bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRS2α-Mediated FGF Signals Suppress Premature Differentiation of Cardiac Stem Cells Through Regulating Autophagy Activity
Authors: Zhang Jue , Liu Junchen , Huang Yanqing , Chang Julia Y.F. , Liu Leyuan , McKeehan Wallace L. , Martin James F. , Wang Fen 
Published: December 2011

Rationale:
Although the fibroblast growth factor (FGF) signaling axis plays important roles in heart development, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood.

Objective:
To investigate the mechanism by which FGF signaling regulates cardiac progenitor cell differentiation.

Methods and Results:

Using mice with tissue-specific ablation of FGF receptors and FGF receptor substrate 2
α
(
Frs2
α
) in heart progenitor cells, we demonstrate that disruption of FGF signaling leads to premature differentiation of cardiac progenitor cells in mice. Using embryoid body cultures of mouse embryonic stem cells, we reveal that FGF signaling promotes mesoderm differentiation in embryonic stem cells but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, we also report that inhibiting FRS2α-mediated signals increases autophagy and that activating autophagy promotes myocardial differentiation and vice versa.

Conclusions:
The results indicate that the FGF/FRS2α-mediated signals prevent premature differentiation of heart progenitor cells through suppressing autophagy. The findings provide the first evidence that autophagy plays a role in heart progenitor differentiation.
Sirolimus as Primary Immunosuppression Attenuates Allograft Vasculopathy With Improved Late Survival and Decreased Cardiac Events After Cardiac Transplantation
Authors: Topilsky Yan , Hasin Tal , Raichlin Eugenia , Boilson Barry A. , Schirger John A. , Pereira Naveen L. , Edwards Brooks S. , Clavell Alfredo L. , Rodeheffer Richard J. , Frantz Robert P. , Maltais Simon , Park Soon J. , Daly Richard C. , Lerman Amir , Kushwaha Sudhir S. 
Published: December 2011

Background—
We retrospectively analyzed the potential of sirolimus as a primary immunosuppressant in the long-term attenuation of cardiac allograft vasculopathy progression and the effects on cardiac-related morbidity and mortality.

Methods and Results—

Forty-five cardiac transplant recipients were converted to sirolimus 1.2 years (0.2, 4.0) after transplantation with complete calcineurin inhibitor withdrawal. Fifty-eight control subjects 2.0 years (0.2, 6.5 years) from transplantation were maintained on calcineurin inhibitors. Age, sex, ejection fraction, and time from transplantation to baseline intravascular ultrasound study were not different (
P
>0.2 for all) between the groups; neither were secondary immunosuppressants and use of steroids. Three-dimensional intravascular ultrasound studies were performed at baseline and 3.1 years (1.3, 4.6 years) later. Plaque index progression (plaque volume/vessel volume) was attenuated in the sirolimus group (0.7±10.5% versus 9.3±10.8%;
P
=0.0003) owing to reduced plaque volume in patients converted to sirolimus early (<2 years) after transplantation (
P
=0.05) and improved positive vascular remodeling (
P
=0.01) in patients analyzed late (>2 years) after transplantation. Outcome analysis in 160 consecutive patients maintained on 1 therapy was performed regardless of performance of intravascular ultrasound examinations. Five-year survival was improved with sirolimus (97.4±1.8% versus 81.8±4.9%;
P
=0.006), as was freedom from cardiac-related events (93.6±3.2% versus 76.9±5.5%;
P
=0.002).

Conclusions—
Substituting calcineurin inhibitor with sirolimus as primary immunosuppressant attenuates long-term cardiac allograft vasculopathy progression and may improve long-term allograft survival owing to favorable coronary remodeling. Because of the lack of randomization and retrospective nature of our analysis, the differences in outcome should be interpreted cautiously, and prospective clinical trials are required.
Insufficient Platelet Inhibition Is Related to Silent Embolic Cerebral Infarctions After Coronary Angiography
Authors: Kim Bum Joon , Lee Seung-Whan , Park Seong-Wook , Kang Dong-Wha , Kim Jong S. , Kwon Sun U. 
Published: December 2011

Background and Purpose—
Considering that insufficient platelet inhibition is related to thrombotic complications after coronary angiography, we hypothesized that the extent of platelet inhibition by antiplatelet agents is related to the occurrence of silent embolic cerebral infarction (SECI) after coronary angiography.

