bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between Glucose Tolerance and Severity of Coronary Artery Disease Using the Gensini Score
Authors: Nurkalem Zekeriya , Hasdemir Hakan , Ergelen Mehmet , Aksu Huseyin , Sahin Irfan , Erer Betul , Yilmaz Hale Y. , Comert Nuri , Sargin Mehmet , Eren Mehmet
Published: June 2010

Consecutive patients (n = 235) with coronary ischemia were studied; 69 patients (29%) had diabetes. An oral glucose tolerance test (OGTT) was administered to the 166 patients without diabetes; 76 (46%) had normal glucose tolerance (group I = NGT), 68 (41%) had impaired glucose tolerance ([IGT] group II = IGT), and 22 (13%) had diabetic glucose tolerance (DGT). The DGT patients were added to the known diabetics forming (Group III; n = 91). Multivessel disease was significantly more prevalent in group III; 30 patients (43%) in group I, 32 patients (51%) in group II, and 57 patients (69%) in group III ( P = .002). Gensini scores were 43.20 ± 24.92 in group I, 54.22 ± 42.61 in group II, and 60.59 ± 38.21 in group III. ( P = .037) The severity of coronary artery disease is related to abnormal glucose tolerance. Patients with IGT could be neglected in terms of interventions focused to improve risk factors.
Silane-functionalized Flame-retardant Aluminum Trihydroxide in Flexible Polyurethane Foam
Authors: König Alexander , Malek Alicia , Fehrenbacher Ulrich , Brunklaus Gunther , Wilhelm Manfred , Hirth Thomas
Published: June 2010

Flexible polyurethane (PU) foams are easily ignitable and show a high burning velocity, mainly due to their high surface area-to-mass ratio and high air permeability. Consequently, flame retardants such as halogenated compounds are applied. However, the use of halogenated flame retardants is not considered beneficial in transport applications, for example, aviation or automobile, in part due to the high smoke generation. Solid nonhalogenated flame retardants, for example, aluminum trihydroxide (ATH), are known as smoke suppressants. The application of ATH in flexible (PU) foam has not yet been reported in the literature. In this study, the application of different types and amounts of ATH and the resulting structure—property relationship in the foam are investigated. The increase in the viscosity of the filled raw materials during the foaming process and the negative effects of the filler on the mechanical properties of the final foam pose particular problems in the application of ATH. To pass the FMVSS 302 test, high amounts of ATH are necessary. To overcome the mentioned drawbacks, ATH particles are functionalized by 3-aminopropyltriethoxysilane under different conditions. The synthesized products were characterized by Fourier transform infrared, energy-dispersive X-ray fluorescence analysis, and 29Si and 1H solid-state nuclear magnetic resonance spectroscopy. The silane-treated ATH particles show a significant decrease in viscosity of the ATH—polyol system of more than 20% at ATH contents of up to 60 phpp. Values of the rising behavior during foaming and the burning velocity are not affected by this silane treatment. However, the compression test of PU foams with the silane-treated ATH particles show a decrease in compression strength of up to 20% compared to untreated ATH particles in the flexible PU foam. At higher ATH contents, no effect of silanization is observed.
Effects of Nucleating Agents’ Shapes and Interfacial Properties on Cell Nucleation
Authors: Leung Siu N. , Park Chul B. , Li Hongbo
Published: June 2010

The classical nucleation theory (CNT) provides the fundamentals to understand the cell nucleation phenomena theoretically during polymeric foaming processing. Since a variety of additives and impurities are ubiquitous in commercial plastic resins and crevices are omnipresent on the internal walls of processing equipment, heterogeneous nucleation plays a significant role in plastic foaming. According to the CNT, interfacial tensions at different interfaces and surface geometries at various heterogeneous nucleating sites are important factors that govern the heterogeneous nucleation rate. Therefore, the elucidation of their roles in cell nucleation will be beneficial to the foaming industry, which can use the information to optimize its foaming technologies and develop effective nucleating agents. In this study, a series of sensitivity analyses were performed; the results indicated that the contact angle ( θc) at the gas—liquid—solid junction and the semi-conical angle ( β) at the nucleating site are critical parameters that govern the free energy barrier to initiate heterogeneous nucleation ( Whet). Moreover, regardless of the surface geometries of the nucleating agents, Whet decreases as θc increases. For moderate values of θc (e.g., θc = 90°), heterogeneous nucleation is promoted in conical cavities with a smaller β. However, a smaller β is unfavorable for cell nucleation when θc is too small.
Shaping Tokyo: Land Development and Planning Practice in the Early Modern Japanese Metropolis
Authors: Hein Carola
Published: June 2010

