bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convective Squalls over the Eastern Equatorial Atlantic
Authors: Berkes Florian , Knippertz Peter , Parker Douglas J. , Jeans Gus , Quiniou-Ramus Valérie 
Published: February 2012

Abstract
The Congo Basin and the adjacent equatorial eastern Atlantic are among the most active regions of the world in terms of intense deep moist convection, leading to frequent lightning and severe squalls. Studying the dynamics and climatology of this convection is difficult due to a very sparse operational network of ground-based observations. Here, a detailed analysis of recently available high temporal resolution meteorological observations from three oil platforms off the coast of Angola spanning the three wet seasons from 2006/07 to 2008/09 is presented. The annual cycle of squall days as identified from wind data closely follows that of convective available potential energy (CAPE) and therefore mirrors the cycle of wet and dry seasons. The diurnal cycle of squall occurrence varies from station to station, most likely related to local features such as coastlines and orography, which control the initiation of storms. An attempt to classify squalls based on the time evolution of the station meteorology and satellite imagery suggests that microbursts account for at least one-third of the strong gusts, while mesoscale squall lines appear to be quite rare. On a daily basis the probability of squall occurrence increases with increasing values of CAPE, downdraft CAPE, and 925–700-hPa wind shear, and decreases for high convective inhibition, all calculated from vertical profiles of temperature and humidity at the nearest grid point in the NCEP–NCAR and ECMWF reanalysis datasets. Both the climatological results and the stability indices can be used for local forecasting to avoid squalls impacting on operations on the offshore platforms.
Baseline characteristics in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)
Authors: Parving Hans-Henrik , Brenner Barry M , McMurray John JV , de Zeeuw Dick , Haffner Steven M , Solomon Scott D , Chaturvedi Nish , Persson Frederik , Nicolaides Maria , Richard Alexia , Xiang Zhihua , Armbrecht Juergen , Pfeffer Marc A ,   (on behalf of the ALTITUDE investigators)
Published: February 2012

Introduction: Patients with type 2 diabetes are at enhanced risk for macro- and microvascular complications. Albuminuria and/or reduced kidney function further enhances the vascular risk. We initiated the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE). Aliskiren, a novel direct renin inhibitor, which lowers plasma renin activity, may thereby provide greater cardio-renal protection compared with angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) alone. Materials and methods: ALTITUDE is a randomized, double-blind, placebo-controlled study in high risk type 2 diabetic patients receiving aliskiren 300 mg once daily or placebo added to recommended cardio-renal protective treatment including ACEi or ARB, but not both. The number of patients randomized was 8606. Results: Baseline characteristics (median, IQR) are: age 65 (58, 72) years, male 68%, BMI 29.1 (25.7, 32.2) kg/m2, cardiovascular disease 47.9%, blood pressure 134.7 (126, 150)/74.3 (67, 81) mmHg, HbA1c 7.5 (6.6, 8.6)%, LDL-cholesterol 2.4 (1.9, 3.0) mmol/L, haemoglobin 130 (119, 143) g/L, serum creatinine 115 (91, 137) µmol/L, eGFR 51.7 (42, 65) ml/min per 1.73 m2, geometric mean UACR 198.9 (52, 2886) mg/g and frequency of micro/macroalbuminuria 25.7% and 58.2%. ALTITUDE is an event-driven trial to continue until 1628 patients experience a primary cardiovascular-renal event. Conclusions: ALTITUDE will determine the potential cardio-renal benefit and safety of aliskiren in combination with ACEi or ARB in high risk patients with type 2 diabetes.
IgG1 and IVIg induce inhibitory ITAM signaling through FcγRIII controlling inflammatory responses
Authors: Aloulou Meryem , Ben Mkaddem Sanae , Biarnes-Pelicot Martine , Boussetta Tarek , Souchet Hervé , Rossato Elisabetta , Benhamou Marc , Crestani Bruno , Zhu Zhou , Blank Ulrich , Launay Pierre , Monteiro Renato C. 
Published: February 2012