Methods—
Among the patients scheduled for coronary artery bypass surgery, we retrospectively analyzed the location of SECI on diffusion-weighted imaging of 272 patients, which was performed after coronary angiography, as a presurgical evaluation in Phase 1 study. In Phase 2 study, we have prospectively recruited 102 patients to compare the extent of platelet inhibition measured by the VerifyNow system among patients with and without SECI.

Results—

SECI is observed in 45 patients (16.5%) in Phase 1 and 17 (16.7%) in Phase 2. The lesions were slightly more frequent in the right hemisphere. In the Phase 2 study, aspirin reaction units and P
2
Y
12
reaction units were higher in the patients with SECI than those without (aspirin reaction units: 490±72 versus 446±53,
P
=0.03; P
2
Y
12
reaction units: 352±65 versus 300±77,
P
=0.009). The incidence of SECI increased with the number of resistant antiplatelets; resistance to both antiplatelet agent (50%), resistance to 1 antiplatelet agent (22%), and no resistance (4%;
P
=0.023). From the result of logistic regression, higher aspirin reaction units, white blood cell count, low hemoglobin, and nonresponsiveness to antiplatelet agents were independent risk factors.

Conclusions—
Insufficient platelet inhibition after administration of antiplatelet agents is related with SECI appearing after coronary angiography.
Rinman, Diderot, and Lavoisier: New Evidence Regarding Guillaume Franois Rouelle's Private Laboratory and Chemistry Course
Authors: Beretta Marco 
Published: December 2011

AbstractThis paper will present two recently discovered documents that shed light on the activities of the French chemist Guillaume Franois Rouelle.In 1746 the Swedish chemist and mineralogist Sven Rinman visited the private chemistry laboratory recently set up by Rouelle in Paris, and he has left us a record of this visit, including some rare sketches. Given the crucial contribution made by Rouelle's laboratory to the development of the science of chemistry in 18th-century Europe, Rinman's description is reproduced here in full.Rouelle also taught an extremely popular chemistry course at the Jardin des Plantes in Paris, and conserved in the archives of Antoine Laurent Lavoisier are some notes taken by Denis Diderot in 1757 which demonstrate that for a period the prominent Enlightenment figure attended these lectures regularly.
Open Skies in turbulence, a well functioning treaty is endangered by outside developments
Authors: Spitzer Hartwig 
Published: December 2011

AbstractToday the Treaty on Open Skies is confronted with contradictory developments: Continuing adherence of all parties, in particular Russia and the United States to the treaty and preparations for modernisation of the technical monitoring capabilities on the one hand, while the general support for conventional arms control and military confidence building in the OSCE region declines. Since January 2011 an intervention of Turkey over the accession application of Cyprus has prevented any regular sessions and decisions of the Open Skies Consultative Commission ( OSCC ). The treaty is taken hostage for an unsolved status conflict which has much wider dimensions. Since the impasse in the OSCC could not be solved on the diplomatic level so far (Oct. 2011), high level political intervention is needed to save the treaty from erosion.
Diplomacy and life on Georgia's boundary line
Authors: van Peski Caecilia J. 
Published: December 2011

AbstractOn the third anniversary of the war over South Ossetia, resumed talks between Georgia and Russia are needed to create positive momentum in a still unstable environment. The article examines the continuing strains and recommends that the two sides engage in direct dialogue in order to de-escalate allegations about the other's involvement in the conflict. While formal diplomatic relations remain more or less suspended, many mutual interests remain. Paramount in this is the fact that Georgia and Russia share interests in improving mutual security, trade and transport.
The impact of the ongoing conflict on Georgia's very diverse communities differs substantially, as do their priorities. Concerns over the future amongst these communities are widespread. The consequences of the violence and subsequent failure to progress resolution of the conflict still affect communities, especially those living along the Administrative Boundary Line between South Ossetia and Georgia proper. Although no major incidents of violence have occurred since 2008 and the level of humanitarian assistance provided to communities around the ABL has been impressive during the first two years following the war, the contact and movement across the ABL has become increasingly difficult, badly affecting those dependent on cross-border interaction for their personal wellbeing and that of their communities. As a result, a range of vulnerabilities is more likely to come to the surface and undermine the future sustainability of communities living along the ABL.
As such, it is essential that local and international actors, including OSCE and EUMM are better able to distinguish between the varied needs of communities living along the ABL , in order to develop appropriate strategies for responding to them.
Reviewing the OSCE Human Dimension events
Authors: Greminger Thomas 
Published: December 2011