From the mid-nineteenth century, Japanese elites experimented with foreign planning concepts and transformed their cities to respond to the demands of modernization. Even though they faced similar situations, knew about established European techniques, and had large open spaces available, they established planning practices that were different from those of their foreign counterparts, building on the country’s own urban history and form, particularities in landownership, development needs, urban planning techniques, and design preferences. This article highlights, first, key issues of landownership, urban form, and urban development in the Edo period (1603—1867) and provides an overview of the urban transformation of Tokyo concentrating on the era from the early Meiji period (1860s) to the reconstruction after the 1923 Great Kanto Earthquake. It then examines the elements set up in the overview more closely through the study of three areas of Tokyo between the 1860s and the 1920s. The article highlights the elite’s pragmatic approach to urban transformation and underlines the importance of land readjustment, a planning technique characterized by a reduction in lot sizes to create public land and to widen and straighten out streets, plots, and blocks. Examined are the transformation of the Ginza townsmen district (with a close look at the Yamashita-chô area), the government-led construction to the east of the palace (notably the Marunouchi area) starting in the 1880s, and the Kanda Misaki-chô area, a smaller daimyo district that had been cleared of all construction. In conclusion, this article argues that Japanese planners developed a practice that departed from European and American design principles but one that was and continues to be appropriate for Japanese needs and one that might even offer lessons to foreign cities and planners.
Extracorporeal membrane oxygenation for diffuse alveolar hemorrhage and severe hypoxemic respiratory failure from silicone embolism
Authors: Mongero LB , Brodie D. , Cunningham J. , Ventetuolo C. , Kim H. , Sylvin E. , Bacchetta MD
Published: June 2010

Liquid silicone is an inert material that may be used for cosmetic procedures by physicians as well as illegally by non-medical personnel. The use of silicone may result in severe complications, disfigurement, and even death. In addition, the indications for extracorporeal membrane oxygenation (ECMO) support have been increasing as a salvage therapy for a variety of life-threatening conditions.

The patient is a 27-year-old woman with no significant medical conditions who developed silicone emboli, and subsequent diffuse alveolar hemorrhage after being injected with silicone in her gluteal region without medical supervision. She became profoundly hypoxemic and suffered a brief asystolic cardiac arrest in this setting.

The patient was placed on veno-venous ECMO support for 14 days. Medical care during ECMO was complicated by pulmonary hemorrhage, hemothorax, pneumothorax, and blood clot, resulting in oxygenator change-out. A modified adult ECMO circuit (Jostra QuadroxD, Maquet Cardiopulmonary, Rastatt, Germany) was used to transport the patient from a nearby community affiliate hospital and then reconfigured for the medical intensive care unit on a standard HL-20 heart-lung console.

Although the use of ECMO for severe hypoxemic respiratory failure has been widely reported, to our knowledge, this is the first reported successful use of ECMO for silicone embolism syndrome associated with diffuse alveolar hemorrhage and severe hypoxemic respiratory failure.
An in vitro comparison of the ability of three commonly used pediatric cardiopulmonary bypass circuits to filter gaseous microemboli
Authors: Melchior Richard W , Rosenthal Tami , Glatz Andrew C
Published: June 2010

Background: The purpose of this study was to compare the ability of three commonly used pediatric cardiopulmonary bypass (CPB) circuits to filter gaseous microemboli (GME) in an in vitro model. Methods: Devices were tested at different levels of two specific independent variables: volume of air injected (1, 3, 5ml) and percentage of each oxygenator’s rated flow (50%, 75%, 100%, 125%). The air-handling ability of each CPB circuit was determined by the Emboli Detection and Classification Quantifier (Luna Innovations Inc., Roanoke,VA). Results: At all tested conditions, the FX-05 allowed a higher percentage of GME when compared to either one or both of the other two CPB circuits. When comparing oxygenators at similar absolute flow rates, the KIDS D100/D130 CPB circuit performed worse compared to the other two CPB circuits. C onclusions: The combination of the Baby RX-05 oxygenator and Capiox AF02 arterial line filter provides the highest level of protection from air emboli in an in vitro investigation.
Darwin’s progress and the problem of slavery
Authors: Moore James
Published: June 2010

Legendary as a ‘genius’ out of time, Charles Darwin is said to have revolutionized our understanding of life on earth by explaining nature-history as the purposeless product of directionless variation naturally selected through a chancy struggle for existence. Yet, whatever may be deduced from his theory of natural selection as understood today, Darwin himself was not bound by any such conclusions. His vision of nature-history, for all its haphazardness, was directional, meliorative and hopeful. In the 1830s he went out of his way to develop privately a subversive theory of human evolution, and he pursued the subject with tenacity for three decades before publishing The descent of man in 1871. Underpinning his research was a belief in racial brotherhood rooted in the greatest moral movement of the age, for the abolition of slavery. Darwin extended the abolitionists’ common-descent image to the rest of life, making not just the races, but all races, kin. Human slavery, however, did not evolve into or out of existence. To Darwin it was a ‘sin’ to ‘expiate’ by moral action, and the Origin of species was written with a view towards undermining slavery’s creationist ideologues, most notably the Harvard professor Louis Agassiz. Intractable slavery collided with Darwin’s post-Christian progressivism in the US Civil War, clouding his hopes for humanity, but the Northern victory in 1865 enabled him to carry ‘the grand idea of God hating sin and loving righteousness’ into The descent of man, where the driving of formerly enslaved races out of existence is naturalized as a byproduct of historical progress in which ‘virtue will be triumphant’ at last.
Gelatine and Gelatine/Elastin Nanocomposites for Vascular Grafts: Processing and Characterization
Authors: Lamprou Dimitris , Zhdan Peter , Labeed Fatima , Lekakou Constantina
Published: June 2010

