bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Model Investigation of Aerosol-Induced Changes in Tropical Circulation
Authors: Ming Yi , Ramaswamy V. 
Published: April 2011

This study investigates how anthropogenic aerosols, alone or in conjunction with radiatively active gases, affect the tropical circulation with an atmosphere/mixed layer–ocean general circulation model. Aerosol-induced cooling gives rise to a substantial increase in the overall strength of the tropical circulation, a robust outcome consistent with a thermodynamical scaling argument. Owing to the interhemispheric asymmetry in aerosol forcing, the zonal-mean (Hadley) and zonally asymmetrical components of the tropical circulation respond differently. The Hadley circulation weakens in the Northern Hemisphere but strengthens in the Southern Hemisphere. The resulting northward cross-equatorial moist static energy flux compensates partly for the aerosol radiative cooling in the Northern Hemisphere. In contrast, the less restricted zonally asymmetrical circulation does not show sensitivity to the spatial structure of aerosols and strengthens in both hemispheres. The results also point to the possible role of aerosols in driving the observed reduction in the equatorial sea level pressure gradient. These circulation changes have profound implications for the hydrological cycle. Aerosols alone make the subtropical dry zones in both hemispheres wetter, as the local hydrological response is controlled thermodynamically by atmospheric moisture content. The deep tropical rainfall undergoes a dynamically induced southward shift, a robust pattern consistent with the adjustments in the zonal-mean circulation and in the meridional moist static energy transport. Less certain is the magnitude of the shift. The nonlinearity exhibited by the combined hydrological response to aerosols and radiatively active gases is dynamical in nature.
Influence of XBT Temperature Bias on Decadal Climate Prediction with a Coupled Climate Model
Authors: Yasunaka Sayaka , Ishii Masayoshi , Kimoto Masahide , Mochizuki Takashi , Shiogama Hideo 
Published: April 2011

Abstract
The influence of the expendable bathythermograph (XBT) depth bias correction on decadal climate prediction is presented by using a coupled atmosphere–ocean general circulation model called the Model for Interdisciplinary Research on Climate 3 (MIROC3). The global mean subsurface ocean temperatures that were simulated by the model with the prescribed anthropogenic and natural forcing are consistent with bias-corrected observations from the mid-1960s onward, but not with uncorrected observations. The latter is reflected by biases in subsurface ocean temperatures, particularly along thermoclines in the tropics and subtropics. When the correction is not applied to XBT observations, these biases are retained in data assimilation results for the model’s initial conditions. Hindcasting past Pacific decadal oscillations (PDOs) is more successful in the experiment with the bias-corrected observations than that without the correction. Improvement of skill in predicting 5-yr mean vertically average ocean subsurface temperature is also seen in the tropical and the central North Pacific where PDO-related signals appear large.
Breaking the Traditional Style of Finnish Civic Activity
Authors: Lappalainen Pertti 
Published: April 2011

In this article, “the basic idea is to introduce the idea of style as an approach to (political) activity and, especially, as an alternative practice to ideological activity.” Using the example of animal-rights activism, the author posits something “decidedly new” in Finnish civic activity, which traditionally has been channelled through institutions: Finnish movements have been state-oriented, with demands being addressed to the government, and have emphasized knowledge-based rationality as the measure for competent activity. The author categorically rejects “the notion that, in politics, style is anything more than a superficial curtain, behind which the true contents of politicking can be found,” and argues that the traditional style of activity has changed recently toward one called action. The most essential dimension of this action style is unpredictability. Choosing this style means making a (political) judgment, situation by situation. The repertoire of collective activity has enlarged, and actors are now ready to act in the most radical and surprising style.
Btk regulation in human and mouse B cells via protein kinase C phosphorylation of IBtkγ
Authors: Janda Elzbieta , Palmieri Camillo , Pisano Antonio , Pontoriero Marilena , Iaccino Enrico , Falcone Cristina , Fiume Giuseppe , Gaspari Marco , Nevolo Maria , Di Salle Emanuela , Rossi Annalisa , De Laurentiis Annamaria , Greco Adelaide , Di Napoli Daniele , Verheij Elwin , Britti Domenico , Lavecchia Luca , Quinto Ileana , Scala Giuseppe 
Published: April 2011

