bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient Ischemic Attack Incidence in Joinville, Brazil, 2010
Authors: Fonseca Patricia G. , Weiss Pedro A.K. , Harger Rodrigo , Moro Carla H.C. , Longo Alexander L. , Gonçalves Anderson R.R. , Whiteley William N. , Cabral Norberto L. 
Published: December 2011

Background and Purpose—
There are scarce data on transient ischemic attack incidence in low- and middle-income countries. We aimed to measure transient ischemic attack incidence and the distribution of the ABCD2 risk score in Joinville, Brazil.

Methods—
In 2009 to 2010, using a multiple overlapping sources, we ascertained all first ever probable and definite transient ischemic attacks.

Results—
We recorded 74 definite and probable transient ischemic attacks. The crude incidence was 15 (12–18) per 100 000 population. Age adjusted to European population the incidence was 28 (22–35). One fourth was in the higher risk of stroke by the ABCD2 scale.

Conclusions—
The transient ischemic attack incidence in Joinville, Brazil, is lower than other well-designed studies. New studies could clarify whether the measured rates were due to underascertainment or reflect a truly low incidence.
The Allegory of War in Johannes Kepler's Astronomia Nova
Authors: Barreca Francesco 
Published: December 2011

AbstractIn the dedicatory letter to Rudolf II that opens his work Astronomia Nova Kepler presents an allegory of war. Taking as its premise that the Habsburg emperor was his specific audience and that the rhetorical guidelines were provided by Melanchthon's Elementorum rhetorices and Crusius' Scholia and Quaestiones, this paper will offer an interpretation of the allegory and discuss the thesis that Kepler's aim, in representing astronomy as war, was to explain his vision of the role of the court astronomer, setting it apart from the traditional roles of the court astrologer and the court artist. This will be explored beginning with an analysis of Kepler's use of rhetoric, based on his training in the methods of Philipp Melanchthon, and will go on to discuss Kepler's allegory in its cultural and political context, and finally examine it from the rhetorical and conceptual points of view.
Improving OSCE Human Dimension events — A never-ending story
Authors: Hazewinkel Harm J. 
Published: December 2011

AbstractAs long as the HDIM and other Human Dimension events exists, there is discussion on the formula and Ambassador Gremiger's attempts, even though not new, should be welcomed. Some intrinsic elements make it however difficult to find a format that is satisfying to all. In the first place there is the fact that the HDIM will not produce a negotiated document, which makes it difficult to capture the interest of governments. Furthermore, the growth of the European Union, which speaks with one voice, entails that interest mainly goes to the fringe of the OSCE area. On the other hand, several seminars (e.g. Roma and Sinti, Religious Freedom and Women's Rights) have contributed to enhanced interest within the OSCE . It should never be forgotten that the HDIM and other meetings are a tool, not an aim in themselves.
Optimization of composition, structure and mechanical strength of bioactive 3-D glass-ceramic scaffolds for bone substitution
Authors: Baino Francesco , Ferraris Monica , Bretcanu Oana , Verné Enrica , Vitale-Brovarone Chiara 
Published: December 2011

Fabrication of 3-D highly porous, bioactive, and mechanically competent scaffolds represents a significant challenge of bone tissue engineering. In this work, Bioglass®-derived glass-ceramic scaffolds actually fulfilling this complex set of requirements were successfully produced through the sponge replication method. Scaffold processing parameters and sintering treatment were carefully designed in order to obtain final porous bodies with pore content (porosity above 70 %vol), trabecular architecture and mechanical properties (compressive strength up to 3 MPa) analogous to those of the cancellous bone. Influence of the Bioglass® particles size on the structural and mechanical features of the sintered scaffolds was considered and discussed. Relationship between porosity and mechanical strength was investigated and modeled. Three-dimensional architecture, porosity, mechanical strength and in vitro bioactivity of the optimized Bioglass®-derived scaffolds were also compared to those of CEL2-based glass-ceramic scaffolds (CEL2 is an experimental bioactive glass originally developed by the authors at Politecnico di Torino) fabricated by the same processing technique, in an attempt at understanding the role of different bioactive glass composition on the major features of scaffolds prepared by the same method.
Effects of surface modification of PLGA-PEG-PLGA nanoparticles on loperamide delivery efficiency across the blood–brain barrier
Authors: Chen Yung-Chu , Hsieh Wen-Yuan , Lee Wen-Fu , Zeng Ding-Tai 
Published: December 2011