This study involves the preparation, microstructural, physical, mechanical, and biological characterization of novel gelatine and gelatine/elastin gels for their use in the tissue engineering of vascular grafts. Gelatine and gelatine/elastin nanocomposite gels were prepared via a sol-gel process, using soluble gelatine. Gelatine was subsequently cross-linked by leaving the gels in 1% glutaraldehyde. The cross-linking time was optimized by assessing the mass loss of the cross-linked gels in water and examining their mechanical properties in dynamic mechanical tests. Atomic force microscopy (AFM) studies revealed elastin nanodomains, homogeneously distributed and embedded in a bed of gelatine nanofibrils in the 30/70 elastin/gelatine gel. It was concluded that the manufactured nanocomposite gels resembled natural arteries in terms of microstructure and stiffness. The biological characterization involved the culture of rat smooth muscle cells (SMCs) on tubular gelatine and gelatine/ elastin nanocomposite gels, and measurements of the scaffold diameter and the cell density as a function of time.
Three-Dimensional Scaffolds as a Model System for Neural and Endothelial ‘In Vitro’ Culture
Authors: Veiga D. Dias , Antunes Joana Costa , Gómez Roberto García , Mano João F. , Ribelles Jose Luis Gómez , Soria Jose Miguel
Published: June 2010

Biomaterials based on the hydrophobic homopolymer poly(ethyl acrylate), PEA, and its copolymers with hydroxyethyl acrylate, p(EA-co-HEA) and methacrylic acid, p(EA-co-MAAc) were prepared as polymeric scaffolds with interconnected pores of 90 microns and tested in vitro as culture substrates and compared for their impact on the differentiation of neural stem cells (NSC) obtained from the subventricular zone (SVZ) of postnatal rats and human endothelial cells (HUVEC). Immunocytochemical staining assay for specific markers show that p(EA-co-MAAc) scaffolds were suitable substrates to promote cell attachment and differentiation of adult NSC and HUVEC cells.
Osteoconductivity and Osteoinductivity of Puros® DBM Putty
Authors: Moore Steven T. , Katz Jordan M. , Zhukauskas Rasa M. , Hernandez Ryanne M. , Lewis Christine S. , Supronowicz Peter Robert , Gill Elise , Grover Susan M. , Long Nathaniel S. , Cobb Ronald R.
Published: June 2010

Bone graft substitutes have been developed due to the limited supply and morbidity associated with using autogenous graft material. Allogeneic demineralized bone matrix (DBM) has been used extensively as a clinical graft material because of its inherent osteoinductive and osteoconductive properties. Differential enhancement of these properties may optimize the performance of these products for various orthopedic and craniofacial applications. Commercially available bone paste products consist of formulations that combine DBM with a carrier to facilitate handling and containment. In the present study, we present results of a comprehensive in vitro and in vivo characterization of a 100% human DBM putty product, Puros DBM Putty. Results indicate the DBM particles are completely dispersed in the putty. Data are presented showing the porosity of and cell attachment to Puros DBM Putty, thereby demonstrating the osteoconductive properties of this DBM. Puros DBM Putty was also shown to be osteoinductive in the rat ectopic pouch model. We demonstrate here for the first time that Puros DBM Putty maintains its activity to markedly stimulate or induce bone formation over the entire period of its shelf life. Taken together, these data demonstrate that the 100% human allograft derived Puros DBM Putty could be an effective bone graft substitute.
Preliminary Evaluation of a Novel Strong/Osteoinductive Calcium Phosphate Cement
Authors: Qu Yili , Yang Yang , Li Juan , Chen Zhiqing , Li Jidong , Tang Kuangyun , Man Yi
Published: June 2010

We developed a novel calcium phosphate cement (CPC) by combining the silk fibroin and osteogenic supplements (β-glycerophosphate, ascorbic acid, and dexamethasone) with α-tricalcium phosphate cement. Mesenchymal stem cells (MSCs) were cultured on the novel CPC scaffold. Results showed that the novel CPC scaffold was biocompatible and favorable for the adhesion, spreading, and proliferation of MSCs. Osteogenic differentiation of MSCs was confirmed by high osteocalcin content and elevated gene expressions of bone markers, such as alkaline phosphatase, collagen type I, and osteocalcin. Therefore, the novel CPC scaffold may be potentially useful for implant fixation and more rapid new bone formation in moderate load-bearing applications.
Effect of Surface Wettability and Topography on the Adhesion of Osteosarcoma Cells on Plasma-modified Polystyrene
Authors: Dowling Denis P. , Miller Ian S. , Ardhaoui Malika , Gallagher William M.
Published: June 2010