AbstractThe inhibitor of Bruton tyrosine kinase γ (IBtkγ) is a negative regulator of the Bruton tyrosine kinase (Btk), which plays a major role in B-cell differentiation; however, the mechanisms of IBtkγ-mediated regulation of Btk are unknown. Here we report that B-cell receptor (BCR) triggering caused serine-phosphorylation of IBtkγ at protein kinase C consensus sites and dissociation from Btk. By liquid chromatography and mass-mass spectrometry and functional analysis, we identified IBtkγ-S87 and -S90 as the critical amino acid residues that regulate the IBtkγ binding affinity to Btk. Consistently, the mutants IBtkγ carrying S87A and S90A mutations bound constitutively to Btk and down-regulated Ca2+ fluxes and NF-κB activation on BCR triggering. Accordingly, spleen B cells from Ibtkγ−/− mice showed an increased activation of Btk, as evaluated by Y551-phosphorylation and sustained Ca2+ mobilization on BCR engagement. These findings identify a novel pathway of Btk regulation via protein kinase C phosphorylation of IBtkγ.
Long-term prognostic significance of response in multiple myeloma after stem cell transplantation
Authors: Martinez-Lopez Joaquin , Blade Joan , Mateos María-Victoria , Grande Carlos , Alegre Adrián , García-Laraña José , Sureda Anna , de la Rubia Javier , Conde Eulogio , Martinez Rafael , de Arriba Felipe , Viguria Maria C. , Besalduch Joan , Cabrera Rafael , Gonzalez-San Miguel José D. , Guzman-Zamudio José Luis , Gomez del Castillo Maria Carmen , Moraleda José Maria , García-Ruiz Juan C. , San Miguel Jesús , Lahuerta Juan José ,   for the GEM (Grupo Español de MM) and PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatía Maligna) Cooperative Study Groups
Published: April 2011

AbstractFor establishing the true effect of different response categories in patients with multiple myeloma (MM) treated with autologous stem cell transplantation, we evaluated, after a median follow-up of 153 months, 344 patients with MM who received a transplant between 1989 and 1998. Overall survival (OS) at 12 years was 35% in complete response (CR) patients, 22% in near complete response (nCR), 16% in very good partial response (VGPR), and 16% in partial response (PR) groups. Significant differences in OS and progression-free survival were found between CR and nCR groups (P = .01 and P = .002, respectively), between CR and VGPR groups (P = .0001 and P = .003), or between CR and PR groups (P = .003 and P = < 10−5); no differences were observed between the nCR and VGPR groups (P = .2 and P = .9) or between these groups and the PR group (P = .1 and P = .8). A landmark study found a plateau phase in OS after 11 years; 35% patients in the CR group and 11% in the nCR+VGPR+PR group are alive at 17 years; 2 cases had relapsed in the nCR+VGPR+PR group. In conclusion, MM achieving CR after autologous stem cell transplantation is a central prognostic factor. The relapse rate is low in patients with > 11 years of follow-up, possibly signifying a cure for patients in CR.
Statistical Test of Expression Pattern (STEPath): a new strategy to integrate gene expression data with genomic information in individual and meta-analysis studies
Authors: Martini Paolo , Risso Davide , Sales Gabriele , Romualdi Chiara , Lanfranchi Gerolamo , Cagnin Stefano 
Published: April 2011

Abstract

Background
In the last decades, microarray technology has spread, leading to a dramatic increase of publicly available datasets. The first statistical tools developed were focused on the identification of significant differentially expressed genes. Later, researchers moved toward the systematic integration of gene expression profiles with additional biological information, such as chromosomal location, ontological annotations or sequence features. The analysis of gene expression linked to physical location of genes on chromosomes allows the identification of transcriptionally imbalanced regions, while, Gene Set Analysis focuses on the detection of coordinated changes in transcriptional levels among sets of biologically related genes.
In this field, meta-analysis offers the possibility to compare different studies, addressing the same biological question to fully exploit public gene expression datasets.

