bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and Properties of Novel Fluoroalkyl End-capped Oligomers/Hydrogarnet Nanocomposites
Authors: Sawada Hideo , Sekiguchi Shigeki , Kakehi Hiroshi , Mori Toshiaki , Miura Masashi , Isu Norifumi
Published: September 2009

Novel fluoroalkyl end-capped oligomers/hydrogarnet (katoite) nanocomposites were prepared by the hydrothermal reactions of a stoichiometric mixture of Ca(OH)2, Al(OH)3, and Al2Si2O 5(OH)4 in the presence of the corresponding fluorinated acrylic acid, acryloylmorpholine, and N,N-dimethylacrylamide oligomers. These fluorinated katoite nanocomposites thus obtained are nanometer size-controlled, and were found to exhibit a good dispersibility in water, methanol, ethanol, and tetrahydrofuran. Fluoroalkyl end-capped oligomers were also applied to the dispersion of parent katoite into these solvents; however, a poor dispersiblity for these solvents was observed. On the other hand, fluoroalkyl end-capped 2-methacryloyloxyethanesulfonic acid oligomer [RF—(MES) n—RF] was able to solubilize katoite into water to afford the transparent colorless solution. The obtained RF—(MES) n—RF/katoite nanocomposites were found to exhibit a good antibacterial activity against Staphylococcus aureus, and were also applied to the surface modification of poly(vinyl alcohol) to exhibit a good oleophobicity imparted by fluorine on the surface.
The Effect of Atmospheric Plasma Treatment on the Chemistry, Morphology and Resultant Bonding Behavior of a Pan-Based Carbon Fiber-Reinforced Epoxy Composite
Authors: Zaldivar R.J. , Nokes J. , Steckel G.L. , Kim H.I. , Morgan B.A.
Published: September 2009

A study was undertaken to evaluate the effect of atmospheric plasma treatments on the surface chemistry, morphology, and mechanical properties of graphite/epoxy composites. Characterization included contact angle measurements, XPS, FTIR, SEM and AFM. Treatment was shown to increase strength by as much as 50% relative to untreated specimens. The improvement was related to the number of passes and can be attributed to chemical surface modifications. While the total amount of oxygen on the surface stabilized quickly after a few plasma passes, the concentration of the carboxyl groups was shown to continuously increase, and correlated well with observed increases in strength.
Expanded Waste Ground Rubber Tire Powder/Polypropylene Composites: Processing-Structure Relationships
Authors: Xin Zhen Xiang , Zhang Zhen Xiu , Zhang Bao Sheng , Pal Kaushik , Deng Xu , Lee Sung Hyo , Kim Jin Kuk
Published: September 2009

The usage of waste tire powder as dispersed phase in polypropylene matrix offers an interesting opportunity for recycling of the waste tire. In order to obtain ‘value added products’ from polypropylene (PP)/waste ground rubber tire powder (WGRT) composites, in this study, the processing of foamedPP/WGRT composites was investigated using a single-screw foam extrusion setup and chemical blowing agent. The regression models were constructed to study the relationships between the foam structure (i.e., void fraction, average cell size, and cell density) of foamed PP/WGRT composites, the processing conditions (extruder’s die temperature and screw speed), and the formulation compositions (WGRT content and blowing agent concentration) by applying a four-factor central composite design (CCD) statistical approach. The response surface plots generated using the regression models allow the rapid selection of the proper process parameters to obtain PP/WGRT composite foams with the desired density and morphology.
Wear Behavior of Plant Fiber (Pine-Bark) and Cement Kiln Dust-Reinforced Polyester Composites Using Taguchi Experimental Model
Authors: Patnaik Amar , Satapathy Alok , Dwivedy Maheshwar , Biswas Sandhyarani
Published: September 2009

Parametric appraisal of a dry sliding wear process is presented for a set of new composites consisting of polyester as the matrix, flakes of pine-bark as the fibrous reinforcing component, and the kiln-dust of a cement plant as the filler. The filler content in the composites is fixed at 50 wt%, while the weight fraction of fiber reinforcement is varied (0—12 wt%) so as to obtain composite samples of three different compositions. Wear tests are carried out with the help of a pin-on-disc test rig employing the design of experiments approach based on Taguchi’s orthogonal arrays. The findings of the experiments indicate that the rate of wear is greatly influenced by various control factors. An optimal parameter combination is determined, which leads to minimization of wear rate. Analysis of variance is performed on the measured data and signal-to-noise (S/N) ratios. A mathematical correlation, consistent with the experimental observations is proposed as a predictive equation for estimation of sliding wear rate of these composites. Finally, optimal factor settings for minimum wear are determined using genetic algorithm.
Individual and Environmental Effects on Assaults and Nonviolent Rule Breaking by Women in Prison
Authors: Steiner Benjamin , Wooldredge John
Published: September 2009

Drawing from micro- and macro-level theories of social control, the authors examined inmate and facility effects on the prevalence of assaults and nonviolent rule infractions committed by female inmates housed in state correctional facilities during 1991 and 1997. Analyses of national samples of more than 2,200 women confined in roughly 40 facilities produced results favoring a control perspective. Characteristics of both inmates (e.g., family status, history of physical or sexual abuse, drug use immediately prior to incarceration, and mental ill health) and facilities (e.g., crowding and security level) were relevant for understanding differences among female inmates in the odds of both assault and nonviolent misconduct.
The Role of Government in Managing Intercultural Relations
Authors: Staniševski Dragan M. , Miller Hugh T.
Published: September 2009