AbstractIntravenous immunoglobulin (IVIg) has been used in the treatment of several autoimmune and inflammatory diseases. However, its mechanism of action remains incompletely understood. Here, we investigated the possibility that IVIg induces its anti-inflammatory effects through activating Fcγ receptors bearing an immunoreceptor tyrosine-based activation motif (ITAM) in the FcRγ signaling adaptor. Recently, the concept of inhibitory ITAM (ITAMi) has emerged as a new means to negatively control the immune response. We found that interaction of FcRγ-associated mouse or human FcγRIII with uncomplexed IgG1 or IVIg, or with bivalent anti-FcγRIII F(ab′)2 reduced calcium responses, reactive oxygen species production, endocytosis, and phagocytosis, induced by heterologous activating receptors on monocyte/macrophages and FcγRIII+ transfectants. Inhibition required the ITAMi configuration of the FcγRIII-associated FcRγ subunit and SHP-1 recruitment involving formation of intracellular “inhibisome” clusters containing FcγRIII, and the targeted heterologous activating receptor. IVIg as well as anti-FcγRIII treatments controlled the development of nonimmune mediated inflammation in vivo independently of FcγRIIB. These results demonstrate that circulating immunoglobulins (Ig)Gs are not functionally inert but act through continuous interaction with FcγRIII-inducing ITAMi signaling to maintain immune homeostasis. These data support a new mechanism of action for IVIg and demonstrate the therapeutic potential of FcγRIIIA targeting in inflammation.
The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO
Authors: Chou Fu-Sheng , Griesinger Andrea , Wunderlich Mark , Lin Shan , Link Kevin A. , Shrestha Mahesh , Goyama Susumu , Mizukawa Benjamin , Shen Shuhong , Marcucci Guido , Mulloy James C. 
Published: February 2012

Abstract
AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO–induced MPL.
Evolutionary history of the recruitment of conserved developmental genes in association to the formation and diversification of a novel trait
Authors: Shirai Leila T , Saenko Suzanne V , Keller Roberto A , Jerónimo Maria A , Brakefield Paul M , Descimon Henri , Wahlberg Niklas , Beldade Patrícia 
Published: February 2012

Abstract

Background
The origin and modification of novel traits are important aspects of biological diversification. Studies combining concepts and approaches of developmental genetics and evolutionary biology have uncovered many examples of the recruitment, or co-option, of genes conserved across lineages for the formation of novel, lineage-restricted traits. However, little is known about the evolutionary history of the recruitment of those genes, and of the relationship between them -for example, whether the co-option involves whole or parts of existing networks, or whether it occurs by redeployment of individual genes with de novo rewiring. We use a model novel trait, color pattern elements on butterfly wings called eyespots, to explore these questions. Eyespots have greatly diversified under natural and sexual selection, and their formation involves genetic circuitries shared across insects.

Results
We investigated the evolutionary history of the recruitment and co-recruitment of four conserved transcription regulators to the larval wing disc region where circular pattern elements develop. The co-localization of Antennapedia, Notch, Distal-less, and Spalt with presumptive (eye)spot organizers was examined in 13 butterfly species, providing the largest comparative dataset available for the system. We found variation between families, between subfamilies, and between tribes. Phylogenetic reconstructions by parsimony and maximum likelihood methods revealed an unambiguous evolutionary history only for Antennapedia, with a resolved single origin of eyespot-associated expression, and many homoplastic events for Notch, Distal-less, and Spalt. The flexibility in the (co-)recruitment of the targeted genes includes cases where different gene combinations are associated with morphologically similar eyespots, as well as cases where identical protein combinations are associated with very different phenotypes.

Conclusions
The evolutionary history of gene (co-)recruitment is consistent with both divergence from a recruited putative ancestral network, and with independent co-option of individual genes. The diversity in the combinations of genes expressed in association with eyespot formation does not parallel diversity in characteristics of the adult phenotype. We discuss these results in the context of inferring homology. Our study underscores the importance of widening the representation of phylogenetic, morphological, and genetic diversity in order to establish general principles about the mechanisms behind the evolution of novel traits.
Sexual and asexual oogenesis require the expression of unique and shared sets of genes in the insect Acyrthosiphon pisum
Authors: Gallot Aurore , Shigenobu Shuji , Hashiyama Tomomi , Jaubert-Possamai Stéphanie , Tagu Denis 
Published: February 2012

AbstractBackgroundAlthough sexual reproduction is dominant within eukaryotes, asexual reproduction is widespread and has evolved independently as a derived trait in almost all major taxa. How asexuality evolved in sexual organisms is unclear. Aphids, such asAcyrthosiphon pisum, alternate between asexual and sexual reproductive means, as the production of parthenogenetic viviparous females or sexual oviparous females and males varies in response to seasonal photoperiodism. Consequently, sexual and asexual development in aphids can be analyzed simultaneously in genetically identical individuals.ResultsWe compared the transcriptomes of aphid embryos in the stages of development during which the trajectory of oogenesis is determined for producing sexual or asexual gametes. This study design aimed at identifying genes involved in the onset of the divergent mechanisms that result in the sexual or asexual phenotype. We detected 33 genes that were differentially transcribed in sexual and asexual embryos. Functional annotation by gene ontology (GO) showed a biological signature of oogenesis, cell cycle regulation, epigenetic regulation and RNA maturation.In situhybridizations demonstrated that 16 of the differentially-transcribed genes were specifically expressed in germ cells and/or oocytes of asexual and/or sexual ovaries, and therefore may contribute to aphid oogenesis. We categorized these 16 genes by their transcription patterns in the two types of ovaries; they were: i) expressed during sexual and asexual oogenesis; ii) expressed during sexual and asexual oogenesis but with different localizations; or iii) expressed only during sexual or asexual oogenesis.ConclusionsOur results show that asexual and sexual oogenesis in aphids share common genetic programs but diverge by adapting specificities in their respective gene expression profiles in germ cells and oocytes.
IL-10 transcription is negatively regulated by BAF180, a component of the SWI/SNF chromatin remodeling enzyme
Authors: Wurster Andrea L , Precht Patricia , Becker Kevin G , Wood William H , Zhang Yongqing , Wang Zhong , Pazin Michael J 
Published: February 2012

