bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced Adverse Event Profile of Orally Inhaled DHE (MAP0004) vs IV DHE: Potential Mechanism
Authors: Cook Robert O. , Shrewsbury Stephen B. , Ramadan Nabih M.
Published: September 2009

Background.— MAP0004 is a novel orally inhaled formulation of dihydroergotamine mesylate (DHE) currently in development that has been clinically observed to provide rapid (∼10 minutes) therapeutic levels of DHE but with lower rates of adverse effects (dizziness, nausea, and paresthesia) compared with intravenous (IV) dosing. Receptor‐based mechanistic studies were conducted to determine if differences between IV DHE and inhaled DHE (MAP0004) binding and functional activity were responsible for the improved adverse event profile.

Methods.— Radioligand competitive binding assays were performed at adrenergic (α1 [non‐specific], α2A, α2B, α2C, β), dopaminergic (D; D1, D2, D3), and at serotonergic (5‐HT; 5‐HT1A, 5‐HT1B, 5‐HT1D, 5‐HT2A, 5‐HT2C, 5‐HT3, 5‐HT4, 5‐HT5A, 5‐HT6, 5‐HT7) receptors. Binding assays were also conducted for the major metabolite of DHE, 8’‐hydroxy‐DHE (8’‐OH‐DHE). Subsequent functional receptor assays were also performed at 5‐HT1B, 5‐HT1D, 5‐HT2A, 5‐HT2C, 5‐HT3, D2, α1A, α2A, α2B, β1, and β2 and muscarinic receptors to ensure that observed receptor binding translated into potential functional response.

Results.— For competitive binding studies, DHE demonstrated extensive activity at IV Cmax for all 5‐HT receptors tested, except 5‐HT3 and 5‐HT4, and α1, α2A, α2B, α2C, and D3 receptors. DHE concentrations used in the studies were equal to the peak plasma concentrations (Cmax) observed in human subjects following IV DHE 1.0 mg (the standard approved dose), and 2 and 4 inhalations MAP0004 which, respectively, produced systemic circulation levels of DHE equivalent to 0.44 mg and 0.88 mg administered IV. MAP0004 binding activity at the Cmax concentrations was lower than IV DHE and no binding was observed for the 8’‐OH‐DHE metabolite. However, MAP0004 preserved potent agonist action at key anti‐migraine 5‐HT1B and 5‐HT1D receptors, even at the lower Cmax concentrations. Functional binding studies displayed similar results whereby IV DHE Cmax concentrations invoked strong agonist/antagonist responses, for instance at adrenergic and 5‐HT2C receptors, which could have been responsible for dizziness. Conversely, at Cmax concentrations of MAP0004, inhaled DHE achieved a significantly lower response or no response at the adrenergic and 5‐HT2C receptors.

Conclusions.— The mechanism by which nausea was experienced with IV DHE – yet not with MAP0004 – was not associated with classic nausea pathways/targets (dopamine, 5‐HT3, or muscarinic receptors) or with peripheral action in the intestine via enterochromaffin cells. Importantly, the maximum DHE concentrations following MAP0004 administration were insufficient to interact with receptors implicated in cardiovascular (5‐HT2B and β1) and pulmonary effects (β2, adenosine, muscarinic, and leukotriene).
A Case of MS Presenting With SUNCT Status
Authors: Bogorad Ilya , Blum Sonja , Green Mark
Published: September 2009

(Headache 2010;50:141‐143)
Clinical Success of Zirconia in Dental Applications
Authors: Özkurt Zeynep , Kazazoğlu Ender
Published: September 2009

The application of ceramic materials for the fabrication of dental restorations is a focus of interest in esthetic dentistry. The ceramic materials of choice are glass ceramics, spinel, alumina, and zirconia. Zirconia was introduced into dentistry in the 1990s because of its good mechanical and chemical properties and is currently being used as a material for frameworks, dowels, implants, abutments, and orthodontic brackets. Many in vitro studies about zirconia use have been published, but clinical long‐term studies are very important. This article presents data regarding the incidence of clinical success and complications of zirconia in these dental applications. Clinical studies published to date seem to indicate that zirconia is well tolerated and sufficiently resistant.
Dynamic Model for Multivariate Markers of Fecundability
Authors: Cai Bo , Dunson David B. , Stanford Joseph B.
Published: September 2009

Summary:  Dynamic latent class models provide a flexible framework for studying biologic processes that evolve over time. Motivated by studies of markers of the fertile days of the menstrual cycle, we propose a discrete‐time dynamic latent class framework, allowing change points to depend on time, fixed predictors, and random effects. Observed data consist of multivariate categorical indicators, which change dynamically in a flexible manner according to latent class status. Given the flexibility of the framework, which incorporates semi‐parametric components using mixtures of betas, identifiability constraints are needed to define the latent classes. Such constraints are most appropriately based on the known biology of the process. The Bayesian method is developed particularly for analyzing mucus symptom data from a study of women using natural family planning.
Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems
Authors: Lü Jian‐Ming , Lin Peter H. , Yao Qizhi , Chen Changyi
Published: September 2009