When intercultural tensions flare up, governments typically must engage the conflict one way or another. This article questions the possible role of government in transforming these difficult social–cultural–political conflicts into democratic moments. Three theoretical approaches to democracy compete for status in the realm of multicultural politics: majoritarian, consociational, and deliberative democracy. The multicultural features of these three theoretical models are compared in the context of one divided society, Macedonia, a place where the government has been assigned a new role: to implement a policy regarding multicultural inclusion. Since the so‐called Framework Agreement of 2001 has been in effect, interethnic conflict in Macedonia has not been the overheated political problem it was at the inception of the Agreement, even though cultural groups remain divided, anxieties continue, and policy processes are mostly top–down.
Inside the Black Box
Authors: West William F.
Published: September 2009

The need to develop specific proposals as a basis for formal participation ensures the most important policy decisions in rulemaking are often made before notice‐and‐comment requirements come to bear. Although informal stakeholder participation in the development of proposed rules is common, it tends to be unstructured and idiosyncratic and to lack the assurances of openness that characterize the comment phase of the process. These observations have important implications for our understanding of the effects and the limitations of procedural constraints on bureaucratic policy making.
Giving and Getting
Authors: Guo Chao , Peck Laura R.
Published: September 2009

This study assesses the extent to which welfare recipients engage in giving money and time to charitable causes. Using the 2003 Center on Philanthropy Panel Study data, this study examines the effects of public assistance—holding constant earned income and demographic traits—on two major types of charitable activities: charitable giving and volunteering. Using a Tobit specification, as appropriate for this type of data, the authors use a creative differencing strategy in an attempt to overcome sticky issues of selection bias. Evidence is found that public assistance receipt tends to suppress monetary donations but may increase volunteer time.
Review Essays: Environmental Policy
Authors: Hamilton-Smith Elery
Published: September 2009

The growing concerns about global environmental changes and the associated predictions of catastrophe have led to a massive growth in the available literature. Works that critically examine and assess various perspectives and claims are indeed welcome, but agreed theory and policy remains nevertheless well behind the frontline of thinking. Within this context, this review essay deals with five books that have met the inherent challenges with varying degrees of success. Each is reviewed separately, and then the reviewer indulges in discussion of the state of the art in environmental sociology. New policies and technologies are playing an increasing role in the dissemination of innovative thinking, but many publishers are responding very slowly.
Is Apoptosis the Cause of Noninsertional Achilles Tendinopathy?
Authors: Pearce Christopher J. , Ismail Muhammad , Calder James D.
Published: September 2009

Background

The pathogenesis of chronic tendinopathy is unclear but it does not appear to be an inflammatory process. Apoptosis may lead to degenerate tissue through a nitric oxide–mediated pathway. Increased levels of nitric oxide have been demonstrated in Achilles tendinopathy.

Hypothesis

Nitric oxide–mediated apoptosis is an important mechanism in the development of Achilles tendinopathy.

Study Design

Controlled laboratory study.

Methods

Samples were obtained from the Achilles tendons of 14 patients with noninsertional Achilles tendinopathy. Control samples were taken from macroscopically normal tendon correlating with areas of normal tissue on magnetic resonance imaging. Immunohistochemical techniques identified the expression of inducible and endothelial nitric oxide synthase as markers of nitric oxide production. Apoptotic cells were identified using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and the demonstration of caspase-3 activation.

Results

Significant differences were found between the diseased tendon and the controls for all parameters. The mean caspase-3 cell count for diseased tendon was 51.9 versus 28.3 for the controls ( P < .001). The mean TUNEL cell count for diseased tendon was 24.1 compared with 14.8 ( P < .001). Inducible nitric oxide synthase (iNOS) densitometry revealed a mean of 26.1 for the diseased tissue versus 15.0 for the controls ( P < .001) and the values for endothelial nitric oxide synthase (eNOS) were 48.3 and 23.7, respectively ( P = .015).

Conclusion

Apoptosis may play a role in the development of noninsertional Achilles tendinopathy and appears to be related to the presence of raised eNOS and iNOS levels.

Clinical Relevance

A clearer understanding of the tendinopathic process may lead to new treatment strategies aimed at modulating apoptosis.
Quantification of Zinc Hydroxystannate** and Stannate** Synergies in Halogen-containing Flame-retardant Polymeric Formulations
Authors: Horrocks A. Richard , Smart Gill , Nazaré Shonali , Kandola Baljinder , Price Dennis
Published: September 2009