AbstractMany voices asking for a review of OSCE Human Dimension events have been heard. This year an increased interest among participating states in reviewing and improving the organization and modalities of the Human Dimension meetings was noticed. The Chair of the Human Dimension Committee, the Swiss Ambassador, Thomas Greminger, has, together with the Lithuanian chairmanship, decided to put this topic on the agenda. In order to support the discussions on this 'difficult' topic in an objective way, a study is currently prepared by an independent Swiss think-tank. While this process will not be an easy task, Ambassador Greminger is committed to leading it through in a transparent and inclusive manner.
Tactical Nuclear Weapons
Authors: Zagorski Andrei 
Published: December 2011

AbstractRussia and the US have significantly reduced their tactical nuclear weapons over the past twenty years. The remaining weapons have been moved from active service and stored separate from their delivery systems. However, both still keep tactical nuclear weapons available for eventual deployment, and Moscow maintains not only a larger but also a much more diverse stockpile of such weapons than the US. The prospects for designing an arms control regime covering TNW are complicated by a series of factors. Technically, verifying any limitations or reductions of non-deployed weapons is an extremely sensitive and challenging task as it would require opening nuclear depots for inspection. Politically, the two countries differ in the assessment of a future role of nuclear arms. While the US anticipates that further development of its advanced conventional capabilities would lead to diminishing the role of nuclear weapons, it is exactly the weakness of its conventional forces which causes the Russian defence establishment to project a growing role for nuclear weapons. These two distinct trajectories largely explain the differences in the two countries' approaches to the TNW arms control and make any agreement less likely to materialize any time soon. They also explain why Moscow has become increasingly sceptical with regard to including TNW within an arms control regime.
Low Conspicuity of Motorcycles for Car Drivers
Authors: Rogé Joceline , Douissembekov Evgueni , Vienne Fabrice 
Published: December 2011

Objective: The aim of this study was to evaluate whether the low visibility of motorcycles is the result of their low cognitive conspicuity and/or their low sensory conspicuity for car drivers. Background: In several cases of collision between a car and a motorcycle, the car driver failed to detect the motorcyclist in time to avoid the collision. Method: To test the low cognitive conspicuity hypothesis, 42 car drivers (32.02 years old) including 21 motorcyclist motorists and 21 non–motorcyclist motorists carried out a motorcycle detection task in a car-driving simulator. To test the low sensory conspicuity hypothesis, the authors studied the effect of the color contrast between motorcycles and the road surface on the ability of car drivers to detect motorcycles when they appear from different parts of the road. Results: A high level of color contrast enhanced the visibility of motorcycles when they appeared in front of the participants. Moreover, when motorcyclists appeared from behind the participants, the motorcyclist motorists detected oncoming motorcycles at a greater distance than did the non–motorcyclist motorists. Motorcyclist motorists carry out more saccades and rapidly capture information (on their rearview mirrors and on the road in front of them). Conclusion: The results related to the sensory conspicuity and cognitive conspicuity of motorcycles for car drivers are discussed from the viewpoint of visual attention theories. Application: The practical implications of these results and future lines of research related to training methods for car drivers are considered.
Assessment of multicomponent hydrogel scaffolds of poly(acrylic acid-2-hydroxy ethyl methacrylate)/gelatin for tissue engineering applications
Authors: Jaiswal Maneesh , Koul Veena 
Published: December 2011