Introduction

Free radical scavenging

Metal ion (Fe2+, Fe3+, Cu2+ and Cu+) chelating

Inhibition of free radical generating enzymes

Activation of internal antioxidant enzymes

Prevention of lipid peroxidation

Prevention of DNA damage

Prevention of protein modification

Conclusions

Free radicals derived from oxygen, nitrogen and sulphur molecules in the biological system are highly active to react with other molecules due to their unpaired electrons. These radicals are important part of groups of molecules called reactive oxygen/nitrogen species (ROS/RNS), which are produced during cellular metabolism and functional activities and have important roles in cell signalling, apoptosis, gene expression and ion transportation. However, excessive ROS attack bases in nucleic acids, amino acid side chains in proteins and double bonds in unsaturated fatty acids, and cause oxidative stress, which can damage DNA, RNA, proteins and lipids resulting in an increased risk for cardiovascular disease, cancer, autism and other diseases. Intracellular antioxidant enzymes and intake of dietary antioxidants may help to maintain an adequate antioxidant status in the body. In the past decades, new molecular techniques, cell cultures and animal models have been established to study the effects and mechanisms of antioxidants on ROS. The chemical and molecular approaches have been used to study the mechanism and kinetics of antioxidants and to identify new potent antioxidants. Antioxidants can decrease the oxidative damage directly via reacting with free radicals or indirectly by inhibiting the activity or expression of free radical generating enzymes or enhancing the activity or expression of intracellular antioxidant enzymes. The new chemical and cell‐free biological system has been applied in dissecting the molecular action of antioxidants. This review focuses on the research approaches that have been used to study oxidative stress and antioxidants in lipid peroxidation, DNA damage, protein modification as well as enzyme activity, with emphasis on the chemical and cell‐free biological system.
Imatinib inhibits vascular smooth muscle proteoglycan synthesis and reduces LDL bindingin vitroand aortic lipid depositionin vivo
Authors: Ballinger Mandy L. , Osman Narin , Hashimura Kazuhiko , Haan Judy B. de , Jandeleit‐Dahm Karin , Allen Terri , Tannock Lisa R. , Rutledge John C. , Little Peter J.
Published: September 2009

The ‘response to retention’ hypothesis of atherogenesis proposes that proteoglycans bind and retain low‐density lipoproteins (LDL) in the vessel wall. Platelet‐derived growth factor (PDGF) is strongly implicated in atherosclerosis and stimulates proteoglycan synthesis. Here we investigated the action of the PDGF receptor inhibitor imatinib on PDGF‐mediated proteoglycan biosynthesisin vitro, lipid deposition in the aortic wallin vivoand the carotid arteryex vivo. In human vSMCs, imatinib inhibited PDGF mediated35S‐SO4incorporation into proteoglycans by 31% (P< 0.01) and inhibited PDGF‐mediated size increases in both chemically cleaved and xyloside associated glycosaminoglycan (GAG) chains by 19%,P< 0.05 and 27%,P< 0.05, respectively. Imatinib decreased PDGF stimulation of the 6:4 position sulphation ratio of disaccharides. The half maximal saturation value for LDL binding for proteoglycans from PDGF stimulated cells in the presence of imatinib was approximately 2.5‐fold higher than for PDGF treatment alone. In high fat fed ApoE−/–mice, imatinib reduced total lipid staining area by ∼31% (P< 0.05). Carotid artery lipid accumulation in imatinib treated mice was also reduced. Furthermore, we demonstrate that imatinib inhibits phosphorylation of tyrosine 857, the autophosphorylation site of the PDGF receptor, in vSMCs. Thus imatinib inhibits GAG synthesis on vascular proteoglycans and reduces LDL bindingin vitroandin vivoand this effect is mediatedviathe PDGF receptor. These findings validate a novel mechanism to prevent cardiac disease.
Monocyte transplantation for neural and cardiovascular ischemia repair
Authors: Sanberg Paul R. , Park Dong‐Hyuk , Kuzmin‐Nichols Nicole , Cruz Eduardo , Hossne Jr Nelson Americo , Buffolo Enio , Willing Alison E.
Published: September 2009

Introduction

Role of monocyte in neovascularization

Monocytes versus stem cells for transplantation

Conclusions

Neovascularization is an integral process of inflammatory reactions and subsequent repair cascades in tissue injury. Monocytes/macrophages play a key role in the inflammatory process including angiogenesis as well as the defence mechanisms by exerting microbicidal and immunomodulatory activity. Current studies have demonstrated that recruited monocytes/macrophages aid in regulating angiogenesis in ischemic tissue, tumours and chronic inflammation. In terms of neovascularization followed by tissue regeneration, monocytes/macrophages should be highly attractive for cell‐based therapy compared to any other stem cells due to their considerable advantages: non‐oncogenic, non‐teratogenic, multiple secretary functions including pro‐angiogenic and growth factors, straightforward cell harvesting procedure and non‐existent ethical controversy. In addition to adult origins such as bone marrow or peripheral blood, umbilical cord blood (UCB) can be a potential source for autologous or allogeneic monocytes/macrophages. Especially, UCB monocytes should be considered as the first candidate owing to their feasibility, low immune rejection and multiple characteristic advantages such as their anti‐inflammatory properties by virtue of their unique immune and inflammatory immaturity, and their pro‐angiogenic ability. In this review, we present general characteristics and potential of monocytes/macrophages for cell‐based therapy, especially focusing on neovascularization and UCB‐derived monocytes.
Chromosomal instability correlates with poor outcome in patients with myelodysplastic syndromes irrespectively of the cytogenetic risk group
Authors: Heilig Christoph E. , Löffler Harald , Mahlknecht Ulrich , Janssen Johannes W.G. , Ho Anthony D. , Jauch Anna , Krämer Alwin
Published: September 2009