Zinc stannate and hydroxystannate are used as synergists in fire-retardant systems in conjunction with halogenated species where their behavior is generally considered to be similar to antimony-containing synergists while offering the additional properties of smoke suppression and relative nontoxicity. The literature most often compares relative synergistic behaviors qualitatively but this article determines such behavior quantitatively using Lewin’s synergistic effectiveness parameter, ES, calculated from sample limiting oxygen index (LOI) data. Flame-retardant formulations comprising zinc stannate (ZS), zinc hydroxystannate (ZHS), or antimony III oxide (ATO) in combination with selected and polymer-compatible bromine-containing flame retardants were formulated in commercial grades of poly(vinyl chloride) (PVC)), thermoset polyester resin, and polyamide 6. PVC formulations simulated both commercial cable and plastisol applications and comprised either a phthalate or aryl phosphate ester as plasticizer in combination with selected synergists. All formulations were subjected to flammability testing using LOI, UL94 (vertical sample mode), and cone calorimetric (including smoke analysis) methods. For all PVC/synergist combinations containing the phthalate plasticizer, synergy was evident with 2.0 > ES > 1.0 and a relative effectiveness order ATO > ZHS > ZS. Zinc borate present as a cosynergist also has a quantifiable, positive effect. In the presence of the phosphate ester plasticizer, the reverse order is observed with marginal levels of synergy being evident (1.2 > ES > 1.0). In polyester resin formulations, ATO and ZHS exhibit similar levels of synergy when present with dibromoneopentyl diglycol with the former being superior when decabromodiphenyl ether is the flame retardant. However, in all polyamide 6 formulations, the highest levels of synergistic effectiveness are observed (ES ≥ 5.0) with ZS. Maximum values of ES correspond to a molar ratio of Sn/Br<0.3 suggesting the formation of SnBr2 and SnBr4 as the effective flame-retarding species.
Cerebellum of the Premature Infant: Rapidly Developing, Vulnerable, Clinically Important
Authors: Volpe Joseph J.
Published: September 2009

Brain abnormality in surviving premature infants is associated with an enormous amount of neurodevelopmental disability, manifested principally by cognitive, behavioral, attentional, and socialization deficits, most commonly with only relatively modest motor deficits. The most recognized contributing neuropathology is cerebral white matter injury. The thesis of this review is that acquired cerebellar abnormality is a relatively less recognized but likely important cause of neurodevelopmental disability in small premature infants. The cerebellar disease may be primarily destructive (eg, hemorrhage, infarction) or primarily underdevelopment. The latter appears to be especially common and relates to a particular vulnerability of the cerebellum of the small premature infant. Central to this vulnerability are the extraordinarily rapid and complex developmental events occurring in the cerebellum. The disturbance of development can be caused either by direct adverse effects on the cerebellum, especially the distinctive transient external granular layer, or by indirect remote trans-synaptic effects. This review describes the fascinating details of cerebellar development, with an emphasis on events in the premature period, the major types of cerebellar abnormality acquired during the premature period, their likely mechanisms of occurrence, and new insights into the relation of cerebellar disease in early life to subsequent cognitive/behavioral/attentional/socialization deficits.
Intrauterine Endotoxin Administration Leads to White Matter Diffusivity Changes in Newborn Rabbits
Authors: Saadani-Makki Fadoua , Kannan Sujatha , Makki Malek , Muzik Otto , Janisse James , Romero Roberto , Chugani Diane
Published: September 2009

Maternal intrauterine inflammation has been implicated in the development of periventricular leukomalacia and white matter injury in the neonate. We hypothesized that intrauterine endotoxin administration would lead to microstructural changes in the neonatal rabbit white matter in vivo that could be detected at birth using diffusion tensor magnetic resonance imaging (MRI). Term newborn rabbit kits (gestational age 31 days) born to dams exposed to saline or endotoxin in utero on gestational day 28 underwent diffusion tensor imaging, and brain sections were stained for microglia. Comparison between normal and endotoxin groups showed significant decreases in both fractional anisotropy and eigenvalue (e1) in all periventricular white matter regions that showed an increase in the number of activated microglial cells, indicating that after maternal inflammation, microglial infiltration may predominantly explain this change in diffusivity in the immediate neonatal period. Diffusion tensor imaging may be a clinically useful tool for detecting neuroinflammation induced by maternal infection in neonatal white matter.
Magnetic Resonance Imaging and Ultrasound Injury in Preterm Infants With Seizures
Authors: Glass Hannah C. , Bonifacio Sonia L. , Sullivan Joseph , Rogers Elizabeth , Ferriero Donna M. , Goldstein Ruth , Barkovich A. James
Published: September 2009

Although the utility of magnetic resonance imaging (MRI) as a universal screening tool in preterm infants has been contested, it is increasingly used to investigate neonatal seizures. The authors evaluated 236 infants <34 weeks’ gestation at birth. Seizures were documented according to the clinical standard of care. Infants underwent MRI and head ultrasound during the neonatal period, and a neuroradiologist and ultrasonologist performed detailed reviews of the images. During the hospital course, 9 infants (3.8%) had clinical suspicion of seizures. Magnetic resonance imaging was abnormal in each case. Periventricular hemorrhagic infarct was more common in infants with seizures. Infants with seizures were more likely to have white matter injury, though the difference was not significant. Head ultrasound failed to detect the extent of brain abnormality in 8 (89%) of the infants. In this large cohort, infants with clinical suspicion of seizures had a high rate of MRI abnormalities that were not as well characterized by head ultrasound. Magnetic resonance imaging may be the study of choice for evaluating preterm infants with seizures.
The Role of Systemic Hemodynamic Disturbances in Prematurity-Related Brain Injury
Authors: du Plessis Adré J.
Published: September 2009