In this study, we developed a nanoparticle system for drug delivery across the blood–brain barrier (BBB). The nanoparticle consisting of loperamide and poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer were prepared by the nanoprecipitation method; then the nanoparticles were coated with poloxamer 188 or polysorbate 80. The effects of poloxamer 188 or polysorbate 80 on the physicochemical and pharmaceutical properties of the coated nanoparticles were investigated. Loperamide, which does not cross the blood–brain barrier (BBB) but exerts antinociceptive effects after direct injection into the brain, was encapsulated by different polymeric materials and used as a model drug. The in vitro BBB penetration study shows that the surfactant-coated PLGA-PEG-PLGA nanoparticles could have penetration of 14.4–21.2%, which was better than the PLGA-PEG-PLGA nanoparticles (PEP) (8.2%) and the PLGA nanoparticles (PN) (4.3%). The biopsy studies also confirm that the PEP coated by surfactant could increase the penetration. The results of nanoparticles accumulation in brain tissue show that the PEP coated by surfactant had a much higher concentration than both the PEP and the PN. Moreover, the maximal possible antinociception effect (MPE) for the surfactant-coated PEP was 21–35% at 150 min after administering the drug intravenously, which was significantly better than just the PEP (MPE: 11.6%). The results of the formalin test show that the surfactant-coated PEP administered intravenously 150 min prior to the formalin injection could greatly reduce the pain response in the first phase. The results demonstrate that the surfactant-coated PEP could help to deliver loperamide across the BBB.
Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene
Authors: Agrawal-Singh Shuchi , Isken Fabienne , Agelopoulos Konstantin , Klein Hans-Ulrich , Thoennissen Nils H. , Koehler Gabriele , Hascher Antje , Bäumer Nicole , Berdel Wolfgang E. , Thiede Christian , Ehninger Gerhard , Becker Anke , Schlenke Peter , Wang Yipeng , McClelland Michael , Krug Utz , Koschmieder Steffen , Büchner Thomas , Yu Dae-Yeul , Singh Shailendra Vikram , Hansen Klaus , Serve Hubert , Dugas Martin , Müller-Tidow Carsten 
Published: December 2011

Abstract
With the use of ChIP on microarray assays in primary leukemia samples, we report that acute myeloid leukemia (AML) blasts exhibit significant alterations in histone H3 acetylation (H3Ac) levels at > 1000 genomic loci compared with CD34+ progenitor cells. Importantly, core promoter regions tended to have lower H3Ac levels in AML compared with progenitor cells, which suggested that a large number of genes are epigenetically silenced in AML. Intriguingly, we identified peroxiredoxin 2 (PRDX2) as a novel potential tumor suppressor gene in AML. H3Ac was decreased at the PRDX2 gene promoter in AML, which correlated with low mRNA and protein expression. We also observed DNA hypermethylation at the PRDX2 promoter in AML. Low protein expression of the antioxidant PRDX2 gene was clinically associated with poor prognosis in patients with AML. Functionally, PRDX2 acted as inhibitor of myeloid cell growth by reducing levels of reactive oxygen species (ROS) generated in response to cytokines. Forced PRDX2 expression inhibited c-Myc–induced leukemogenesis in vivo on BM transplantation in mice. Taken together, epigenome-wide analyses of H3Ac in AML led to the identification of PRDX2 as an epigenetically silenced growth suppressor, suggesting a possible role of ROS in the malignant phenotype in AML.
The disulfide isomerase ERp57 mediates platelet aggregation, hemostasis, and thrombosis
Authors: Wu Yi , Ahmad Syed S. , Zhou Junsong , Wang Lu , Cully Matthew P. , Essex David W. 
Published: December 2011