Biomaterials interact with the biological environment at their surface, making accurate biophysical characterization of the surface crucially important for understanding subsequent biological effects. In this study, the surface of polystyrene (PS) was systematically altered in order to determine the effect of plasma treatment and surface roughness on cell adhesion and spreading. Surfaces with water contact angle from hydrophilic (12°) to superhydrophobic (155°) were obtained through a combination of modifying surface roughness ( Ra), the deposition of siloxane coatings and the fluorination of the PS surface. Ra values in the range of 19—2365 nm were obtained by grinding the PS surface. The nanometer-thick siloxane coatings were deposited using an atmospheric pressure plasma system, while the fluorination of the PS was carried out using a low-pressure radio frequency (RF) plasma. The siloxane coatings were obtained using a liquid poly(dimethylsiloxane) precursor that was nebulized into helium or helium/oxygen plasmas. Water contact angles in the range of 12—122° were obtained with these coatings. Cell adhesion studies were carried out using human MG63 osteosarcoma cells. It was observed that higher polymer surface roughness enhanced cell adhesion, but had a negative effect on cell spreading. Optimum cell adhesion was observed at ∼64° for the siloxane coatings, with a decrease in adhesion observed for the more hydrophilic and hydrophobic coatings. This decrease in cell adhesion with an increase in hydrophobicity was also observed for the fluorinated PS surfaces with water contact angles in the range of 110—155°.
Resorbable Glass–Ceramic Phosphate-based Scaffolds for Bone Tissue Engineering: Synthesis, Properties, and In vitro Effects on Human Marrow Stromal Cells
Authors: Vitale-Brovarone Chiara , Ciapetti Gabriela , Leonardi Elisa , Baldini Nicola , Bretcanu Oana , Verné Enrica , Baino Francesco
Published: June 2010

Highly porous bioresorbable glass–ceramic scaffolds were prepared via sponge replication method by using an open-cell polyurethane foam as a template and phosphate-based glass powders. The glass, belonging to the P2O5–SiO2–CaO–MgO–Na2O–K2O system, was synthesized by a melting–quenching route, ground, and sieved to obtain powders with a grain size of less than 30 μm. A slurry containing glass powders, polyvinyl alcohol, and water was prepared to coat the polymeric template. The removal of the polymer and the sintering of the glass powders were performed by a thermal treatment, in order to obtain an inorganic replica of the template structure. The structure and properties of the scaffold were investigated from structural, morphological, and mechanical viewpoints by means of X-ray diffraction, scanning electron microscopy, density measurements, image analysis, and compressive tests. The scaffolds exhibited a trabecular architecture that closely mimics the structure of a natural spongy bone. The solubility of the porous structures was assessed by soaking the samples in acellular simulated body fluid (SBF) and Tris–HCl for different time frames and then by assessing the scaffold weight loss. As far as the test in SBF is concerned, the nucleation of hydroxyapatite on the scaffold trabeculae demonstrates the bioactivity of the material. Biological tests were carried out using human bone marrow stromal cells to test the osteoconductivity of the material. The cells adhered to the scaffold struts and were metabolically active; it was found that cell differentiation over proliferation occurred. Therefore, the produced scaffolds, being biocompatible, bioactive, resorbable, and structurally similar to a spongy bone, can be proposed as interesting candidates for bone grafting.
A Direction for Clothing and Textile Design Research
Authors: Bye Elizabeth
Published: June 2010

Clothing and textile design is a discipline of practice, scholarship, and research, sharing many characteristics and issues with the broader discipline of design. This manuscript briefly introduces some of the history and main concepts of the design discipline and design research; presents a framework for Design Scholarship to initiate a discussion about research, and suggests ways to contribute to the larger academic dialogue on forming a design discipline. The main thrust is to argue that a different context is needed for creative scholarship; one of design research that can add to the knowledge base and help build theory in the field. The tacit knowledge of hands-on experience is distinct, but cannot remain solely with the practitioner or the artifact. Clothing and textile design has a long tradition in creative practice, but due to the increasing complexity of our world, there is a need to formally capture the knowledge of the field.
Platelet Biology and Implications for Antiplatelet Therapy in Atherothrombotic Disease
Authors: Montalescot Gilles
Published: June 2010

Platelet activation is crucial for wound healing at sites of endothelial cell injury and involves multiple factors that mediate platelet recruitment, adherence, and aggregation. Platelet activation in response to atherosclerotic plaque rupture or endothelial cell detachment can result in pathologic thrombus formation and acute ischemic events. Current oral antiplatelet agents, aspirin and adenosine diphosphate (ADP) receptor antagonists, are effective but associated with bleeding as they target activation pathways critical for protective hemostasis and pathologic thrombosis. Each inhibits a single platelet activation pathway and does not impact activation by thrombin. The lack of complete inhibition of platelet function allows continued thrombus formation and recurrent thrombotic events. Inhibition of the protease-activated receptor 1 (PAR-1) stimulated by thrombin offers a rational strategy to achieve more comprehensive platelet inhibition when used in combination with standard-of-care, dual antiplatelet therapy. We expect that this new approach may mitigate bleeding risk, because PAR-1 is not essential for hemostasis.
Contingent communication in a hybrid multi-media world: Analysing the campaigning strategies of SHAC
Authors: Upton Andrew
Published: June 2010

Drawing upon Niklas Luhmann’s theoretical work, this article considers the strategic and tactical use of contingent communication within Stop Huntingdon Animal Cruelty’s (SHAC) communication subsystem network. While acknowledging the importance of system stability to the functioning of social systems, the article pinpoints Luhmann’s underestimation of uncertainties within communication as a significant error in theorizing relationships between systems and their environments. It also considers how new media and information communication technologies (ICTs) have enabled SHAC, a British-based though internationally renowned animal rights protest group, to both reinforce the universal connections existing between all its communicating agents and maintain the operation of communication within the social subsystem. Through a critical examination of the eight stages of SHAC’s communication subsystem network, the article underscores how these communicative forms are constantly displaced by context, user, medium and receiver, because indeterminacies are constitutive of communication.
Augmented deliberation: Merging physical and virtual interaction to engage communities in urban planning
Authors: Gordon Eric , Manosevitch Edith
Published: June 2010