Premature infants who experience cerebrovascular injury frequently have acute and long-term neurologic complications. In this article, we explore the relationship between systemic hemodynamic insults and brain injury in this patient population and the mechanisms that might be at play.
Do Environmental Regulations Impede Economic Growth? A Case Study of the Metal Finishing Industry in the South Coast Basin of Southern California
Authors: Thomas Ward
Published: September 2009

Air pollution emitted from firms and industries in the United States poses a significant threat to human health and the environment. Economists have traditionally opposed environmental regulations based on the argument that regulations reduce economic growth. Some scholars, however, have argued that polluting firms often adjust to environmental regulations through technological innovations that have the opposite effect. This study examines the effects of environmental regulations on economic growth through a case study of the metal finishing industry in the South Coast Basin of Southern California. The industry in the Basin has been regulated since 1988 by the South Coast Air Quality Management District (AQMD) as a result of the industry’s use of hexavalent chromium. Based on a comparative analysis of the metal finishing industries in Chicago and Detroit, it appears that the AQMD regulations have not had a detrimental impact on the growth of the industry in the Basin.
Fabrication and Characterization of High-density Polyethylene - Coconut Coir Composites with Stearic Acid as Compatibilizer
Authors: Enriquez Joseph King Eos Dawn V. , Macalino Santiago Peter June , Funcion Ong Timothy , Chakraborty Soma
Published: September 2009

Composites of high-density polyethylene (HDPE) with coconut coir as the fiber and stearic acid (SA) as the coupling agent were fabricated by compression molding. Coconut coir in the form of braided fibers and whiskers were used for the study. Incorporation of the coir, buckled the composites and decreased their tensile strength and elongation at break. The extent of buckling and deterioration in the mechanical properties was proportional to the amount of coir loaded as filler. Treatment of the coir with SA as the coupling agent enhanced the mechanical properties and the thermal stability of the composites. It also reduced the extent of buckling and prevented aging of the composites to certain extent in aqueous and strong acidic and alkaline media. Scanning electron micrographs of the fractured samples showed improved adhesion between coir and HDPE matrix upon treatment with SA.
Numerical Analysis and Experimental Validation of Interlaminar Stresses of Quasi-isotropic APC-2/AS-4 Laminate with a Central Hole Loaded in Tension
Authors: Zhao G.H. , Tong J.W. , Shen M.
Published: September 2009

This article addresses the distributions of interlaminar stresses of centrally notched quasi-isotropic APC-2/AS-4 laminate ([0/±45/90]2s) in tension by finite element method (FEM). Results include the concentration of interlaminar stresses in the vicinity of free boundaries (including hole edge and free sides); The concentration of interlaminar shear stress dominates at interfaces of -45°/+45° and +45°/0°, and the concentration of interlaminar normal stress, which occurs at the 90°/-45° and 0°/90° interfaces. Further analysis demonstrates that the concentration of interlaminar shear stress is more severe as a whole and the highest interlaminar shear stress occurs near the hole edge. The results of digital speckle correlation measurement experiment validate the FEM result.
The Thermal Stabilization Effect of Biphenol Monoacrylate on Polyoxymethylene
Authors: Lu Gan  , Lin Ye
Published: September 2009

Biphenol monoacrylate (BMA) was applied to be combined with the traditional hindered phenolic-based binary antioxidant system to form the ternary antioxidant system for the purpose of further improving the thermal oxidative stability of polyoxymethylene (POM). The thermal stabilization effect of BMA on POM was studied by the measurements of isothermal and nonisothermal degradation, formaldehyde emission amount, and balance torque. The thermal stability of the stabilized POM under multiple processing and long-term aging was further studied in comparison with the commonly used antioxidant Irganox245. The results showed that the antioxidant BMA can improve the thermal stability of POM effectively through a unique bifunctional stabilizing mechanism, and much low content of BMA-based ternary antioxidant system can reach the same level of thermal stabilization effect on POM as with Irganox245, which can replace Irganox245 to be applied in the production of POM due to its low dosage and low production cost.
African American Families in the Special Education Process
Authors: Brandon Regina R. , Brown Monica R.
Published: September 2009

African American children continue to be overrepresented in special education classrooms. Despite this overrepresentation, there is a noticeable void in the literature concerning the family perceptions of special education and the impact these perceptions may have on parents’ level of involvement. Therefore, this article discusses (a) African American family involvement in the educational process, including special education; (b) the perceptions of African American families concerning special education and how these perceptions might prevent parents from participating; (c) potential barriers to participation; and (d) suggestions for increasing the level of participation of African American families in the educational process.
Puerto Rican Women’s Perceptions of Heart Disease Risk
Authors: Lange Jean , Evans-Benard Sharon , Cooper Jennifer , Fahey Ellen , Kalapos Marlain , Tice Donna , Wang-D'Amato Nancy , Watsky Nancy
Published: September 2009