AbstractA close homologue to protein disulfide isomerase (PDI) called ERp57 forms disulfide bonds in glycoproteins in the endoplasmic reticulum and is expressed on the platelet surface. We generated 2 rabbit Abs to ERp57. One Ab strongly inhibited ERp57 in a functional assay and strongly inhibited platelet aggregation. There was minimal cross-reactivity of this Ab with PDI by Western blot or in the functional assay. This Ab substantially inhibited activation of the αIIbβ3 fibrinogen receptor and P-selectin expression. Furthermore, adding ERp57 to platelets potentiated aggregation. In contrast, adding a catalytically inactive ERp57 inhibited platelet aggregation. When infused into mice the inactive ERp57 prolonged the tail bleeding times. We generated 2 IgG2a mAbs that reacted with ERp57 by immunoblot. One of these Abs inhibited both ERp57 activity and platelet aggregation. The other Ab did not inhibit ERp57 activity or platelet aggregation. The inhibitory Ab inhibited activation of αIIbβ3 and P-selectin expression, prolonged tail bleeding times, and inhibited FeCl3-induced thrombosis in mice. Finally, we found that a commonly used mAb to PDI also inhibited ERp57 activity. We conclude that a glycoprotein-specific member of the PDI family, ERp57, is required for platelet aggregation, hemostasis, and thrombosis.
miR-27b controls venous specification and tip cell fate
Authors: Biyashev Dauren , Veliceasa Dorina , Topczewski Jacek , Topczewska Jolanta M. , Mizgirev Igor , Vinokour Elena , Reddi Alagarsamy L. , Licht Jonathan D. , Revskoy Sergei Y. , Volpert Olga V. 
Published: December 2011

Abstract
We discovered that miR-27b controls 2 critical vascular functions: it turns the angiogenic switch on by promoting endothelial tip cell fate and sprouting and it promotes venous differentiation. We have identified its targets, a Notch ligand Delta-like ligand 4 (Dll4) and Sprouty homologue 2 (Spry2). miR-27b knockdown in zebrafish and mouse tissues severely impaired vessel sprouting and filopodia formation. Moreover, miR-27b was necessary for the formation of the first embryonic vein in fish and controlled the expression of arterial and venous markers in human endothelium, including Ephrin B2 (EphB2), EphB4, FMS-related tyrosine kinase 1 (Flt1), and Flt4. In zebrafish, Dll4 inhibition caused increased sprouting and longer intersegmental vessels and exacerbated tip cell migration. Blocking Spry2 caused premature vessel branching. In contrast, Spry2 overexpression eliminated the tip cell branching in the intersegmental vessels. Blockade of Dll4 and Spry2 disrupted arterial specification and augmented the expression of venous markers. Blocking either Spry2 or Dll4 rescued the miR-27b knockdown phenotype in zebrafish and in mouse vascular explants, pointing to essential roles of these targets downstream of miR-27b. Our study identifies critical role of miR-27b in the control of endothelial tip cell fate, branching, and venous specification and determines Spry2 and Dll4 as its essential targets.
Prognostic value of monosomal karyotype in comparison to complex aberrant karyotype in acute myeloid leukemia: a study on 824 cases with aberrant karyotype
Authors: Haferlach Claudia , Alpermann Tamara , Schnittger Susanne , Kern Wolfgang , Chromik Jörg , Schmid Christoph , Pielken Hermann Josef , Kreuzer Karl-Anton , Höffkes Heinz-Gert , Haferlach Torsten 
Published: December 2011

Abstract
In acute myeloid leukemia (AML) the subset with complex karyotype (CK) is traditionally regarded as the worst prognostic group. However, ≥ 3, ≥ 4, or ≥ 5 abnormalities have been variably used for its definition. Recently, monosomal karyotype (MSK) was suggested to indicate an even inferior outcome. We tested which definition fits best to identify the most unfavorable subgroup. After excluding patients with t(15;17)/PML-RARA, t(8;21)/RUNX1-RUNX1T1, inv (16)/t(16;16)/CBFB-MYH11, and normal karyotype, 824 patients with AML with cytogenetic abnormalities were analyzed. Patients with MSK or CK defined as ≥ 3, ≥ 4, or ≥ 5 abnormalities showed an inferior overall survival compared with the respective remaining patients not fulfilling these criteria (for all, P < .001). Hazard ratios were 1.93, 1.68, 1.94, and 1.92. CK ≥ 4 as a single parameter identified the largest proportion of patients with very poor risk. However, combining CK ≥ 4 and MSK detected an even larger number of patients with very unfavorable outcome (261 of 824; 31.7%).
Thermodynamic and structural description of allosterically regulated VEGFR-2 dimerization
Authors: Brozzo Maurice S. , Bjelić Saša , Kisko Kaisa , Schleier Thomas , Leppänen Veli-Matti , Alitalo Kari , Winkler Fritz K. , Ballmer-Hofer Kurt 
Published: December 2011