Chromosomal instability (CIN), defined by an elevated frequency of the occurrence of novel chromosomal aberrations, is strongly implicated in the generation of aneuploidy, one of the hallmarks of human cancers. As for aneuploidy itself, the role of CIN in the evolution and progression of malignancy is a matter still open to debate. We investigated numerical as well as structural CIN in primary CD34‐positive cells by determining the cell‐to‐cell variability of the chromosome content using fluorescence‐in situ‐hybridization (FISH). Thereby, CIN was measured in 65 patients with myelodysplastic syndromes (MDS), acute myeloid leukaemia (AML) and control subjects. Among MDS patients, a subgroup with elevated levels of CIN was identified. At a median follow‐up of 17.2 months, all patients within this ‘high CIN’ subgroup had died or progressed to AML, while 80% of MDS patients with normal CIN levels had stable disease (P < 0.001). Notably, there was no statistically significant difference between ‘normal CIN’ and ‘high CIN’ MDS patients regarding established risk factors. Hence, elevated CIN levels were associated with poor outcome, and our method provided additional prognostic information beyond conventional cytogenetics. Furthermore, in all three MDS patients for whom serial measurements were available, development of AML was preceded by increasing CIN levels. In conclusion, elevated CIN levels may be valuable as an early indicator of poor prognosis in MDS, hence corroborating the concept of CIN as a driving force in tumour progression.
Histopathology of a granulomatous lobular panniculitis in acute Q fever: a case report
Authors: Soulard R , Souraud JB , Landais C , Le Hemon A , Gaillard T , Fouet B
Published: September 2009

Q fever is a zoonotic infection caused by Coxiella burnetii. Two forms of the disease have been described: an acute form with pneumonia, hepatitis or a flu‐like syndrome; and a chronic form in which endocarditis is the most frequent clinical expression. We report a 77 year old male with fever and an erythematous nodule on the right leg. Biopsy revealed a granulomatous lobular panniculitis with some granulomas rimmed by an eosinophilic material, giving a “doughnut” or “fibrin‐ring” appearance. Q fever serological studies were positive. Cutaneous signs, among them panniculitis, are probably underestimated during the acute phase of the disease, and recognizing different granulomatous patterns may contribute to the diagnosis.

Soulard R. Histopathology of a granulomatous lobular panniculitis in acute Q fever: a case report.
Long‐term cognitive enrichment affects opioid receptor expression in the amygdala of domestic pigs
Authors: Kalbe C. , Puppe B.
Published: September 2009

Enriching the housing environment by stimuli that challenge both reward and cognitive mechanisms may enhance behavioural experiences and can improve animal welfare, particularly in farm animals. A newly developed experimental feeding system for domestic pigs using food‐rewarded learning of discriminatory and instrumental tasks enabled the animals to successfully master a cognitive challenge and to be rewarded ca. 30 times per day with small food portions. Reward‐related behaviour is expected to be modulated by endogenous opioid systems. Furthermore, recent evidence supports a role for the amygdala in processing positive affects by stimulus‐reward learning. Hence, the present study investigates mRNA expression of cerebral receptors, which are involved in these processes. In an initial step, reverse transcription–polymerase chain reaction (RT‐PCR) provided the first evidence that transcripts of three different opioid receptors (MOR,DOR,KOR), as well as the neuropeptide Y 5 receptor (NPY5R), leptin receptor (LEPR) and proopiomelanocortin (POMC), are expressed in both the porcine amygdala and hypothalamus. Using real‐time PCR we could show that the expression of two receptors of the opioid system (amygdala:KOR,DOR), in addition to the expression ofNPY5R(hypothalamus) in eight enriched housed pigs was markedly downregulated compared to that of conventionally housed and fed pigs. Focusing on opioid receptors in the amygdala, the present study shows that long‐term cognitive enrichment acts as a biologically relevant stimulus that causes modifications of gene expression of reward‐sensitive cerebral receptors in domestic pigs.
Research in practice: the second barrier of the human skin
Authors: Baron Jens Malte , Skazik Claudia
Published: September 2009

A major function of human skin is to form an effective barrier between the environment and the inside of the organism. Especially important for this function is the activity of the physical barrier of the skin, which is mainly located in the stratum corneum. To improve this barrier function of the skin, skin protection agents are used. Recent studies have revealed that application of skin protection agents before exposition to xenobiotics does not generally reduce the percutaneous uptake of these compounds. These findings indicate that besides new study designs and improved test systems, there seems to be a need for new therapeutic approaches for more effective skin protection. In this light, new findings regarding a second barrier function of the human skin, the biochemical/toxicological barrier, could be of interest. A crucial part of this barrier function are members of the cytochrome P450 (CYP) family and efflux‐transport proteins of the multidrug resistance‐related protein family (MRPs), which are mainly expressed by basal layer keratinocytes. Recent studies have revealed that besides the physiological and protective function of these transport proteins and CYP enzymes in skin cells, the same proteins also play a role in the transport of contact allergens and activation of prohaptens to haptens causing contact dermatitis. Inhibition of this metabolism mediated activation of prohaptens and stimulation of the active elimination of contact allergens from skin cells could represent novel mechanisms improving the established tools for skin protection.
ORIGINAL RESEARCH—INTERSEX AND GENDER IDENTITY DISORDERS: Neuroimaging Differences in Spatial Cognition between Men and Male-to-Female Transsexuals Before and During Hormone Therapy
Authors: Schöning Sonja , Engelien Almut , Bauer Christine , Kugel Harald , Kersting Anette , Roestel Cornelia , Zwitserlood Pienie , Pyka Martin , Dannlowski Udo , Lehmann Wolfgang , Heindel Walter , Arolt Volker , Konrad Carsten
Published: September 2009

Introduction

Neuropsychological abnormalities in transsexual patients have been reported in comparison with subjects without gender identity disorder (GID), suggesting differences in underlying neurobiological processes. However, these results have not consistently been confirmed. Furthermore, studies on cognitive effects of cross-sex hormone therapy also yield heterogeneous results.