Women frequently fail to recognize that coronary heart disease (CHD), not breast cancer, is the primary cause of female mortality. CHD mortality among U.S. mainland Puerto Rican (PR) women is second only to African American women. It is unknown what PR women understand about their risk, what factors they believe contribute to CHD, or whether they know the atypical symptoms often experienced by women. Most CHD studies exclude Hispanic women. Those that do often aggregate their results, making subgroup variations invisible. This study explored awareness of CHD symptoms, risks, and help-seeking behaviors among 12 PR women. Focus group methodology revealed that participants were unaware of their risk and had misconceptions about CHD symptoms and contributing factors. Barriers to early recognition and treatment included lack of knowledge, gender role conflict (caregiver vs. care recipient), and fears of falsely alarming family members or the embarrassment of feeling “dismissed” by health care providers.
What Is the Optimal Postconditioning Algorithm?
Authors: Iliodromitis Efstathios K. , Downey James M. , Heusch Gerd , Kremastinos Dimitrios T.
Published: September 2009

Ischemic postconditioning has emerged as a clinically feasible intervention for limiting infarction in the setting of percutaneous intervention. In ischemic postconditioning, a number of cycles of a brief period of reperfusion followed by a brief period of occlusion are applied immediately upon reperfusion of the ischemic heart. Although ischemic postconditioning is protective in both animals and man, the animal studies reveal that the algorithm used in selecting the duration of the occlusion and reperfusion periods is critical to the degree of protection realized and it varies with species. The question then arises what is the best algorithm for man? The available animal and clinical data are examined in an attempt to shed light on this perplexing problem.
Major Computer Science Challenges At Exascale
Authors: Geist Al , Lucas Robert
Published: September 2009

Exascale systems will provide an unprecedented opportunity for science, one that will make it possible to use computation not only as a critical tool along with theory and experiment in understanding the behavior of the fundamental components of nature, but also for critical advances for the nation’s energy needs and security. To create exascale systems and software that will enable the US Department of Energy (DOE) to meet the science goals critical to the nation’s energy, ecological sustainability, and global security, we must focus on major architecture, software, algorithm, and data challenges, and build on newly emerging programming environments. Only with this new infrastructure will applications be able to scale up to the required levels of parallelism and integrate technologies into complex coupled systems for real-world multidisciplinary modeling and simulation. Achieving this goal will likely involve a shift from current static approaches for application development and execution to a combination of new software tools, algorithms, and dynamically adaptive methods.
XXL Simulation for XXIst Century Power Systems Operation
Authors: Berthou Jean-Yves , Hamelin Jean-François , de Rocquigny Etienne
Published: September 2009

As an industrial user with very high stakes in the operation and maintenance of complex systems such as nuclear power plants, EDF has been engaged in simulation for many years. We feel that exaflops software should not only be thought of as a way of tackling daunting research problems but should also take into account the sometimes equally daunting requirements that stem from an industrial usage perspective. We do feel that, whatever the hard changes that will probably have to be made to various software aspects, we should not lose sight of the fact that continuity paths also have to be found in order to make those big changes acceptable and profitable to many. We identify in this paper what we think are priority research themes that could benefit from an international collaboration.
Repulsive axon guidance molecule Slit3 is a novel angiogenic factor
Authors: Zhang Bing , Dietrich Ursula M. , Geng Jian-Guo , Bicknell Roy , Esko Jeffrey D. , Wang Lianchun
Published: September 2009

Slits are large, secreted repulsive axon guidance molecules. Recent genetic studies revealed that the Slit3 is dispensable for neural development but required for non-neuron–related developmental processes, such as the genesis of the diaphragm and kidney. Here we report that Slit3 potently promotes angiogenesis, a process essential for proper organogenesis during embryonic development. We observed that Slit3 is expressed and secreted by both endothelial cells and vascular smooth muscle cells in vasculature and that the Slit cognate receptors Robo1 and Robo4 are universally expressed by endothelial cells, suggesting that Slit3 may act in paracrine and autocrine manners to regulate endothelial cells. Cellular function studies revealed that Slit3 stimulates endothelial-cell proliferation, promotes endothelial-cell motility and chemotaxis via interaction with Robo4, and accelerates endothelial-cell vascular network formation in vitro with a specific activity comparable with vascular endothelial growth factor. Furthermore, Slit3 stimulates neovessel sprouting ex vivo and new blood vessel growth in vivo. Consistent with these observations, the Slit3 knockout mice display disrupted angiogenesis during embryogenesis. Taken together, our studies reveal that the repulsive axon guidance molecule Slit3 is a novel and potent angiogenic factor and functions to promote angiogenesis in coordinating organogenesis during embryonic development.
Human platelets produced in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice upon transplantation of human cord blood CD34+ cells are functionally active in an ex vivo flow model of thrombosis
Authors: Salles Isabelle I. , Thijs Tim , Brunaud Christine , De Meyer Simon F. , Thys Johan , Vanhoorelbeke Karen , Deckmyn Hans
Published: September 2009

