo output from several current-generation climate models [from the Coupled Model Intercomparison Project, phase 3 (CMIP3), archive]. Although the multimodel mean cloud albedo estimates agree to within 20% with the satellite-based estimates for the three focus regions, model-based estimates of cloud albedo are found to display much larger variability than do the observations, within individual models as well as between models.
Ice Crystals Growing from Vapor in Supercooled Clouds between −2.5° and −22°C: Testing Current Parameterization Methods Using Laboratory Data
Authors: Westbrook C. D. , Heymsfield A. J. 
Published: June 2011

Abstract
The physical and empirical relationships used by microphysics schemes to control the rate at which vapor is transferred to ice crystals growing in supercooled clouds are compared with laboratory data to evaluate the realism of various model formulations.
Ice crystal growth rates predicted from capacitance theory are compared with measurements from three independent laboratory studies. When the growth is diffusion- limited, the predicted growth rates are consistent with the measured values to within about 20% in 14 of the experiments analyzed, over the temperature range −2.5° to −22°C. Only two experiments showed significant disagreement with theory (growth rate overestimated by about 30%–40% at −3.7° and −10.6°C).
Growth predictions using various ventilation factor parameterizations were also calculated and compared with supercooled wind tunnel data. It was found that neither of the standard parameterizations used for ventilation adequately described both needle and dendrite growth; however, by choosing habit-specific ventilation factors from previous numerical work it was possible to match the experimental data in both regimes.
The relationships between crystal mass, capacitance, and fall velocity were investigated based on the laboratory data. It was found that for a given crystal size the capacitance was significantly overestimated by two of the microphysics schemes considered here, yet for a given crystal mass the growth rate was underestimated by those same schemes because of unrealistic mass/size assumptions. The fall speed for a given capacitance (controlling the residence time of a crystal in the supercooled layer relative to its effectiveness as a vapor sink, and the relative importance of ventilation effects) was found to be overpredicted by all the schemes in which fallout is permitted, implying that the modeled crystals reside for too short a time within the cloud layer and that the parameterized ventilation effect is too strong.
Mechanisms of the Tropical Upwelling Branch of the Brewer–Dobson Circulation: The Role of Extratropical Waves
Authors: Chen Gang , Sun Lantao 
Published: June 2011

Abstract
The role of extratropical waves in the tropical upwelling branch of the Brewer–Dobson circulation is investigated in an idealized model of the stratosphere and troposphere. To simulate different stratospheric seasonal cycles of planetary waves in the two hemispheres, seasonally varying radiative heating is imposed only in the stratosphere, and surface topographic forcing is prescribed only in the Northern Hemisphere (NH). A zonally symmetric version of the same model is used to diagnose the effects of different wavenumbers and different regions of the total forcing on tropical stratospheric upwelling.
The simple configuration can simulate a reasonable seasonal cycle of the tropical upwelling in the lower stratosphere with a stronger amplitude in January (NH midwinter) than in July (NH midsummer), as in the observations. It is shown that the seasonal cycle of stratospheric planetary waves and tropical upwelling responds nonlinearly to the strength of the tropospheric forcing, with a midwinter maximum under strong NH-like tropospheric forcing and double peaks in the fall and spring under weak Southern Hemisphere (SH)-like forcing. The planetary wave component of the total forcing can approximately reproduce the seasonal cycle of tropical stratospheric upwelling in the zonally symmetric model.
The zonally symmetric model further demonstrates that the planetary wave forcing in the winter tropical and subtropical stratosphere contributes most to the seasonal cycle of tropical stratospheric upwelling, rather than the high-latitude wave forcing. This suggests that the planetary wave forcing, prescribed mostly in the extratropics in the model, has to propagate equatorward into the subtropical latitudes to induce sufficient tropical upwelling. Another interesting finding is that the planetary waves in the summer lower stratosphere can drive a shallow residual circulation rising in the subtropics and subsiding in the extratropics.
Lateral Mixing in the Pycnocline by Baroclinic Mixed Layer Eddies
Authors: Badin Gualtiero , Tandon Amit , Mahadevan Amala 
Published: June 2011

Abstract
Using a process study model, the effect of mixed layer submesoscale instabilities on the lateral mixing of passive tracers in the pycnocline is explored. Mixed layer eddies that are generated from the baroclinic instability of a front within the mixed layer are found to penetrate into the pycnocline leading to an eddying flow field that acts to mix properties laterally along isopycnal surfaces. The mixing of passive tracers released on such isopycnal surfaces is quantified by estimating the variance of the tracer distribution over time. The evolution of the tracer variance reveals that the flow undergoes three different turbulent regimes. The first regime, lasting about 3–4 days (about 5 inertial periods) exhibits near-diffusive behavior; dispersion of the tracer grows nearly linearly with time. In the second regime, which lasts for about 10 days (about 14 inertial periods), tracer dispersion exhibits exponential growth because of the integrated action of high strain rates created by the instabilities. In the third regime, tracer dispersion follows Richardson’s power law. The Nakamura effective diffusivity is used to study the role of individual dynamical filaments in lateral mixing. The filaments, which carry a high concentration of tracer, are characterized by the coincidence of large horizontal strain rate with large vertical vorticity. Within filaments, tracer is sheared without being dispersed, and consequently the effective diffusivity is small in filaments. While the filament centers act as barriers to transport, eddy fluxes are enhanced at the filament edges where gradients are large.
Tympanic Membrane Rupture in the Survivors of the July 7, 2005, London Bombings
Authors: Radford Peter , Patel Hasu D. L. , Hamilton Nicholas , Collins Mark , Dryden Steven 
Published: June 2011