Abstract
VEGFs activate 3 receptor tyrosine kinases, VEGFR-1, VEGFR-2, and VEGFR-3, promoting angiogenic and lymphangiogenic signaling. The extracellular receptor domain (ECD) consists of 7 Ig-homology domains; domains 2 and 3 (D23) represent the ligand-binding domain, whereas the function of D4-7 is unclear. Ligand binding promotes receptor dimerization and instigates transmembrane signaling and receptor kinase activation. In the present study, isothermal titration calorimetry showed that the Gibbs free energy of VEGF-A, VEGF-C, or VEGF-E binding to D23 or the full-length ECD of VEGFR-2 is dominated by favorable entropic contribution with enthalpic penalty. The free energy of VEGF binding to the ECD is 1.0-1.7 kcal/mol less favorable than for binding to D23. A model of the VEGF-E/VEGFR-2 ECD complex derived from small-angle scattering data provided evidence for homotypic interactions in D4-7. We also solved the crystal structures of complexes between VEGF-A or VEGF-E with D23, which revealed comparable binding surfaces and similar interactions between the ligands and the receptor, but showed variation in D23 twist angles. The energetically unfavorable homotypic interactions in D4-7 may be required for re-orientation of receptor monomers, and this mechanism might prevent ligand-independent activation of VEGFR-2 to evade the deleterious consequences for blood and lymph vessel homeostasis arising from inappropriate receptor activation.
Dynamics of HBV cccDNA expression and transcription in different cell growth phase
Authors: Chong Chin-Liew , Chen Mong-Liang , Wu Yi-Chieh , Tsai Kuen-Nan , Huang Chien-Chiao , Hu Cheng-po , Jeng King-Song , Chou Yu-Chi , Chang Chungming 
Published: December 2011

Abstract

Background
The covalently closed-circular DNA (cccDNA) of hepatitis B virus (HBV) is associated with viral persistence in HBV-infected hepatocytes. However, the regulation of cccDNA and its transcription in the host cells at different growth stages is not well understood.

Methods
We took advantages of a stably HBV-producing cell line, 1.3ES2, and examine the dynamic changes of HBV cccDNA, viral transcripts, and viral replication intermediates in different cellular growth stages.

Results
In this study, we showed that cccDNA increased suddenly in the initial proliferation phase of cell growth, probably attributable to its nuclear replenishment by intracellular nucleocapsids. The amount of cccDNA then decreased dramatically in the cells during their exponential proliferation similar to the loss of extrachromosomal plasmid DNA during cell division, after which it accumulated gradually while the host cells grew to confluency. We found that cccDNA was reduced in dividing cells and could be removed when proliferating cells were subjected to long term of lamivudine (3TC) treatment. The amounts of viral replicative intermediates were rapidly reduced in these proliferating cells and were significantly increased after cells reaching confluency. The expression levels of viral transcripts were increased in parallel with the elevated expression of hepatic transcription factors (HNF4α, CEBPα, PPARα, etc.) during cell growth confluency. The HBV transcripts were transcribed from both integrated viral genome and cccDNA, however the transcriptional abilities of cccDNA was less efficient then that from integrated viral genome in all cell growth stages. We also noted increases in the accumulation of intracellular viral particles and the secretion of mature virions as the cells reached confluency and ceased to grow.

Conclusions
Based on the dynamics of HBV replication, we propose that HBV replication is modulated differently in the different stages of cell growth, and can be divided into three phases (initial proliferation phase, exponential proliferation phase and growth confluency phase) according to the cell growth curve. The regulation of cccDNA in different cell growth phase and its importance regarding HBV replication are discussed.
MotifMap: integrative genome-wide maps of regulatory motif sites for model species
Authors: Daily Kenneth , Patel Vishal R , Rigor Paul , Xie Xiaohui , Baldi Pierre 
Published: December 2011

Abstract

Background
A central challenge of biology is to map and understand gene regulation on a genome-wide scale. For any given genome, only a small fraction of the regulatory elements embedded in the DNA sequence have been characterized, and there is great interest in developing computational methods to systematically map all these elements and understand their relationships. Such computational efforts, however, are significantly hindered by the overwhelming size of non-coding regions and the statistical variability and complex spatial organizations of regulatory elements and interactions. Genome-wide catalogs of regulatory elements for all model species simply do not yet exist.