Abstract

Background
SWI/SNF chromatin remodeling enzymes play a critical role in the development of T helper lymphocytes, including Th2 cells, and directly program chromatin structure at Th2 cytokine genes. Different versions of SWI/SNF complexes, including BAF and PBAF, have been described based on unique subunit composition. However, the relative role of BAF and PBAF in Th cell function and cytokine expression has not been reported.

Results
Here we examine the role of the PBAF SWI/SNF complex in Th cell development and gene expression using mice deficient for a PBAF-specific component, BAF180. We find that T cell development in the thymus and lymphoid periphery is largely normal when the BAF180 gene is deleted late in thymic development. However, BAF180-deficient Th2 cells express high levels of the immunoregulatory cytokine IL-10. BAF180 binds directly to regulatory elements in the Il-10 locus but is replaced by BAF250 BAF complexes in the absence of BAF180, resulting in increased histone acetylation and CBP recruitment to the IL-10 locus.

Conclusions
These results demonstrate that BAF180 is a repressor of IL-10 transcription in Th2 cells and suggest that the differential recruitment of different SWI/SNF subtypes can have direct consequences on chromatin structure and gene transcription.
Angiotensin converting enzyme DD genotype is associated with acute coronary syndrome severity and sudden cardiac death in Taiwan: a case-control emergency room study
Authors: Chen Ying-Hsin , Liu Jui-Ming , Hsu Ren-Jun , Hu Sheng-Chuan , Harn Horng-Jyh , Chen Shee-Ping , Jeng Jing-Ren , Wu Chieh-Lin , Ho Jar-Yi , Yu Cheng-Ping 
Published: February 2012

Abstract

Background
Angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms have been associated with acute coronary syndrome (ACS); however, several controversial results have also been found in different studied populations. This hospital-based, emergency room, case-control study in Taiwan retrospectively investigated 111 ACS patients, and 195 non-coronary subjects as a control group, to study the effects of ACE I/D polymorphism in the most urgent ACS patients. ACE I/D polymorphisms were determined by polymerase chain reaction-based assays and their associations with ACS risk, severity, and sudden cardiac death were determined.

Results
The ACE DD genotype was associated with ACS incidence. The DD genotype was associated with a significant 4-fold higher risk of ACS in multivariate analysis (odds ratio (OR) = 4.295; 95% confidence interval (CI): 1.436-12.851, p = 0.009), and a 3.35-fold higher risk of acute myocardial infarction. DD genotype carriers also had more than 3-fold higher risks of stenosis in all the three coronary arteries, left anterior descending artery infarction, and anterior wall infarction. In addition, the DD genotype was also associated with a higher risk of sudden cardiac death (OR = 6.484, 95% CI: 1.036-40.598, p = 0.046).

Conclusions
This study demonstrated that the ACE DD genotype is an independent risk factor for ACS, and in particular, for acute myocardial infarction. In addition, the ACE DD genotype is also associated with greater ACS severity and a higher risk of sudden cardiac death. ACE genotyping is recommended for patients with a history of ACS, and more intensive preventive care is suggested for patients with the DD genotype.
Regulation of p14ARF expression by miR-24: a potential mechanism compromising the p53 response during retinoblastoma development
Authors: To Kwong-Him , Pajovic Sanja , Gallie Brenda L , Thériault Brigitte L 
Published: February 2012

Abstract

Background
Most human cancers show inactivation of both pRB- and p53-pathways. While retinoblastomas are initiated by loss of the RB1 tumor suppressor gene, TP53 mutations have not been found. High expression of the p53-antagonist MDM2 in human retinoblastomas may compromise p53 tumor surveillance so that TP53 mutations are not selected for in retinoblastoma tumorigenesis. We previously showed that p14ARF protein, which activates p53 by inhibiting MDM2, is low in retinoblastomas despite high mRNA expression.

Methods
In human fetal retinas, adult retinas, and retinoblastoma cells, we determined endogenous p14

ARF
mRNA, ARF protein, and miR-24 expression, while integrity of p53 signalling in WERI-Rb1 cells was tested using an adenovirus vector expressing p14ARF. To study p14ARF biogenesis, retinoblastoma cells were treated with the proteasome inhibitor, MG132, and siRNA against miR-24.