The goal of this article is two-fold: to introduce the concept of augmented deliberation and to demonstrate its implementation in a pilot project.We look specifically at a project called Hub2. This community engagement project employed the online virtual world Second Life to augment community deliberation in the planning of a neighborhood park in Boston, Massachusetts. The local community was invited to gather in a physical space and a virtual space simultaneously, and a physical moderator and virtual designer orchestrated deliberation.This project demonstrates the design values central to augmented deliberation: (1) it is a multimedia group communication process which balances the specific affordances of digital technologies with the established qualities of face-to-face group deliberation; (2) it emphasizes the power of experience; and (3) it promotes sustainability and reproducibility through digital tracking. Augmented deliberation, when properly designed, provides a powerful mechanism to enable productive and meaningful public deliberation. The article concludes with directions for further research.
The Slow Death of Formal Learning: A Polemic
Authors: McGuire David , Gubbins Claire
Published: June 2010

Over recent years, approaches to education and training have become more informal, situated, outcome focused and experiential. Within this context, formal learning now plays a greatly diminished role, being supplanted by activity-based and technologically-based learning. This article, structured in the form of a polemic challenges readers to critically examine the importance and value of formal learning in modern learning environments. It reviews four propositions charting changes to the learning environment arguing that formal learning plays a central role in deepening an individual’s functional and general knowledge. It questions the branding of formal learning as an outdated delivery mode associated with an old-fashioned antiquated pedagogy and argues that decisions on learning styles should be based upon sound evidence-based research.
Therapeutic strategies in childhood multiple sclerosis
Authors: Ghezzi Angelo
Published: June 2010

Multiple sclerosis (MS) in children and adolescents accounts for 3—10% of the whole MS population, and is characterized by a relapsing course in almost all cases. The frequency of relapses is higher than in adult onset MS, at least in the first years of evolution. The objective of treatment is to speed the recovery after a relapse, to prevent the occurrence of relapses, and to prevent disease progression and neurodegeneration. The use of drugs for MS in children and adolescents has not been studied in clinical trials, so their use is mainly based on results from trials in adults and from observational studies. There is a consensus to treat acute relapses with intravenous high-dose corticosteroids. The possibility of preventing relapses and disease progression is based on the use of immunomodulatory agents. Interferon-beta (IFNB) and glatiramer acetate (GA) have been demonstrated to be safe and well tolerated in pediatric MS patients, and also to reduce relapse rate and disease progression. Cyclophosphamide and natalizumab could be offered as second-line treatment in patients with a poor response to IFNB or GA. New oral and injectable drugs will be available in the near future: if safe and well tolerated in the long-term follow up of adults with MS, they could be tested in the pediatric MS population.
Structure refinement of pure Mg under pulsed magnetic field
Authors: Wang B. , Yang Y. S. , Zhou J. , Tong W.
Published: June 2010

A pulsed magnetic field (PMF) was introduced into the solidification of pure Mg. Fine uniform equiaxed grains are acquired in the whole ingot from the PMF treatment, in contrast with the coarse columnar grains observed in conventional casting, and the average grain size is refined to 260 μm with a 200 V PMF treatment. Pulsed magnetic field increases melt convection during solidification, and the violent agitation causes warmer liquid to fracture the tip of columnar dendrites or to break off dendrite branches to promote the formation of an equiaxed structure, with the broken pieces transported into the bulk liquid acting as nuclei. In addition, the uniform temperature field resulting from the stirring increases the likelihood of nuclei survival. The Joule heat effect also participates in the structure refinement. The pure Mg produced with a 200 V PMF treatment exhibits improved mechanical properties, such as the ultimate compressive strength (227 MPa) and fracture strain (33·2).
Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial
Authors: Lee Jong Wook , Yoon Sung-Soo , Xiang Shen Zhi , Ganser Arnold , Hsu Hui-Chi , Habr Dany , Domokos Gabor , Roubert Bernard , Porter John B. ,   on behalf of the EPIC study investigators
Published: June 2010

The prospective 1-year Evaluation of Patients' Iron Chelation with Exjade (EPIC) study enrolled a large cohort of 116 patients with aplastic anemia; the present analyses evaluated the efficacy and safety of deferasirox in this patient population. After 1 year, median serum ferritin decreased significantly from 3254 ng/mL at baseline to 1854 ng/mL (P < .001). Decreases occurred in chelation-naive (3229-1520 ng/mL; P < .001, last-observation-carried-forward analysis), and previously chelated (3263-2585 ng/mL; P = .21, last-observation-carried-forward analysis) patients and were reflective of dose adjustments and ongoing iron intake. Baseline labile plasma iron levels were within normal range despite high serum ferritin levels. The most common drug-related adverse events were nausea (22%) and diarrhea (16%). Serum creatinine increases more than 33% above baseline and the upper limit of normal occurred in 29 patients (25%), but there were no progressive increases; concomitant use of cyclosporine had a significant impact on serum creatinine levels. The decrease in mean alanine aminotransferase levels at 1 year correlated significantly with reduction in serum ferritin (r = 0.40, P < .001). Mean absolute neutrophil and platelet counts remained stable during treatment, and there were no drug-related cytopenias. This prospective dataset confirms the efficacy and well characterizes the tolerability profile of deferasirox in a large population of patients with aplastic anemia. This study was registered at www.clinicaltrials.gov as #NCT00171821.
Drug-induced thrombocytopenia: development of a novel NOD/SCID mouse model to evaluate clearance of circulating platelets by drug-dependent antibodies and the efficacy of IVIG
Authors: Liang Simon X. , Pinkevych Mykola , Khachigian Levon M. , Parish Christopher R. , Davenport Miles P. , Chong Beng H.
Published: June 2010