Results
We describe STEPath, a method that starts from gene expression profiles and integrates the analysis of imbalanced region as an a priori step before performing gene set analysis. The application of STEPath in individual studies produced gene set scores weighted by chromosomal activation. As a final step, we propose a way to compare these scores across different studies (meta-analysis) on related biological issues. One complication with meta-analysis is batch effects, which occur because molecular measurements are affected by laboratory conditions, reagent lots and personnel differences. Major problems occur when batch effects are correlated with an outcome of interest and lead to incorrect conclusions. We evaluated the power of combining chromosome mapping and gene set enrichment analysis, performing the analysis on a dataset of leukaemia (example of individual study) and on a dataset of skeletal muscle diseases (meta-analysis approach).
In leukaemia, we identified the Hox gene set, a gene set closely related to the pathology that other algorithms of gene set analysis do not identify, while the meta-analysis approach on muscular disease discriminates between related pathologies and correlates similar ones from different studies.

Conclusions
STEPath is a new method that integrates gene expression profiles, genomic co-expressed regions and the information about the biological function of genes. The usage of the STEPath-computed gene set scores overcomes batch effects in the meta-analysis approaches allowing the direct comparison of different pathologies and different studies on a gene set activation level.
Detection of viral sequence fragments of HIV-1 subfamilies yet unknown
Authors: Unterthiner Thomas , Schultz Anne-Kathrin , Bulla Jan , Morgenstern Burkhard , Stanke Mario , Bulla Ingo 
Published: April 2011

Abstract

Background
Methods of determining whether or not any particular HIV-1 sequence stems - completely or in part - from some unknown HIV-1 subtype are important for the design of vaccines and molecular detection systems, as well as for epidemiological monitoring. Nevertheless, a single algorithm only, the Branching Index (BI), has been developed for this task so far. Moving along the genome of a query sequence in a sliding window, the BI computes a ratio quantifying how closely the query sequence clusters with a subtype clade. In its current version, however, the BI does not provide predicted boundaries of unknown fragments.

Results
We have developed Unknown Subtype Finder (USF), an algorithm based on a probabilistic model, which automatically determines which parts of an input sequence originate from a subtype yet unknown. The underlying model is based on a simple profile hidden Markov model (pHMM) for each known subtype and an additional pHMM for an unknown subtype. The emission probabilities of the latter are estimated using the emission frequencies of the known subtypes by means of a (position-wise) probabilistic model for the emergence of new subtypes. We have applied USF to SIV and HIV-1 sequences formerly classified as having emerged from an unknown subtype. Moreover, we have evaluated its performance on artificial HIV-1 recombinants and non-recombinant HIV-1 sequences. The results have been compared with the corresponding results of the BI.

Conclusions
Our results demonstrate that USF is suitable for detecting segments in HIV-1 sequences stemming from yet unknown subtypes. Comparing USF with the BI shows that our algorithm performs as good as the BI or better.
Gene expression profiles in rat mesenteric lymph nodes upon supplementation with Conjugated Linoleic Acid during gestation and suckling
Authors: Selga Elisabet , Pérez-Cano Francisco J , Franch Àngels , Ramírez-Santana Carolina , Rivero Montserrat , Ciudad Carlos J , Castellote Cristina , Noé Véronique 
Published: April 2011

AbstractBackgroundDiet plays a role on the development of the immune system, and polyunsaturated fatty acids can modulate the expression of a variety of genes. Human milk contains conjugated linoleic acid (CLA), a fatty acid that seems to contribute to immune development. Indeed, recent studies carried out in our group in suckling animals have shown that the immune function is enhanced after feeding them with an 80:20 isomer mix composed of c9,t11 and t10,c12 CLA. However, little work has been done on the effects of CLA on gene expression, and even less regarding immune system development in early life.ResultsThe expression profile of mesenteric lymph nodes from animals supplemented with CLA during gestation and suckling through dam's milk (Group A) or by oral gavage (Group B), supplemented just during suckling (Group C) and control animals (Group D) was determined with the aid of the specific GeneChip®Rat Genome 230 2.0 (Affymettrix). Bioinformatics analyses were performed using the GeneSpring GX software package v10.0.2 and lead to the identification of 89 genes differentially expressed in all three dietary approaches. Generation of a biological association network evidenced several genes, such as connective tissue growth factor (Ctgf), tissue inhibitor of metalloproteinase 1 (Timp1), galanin (Gal), synaptotagmin 1 (Syt1), growth factor receptor bound protein 2 (Grb2), actin gamma 2 (Actg2) and smooth muscle alpha actin (Acta2), as highly interconnected nodes of the resulting network. Gene underexpression was confirmed by Real-Time RT-PCR.ConclusionsCtgf, Timp1, Gal and Syt1, among others, are genes modulated by CLA supplementation that may have a role on mucosal immune responses in early life.
The role of reactive oxygen intermediates in experimental coccidioidomycois in mice
Authors: Margolis David A , Viriyakosol Suganya , Fierer Joshua , Kirkland Theo N 
Published: April 2011