The article describes the design of the multicomponent hydrogel system of poly(acrylic acid-HEMA)/gelatin for tissue engineering application. Derivative of polycaprolactone-diol (polycaprolactone diacrylate (PCL-DAr)) was used to cross-link acrylate monomers whereas gelatin was kept free for cell proliferation. Epigallocatechin gallate (EGCG), an anti-oxidant phytochemical, was loaded by diffusion method. Its in vitro release study in PBS (pH 6.5) at 37 ± 0.2°C (75 rpm) revealed a sustained release profile upto 20 days. Fitting of drug release data in Korsmeyer-Peppas model equation revealed probable release mechanism through the value of release coefficient ( n), which was found to depend on formulations composition. Drug-polymer interaction, thermal behavior, and surface morphology were investigated by attenuated total reflectance–Fourier transform infrared (ATR-FTIR) spectroscopy, thermogravimetric analysis (TGA), and scanning electron microscopic (SEM). Swelling behavior of hydrogel in PBS (pH 6.5 and 7.4, 0.2 M) and in distilled water was found to increase with increasing AAc/HEMA ratio. Compression modulus decreased from 203 ± 3.7 KPa to 11.6 ± 1.1KPa, at 30% strain, whereas displacement values significantly increased from 3.2 ± 0.2 to 4.7 ± 0.6 mm at 20 N force ( p < 0.05), with increasing AAc/HEMA ratio. Percentage cell viability was analyzed using indirect 3-[4, 5-dimethylthiazolyl-2]-2,5-diphenyltetrazo-liumbromide (MTT) assay with fibroblast L929 cells; showed ≥92.3% cell viability after 24 h incubation. Cell proliferation on the scaffold surface was found to increase with incorporation of HEMA in P(AAc)/G cross-linked hydrogel matrix upto a certain extent. These biocompatible, elastic, and swellable hydrogels can serve as a matrix for drug delivery and tissue engineering applications.
Neomycin and carbodiimide crosslinking as an alternative to glutaraldehyde for enhanced durability of bioprosthetic heart valves
Authors: Leong Joshua , Munnelly Amy , Liberio Brianna , Cochrane Leonard , Vyavahare Naren 
Published: December 2011

Glutaraldehyde cross-linked porcine aortic valves, referred to as bioprosthetic heart valves (BHVs), are often used in heart valve replacements. Glutaraldehyde does not stabilize glycosaminoglycans (GAGs) and they are lost during preparation, in vivo implantation, cyclic fatigue, and storage. We report that binding of neomycin, a hyaluronidase inhibitor, to the tissues with carbodiimide cross-linking improves GAG retention without reducing collagen and elastin stability. It also led to improved biomechanical properties. Neomycin carbodiimide cross-linking did not significantly reduce calcification in a rat subdermal implantation model when they were stored in formaldehyde after cross-linking. Removal of formaldehyde storage significantly reduced calcification.
A new strategy for better genome assembly from very short reads
Authors: Ji Yan , Shi Yixiang , Ding Guohui , Li Yixue 
Published: December 2011

Abstract

Background
With the rapid development of the next generation sequencing (NGS) technology, large quantities of genome sequencing data have been generated. Because of repetitive regions of genomes and some other factors, assembly of very short reads is still a challenging issue.

Results
A novel strategy for improving genome assembly from very short reads is proposed. It can increase accuracies of assemblies by integrating de novo contigs, and produce comparative contigs by allowing multiple references without limiting to genomes of closely related strains. Comparative contigs are used to scaffold de novo contigs. Using simulated and real datasets, it is shown that our strategy can effectively improve qualities of assemblies of isolated microbial genomes and metagenomes.

Conclusions
With more and more reference genomes available, our strategy will be useful to improve qualities of genome assemblies from very short reads. Some scripts are provided to make our strategy applicable at http://code.google.com/p/cd-hybrid/.
Identifying elemental genomic track types and representing them uniformly
Authors: Gundersen Sveinung , Kalaš Matúš , Abul Osman , Frigessi Arnoldo , Hovig Eivind , Sandve Geir Kjetil 
Published: December 2011

Abstract

Background
With the recent advances and availability of various high-throughput sequencing technologies, data on many molecular aspects, such as gene regulation, chromatin dynamics, and the three-dimensional organization of DNA, are rapidly being generated in an increasing number of laboratories. The variation in biological context, and the increasingly dispersed mode of data generation, imply a need for precise, interoperable and flexible representations of genomic features through formats that are easy to parse. A host of alternative formats are currently available and in use, complicating analysis and tool development. The issue of whether and how the multitude of formats reflects varying underlying characteristics of data has to our knowledge not previously been systematically treated.