Aim

We hypothesized that untreated transsexual patients differ from men without GID in activation pattern associated with a mental rotation task and that these differences may further increase after commencing of hormonal treatment.

Method

The present study investigated 11 male-to-female transsexual (MFTS) patients prior to cross-sex hormone therapy and 11 MFTS patients during hormone therapy in comparison with healthy men without GID. Using functional magnetic resonance imaging at 3-Tesla, a mental rotation paradigm with proven sexual dimorphism was applied to all subjects. Data were analyzed with SPM5.

Main Outcome Measures

Patterns of brain activation associated with a mental rotation task.

Results

The classical mental rotation network was activated in all three groups, but significant differences within this network were observed. Men without GID exhibited significantly greater activation of the left parietal cortex (BA 40), a key region for mental rotation processes. Both transsexual groups revealed stronger activation of temporo-occipital regions in comparison with men without GID.

Conclusions

Our results confirmed previously reported deviances of brain activation patterns in transsexual men from men without GID and also corroborated these findings in a group of transsexual patients receiving cross-sex hormone therapy. The present study indicates that there are a priori differences between men and transsexual patients caused by different neurobiological processes or task-solving strategies and that these differences remain stable over the course of hormonal treatment.
Immunity against Cyclin B1 Tumor Antigen Delays Development of Spontaneous Cyclin B1‐Positive Tumors in p53−/− Mice
Authors: Vella Laura A. , Yu Min , Phillips Amy B. , Finn Olivera J.
Published: September 2009

We previously identified cyclin B1‐specific T cells and antibodies in cancer patients with cyclin B1‐positive (+) tumors and also in some healthy individuals. We also demonstrated that these responses may be important in cancer immunosurveillance by showing that vaccination against cyclin B1 prevents growth of transplantable cyclin B1+ tumors in mice. Constitutive overexpression of cyclin B1 was determined to correlate with the lack of p53 function. This allowed us to use p53−/− mice as a model that better approximates human disease. These p53−/− mice spontaneously develop cyclin B1+ tumors. At 5–6 weeks of age, when the mice were still healthy with no evidence of tumor, they received the cyclin B1 vaccine and were then observed for tumor growth. We demonstrate that cyclin B1 vaccination delays spontaneous cyclin B1+ tumor growth and increases median survival of tumor‐bearing p53−/− mice.
Antibodies Determine Virulence in Dengue
Authors: Halstead Scott B.
Published: September 2009

Four dengue viruses (DENV) cause syndromes that are self‐limited or severe. The severe syndrome, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), characterized by sudden vascular permeability, is not caused by inherently virulent DENV. This syndrome has consistently been observed to accompany dengue infections in individuals circulating heterotypic dengue antibodies at enhancing concentrations. In humans, dengue infections target monocytes/macrophages where, absent neutralization, heterotypic antibodies, perhaps directed at domain I‐II of the envelope protein form immune complexes, attach to Fc receptors, suppress innate immunity, and increase productive infection. Diverse clinical responses to primary infections with different DENV strains do occur and occasionally result in subclinical vascular permeability observed as hypovolemia. The fact that American (AM) genotype DENV 2 produce only mild disease during secondary dengue infections is best explained by the downregulation of disease by DENV 1 antibodies directed at a unique antigenic structure expressed on AM DENV 2.
T Lymphocyte Responses to Heterologous Secondary Dengue Virus Infections
Authors: Rothman Alan L.
Published: September 2009

The available evidence suggests that plasma leakage in dengue hemorrhagic fever is caused by the action of circulating mediators on the vascular endothelium, and that the host immune response is a critical determinant of this response. We have been exploring the role of dengue virus–specific T lymphocytes in the immunopathogenesis of plasma leakage. Memory dengue virus–specific T cells induced during a primary dengue virus infection are reactivated by the heterologous viral serotype during a secondary infection to expand to high levels and produce a skewed cytokine profile. Investigations are underway to identify the immunologic profiles associated with increased or decreased risk for severe disease.
Some Scientific and Organizational Challenges in Cancer Immunology
Authors: Steinman Ralph M.
Published: September 2009

This volume provides a small sampling of the rapidly growing science of cancer immunology. Growth in the field includes advances on the requirements for immunization or vaccination and the ways in which immunity can be suppressed or blocked, including active tumor‐based mechanisms. I would like to introduce the papers in this volume and then deal with a subject that pervaded many discussions among symposium participants. The subject is the need for a much better supported and organized effort to design optimal studies of immunology in cancer patients so that cancer vaccines can become a major means to prevent and treat this disease.
Analysis of controlled mixed-phase (amorphous+microcrystalline) silicon thin films by real time spectroscopic ellipsometry
Authors: Podraza N. J. , Li Jing , Wronski C. R. , Dickey E. C. , Collins R. W.
Published: September 2009