Drug-induced immune thrombocytopenia (DITP) is an adverse drug effect mediated by drug-dependent antibodies. Intravenous immunoglobulin (IVIG) is frequently used to treat DITP and primary immune thrombocytopenia (ITP). Despite IVIG's proven beneficial effects in ITP, its efficacy in DITP is unclear. We have established a nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of DITP in which human platelets survive for more than 24 hours, allowing platelet clearance by DITP/ITP antibodies to be studied. Rapid human platelet clearance was uniformly observed with all quinine-induced thrombocytopenia (QITP) patient sera studied (mean platelet lifespans: QITP 1.5 ± 0.3 hours vs controls 16.5 ± 4.3 hours), consistent with the clinical presentation of DITP. In contrast, clearance rates with ITP antibodies were more variable. IVIG treatment partially prevented platelet clearance by DITP and ITP antibodies. Our results suggest that the NOD/SCID mouse model is useful for investigating the efficacy of current and future DITP therapies, an area in which there is little experimental evidence to guide treatment.
Gel point and fractal microstructure of incipient blood clots are significant new markers of hemostasis for healthy and anticoagulated blood
Authors: Evans Phillip A. , Hawkins Karl , Morris Roger H. K. , Thirumalai Naresh , Munro Roger , Wakeman Lisa , Lawrence Matthew J. , Williams P. Rhodri
Published: June 2010

Here we report the first application of a fractal analysis of the viscoelastic properties of incipient blood clots. We sought to ascertain whether the incipient clot's fractal dimension, Df, could be used as a functional biomarker of hemostasis. The incipient clot is formed at the gel point (GP) of coagulating blood, the GP demarcating a functional change from viscoelastic liquid to a viscoelastic solid. Incipient clots formed in whole healthy blood show a clearly defined value of Df within a narrow range that represents an index of clotting in health, where Df = 1.74 (± 0.07). A significant relationship is found between the incipient clot formation time, TGP, and the activated partial thromboplastin time, whereas the association of Df with the microstructural characteristics of the incipient clot is supported by its significant correlation with fibrinogen. Our study reveals that unfractionated heparin not only prolongs the onset of clot formation but has a significant effect on its fractal microstructure. A progressive increase in unfractionated heparin concentration results in a linear decrease in Df and a corresponding prolongation in TGP. The results represent a new, quantitative measure of clot quality derived from measurements on whole blood samples.
Changes in creatine transporter function during cardiac maturation in the rat
Authors: Fischer Alexandra , ten Hove Michiel , Sebag-Montefiore Liam , Wagner Helga , Clarke Kieran , Watkins Hugh , Lygate Craig A , Neubauer Stefan
Published: June 2010

Background

It is well established that the immature myocardium preferentially utilises non-oxidative energy-generating pathways. It exhibits low energy-transfer capacity via the creatine kinase (CK) shuttle, reflected in phosphocreatine (PCr), total creatine and CK levels that are much lower than those of adult myocardium. The mechanisms leading to gradually increasing energy transfer capacity during maturation are poorly understood. Creatine is not synthesised in the heart, but taken up exclusively by the action of the creatine transporter protein (CrT). To determine whether this transporter is ontogenically regulated, the present study serially examined CrT gene expression pattern, together with creatine uptake kinetics and resulting myocardial creatine levels, in rats over the first 80 days of age.

Results

Rats were studied during the late prenatal period (-2 days before birth) and 7, 13, 21, 33, 50 and 80 days after birth. Activity of cardiac citrate synthase, creatine kinase and its isoenzymes as well as lactate dehydrogenase (LDH) and its isoenzymes demonstrated the well-described shift from anaerobic towards aerobic metabolism. mRNA levels of CrT in the foetal rat hearts, as determined by real-time PCR, were about 30% of the mRNA levels in the adult rat heart and gradually increased during development. Creatine uptake in isolated perfused rat hearts increased significantly from 3.0 nmol/min/gww at 13 days old to 4.9 nmol/min/gww in 80 day old rats. Accordingly, total creatine content in hearts, measured by HPLC, increased steadily during maturation (30 nmol/mg protein (-2 days) vs 87 nmol/mg protein (80 days)), and correlated closely with CrT gene expression.

Conclusions

The maturation-dependant alterations of CK and LDH isoenzyme activities and of mitochondrial oxidative capacity were paralleled by a progressive increase of CrT expression, creatine uptake kinetics and creatine content in the heart.
Mastacembelid eels support Lake Tanganyika as an evolutionary hotspot of diversification
Authors: Brown Katherine J , Rüber Lukas , Bills Roger , Day Julia J
Published: June 2010

Background

Lake Tanganyika (LT) is the oldest of the African Rift Lakes and is one of the richest freshwater ecosystems on Earth, with high levels of faunal diversity and endemism. The endemic species flocks that occur in this lake, such as cichlid fishes, gastropods, catfish and crabs, provide unique comparative systems for the study of patterns and processes of speciation. Mastacembelid eels (Teleostei: Mastacembelidae) are a predominately riverine family of freshwater fish, occurring across Africa and Asia, but which also form a small species flock in LT.