ObjectiveThe goal of this study was to analyze the prevalence of tympanic membrane rupture in the survivors of the London bombings of July 2005 and to assess whether tympanic membrane rupture provides a useful biomarker for underlying primary blast injuries.Study DesignCross‐sectional study.Subjects and MethodsSurvivors of the 4 blasts of London bombings on July 7, 2005. Data were gathered from medical records and the London’s Metropolitan Police evidence documenting the injuries sustained by 143 survivors of the blasts. All patients with tympanic membrane rupture or primary blast injury were indentified. Analysis was made of distance against prevalence of tympanic membrane rupture. Correlation between tympanic membrane rupture and other forms of primary blast injury was then assessed.ResultsResults from the 143 survivors showed a 48% prevalence of tympanic membrane rupture across all 4 sites. Fifty‐one patients had isolated tympanic membrane rupture with no other primary blast injuries. Eleven patients had tympanic membrane rupture and other primary blast injuries, but only one of these was an initially concealed injury (blast lung).ConclusionsTympanic membrane rupture in survivors of the London bombings on July 7, 2005, had a high prevalence affecting half of patients across a range of distances from the blasts. Tympanic membrane did not act as an effective biomarker of underlying blast lung. In a mass casualty event, patients with isolated tympanic membrane rupture with normal observations and chest radiography can be monitored for a short period and safely discharged with arrangement for ear, nose, and throat follow‐up.
Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980-2009: an international collaborative study
Authors: Moratto Daniele , Giliani Silvia , Bonfim Carmem , Mazzolari Evelina , Fischer Alain , Ochs Hans D. , Cant Andrew J. , Thrasher Adrian J. , Cowan Morton J. , Albert Michael H. , Small Trudy , Pai Sung-Yun , Haddad Elie , Lisa Antonella , Hambleton Sophie , Slatter Mary , Cavazzana-Calvo Marina , Mahlaoui Nizar , Picard Capucine , Torgerson Troy R. , Burroughs Lauri , Koliski Adriana , Neto Jose Zanis , Porta Fulvio , Qasim Waseem , Veys Paul , Kavanau Kristina , Hönig Manfred , Schulz Ansgar , Friedrich Wilhelm , Notarangelo Luigi D. 
Published: June 2011

Abstract
In this retrospective collaborative study, we have analyzed long-term outcome and donor cell engraftment in 194 patients with Wiskott-Aldrich syndrome (WAS) who have been treated by hematopoietic cell transplantation (HCT) in the period 1980- 2009. Overall survival was 84.0% and was even higher (89.1% 5-year survival) for those who received HCT since the year 2000, reflecting recent improvement of outcome after transplantation from mismatched family donors and for patients who received HCT from an unrelated donor at older than 5 years. Patients who went to transplantation in better clinical conditions had a lower rate of post-HCT complications. Retrospective analysis of lineage-specific donor cell engraftment showed that stable full donor chimerism was attained by 72.3% of the patients who survived for at least 1 year after HCT. Mixed chimerism was associated with an increased risk of incomplete reconstitution of lymphocyte count and post-HCT autoimmunity, and myeloid donor cell chimerism < 50% was associated with persistent thrombocytopenia. These observations indicate continuous improvement of outcome after HCT for WAS and may have important implications for the development of novel protocols aiming to obtain full correction of the disease and reduce post-HCT complications.
Delivery of progenitors to the thymus limits T-lineage reconstitution after bone marrow transplantation
Authors: Zlotoff Daniel A. , Zhang Shirley L. , De Obaldia Maria Elena , Hess Paul R. , Todd Sarah P. , Logan Theodore D. , Bhandoola Avinash 
Published: June 2011

AbstractT-cell production depends on the recruitment of hematopoietic progenitors into the thymus. T cells are among the last of the hematopoietic lineages to recover after bone marrow transplantation (BMT), but the reasons for this delay are not well understood. Under normal physiologic conditions, thymic settling is selective and either CCR7 or CCR9 is required for progenitor access into the thymus. The mechanisms of early thymic reconstitution after BMT, however, are unknown. Here we report that thymic settling is briefly CCR7/CCR9-independent after BMT but continues to rely on the selectin ligand PSGL-1. The CCR7/CCR9 independence is transient, and by 3 weeks after BMT these receptors are again strictly required. Despite the normalization of thymic settling signals, the rare bone marrow progenitors that can efficiently repopulate the thymus are poorly reconstituted for at least 4 weeks after BMT. Consistent with reduced progenitor input to the thymus, intrathymic progenitor niches remain unsaturated for at least 10 weeks after BMT. Finally, we show that thymic recovery is limited by the number of progenitors entering the thymus after BMT. Hence, T-lineage reconstitution after BMT is limited by progenitor supply to the thymus.
Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1–expressing myeloma cells
Authors: Morales Alejo A. , Kurtoglu Metin , Matulis Shannon M. , Liu Jiangxia , Siefker David , Gutman Delia M. , Kaufman Jonathan L. , Lee Kelvin P. , Lonial Sagar , Boise Lawrence H. 
Published: June 2011