Engineered thin films consisting of periodic arrays of silicon microcrystallites in a hydrogenated amorphous silicon host matrix have been prepared by plasma-enhanced chemical vapor deposition where the hydrogen dilution of silane is modulated in multiple cycles. These types of films have been guided by a phase evolution diagram, depicting the deposition conditions and film thickness at which the material exhibits amorphous, microcrystalline, or mixed-phase (amorphous+microcrystalline) characteristics, developed for intrinsic Si:H prepared with varying H2 dilution on unhydrogenated a-Si:H. Real time spectroscopic ellipsometry (RTSE) has been used in situ to noninvasively determine the phase evolution of the resulting hydrogenated mixed-phase (amorphous+microcrystalline) silicon thin films and corroborated with dark-field transmission electron microscopy. Such tailored microstructures are of growing interest as components of thin film photovoltaic devices, and RTSE is shown to be a key technique for structure verification.
Platinum-group minerals in the middle group of chromitite layers at Marikana, western Bushveld Complex: indications for collection mechanisms and postmagmatic modification
Authors: Merkle Roland K. W.
Published: September 2009

The platinum-group minerals in a drill core taken through the middle group of chromitite layers in the Critical Zone at Marikana in the western Bushveld Complex were found to consist mainly of laurite as inclusions in chromite grains. The platinum-group minerals containing Pt, Pd, and Rh are concentrated in the intercumulus silicates and frequently associated with base-metal sulphides. Up to about 20% of all platinum-group minerals in the investigated chromitite layers contain sub stantial amounts of As. The base-metal sulphides are strongly modified in the postmagmatic stage, which led to a significant loss of Fe and S, in this way concentrating Cu, Ni, and the platinum-group elements by factors of up to 10. Interaction between chromite and base-metal sulphides cannot account for all the Fe lost in chromite-poor samples, and the importance of additional processes is indicated. Inclusions in chromite and orthopyroxene indicate the formation of discrete platinum-group minerals and As-rich phases before the formation of an immiscible sulphide melt. Resorption of earlier formed platinum-group minerals into the immiscible sulphide melt and postmagmatic sulphidation destroyed most of the evidence of the early formed platinum-group minerals.
The frequency of ice-wedge cracking (1967–1987) at Garry Island, western Arctic coast, Canada
Authors: Mackay J. Ross
Published: September 2009

The frequency of ice-wedge cracking has been studied at Garry Island, Northwest Territories, for the 1967–1987 period. Sites have included low-centre polygons, intermediate-centre polygons, and polygons that do not fit any classification system. Analyses of crack frequency have included trough characteristics, polygon characteristics, and ice-wedge types. The results show that crack frequencies are highly variable within one site and also between two adjacent sites. The correlation between crack frequency and a low air temperature is poor. Crack frequencies for a site with 59 wedges ranged from 8 to 42% between 1967 and 1979 and for a nearby site with 32 wedges from 22 to 75% between 1967 and 1987. In view of the wide range in crack frequencies at a given site, the use of mean ice-wedge growth rates for estimating ages of ice wedges and their casts in environmental reconstruction may be hazardous. The data show that the common twofold classification into active and inactive wedges is difficult to apply because crack frequencies are gradational and dependent on such factors as the number of ice wedges being monitored, the size of the area, the types of ice wedges, and the length of the observation period. A system for classifying crack frequency is proposed.
U–Pb and 40Ar/39Ar mineral ages from Cape North, northern Cape Breton Island: implications for accretion of the Avalon Composite Terrane
Authors: Keppie J. D. , Dallmeyer R. D. , Krogh T. E.
Published: September 2009

Isotopic studies have been used to determine protolith and tectonothermal ages in rocks of the Cape North and Money Point groups and two plutons, that form part of the Avalon Composite Terrane. Colourless, euhedral zircon crystals from low-grade metarhyolite in the Money Point Group record a concordant U–Pb age of 427.5 ± 4 Ma, which is interpreted to date the time of extrusion. This provides a maximum age of middle Silurian for polyphase deformation and concomitant greenschist–amphibolite-facies metamorphism that affected the Cape North area in the eastern half of a major, sinistral, positive flower structure. Monazite from the Cape North granite, intruded during peak metamorphic conditions, yielded nearly concordant data with a 207Pb/235U age of 414 ± 3 Ma. This dates the time of crystallization of the Cape North granite. Metamorphic hornblende from the Cape North and Money Point groups records variably discordant 40Ar/39Ar age spectra that define plateau and (or) isotope correlation ages of ca. 380–390 Ma. Muscovite from these units displays generally concordant spectra that define plateau ages ranging between ca. 365 and 375 Ma. Muscovites from the syntectonic Cape North granite and the posttectonic Relay Station granite record plateau ages of ca. 380–382 Ma. The 40Ar/39Ar ages suggest that relatively rapid postmetamorphic cooling occurred during the Devonian. These isotopic results and petrological data indicate that burial of the Cape North units to ca. 18 km, metamorphism, uplift, and erosion occurred in ca. 60 Ma. Such rates are comparable with those recorded in modern transpressive tectonic regimes. The calc-alkaline nature of the Money Point volcanic rocks suggests derivation above a subduction zone. A correlative Silurian–Devonian tectonothermal event recorded in southern Newfoundland probably records the accretion of the Avalon Composite Terrane with the Dunnage Zone.
Rescaled range analysis of paleoclimatic proxies
Authors: Wang Y. , Evans M. E. , Xu T. C. , Rutter N. , Ding Z. , Liu X. M.
Published: September 2009