AbstractBackgroundCoccidioidomycosis is usually a self-limited infection in immunocompentent people. In immunocompentent human beings second infections due toCoccidioidesare very rare, indicating that recovery from infection results in protective immunity. In experimental animals, immunization with several different proteins or attenuated mutants protects against a virulent challenge. To explore what mechanisms are responsible for protective immunity, we investigated the course ofCoccidioidesinfection in the gp91phoxknock out mouse that has a defect in the oxidative burst that results in chronic granulomatous disease.ResultsWe found that the gp91phoxknock out mice were somewhat more resistant to intraperitoneal infection and equally as resistant to low dose intranasal infection, but slightly more susceptible to high dose intranasal infection compared to control mice. The gp91phoxknock out mice made a more robust inflammatory response to infection than controls, as measured by histology and production of inflammatory cytokines. The gp91phoxknock out mice were as protected by immunization with the recombinantCoccidioidesprotein Ag2/PRA as the controls were against either intraperitoneal or intranasal infection.Coccidioides immitisarthroconidia and spherules were significantly more resistant to H2O2treatment in vitro thanAspergillus fumigatusspores.ConclusionThese data suggest that oxidative burst may not be required for protective immunity to coccidioidomycois.
Clinical management and burden of bipolar disorder: a multinational longitudinal study (WAVE-bd Study)
Authors: Vieta Eduard , Blasco-Colmenares Elena , Figueira Maria Luisa , Langosch Jens M , Moreno-Manzanaro Miriam , Medina Esteban ,   WAVE-bd Study Group
Published: April 2011

Abstract

Background
Studies in bipolar disorder (BD) to date are limited in their ability to provide a whole-disease perspective - their scope has generally been confined to a single disease phase and/or a specific treatment. Moreover, most clinical trials have focused on the manic phase of disease, and not on depression, which is associated with the greatest disease burden. There are few longitudinal studies covering both types of patients with BD (I and II) and the whole course of the disease, regardless of patients' symptomatology. Therefore, the Wide AmbispectiVE study of the clinical management and burden of Bipolar Disorder (WAVE-bd) (NCT01062607) aims to provide reliable information on the management of patients with BD in daily clinical practice. It also seeks to determine factors influencing clinical outcomes and resource use in relation to the management of BD.

Methods
WAVE-bd is a multinational, multicentre, non-interventional, longitudinal study. Approximately 3000 patients diagnosed with BD type I or II with at least one mood event in the preceding 12 months were recruited at centres in Austria, Belgium, Brazil, France, Germany, Portugal, Romania, Turkey, Ukraine and Venezuela. Site selection methodology aimed to provide a balanced cross-section of patients cared for by different types of providers of medical aid (e.g. academic hospitals, private practices) in each country. Target recruitment percentages were derived either from scientific publications or from expert panels in each participating country. The minimum follow-up period will be 12 months, with a maximum of 27 months, taking into account the retrospective and the prospective parts of the study. Data on demographics, diagnosis, medical history, clinical management, clinical and functional outcomes (CGI-BP and FAST scales), adherence to treatment (DAI-10 scale and Medication Possession Ratio), quality of life (EQ-5D scale), healthcare resources, and caregiver burden (BAS scale) will be collected. Descriptive analysis with common statistics will be performed.