Methods

Including 25 species across Africa, plus Asian representatives as outgroups, we present the first molecular phylogenetic analysis for the group, focusing particularly on the evolutionary history and biodiversity of LT mastacembelid eels. A combined matrix of nuclear and mitochondrial genes based on 3118 bp are analysed implementing different phylogenetic methods, including Bayesian inference and maximum likelihood.

Results

LTMastacembelusare recovered as monophyletic, and analyses reveal the rapid diversification of five main LT lineages. Relaxed molecular clock dates provide age estimates for the LT flock at ~7-8 Myr, indicating intralacustrine diversification, with further speciation events coinciding with periods of lower lake level. Our analyses also reveal as yet undescribed diversity of lacustrine and riverine species. A Southern-Eastern African clade, that is younger than the LT flock, is also recovered, while West African taxa are basal members of the African mastacembelid clade.

Conclusions

That the LT species flock of mastacembelid eels appears to have colonised and immediately diversified soon after the formation of the lake, supports the view of LT as an evolutionary hotspot of diversification. We find evidence for biogeographic clades mirroring a similar pattern to other ichthyological faunas. In addition, our analyses also highlight a split of African and Asian mastacembelid eels at ~19 Myr that is considerably younger than the split between their associated continents, suggesting a dispersal scenario for their current distribution.
Comparative genomics reveals conservative evolution of the xylem transcriptome in vascular plants
Authors: Li Xinguo , Wu Harry X , Southerton Simon G
Published: June 2010

Background

Wood is a valuable natural resource and a major carbon sink. Wood formation is an important developmental process in vascular plants which played a crucial role in plant evolution. Although genes involved in xylem formation have been investigated, the molecular mechanisms of xylem evolution are not well understood. We use comparative genomics to examine evolution of the xylem transcriptome to gain insights into xylem evolution.

Results

The xylem transcriptome is highly conserved in conifers, but considerably divergent in angiosperms. The functional domains of genes in the xylem transcriptome are moderately to highly conserved in vascular plants, suggesting the existence of a common ancestral xylem transcriptome. Compared to the total transcriptome derived from a range of tissues, the xylem transcriptome is relatively conserved in vascular plants. Of the xylem transcriptome, cell wall genes, ancestral xylem genes, known proteins and transcription factors are relatively more conserved in vascular plants. A total of 527 putative xylem orthologs were identified, which are unevenly distributed across the Arabidopsis chromosomes with eight hot spots observed. Phylogenetic analysis revealed that evolution of the xylem transcriptome has paralleled plant evolution. We also identified 274 conifer-specific xylem unigenes, all of which are of unknown function. These xylem orthologs and conifer-specific unigenes are likely to have played a crucial role in xylem evolution.

Conclusions

Conifers have highly conserved xylem transcriptomes, while angiosperm xylem transcriptomes are relatively diversified. Vascular plants share a common ancestral xylem transcriptome. The xylem transcriptomes of vascular plants are more conserved than the total transcriptomes. Evolution of the xylem transcriptome has largely followed the trend of plant evolution.
A phylogenetic mosaic plastid proteome and unusual plastid-targeting signals in the green-colored dinoflagellate Lepidodinium chlorophorum
Authors: Minge Marianne A , Shalchian-Tabrizi Kamran , Tørresen Ole K , Takishita Kiyotaka , Probert Ian , Inagaki Yuji , Klaveness Dag , Jakobsen Kjetill S
Published: June 2010

Background

Plastid replacements through secondary endosymbioses include massive transfer of genes from the endosymbiont to the host nucleus and require a new targeting system to enable transport of the plastid-targeted proteins across 3-4 plastid membranes. The dinoflagellates are the only eukaryotic lineage that has been shown to have undergone several plastid replacement events, and this group is thus highly relevant for studying the processes involved in plastid evolution. In this study, we analyzed the phylogenetic origin and N-terminal extensions of plastid-targeted proteins from Lepidodinium chlorophorum, a member of the only dinoflagellate genus that harbors a green secondary plastid rather than the red algal-derived, peridinin-containing plastid usually found in photosynthetic dinoflagellates.

Results

We sequenced 4,746 randomly picked clones from a L. chlorophorum cDNA library. 22 of the assembled genes were identified as genes encoding proteins functioning in plastids. Some of these were of green algal origin. This confirms that genes have been transferred from the plastid to the host nucleus of L. chlorophorum and indicates that the plastid is fully integrated as an organelle in the host. Other nuclear-encoded plastid-targeted protein genes, however, are clearly not of green algal origin, but have been derived from a number of different algal groups, including dinoflagellates, streptophytes, heterokonts, and red algae. The characteristics of N-terminal plastid-targeting peptides of all of these genes are substantially different from those found in peridinin-containing dinoflagellates and green algae.