Two geophysical measurements have been widely used as paleoclimatic indicators: oxygen-isotope ratios from deep-sea cores and magnetic susceptibility of loess sediments. Both types of record have been shown to possess climatic information, as they share the same dominant frequencies of the Earth's orbital movements, which, according to Milankovitch's theory, drive the climatic system. But these two physical quantities may respond to climatic variations in different ways. Consequently, they may possess different long-term characteristics, which can be detected by the technique of rescaled range (R/S) analysis. Here we report results from four sets of data: two oxygen-isotope records and two loess susceptibility profiles. Analysis indicates that Hurst exponents of about 0.8 are typical for deep-sea oxygen data, whereas values of about 0.9 characterize loess susceptibility sequences. If Mandelbrot's explanation is taken, these distinct values imply that the loess data are more self-correlated and possess stronger persistence compared with the deep-sea records. This may reflect differences in the ways in which these proxy recorders respond to climatic variations, or differences between continental and oceanic climates.
Synthèse géologique et géophysique de la région de Chapais : portion orientale de la ceinture de l'Abitibi québécoise
Authors: Dion Denis-Jacques , Morin Rémy , Keating Pierre
Published: September 2009

The Chapais region has been extensively studied during the last 40 years. Recent work in this area has provided information that can be used to assess the various models proposed for similar volcano-sedimentary belts. By using the known surface geology and measured rock densities, gravity interpretation can define the structure of the geological formations. Aeromagnetic data have been used to improve surface mapping in areas of few or no outcrop. We conclude that the Chibougamau syncline has a depth extension of about 4 km. The depth extension of the granitic intrusives cannot be accurately determined because of our lack of knowledge of their density variation with depth. Any geological model must satisfy potential field data constraints, especially those given by gravity data. In the present case, we have shown that only those models indicating a limited thickness of volcano-sedimentary rocks are acceptable.
Note on the occurrence of the marine turtle Desmatochelys (Reptilia: Chelonioidea) from the Upper Cretaceous of Vancouver Island
Authors: Nicholls Elizabeth L.
Published: September 2009

An incomplete specimen of Desmatochelys cf. D. lowi (Reptilia: Chelonioidea) from the Trent River Formation (Santonian–Campanian) of the Comox Basin of eastern Vancouver Island is the first documented account of Cretaceous marine vertebrates from the Pacific coast of Canada. It represents both stratigraphic and geographic range extensions for the genus Desmatochelys.
THE TRANSITION RATE OF THE GROUND STATE OF POLARON IN A PARABOLIC QUANTUM DOT
Authors: LI WEI-PING , YIN JI-WEN , YU YI-FU , XIAO JING-LIN , WANG ZI-WU
Published: September 2009

The ground-state energy of polaron was obtained with strong electron-LO-phonon coupling by using a variational method of the Pekar type in a parabolic quantum dot (QD). Quantum transition occurred in the quantum system due to the electron–phonon interaction and the influence of temperature. That is, the polaron transits from the ground state to the first excited state after absorbing a LO-phonon. Numerical calculations are performed and the results illustrate the relations of the transition rate of the polaron on the ground-state energy of polaron, the cyclotron frequency parameter, the Coulomb binding parameter, the temperature, the electron-LO-phonon coupling strength and the confinement length of the quantum dot.
SYNCHRONIZATION OF IMPURITIES INFUSION FOR PRODUCTION OF A SEQUENCE OF DIFFUSED-JUNCTION RECTIFIERS
Authors: PANKRATOV E. L.
Published: September 2009

An approach to increase both the sharpness of a series of diffused-junction rectifiers and to increase the homogeneity of dopant distribution in dopant-enriched areas has been considered. The conditions to obtain both the effects are determined. Annealing time has been optimized for increasing simultaneously the sharpness and the homogeneity. The dependence of the optimal annealing time on several parameters of the model have been analyzed.
Pipeline FFT Architectures Optimized for FPGAs
Authors: Zhou Bin , Peng Yingning , Hwang David
Published: September 2009

This paper presents optimized implementations of two different pipeline FFT processors on Xilinx Spartan‐3 and Virtex‐4 FPGAs. Different optimization techniques and rounding schemes were explored. The implementation results achieved better performance with lower resource usage than prior art. The 16‐bit 1024‐point FFT with the R22SDF architecture had a maximum clock frequency of 95.2 MHz and used 2802 slices on the Spartan‐3, a throughput per area ratio of 0.034 Msamples/s/slice. The R4SDC architecture ran at 123.8 MHz and used 4409 slices on the Spartan‐3, a throughput per area ratio of 0.028 Msamples/s/slice. On Virtex‐4, the 16‐bit 1024‐point R22SDF architecture ran at 235.6 MHz and used 2256 slice, giving a 0.104 Msamples/s/slice ratio; the 16‐bit 1024‐point R4SDC architecture ran at 219.2 MHz and used 3064 slices, giving a 0.072 Msamples/s/slice ratio. The R22SDF was more efficient than the R4SDC in terms of throughput per area due to a simpler controller and an easier balanced rounding scheme. This paper also shows that balanced stage rounding is an appropriate rounding scheme for pipeline FFT processors.
Remote System for Detection of Low‐Levels of Methane Based on Photonic Crystal Fibres and Wavelength Modulation Spectroscopy
Authors: Carvalho J. P. , Lehmann H. , Bartelt H. , Magalhães F. , Amezcua-Correa R. , Santos J. L. , Roosbroeck J. Van , Araújo F. M. , Ferreira L. A. , Knight J. C.
Published: September 2009

In this work we described an optical fibre sensing system for detecting low levels of methane. The properties of hollow‐core photonic crystal fibres are explored to have a sensing head with favourable characteristics for gas sensing, particularly in what concerns intrinsic readout sensitivity and gas diffusion time in the sensing structure. The sensor interrogation was performed applying the Wavelength Modulation Spectroscopy technique, and a portable measurement unit was developed with performance suitable for remote detection of low levels of methane. This portable system has the capacity to simultaneously interrogate four remote photonic crystal fibre sensing heads.
Smooth Crossing of wΛ = −1 Line in a Single Scalar Field Model
Authors: Sanyal Abhik Kumar
Published: September 2009