Xenotransplantation systems have been used with increasing success to better understand human hematopoiesis and thrombopoiesis. In this study, we demonstrate that production of human platelets in nonobese diabetic/severe combined immunodeficient mice after transplantation of unexpanded cord-blood CD34+ cells was detected within 10 days after transplantation, with the number of circulating human platelets peaking at 2 weeks (up to 87 × 103/μL). This rapid human platelet production was followed by a second wave of platelet formation 5 weeks after transplantation, with a population of 5% still detected after 8 weeks, attesting for long-term engraftment. Platelets issued from human hematopoietic stem cell progenitors are functional, as assessed by increased CD62P expression and PAC1 binding in response to collagen-related peptide and thrombin receptor-activating peptide activation and their ability to incorporate into thrombi formed on a collagen-coated surface in an ex vivo flow model of thrombosis. This interaction was abrogated by addition of inhibitory monoclonal antibodies against human glycoprotein Ibα (GPIbα) and GPIIb/IIIa. Thus, our mouse model with production of human platelets may be further explored to study the function of genetically modified platelets, but also to investigate the effect of stimulators or inhibitors of human thrombopoiesis in vivo.
How I treat postthrombotic syndrome
Authors: Kahn Susan R.
Published: September 2009

Postthrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT) that reduces quality of life and has important socioeconomic consequences. More than one-third of patients with DVT will develop PTS, and 5% to 10% of patients will develop severe PTS, which may manifest as venous ulceration. The principal risk factors for PTS are persistent leg symptoms 1 month after the acute episode of DVT, extensive DVT, recurrent ipsilateral DVT, obesity, and older age. Daily use of elastic compression stockings (ECSs) for 2 years after proximal DVT appears to reduce the risk of PTS; however, there is uncertainty about optimal duration of use and compression strength of ECSs and the magnitude of their effect. The cornerstone of managing PTS is compression therapy, primarily using ECSs. Venoactive medications such as aescin and rutoside may provide short-term relief of PTS symptoms. The likelihood of developing PTS after DVT should be discussed with patients, and symptoms and signs of PTS should be monitored during clinical follow-up. Further studies to elucidate the pathophysiology of PTS, to identify clinical and biologic risk factors, and to test new preventive and therapeutic approaches to PTS are needed to ultimately improve the long-term prognosis of patients with DVT.
National income, self-reported wheezing and asthma diagnosis from the World Health Survey
Authors: Sembajwe G. , Cifuentes M. , Tak S. W. , Kriebel D. , Gore R. , Punnett L.
Published: September 2009

The aims of this study were to quantify and describe the variations in respiratory symptoms and diagnosis prevalence across regions of the world according to national income.

In 2002 and 2003, the World Health Organization implemented the World Health Survey (WHS), which used a standardised survey instrument to compile comprehensive baseline information on health and healthcare expenditure. We analysed the WHS data to assess the global patterns of self-reported wheeze and doctor-diagnosed asthma, two commonly reported measures of respiratory health.

In total there were 308,218 participants with complete records, from 64 countries. The weighted mean age of the survey population was 43 yrs. Global prevalence of current wheezing symptoms ranged from 2.4% in Vietnam to 24% in Brazil; the prevalence of diagnosed asthma ranged from 1.8% in Vietnam to 32.8% in Australia. Overall, the prevalence of symptoms and diagnosis showed a U-shaped pattern with the largest prevalence reported in low- and high-income countries. The smallest prevalence was consistently found in middle-income countries.

These WHS analyses have provided global prevalence estimates of wheeze and doctor-diagnosed asthma using data gathered simultaneously and consistently across six continents. These findings support the need for continued global respiratory illness surveillance for disease prevention, health policy and management.
HMOX1andGSTvariants modify attenuation of FEF25–75%decline due to PM10reduction
Authors: Curjuric I. , Imboden M. , Schindler C. , Downs S.H. , Hersberger M. , Liu S.L.J. , Matyas G. , Russi E.W. , Schwartz J. , Thun G.A. , Postma D.S. , Rochat T. , Probst-Hensch N.M.
Published: September 2009

Reduced exposure to particulate matter with a 50% cut-off aerodynamic diameter of 10 μm (PM10) attenuated age-related lung function decline in our cohort, particularly in the small airways. We hypothesised that polymorphisms in glutathioneS-transferase (GST) and haem oxygenase-1 (HMOX1) genes, important for oxidative stress defence, modify these beneficial effects.

A population-based sample of 4,365 adults was followed up after 11 yrs, including questionnaire, spirometry and DNA blood sampling. PM10exposure was estimated by dispersion modelling and temporal interpolation. The main effects on annual decline in forced expiratory flow at 25–75% of forced vital capacity (FEF25–75%) and interactions with PM10reduction were investigated for polymorphismsHMOX1rs2071746 (T/A), rs735266 (T/A) and rs5995098 (G/C),HMOX1(GT)npromoter repeat,GSTM1andGSTT1deletions, andGSTP1p.Ile105Val, using mixed linear regression models.

HMOX1rs5995098,HMOX1haplotype TTG andGSTP1showed significant genetic main effects. Interactions with PM10reduction were detected: a 10 μg·m−3reduction significantly attenuated annual FEF25–75%decline by 15.3 mL·s−1only in the absence ofHMOX1haplotype ATC. Similarly, carriers of long (GT)npromoter repeat alleles or theGSTP1Val/Val genotype profited significantly more from a 10 μg·m−3reduction (26.5 mL·s−1and 27.3 mL·s−1respectively) than non-carriers.