Results
In human retinoblastoma cell lines, p14

ARF
mRNA was disproportionally high relative to the level of p14ARF protein expression, suggesting a perturbation of p14ARF regulation. When p14ARF was over-expressed by an adenovirus vector, expression of p53 and downstream targets increased and cell growth was inhibited indicating an intact p14ARF-p53 axis. To investigate the discrepancy between p14

ARF
mRNA and protein in retinoblastoma, we examined p14ARF biogenesis. The proteasome inhibitor, MG132, did not cause p14ARF accumulation, although p14ARF normally is degraded by proteasomes. miR-24, a microRNA that represses p14ARF expression, is expressed in retinoblastoma cell lines and correlates with lower protein expression when compared to other cell lines with high p14

ARF
mRNA. Transient over-expression of siRNA against miR-24 led to elevated p14ARF protein in retinoblastoma cells.

Conclusions
In retinoblastoma cells where high levels of p14

ARF
mRNA are not accompanied by high p14ARF protein, we found a correlation between miR-24 expression and low p14ARF protein. p14ARF protein levels were restored without change in mRNA abundance upon miR-24 inhibition suggesting that miR-24 could functionally repress expression, effectively blocking p53 tumor surveillance. During retinal tumorigenesis, miR-24 may intrinsically compromise the p53 response to RB1 loss.
Predicting sample size required for classification performance
Authors: Figueroa Rosa L , Zeng-Treitler Qing , Kandula Sasikiran , Ngo Long H 
Published: February 2012

Abstract

Background
Supervised learning methods need annotated data in order to generate efficient models. Annotated data, however, is a relatively scarce resource and can be expensive to obtain. For both passive and active learning methods, there is a need to estimate the size of the annotated sample required to reach a performance target.

Methods
We designed and implemented a method that fits an inverse power law model to points of a given learning curve created using a small annotated training set. Fitting is carried out using nonlinear weighted least squares optimization. The fitted model is then used to predict the classifier's performance and confidence interval for larger sample sizes. For evaluation, the nonlinear weighted curve fitting method was applied to a set of learning curves generated using clinical text and waveform classification tasks with active and passive sampling methods, and predictions were validated using standard goodness of fit measures. As control we used an un-weighted fitting method.

Results
A total of 568 models were fitted and the model predictions were compared with the observed performances. Depending on the data set and sampling method, it took between 80 to 560 annotated samples to achieve mean average and root mean squared error below 0.01. Results also show that our weighted fitting method outperformed the baseline un-weighted method (p < 0.05).

Conclusions
This paper describes a simple and effective sample size prediction algorithm that conducts weighted fitting of learning curves. The algorithm outperformed an un-weighted algorithm described in previous literature. It can help researchers determine annotation sample size for supervised machine learning.
Expression and extracellular release of a functional anti-trypanosome Nanobody® in Sodalis glossinidius, a bacterial symbiont of the tsetse fly
Authors: De Vooght Linda , Caljon Guy , Stijlemans Benoît , De Baetselier Patrick , Coosemans Marc , Van Den Abbeele Jan 
Published: February 2012

Abstract

Background

Sodalis glossinidius, a gram-negative bacterial endosymbiont of the tsetse fly, has been proposed as a potential in vivo drug delivery vehicle to control trypanosome parasite development in the fly, an approach known as paratransgenesis. Despite this interest of S. glossinidius as a paratransgenic platform organism in tsetse flies, few potential effector molecules have been identified so far and to date none of these molecules have been successfully expressed in this bacterium.

Results
In this study, S. glossinidius was transformed to express a single domain antibody, (Nanobody®) Nb_An33, that efficiently targets conserved cryptic epitopes of the variant surface glycoprotein (VSG) of the parasite Trypanosoma brucei. Next, we analyzed the capability of two predicted secretion signals to direct the extracellular delivery of significant levels of active Nb_An33. We show that the pelB leader peptide was successful in directing the export of fully functional Nb_An33 to the periplasm of S. glossinidius resulting in significant levels of extracellular release. Finally, S. glossinidius expressing pelBNb_An33 exhibited no significant reduction in terms of fitness, determined by in vitro growth kinetics, compared to the wild-type strain.

Conclusions
These data are the first demonstration of the expression and extracellular release of functional trypanosome-interfering Nanobodies® in S. glossinidius. Furthermore, Sodalis strains that efficiently released the effector protein were not affected in their growth, suggesting that they may be competitive with endogenous microbiota in the midgut environment of the tsetse fly. Collectively, these data reinforce the notion for the potential of S. glossinidius to be developed into a paratransgenic platform organism.