Results
The MotifMap system uses databases of transcription factor binding motifs, refined genome alignments, and a comparative genomic statistical approach to provide comprehensive maps of candidate regulatory elements encoded in the genomes of model species. The system is used to derive new genome-wide maps for yeast, fly, worm, mouse, and human. The human map contains 519,108 sites for 570 matrices with a False Discovery Rate of 0.1 or less. The new maps are assessed in several ways, for instance using high-throughput experimental ChIP-seq data and AUC statistics, providing strong evidence for their accuracy and coverage. The maps can be usefully integrated with many other kinds of omic data and are available at http://motifmap.igb.uci.edu/.

Conclusions
MotifMap and its integration with other data provide a foundation for analyzing gene regulation on a genome-wide scale, and for automatically generating regulatory pathways and hypotheses. The power of this approach is demonstrated and discussed using the P53 apoptotic pathway and the Gli hedgehog pathways as examples.
Refinement of Bos taurus sequence assembly based on BAC-FISH experiments
Authors: Partipilo Giulia , D'Addabbo Pietro , Lacalandra Giovanni M , Liu George E , Rocchi Mariano 
Published: December 2011

Abstract

Background
The sequencing of the cow genome was recently published (Btau_4.0 assembly). A second, alternate cow genome assembly (UMD2), based on the same raw sequence data, was also published. The two assemblies have been subsequently updated to Btau_4.2 and UMD3.1, respectively.

Results
We compared the Btau_4.2 and UMD3.1 alternate assemblies. Inconsistencies were grouped into three main categories: (i) DNA segments showing almost coincidental chromosomal mapping but discordant orientation (inversions); (ii) DNA segments showing a discordant map position along the same chromosome; and (iii) sequences present in one chromosomal assembly but absent in the corresponding chromosome of the other assembly. The latter category mainly consisted of large amounts of scaffolds that were unassigned in Btau_4.2 but successfully mapped in UMD3.1. We sampled 70 inconsistencies and identified appropriate cow BACs for each of them. These clones were then utilized in FISH experiments on cow metaphase or interphase nuclei in order to disambiguate the discrepancies. In almost all instances the FISH results agreed with the UMD3.1 assembly. Occasionally, however, the mapping data of both assemblies were discordant with the FISH results.

Conclusions
Our work demonstrates how FISH, which is assembly independent, can be efficiently used to solve assembly problems frequently encountered using the shotgun approach.
Neuroantigen-specific, tolerogenic vaccines: GM-CSF is a fusion partner that facilitates tolerance rather than immunity to dominant self-epitopes of myelin in murine models of experimental autoimmune encephalomyelitis (EAE)
Authors: Abbott Derek J , Blanchfield J Lori , Martinson David A , Russell Sean C , Taslim Najla , Curtis Alan D , Mannie Mark D 
Published: December 2011

AbstractBackgroundVaccination strategies that elicit antigen-specific tolerance are needed as therapies for autoimmune disease. This study focused on whether cytokine-neuroantigen (NAg) fusion proteins could inhibit disease in chronic murine models of experimental autoimmune encephalomyelitis (EAE) and thus serve as potential therapeutic modalities for multiple sclerosis.ResultsA fusion protein comprised of murine GM-CSF as the N-terminal domain and the encephalitogenic MOG35-55 peptide as the C-terminal domain was tested as a tolerogenic, therapeutic vaccine (TTV) in the C57BL/6 model of EAE. Administration of GMCSF-MOG before active induction of EAE, or alternatively, at the onset of EAE blocked the development and progression of EAE. Covalent linkage of the GM-CSF and MOG35-55 domains was required for tolerogenic activity. Likewise, a TTV comprised of GM-CSF and PLP139-151 was a tolerogen in the SJL model of EAE.ConclusionThese data indicated that fusion proteins containing GM-CSF coupled to myelin auto-antigens elicit tolerance rather than immunity.