Benefits of a reduction in PM10exposure are not equally distributed across the population but are modified by the individual genetic make-up determining oxidative stress defence.
Determining the aetiology of pulmonary oedema by the oedema fluid-to-plasma protein ratio
Authors: Ware L. B. , Fremont R. D. , Bastarache J. A. , Calfee C. S. , Matthay M. A.
Published: September 2009

We hypothesised that the oedema fluid-to-plasma protein (EF/PL) ratio, a noninvasive measure of alveolar capillary membrane permeability, can accurately determine the aetiology of acute pulmonary oedema.

390 mechanically ventilated patients with acute pulmonary oedema were enrolled. A clinical diagnosis of acute lung injury (ALI), cardiogenic pulmonary oedema or a mixed aetiology was based on expert medical record review at the end of hospitalisation. The EF/PL ratio was measured from pulmonary oedema fluid and plasma samples collected at intubation.

209 patients had a clinical diagnosis of ALI, 147 had a diagnosis of cardiogenic pulmonary oedema and 34 had a mixed aetiology. The EF/PL ratio had an area under the receiver-operating curve of 0.84 for differentiating ALI from cardiogenic pulmonary oedema. Using a predefined cut-off of 0.65, the EF/PL ratio had a sensitivity of 81% and a specificity of 81% for the diagnosis of ALI. An EF/PL ratio ≥0.65 was also associated with significantly higher mortality and fewer ventilator-free days.

Noninvasive measurement of the EF/PL ratio is a safe and reliable bedside method for rapidly determining the aetiology of acute pulmonary oedema that can be used at the bedside in both developed and developing countries.
FGFRL1 is a neglected putative actor of the FGF signalling pathway present in all major metazoan phyla
Authors: Bertrand Stephanie , Somorjai Ildiko , Garcia-Fernandez Jordi , Lamonerie Thomas , Escriva Hector
Published: September 2009

Background

Fibroblast Growth Factors (FGF) and their receptors are well known for having major implications in cell signalling controlling embryonic development. Recently, a gene coding for a protein closely related to FGFRs (Fibroblast Growth Factor Receptors) called FGFR5 or FGFR-like 1 (FGFRL1), has been described in vertebrates. An orthologous gene was also found in the cephalochordate amphioxus, but no orthologous genes were found by the authors in other non-vertebrate species, even if a FGFRL1 gene was identified in the sea urchin genome, as well as a closely related gene, named nou-darake, in the planarian Dugesia japonica. These intriguing data of a deuterostome-specific gene that might be implicated in FGF signalling prompted us to search for putative FGFRL1 orthologues in the completely sequenced genomes of metazoans.

Results

We found FGFRL1 genes in the cnidarian Nematostella vectensis as well as in many bilaterian species. Our analysis also shows that FGFRL1 orthologous genes are linked in the genome with other members of the FGF signalling pathway from cnidarians to bilaterians (distance < 10 Mb). To better understand the implication of FGFRL1 genes in chordate embryonic development, we have analyzed expression patterns of the amphioxus and the mouse genes by whole mount in situ hybridization. We show that some homologous expression territories can be defined, and we propose that FGFRL1 and FGF8/17/18 were already co-expressed in the pharyngeal endoderm in the ancestor of chordates.

Conclusion

Our work sheds light on the existence of a putative FGF signalling pathway actor present in the ancestor of probably all metazoans, the function of which has received little attention until now.
Improvement of the clinical applicability of the Genomic Grade Index through a qRT-PCR test performed on frozen and formalin-fixed paraffin-embedded tissues
Authors: Toussaint Jérôme , Sieuwerts Anieta M , Haibe-Kains Benjamin , Desmedt Christine , Rouas Ghizlane , Harris Adrian L , Larsimont Denis , Piccart Martine , Foekens John A , Durbecq Virginie , Sotiriou Christos
Published: September 2009

Background

Proliferation and tumor differentiation captured by the genomic grade index (GGI) are important prognostic indicators in breast cancer (BC) especially for the estrogen receptor positive (ER+) disease. The aims of this study were to convert this microarray index to a qRT-PCR assay (PCR-GGI), which could be realized on formalin fixed paraffin embedded samples (FFPE), and to assess its prognostic performance and predictive value of clinical benefit in early and advanced ER+ BC patients treated with tamoxifen.

Methods

The accuracy and concordance of the PCR-GGI with the GGI was assessed using BC patients for which frozen and FFPE tissues as well as microarray data were available (n = 19). The evaluation of the prognostic value of the PCR-GGI was assessed on FFPE material using a consecutive series of 212 systemically treated early BC patients. The predictive performance for tamoxifen benefit was assessed using two ER+ BC populations treated either with adjuvant tamoxifen only (n = 77+139) or first-line tamoxifen for advanced disease (n = 270).

Results

The PCR-GGI is based on the expression of 8 genes (4 representative of the GGI and 4 reference genes). A significant correlation was observed between the microarray-derived GGI and the qRT-PCR assay using frozen (ρ = 0.95, p < 10E-06) and FFPE material (ρ = 0.89, p < 10E-06). The prognostic performance of the PCR-GGI was confirmed on FFPE samples (HRunivar. = 1.89; [95CI:1.01-3.54], p = 0.05). The PCR-GGI further identified two subgroups of patients with statistically different time to distant metastasis free survival (DMFS) across the two cohorts of ER+ BC patients treated with adjuvant tamoxifen. Additionally, the PCR-GGI was associated with response to tamoxifen in the advanced setting (HRunivar. = 1.98; [95CI:1.51-2.59], p = 6.9E-07).