Smooth double crossing of the phantom divide line wΛ = −1 has been found possible with a single minimally
coupled scalar field for the most simple form of generalized k‐essence cosmological model, in the presence of
background cold dark matter. Such crossing is a sufficiently late time transient phenomenon and does not have
any pathological behaviour.
Peroxisome Proliferator‐Activated Receptor and Retinoic X Receptor in Alcoholic Liver Disease
Authors: Mello Tommaso , Polvani Simone , Galli Andrea
Published: September 2009

A growing number of new studies demonstrate that nuclear receptors are involved in the development of alcoholic liver disease (ALD). Ethanol metabolism and RXR/PPAR functions are tightly interconnected in the liver. Several ethanol metabolizing enzymes are potently regulated by RXR and PPARαafter alcohol consumption. The increased ethanol metabolism, in turn, leads to alteration of the redox balance of the cells and impairment of RXR/PPAR functions by direct and indirect effects of acetaldehyde, resulting in deranged lipid metabolism, oxidative stress, and release of proinflammatory cytokines. The use of animal models played a crucial role in understanding the molecular mechanisms of ALD. In this paper we summarize the reciprocal interactions between ethanol metabolism and RXR/PPAR functions. In conclusion, RXR and PPAR play a central role in the onset and perpetuation of the mechanisms underling all steps of the clinical progression in ALD.
Catheter Ablation of Atrial Fibrillation Without Fluoroscopy Using Intracardiac Echocardiography and Electroanatomic Mapping
Authors: Ferguson John D. , Helms Adam , Mangrum J. Michael , Mahapatra Srijoy , Mason Pamela , Bilchick Ken , McDaniel George , Wiggins David , DiMarco John P.
Published: September 2009

Background—

Catheter ablation of atrial fibrillation is currently guided by x-ray fluoroscopy. The associated radiation risk to patients and medical staff may be significant. We report an atrial fibrillation ablation technique using intracardiac echocardiography (ICE) and electroanatomic mapping without fluoroscopy.

Methods and Results—

Twenty-one patients with atrial fibrillation (age, 42 to 73 years; 14 male; 14 paroxysmal, 7 persistent; body mass index, 26 to 38) underwent ablation. A decapolar catheter was advanced through the left subclavian vein until stable coronary sinus electrograms appeared on all electrodes. Two 9F sheaths were advanced transfemorally over a guide wire to the right atrium. A rotational ICE catheter was advanced through a deflectable sheath. Double transseptal puncture was performed with ICE guidance and facilitated by electrocautery. A 3D MRI left atrial image was registered to the ostia of the pulmonary veins using ICE. Catheter ablation was performed using ICE and electroanatomic mapping navigation. In 19 cases, no fluoroscopy was used and the staff did not wear protective lead. In 2 cases, 2 to 16 minutes of fluoroscopy was used to assist transseptal puncture. Median procedure time was 208 (188 to 221) minutes; coronary sinus cannulation took 5 (2 to 26) minutes; double transseptal took 26 (17 to 40) minutes; left atrial ablation time was 103 (90 to 127) minutes. All patients underwent circumferential pulmonary vein ablation and 8 patients underwent additional left atrial ablation. There were no procedure-related complications.

Conclusions—

Catheter ablation of atrial fibrillation without fluoroscopy is feasible and merits further attention. This technique may be especially helpful in preventing x-ray exposure in children, pregnant women, and obese patients undergoing left atrial ablation.
Survival in Patients With Severe Aortic Regurgitation and Severe Left Ventricular Dysfunction Is Improved by Aortic Valve Replacement
Authors: Kamath Ashvin R. , Varadarajan Padmini , Turk Rami , Sampat Unnati , Patel Reena , Khandhar Sumit , Pai Ramdas G.
Published: September 2009

Background—

Aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR) and left ventricular (LV) dysfunction entails a higher surgical risk. Though it may improve symptoms and LV size, it is not known whether it translates into a survival benefit.

Methods and Results—

This retrospective cohort study included patients screened from our echocardiographic database between 1993 and 2007 for patients with severe AR and LV ejection fraction (EF) ≤35%. Charts reviews were conducted for clinical, pharmacological, and surgical information. Mortality data were obtained from the social security death index and analyzed as a function of AVR adjusted for the propensity score. Of the 785 patients with severe AR, 166 patients had severe LV dysfunction defined as an EF ≤35%: 69% of these were men, age 65±16 years, and LV EF was 23±8%. Kaplan–Meier analysis revealed that performance of AVR (n=53) was associated with a better survival (
P
=0.001). Adjusted for the propensity score, AVR was associated with a significantly lower mortality hazard (HR 0.59, CI 0.42 to 0.98,
P
=0.04).

Conclusions—

There is a clear reluctance to offer AVR in a large number of patients with severe AR associated with LV dysfunction. However, the performance of AVR in these patients is associated with a mortality benefit supporting the current ACC/AHA guidelines.
Minimally Invasive Coronary Artery Bypass Grafting
Authors: McGinn Joseph T. , Usman Saif , Lapierre Harry , Pothula Vijayasimha R. , Mesana Thierry G. , Ruel Marc
Published: September 2009

Background—

Minimally invasive coronary artery bypass grafting (MICS CABG) is a novel coronary operation that does not require infrastructure and is potentially available to all cardiac surgeons. It aims at decreasing the invasiveness of conventional CABG while preserving the applicability and durability of surgical revascularization. We examined the feasibility and safety of MICS CABG in the first large series of this operation to date.