Results
We here identify intrinsic distinctions between genomic features, and argue that the distinctions imply that a certain variation in the representation of features as genomic tracks is warranted. Four core informational properties of tracks are discussed: gaps, lengths, values and interconnections. From this we delineate fifteen generic track types. Based on the track type distinctions, we characterize major existing representational formats and find that the track types are not adequately supported by any single format. We also find, in contrast to the XML formats, that none of the existing tabular formats are conveniently extendable to support all track types. We thus propose two unified formats for track data, an improved XML format, BioXSD 1.1, and a new tabular format, GTrack 1.0.

Conclusions
The defined track types are shown to capture relevant distinctions between genomic annotation tracks, resulting in varying representational needs and analysis possibilities. The proposed formats, GTrack 1.0 and BioXSD 1.1, cater to the identified track distinctions and emphasize preciseness, flexibility and parsing convenience.
Ancient Pbx-Hox signatures define hundreds of vertebrate developmental enhancers
Authors: Parker Hugo J , Piccinelli Paul , Sauka-Spengler Tatjana , Bronner Marianne , Elgar Greg 
Published: December 2011

Abstract

Background
Gene regulation through cis-regulatory elements plays a crucial role in development and disease. A major aim of the post-genomic era is to be able to read the function of cis-regulatory elements through scrutiny of their DNA sequence. Whilst comparative genomics approaches have identified thousands of putative regulatory elements, our knowledge of their mechanism of action is poor and very little progress has been made in systematically de-coding them.

Results
Here, we identify ancient functional signatures within vertebrate conserved non-coding elements (CNEs) through a combination of phylogenetic footprinting and functional assay, using genomic sequence from the sea lamprey as a reference. We uncover a striking enrichment within vertebrate CNEs for conserved binding-site motifs of the Pbx-Hox hetero-dimer. We further show that these predict reporter gene expression in a segment specific manner in the hindbrain and pharyngeal arches during zebrafish development.

Conclusions
These findings evoke an evolutionary scenario in which many CNEs evolved early in the vertebrate lineage to co-ordinate Hox-dependent gene-regulatory interactions that pattern the vertebrate head. In a broader context, our evolutionary analyses reveal that CNEs are composed of tightly linked transcription-factor binding-sites (TFBSs), which can be systematically identified through phylogenetic footprinting approaches. By placing a large number of ancient vertebrate CNEs into a developmental context, our findings promise to have a significant impact on efforts toward de-coding gene-regulatory elements that underlie vertebrate development, and will facilitate building general models of regulatory element evolution.
Selectively enhanced expression of prophenoloxidase activating enzyme 1 (PPAE1) at a bacteria clearance site in the white shrimp, Litopenaeus vannamei
Authors: Jang In-Kwon , Pang Zhenguo , Yu Jiaping , Kim Su-Kyoung , Seo Hyung-Cheol , Cho Yeong-Rok 
Published: December 2011

Abstract

Background
The prophenoloxidase-activating (PO activating) system plays an important role in the crustacean innate immunity, particularly in wound healing and pathogen defense. A key member of this system is prophenoloxidase-activating enzyme (PPAE), which is the direct activator of prophenoloxidase (proPO). Despite their importance in crustacean PO activating system, the studies on them remain limited.

Results
Here we report on a PPAE of white shrimp, Litopenaeus vannamei (lvPPAE1), which showed 94% similarity to PPAE1 of Penaeus monodon. We found that lvPPAE1 in fluid hemocytes was down regulated after challenge by Vibrio harveyi but was enhanced when shrimps were exposed to a bacteria-rich environment for long-term. In vivo gene silence of lvPPAE1 by RNAi can significantly reduce the phenoloxidase activity (PO) and increase the susceptibility of shrimps to V. harveyi. Although lvPPAE1 was down-regulated in fluid hemocytes by Vibrio challenge, its expression increased significantly in gill after bacteria injection, which is the primary bacteria-clearance tissue.

Conclusion
Suppressed expression in fluid hemocytes and enhanced expression in gill indicates selectively enhanced expression at the bacterial clearance site. This is a novel feature for PPAE expression. The results will contribute to our understanding of the PO activating system in crustaceans.