Conclusion

PCR-GGI recapitulates in an accurate and reproducible manner the performances of the GGI using frozen and FFPE samples.
Mycoplasma pneumoniae and/or Chlamydophila pneumoniae inoculation causing different aggravations in cholesterol-induced atherosclerosis in apoE KO male mice
Authors: Damy Sueli B , Higuchi Maria L , Timenetsky Jorge , Reis Márcia M , Palomino Suely P , Ikegami Renata N , Santos Fabiana P , Osaka Junko T , Figueiredo Luiz P
Published: September 2009

Background

Chamydophila pneumoniae (CP) and/or Mycoplasma pneumoniae (MP) are two bacteria detected in vulnerable atheromas. In this study we aimed to analyze whether CP and/or MP aggravates atherosclerosis induced by cholesterol-enriched diet in C57BL/6 apoE KO male mice. Thirty male apoE KO mice aged eight weeks fed by a diet containing 1% cholesterol until 32 weeks of age were divided into four groups: the first was inoculated with CP (n = 7), the second with MP (n = 12), the third with both CP + MP (n = 5), and the fourth with saline (sham n = 6). The animals were re-inoculated at 36 weeks of age, and sacrificed at 40 weeks of age. Two ascending aorta and one aortic arch segments were sampled. In the most severely obstructed segment, vessel diameter, plaque height, percentage of luminal obstruction and the degree of adventitial inflammation were analyzed. The plaque area/intimal surface ratio was obtained by measuring all three segments. The adventitial inflammation was semiquantified (0 absent, 1 mild, 2 moderate, and 3 diffuse).

Results

The mean and standard deviation of plaque height, % luminal obstruction, external diameter, the plaque area/intimal surface ratio and the adventitial inflammation values are the following for each group: MP (0.20 +/- 0.12 mm, 69 +/- 26%, 0.38 +/- 0.11 mm, 0.04 +/- 0.04 and 0.22 +/- 0.67), CP (0.23 +/- 0.08 mm, 90 +/- 26%, 0.37 +/- 0.08 mm, 0.04 +/- 0.03, and 0.44 +/- 0.53), MP + CP (18 +/- 0.08 mm, 84 +/- 4.0%, 0.35 +/- 0.25 mm, 0.03 +/- 0.03 and 1.33 +/- 0.82) and sham (0.08 +/- 0.09 mm, 42 +/- 46%, 0.30 +/- 0.10 mm, 0.02 +/- 0.03 and 0.71 ± 0.76). A wider area of plaque/intimal surface was observed in MP + CP inoculated groups (p = 0.07 and 0.06) as well as an increased plaque height in CP (p = 0.01) in comparison with sham group. There was also an increased luminal obstruction (p = 0.047) in CP inoculated group in comparison to sham group. Adventitial inflammation in MP + CP inoculated group was higher than MP, CP and the sham groups (p = 0.02).

Conclusion

Inoculation of CP, MP or both agents in C57BL/6 apoE KO male mice caused aggravation of experimental atherosclerosis induced by cholesterol-enriched diet, with distinct characteristics. CP inoculation increased the plaque height with positive vessel remodeling and co-inoculation of MP + CP caused the highest adventitial inflammation measures.
Identification of Achaete-scute complex-like 1 (ASCL1) target genes and evaluation of DKK1 and TPH1 expression in pancreatic endocrine tumours
Authors: Johansson Térèse A , Westin Gunnar , Skogseid Britt
Published: September 2009

Background

ASCL1role in pancreatic endocrine tumourigenesis has not been established. Recently it was suggested that ASCL1 negatively controls expression of the Wnt signalling antagonistDKK1. Notch signalling regulates expression of TPH1, the rate limiting enzyme in the biosyntesis of serotonin. Understanding the development and proliferation of pancreatic endocrine tumours (PETs) is essential for the development of new therapies.

Methods

ASCL1target genes in the pancreatic endocrine tumour cell line BON1 were identified by RNA interference and microarray expression analysis. Protein expressions of selected target genes in PETs were evaluated by immunohistochemistry.

Results

158 annotatedASCL1target genes were identified in BON1 cells, among them DKK1 and TPH1 that were negatively regulated by ASCL1. An inverse relation of ASCL1 to DKK1 protein expression was observed for 15 out of 22 tumours (68%). Nine tumours displayed low ASCL1/high DKK1 and six tumours high ASCL1/low DKK1 expression. Remaining PETs showed high ASCL1/high DKK1 (n = 4) or low ASCL1/low DKK1 (n = 3) expression. Nine of twelve analysed PETs (75%) showed TPH1 expression with no relation to ASCL1.

Conclusion

A number of genes with potential importance for PET tumourigenesis have been identified.ASCL1negatively regulated the Wnt signalling antagonistDKK1, andTPH1expression in BON1 cells. In concordance with these findings DKK1 showed an inverse relation to ASCL1 expression in a subset of PETs, which may affect growth control by the Wnt signalling pathway.