Discussion
This study will provide detailed descriptions of the management of BD in different countries, particularly in terms of clinical outcomes and resources used. Thus, it should provide psychiatrists with reliable and up-to-date information about those factors associated with different management patterns of BD.

Trial registration no
ClinicalTrials.gov: NCT01062607
Surface display of Salmonella epitopes in Escherichia coli and Staphylococcus carnosus
Authors: Nhan Nguyen Thanh , de Valdivia Ernesto Gonzalez , Gustavsson Martin , Hai Truong Nam , Larsson Gen 
Published: April 2011

AbstractBackgroundSalmonella entericaserotype Enteritidis (SE) is considered to be one of the most potent pathogenicSalmonellaserotypes causing food-borne disease in humans. Since a live bacterial vaccine based on surface display of antigens has many advantages over traditional vaccines, we have studied the surface display of the SE antigenic proteins, H:gm and SefA inEscherichia coliby the β-autotransporter system, AIDA. This procedure was compared to protein translocation inStaphylococcus carnosus, using a staphylococci hybrid vector earlier developed for surface display of other vaccine epitopes.ResultsBoth SefA and H:gm were translocated to the outer membrane inEscherichia coli. SefA was expressed to full length but H:gm was shorter than expected, probably due to a proteolytic cleavage of the N-terminal during passage either through the periplasm or over the membrane. FACS analysis confirmed that SefA was facing the extracellular environment, but this could not be conclusively established for H:gm since the N-terminal detection tag (His6) was cleaved off. Polyclonal salmonella antibodies confirmed the sustained antibody-antigen binding towards both proteins. The surface expression data fromStaphylococcus carnosussuggested that the H:gm and SefA proteins were transported to the cell wall since the detection marker was displayed by FACS analysis.ConclusionApart from the accumulated knowledge and the existence of a wealth of equipment and techniques, the results indicate the selection ofE. colifor further studies for surface expression of salmonella antigens. Surface expression of the full length protein facing the cell environment was positively proven by standard analysis, and the FACS signal comparison to expression inStaphylococcus carnosusshows that the distribution of the surface protein on each cell was comparatively very narrow inE. coli, theE. coliouter membrane molecules can serve as an adjuvant for the surface antigenic proteins and multimeric forms of the SefA protein were detected which would probably be positive for the realisation of a strong antigenic property. The detection of specific and similar proteolytic cleavage patterns for both the proteins provides a further starting point for the investigation and development of theEscherichia coliAIDA autotransporter efficiency.
Quantitative analysis of nanoparticle internalization in mammalian cells by high resolution X-ray microscopy
Authors: Chen Hsiang-Hsin , Chien Chia-Chi , Petibois Cyril , Wang Cheng-Liang , Chu Yong S , Lai Sheng-Feng , Hua Tzu-En , Chen Yi-Yun , Cai Xiaoqing , Kempson Ivan M , Hwu Yeukuang , Margaritondo Giorgio 
Published: April 2011

Abstract

Background
Quantitative analysis of nanoparticle uptake at the cellular level is critical to nanomedicine procedures. In particular, it is required for a realistic evaluation of their effects. Unfortunately, quantitative measurements of nanoparticle uptake still pose a formidable technical challenge. We present here a method to tackle this problem and analyze the number of metal nanoparticles present in different types of cells. The method relies on high-lateral-resolution (better than 30 nm) transmission x-ray microimages with both absorption contrast and phase contrast -- including two-dimensional (2D) projection images and three-dimensional (3D) tomographic reconstructions that directly show the nanoparticles.

Results
Practical tests were successfully conducted on bare and polyethylene glycol (PEG) coated gold nanoparticles obtained by x-ray irradiation. Using two different cell lines, EMT and HeLa, we obtained the number of nanoparticle clusters uptaken by each cell and the cluster size. Furthermore, the analysis revealed interesting differences between 2D and 3D cultured cells as well as between 2D and 3D data for the same 3D specimen.

Conclusions
We demonstrated the feasibility and effectiveness of our method, proving that it is accurate enough to measure the nanoparticle uptake differences between cells as well as the sizes of the formed nanoparticle clusters. The differences between 2D and 3D cultures and 2D and 3D images stress the importance of the 3D analysis which is made possible by our approach.