Conclusions

L. chlorophorum expresses plastid-targeted proteins with a range of different origins, which probably arose through endosymbiotic gene transfer (EGT) and horizontal gene transfer (HGT). The N-terminal extension of the genes is different from the extensions found in green alga and other dinoflagellates (peridinin- and haptophyte plastids). These modifications have likely enabled the mosaic proteome of L. chlorophorum.
Whole-proteome phylogeny of large dsDNA viruses and parvoviruses through a composition vector method related to dynamical language model
Authors: Yu Zu-Guo , Chu Ka Hou , Li Chi Pang , Anh Vo , Zhou Li-Qian , Wang Roger Wei
Published: June 2010

Background

The vast sequence divergence among different virus groups has presented a great challenge to alignment-based analysis of virus phylogeny. Due to the problems caused by the uncertainty in alignment, existing tools for phylogenetic analysis based on multiple alignment could not be directly applied to the whole-genome comparison and phylogenomic studies of viruses. There has been a growing interest in alignment-free methods for phylogenetic analysis using complete genome data. Among the alignment-free methods, a dynamical language (DL) method proposed by our group has successfully been applied to the phylogenetic analysis of bacteria and chloroplast genomes.

Results

In this paper, the DL method is used to analyze the whole-proteome phylogeny of 124 large dsDNA viruses and 30 parvoviruses, two data sets with large difference in genome size. The trees from our analyses are in good agreement to the latest classification of large dsDNA viruses and parvoviruses by the International Committee on Taxonomy of Viruses (ICTV).

Conclusions

The present method provides a new way for recovering the phylogeny of large dsDNA viruses and parvoviruses, and also some insights on the affiliation of a number of unclassified viruses. In comparison, some alignment-free methods such as the CV Tree method can be used for recovering the phylogeny of large dsDNA viruses, but they are not suitable for resolving the phylogeny of parvoviruses with a much smaller genome size.
Haplotypes that include the integrin alpha 11 gene are associated with tick burden in cattle
Authors: Porto Neto Laercio R , Bunch Rowan J , Harrison Blair E , Prayaga Kishore C , Barendse William
Published: June 2010

Background

Infestations on cattle by the ectoparasite Boophilus (Rhipicephalus) microplus (cattle tick) impact negatively on animal production systems. Host resistance to tick infestation has a low to moderate heritability in the range 0.13 - 0.64 in Australia. Previous studies identified a QTL on bovine chromosome 10 (BTA10) linked to tick burden in cattle.

Results

To confirm these associations, we collected genotypes of 17 SNP from BTA10, including three obtained by sequencing part of the ITGA11 (Integrin alpha 11) gene. Initially, we genotyped 1,055 dairy cattle for the 17 SNP, and then genotyped 557 Brahman and 216 Tropical Composite beef cattle for 11 of the 17 SNP. In total, 7 of the SNP were significantly (P < 0.05) associated with tick burden tested in any of the samples. One SNP, ss161109814, was significantly (P < 0.05) associated with tick burden in both the taurine and the Brahman sample, but the favourable allele was different. Haplotypes for three and for 10 SNP were more significantly (P < 0.001) associated with tick burden than SNP analysed individually. Some of the common haplotypes with the largest sample sizes explained between 1.3% and 1.5% of the residual variance in tick burden.

Conclusions

These analyses confirm the location of a QTL affecting tick burden on BTA10 and position it close to the ITGA11 gene. The presence of a significant association in such widely divergent animals suggests that further SNP discovery in this region to detect causal mutations would be warranted.
Development of an oligo DNA microarray for the European sea bass and its application to expression profiling of jaw deformity
Authors: Ferraresso Serena , Milan Massimo , Pellizzari Caterina , Vitulo Nicola , Reinhardt Richard , Canario Adelino VM , Patarnello Tomaso , Bargelloni Luca
Published: June 2010

Background

The European sea bass (Dicentrarchus labrax) is a marine fish of great importance for fisheries and aquaculture. Functional genomics offers the possibility to discover the molecular mechanisms underlying productive traits in farmed fish, and a step towards the application of marker assisted selection methods in this species. To this end, we report here on the development of an oligo DNA microarray for D. labrax.

Results

A database consisting of 19,048 unique transcripts was constructed, of which 12,008 (63%) could be annotated by similarity and 4,692 received a GO functional annotation. Two non-overlapping 60mer probes were designed for each unique transcript and in-situ synthesized on glass slides using Agilent SurePrint™ technology. Probe design was positively completed for 19,035 target clusters; the oligo microarray was then applied to profile gene expression in mandibles and whole-heads of fish affected by prognathism, a skeletal malformation that strongly affects sea bass production. Statistical analysis identified 242 transcripts that are significantly down-regulated in deformed individuals compared to normal fish, with a significant enrichment in genes related to nervous system development and functioning. A set of genes spanning a wide dynamic range in gene expression level were selected for quantitative RT-PCR validation. Fold change correlation between microarray and qPCR data was always significant.

Conclusions

The microarray platform developed for the European sea bass has a high level of flexibility, reliability, and reproducibility. Despite the well known limitations in achieving a proper functional annotation in non-model species, sufficient information was obtained to identify biological processes that are significantly enriched among differentially expressed genes. New insights were obtained on putative mechanisms involved on mandibular prognathism, suggesting that bone/nervous system development might play a role in this phenomenon.