Abstract
Dependence on Bcl-2 proteins is a common feature of cancer cells and provides a therapeutic opportunity. ABT-737 is an antagonist of antiapoptotic Bcl-2 proteins and therefore is a good predictor of Bcl-xL/Bcl-2 dependence. Surprisingly, analysis of Mcl-1–dependent multiple myeloma cell lines revealed codependence on Bcl-2/Bcl-xL in half the cells tested. Codependence is not predicted by the expression level of antiapoptotic proteins, rather through interactions with Bim. Consistent with these findings, acquired resistance to ABT-737 results in loss of codependence through redistribution of Bim to Mcl-1. Overall, these results suggest that complex interactions, and not simply expression patterns of Bcl-2 proteins, need to be investigated to understand Bcl-2 dependence and how to better use agents, such as ABT-737.
Translocation of signalling proteins to the plasma membrane revealed by a new bioluminescent procedure
Authors: Giorgi Carlotta , Romagnoli Anna , Agnoletto Chiara , Bergamelli Leda , Sorrentino Giovanni , Brini Marisa , Pozzan Tullio , Meldolesi Jacopo , Pinton Paolo , Rizzuto Rosario 
Published: June 2011

AbstractBackgroundActivation by extracellular ligands of G protein-coupled (GPCRs) and tyrosine kinase receptors (RTKs), results in the generation of second messengers that in turn control specific cell functions. Further, modulation/amplification or inhibition of the initial signalling events, depend on the recruitment onto the plasma membrane of soluble protein effectors.High throughput methodologies to monitor quantitatively second messenger production, have been developed over the last years and are largely used to screen chemical libraries for drug development. On the contrary, no such high throughput methods are yet available for the other aspect of GPCRs regulation, i.e. protein translocation to the plasma membrane, despite the enormous interest of this phenomenon for the modulation of receptor downstream functions. Indeed, to date, the experimental procedures available are either inadequate or complex and expensive.ResultsHere we describe the development of a novel conceptual approach to the study of cytosolic proteins translocation to the inner surface of the plasma membrane. The basis of the technique consists in: i) generating chimeras between the protein of interests and the calcium (Ca2+)-sensitive, luminescent photo-protein, aequorin and ii) taking advantage of the large Ca2+concentration [Ca2+] difference between bulk cytosolic and the sub-plasma membrane rim.ConclusionThis approach, that keeps unaffected the translocation properties of the signalling protein, can in principle be applied to any protein that, upon activation, moves from the cytosol to the plasma membrane.Thus, not only the modulation of GPCRs and RTKs can be investigated in this way, but that of all other proteins that can be recruited to the plasma membrane also independently of receptor activation.Moreover, its automated version, which can provide information about the kinetics and concentration-dependence of the process, is also applicable to high throughput screening of drugs affecting the translocation process.
Heterologous expression of pathogen-specific genes ligA and ligB in the saprophyte Leptospira biflexaconfers enhanced adhesion to cultured cells and fibronectin
Authors: Figueira Cláudio Pereira , Croda Julio , Choy Henry A , Haake David A , Reis Mitermayer G , Ko Albert I , Picardeau Mathieu 
Published: June 2011

Abstract

Background
In comparison to other bacterial pathogens, our knowledge of the molecular basis of the pathogenesis of leptospirosis is extremely limited. An improved understanding of leptospiral pathogenetic mechanisms requires reliable tools for functional genetic analysis. Leptospiral immunoglobulin-like (Lig) proteins are surface proteins found in pathogenic Leptospira, but not in saprophytes. Here, we describe a system for heterologous expression of the Leptospira interrogans genes ligA and ligB in the saprophyte Leptospira biflexa serovar Patoc.

Results
The genes encoding LigA and LigB under the control of a constitutive spirochaetal promoter were inserted into the L. biflexa replicative plasmid. We were able to demonstrate expression and surface localization of LigA and LigB in L. biflexa. We found that the expression of the lig genes significantly enhanced the ability of transformed L. biflexa to adhere in vitro to extracellular matrix components and cultured cells, suggesting the involvement of Lig proteins in cell adhesion.

Conclusions
This work reports a complete description of the system we have developed for heterologous expression of pathogen-specific proteins in the saprophytic L. biflexa. We show that expression of LigA and LigB proteins from the pathogen confers a virulence-associated phenotype on L. biflexa, namely adhesion to eukaryotic cells and fibronectin in vitro. This study indicates that L. biflexa can serve as a surrogate host to characterize the role of key virulence factors of the causative agent of leptospirosis.