Methods and Results—

All myocardial territories are accessed via a 4- to 6-cm left fifth intercostal thoracotomy. An apical positioner and epicardial stabilizer are introduced into the chest through the subxyphoid and left seventh intercostal spaces, respectively. The left internal thoracic artery is used to graft the left anterior descending artery, and radial artery or saphenous vein segments are used to graft the lateral and inferior myocardial territories. Proximal anastomoses are performed directly onto the aorta or from the left internal thoracic artery as a T-graft. In the first 450 consecutive MICS CABG procedures at our 2 centers, mean±SD age was 62.3±10.7 years and 123 patients were female (27%). The average number of grafts was 2.1±0.7, with complete revascularization in 95% of patients. There were 34 patients in whom cardiopulmonary bypass was used (7.6%), 17 conversions to sternotomy (3.8%), and 10 reinterventions for bleeding (2.2%). Perioperative mortality occurred in 6 patients (1.3%).

Conclusions—

MICS CABG is feasible and has excellent procedural and short-term outcomes. This operation could potentially make multivessel minimally invasive coronary surgery safe, effective, and more widely available.
Prophylactic Intravenous Magnesium Sulphate in Addition to Oral β-Blockade Does Not Prevent Atrial Arrhythmias After Coronary Artery or Valvular Heart Surgery
Authors: Cook Richard C. , Humphries Karin H. , Gin Kenneth , Janusz Michael T. , Slavik Richard S. , Bernstein Victoria , Tholin Mats , Lee May K.
Published: September 2009

Background—

Atrial arrhythmias (AA) are an important cause of morbidity after cardiac surgery. Efforts at prevention of postoperative AA have been suboptimal. Perioperative beta-blocker administration is the standard of care at many centers. Although prophylactic administration of magnesium sulfate (MgSO
4
) has been recommended, review of all previously published trials of MgSO
4
reveals conflicting results. This study was designed to address methodological shortcomings from previous studies and is the largest randomized, placebo-controlled trial of intravenous (IV) MgSO
4
for the prevention of AA after coronary artery bypass grafting or cardiac valvular surgery.

Methods and Results—

A total of 927 nonemergent cardiac surgery patients were stratified into 2 groups: isolated coronary artery bypass grafting (n=694), or valve surgery with or without coronary artery bypass grafting (n=233), and randomized to receive either 5g IV MgSO
4
or placebo on removal of the cross-clamp, followed by daily 4-hour infusions, from postoperative day 1 until postoperative day 4. All patients were treated according to an established oral β-blocker protocol. Postoperative serum Mg levels were checked and standard of care was to administer IV MgSO
4
for low serum levels. The primary end point was AA lasting ≥30 minutes or requiring treatment for hemodynamic compromise. There were no differences in the incidence of AA between patients who received IV MgSO
4
or placebo (26.4% versus 24.3%, respectively). The results were similar when broken down according to stratified groups.

Conclusions—

In patients treated with a protocol for postoperative oral β-blocker after nonemergent cardiac surgery, the addition of prophylactic IV MgSO
4
did not reduce the incidence of AA.
Effects of Preoperative Aortic Insufficiency on Outcome After Aortic Valve–Sparing Surgery
Authors: de Kerchove Laurent , Boodhwani Munir , Glineur David , Poncelet Alain , Verhelst Robert , Astarci Parla , Lacroix Valérie , Rubay Jean , Vandyck Michel , Vanoverschelde Jean-Louis , Noirhomme Philippe , El Khoury Gebrine
Published: September 2009

Background—

The presence of significant preoperative aortic insufficiency (AI) or the need for cusp repair has been suggested as a risk factor for poorer outcomes after aortic valve (AV)–sparing surgery. We analyzed the influence of these factors on the mid-term outcomes of AV surgery.

Methods and Results—

Between 1996 and 2008, 164 consecutive patients underwent elective AV-sparing surgery. Severe preoperative AI (grade ≥3+) was present in 93 patients (57%), and 54 (33%) had a bicuspid valve. Root repair was performed with either the reimplantation (74%) or the remodeling (26%) technique, and cusp repair was performed in 90 patients (55%). Mean clinical follow-up was 57 months. Hospital mortality was 0.6%. Cusp repair was required in 52% of the patients with preoperative AI ≤2+ and in 57% of those with AI ≥3+ (
P
=0.6). Cusp repair was required more frequently in bicuspid versus tricuspid valves (91% versus 38%,
P
<0.001). Overall survival at 8 years was 88±8%. Freedom from AV reoperation at 8 years was similar with preoperative AI ≤2+ versus preoperative AI ≥3+ (89±11% versus 90±7%,
P
=0.7) and with versus without cusp repair (84±17% versus 92±8%,
P
=0.5). Freedom from recurrent AI (grade ≥3+) at 5 years was also similar between groups (90±10% versus 89±8%,
P
=0.9, and 90±8% versus 89±9%,
P
=0.8, respectively). By multivariate analyses, predictors of recurrent AI ≥2+ were preoperative left ventricle end-diastolic diameter and AI >1+ on discharge echocardiography.

Conclusions—

With a systematic approach to cusp assessment and repair, AV-sparing surgery for root pathology has an acceptable mid-term outcome, irrespective of preoperative AI or need for cusp repair.