bluuebunny/crossref_metadata_2025 huggingface dataset:
DIRECT AND LOCAL DEFINITIONS OF THE TURING JUMP
Authors: SHORE RICHARD A.
Published: May 2008

We show that there are Π5 formulas in the language of the Turing degrees, [Formula: see text], with ≤, ∨ and ∧, that define the relations x″ ≤ y″, x″ = y″ and so {x ∈ L2(y) = x ≥ y|x″ = y″} in any jump ideal containing 0(ω). There are also Σ6&Π6 and Π8 formulas that define the relations w = x″ and w = x', respectively, in any such ideal [Formula: see text]. In the language with just ≤ the quantifier complexity of each of these definitions increases by one. For a lower bound on definability, we show that no Π2 or Σ2 formula in the language with just ≤ defines L2 or L2(y). Our arguments and constructions are purely degree theoretic without any appeals to absoluteness considerations, set theoretic methods or coding of models of arithmetic. As a corollary, we see that every automorphism of [Formula: see text] is fixed on every degree above 0″ and every relation on [Formula: see text] which is invariant under the double jump or under join with 0″ is definable over [Formula: see text] if and only if it is definable in second order arithmetic with set quantification ranging over sets whose degrees are in [Formula: see text].
Terrain evaluation for Allied military operations in Europe and the Far East during World War II: ‘secret’ British reports and specialist maps generated by the Geological Section, Inter-Service Topographical Department
Authors: Rose E.P.F. , Clatworthy J.C.
Published: May 2008

Between November 1943 and June 1946, at least 16 geologists assisted the Inter-Service Topographical Department (ISTD), a British military unit primarily of geographers, under Royal Navy auspices, to prepare reports and geotechnical maps to guide planning of Allied military operations. Reports assessing terrain factors were generated with geologist assistance for parts of Italy, France, Germany, Austria, the Low Countries and the Balkan region; also for Malaya, parts of Indonesia, Thailand, Indo-China, Formosa, Hainan, Hong Kong and the nearby Chinese mainland. The Geological Section ISTD, as it was officially designated from August 1944, based at Oxford, had an authorized establishment of four Royal Engineers officers (briefly assisted by a few US, Canadian and Dutch military personnel), but simultaneously involved up to 12 earth scientists or engineers by August 1945; it was the only team of British military geologists to be constituted (except in India) in either World War. Its work marks a significant if largely unknown phase in the development of engineering and hydrogeological terrain evaluation skills prior to the evolution of terrain analysis as a major discipline postwar, revealed by declassified reports now preserved in the UK within the National Archives and the Royal Geographical Society's library; maps at the British and the Bodleian libraries; and documents in the University of Birmingham's Lapworth Museum of Geology.
Fred Shotton: a ‘hero’ of military applications of geology during World War II
Authors: Rose E.P.F. , Clatworthy J.C.
Published: May 2008

F. W. Shotton, FRS, Professor of Geology at the University of Sheffield 1945–1949, and at Birmingham 1949–1974, is best known for his research on Pleistocene geology of the English Midlands. However, during the Second World War he became a distinguished military geologist. From May 1941 to September 1943, based in Egypt, he used hydrogeology to guide development of potable water supplies for British forces operational in the Middle East and northern Africa. Recalled to the UK after campaign victory, from October 1943 he helped plan for the Allied liberation of Normandy by providing terrain evaluation (primarily through preparation of specialist maps and contribution of technical advice) relating to beach conditions, suitability of ground for the rapid construction of temporary airfields, and water supply. Following D-Day, 6 June 1944, he was based in northern France and later Belgium, and was involved with further water supply tasks, discussions on quarrying of aggregate, and assessment of soil conditions likely to influence off-road vehicle mobility or the siting of airfields and military depots, thus contributing to Allied victory in Europe in May 1945. Preparing to go into Germany, he was granted early demobilization to resume his academic career. Wartime achievements generated few of his hundred significant publications, but postwar influenced his inspirational teaching and academic leadership.
William Smith and the development of engineering geology in England
Authors: Forster A. , Reeves H.J.
Published: May 2008

William Smith started his career in a world where much was known of geological matters and, with the publication of Hutton's
Theory of the Earth
, knowledge was being tempered by understanding. His early training as a surveyor gave him the skills of accurate observation and recording together with a geographically wide experience that enabled him to recognize that strata could be ordered, and outcrops correlated, by the fossils that they contained. He first recorded this new concept in 1797 and used it to create the world's first geological map (of the area around Bath) in 1799 and the first geological map of England and Wales in 1815. The national map was not only geologically detailed and accurate but also showed collieries, mines, canals and reclaimed land. Smith's intention was for it to show where to look for (and not look for) minerals. Thus, his recognition of ordered correlatable strata, his creation of the first geological map, his expertise in draining land, stabilizing landslides and planning canal routes amply demonstrates his ability to create, and apply, the 3D geological model that is a prime requisite in modern engineering geological practice. Therefore, he should be regarded as the first engineering geologist of the modern world. This paper will demonstrate the validity of this assertion.
Transcriptional activation by growth hormone of HNF-6-regulated hepatic genes, a potential mechanism for improved liver repair during biliary injury in mice
Authors: Wang Minhua , Chen Michael , Zheng Guoqiang , Dillard Barney , Tallarico Mike , Ortiz Zorayda , Holterman Ai-Xuan
Published: May 2008

Growth hormone (GH) function is mediated through multiple endocrine pathways. In the liver, GH also transcriptionally activates hepatocyte nuclear factor-6 (HNF-6; OC-1), a liver-enriched transcription factor that regulates the expression of genes essential to hepatic function. We hypothesize that GH modulates hepatic function in the normal and injured liver through HNF-6 and HNF-6 target genes. CD1 mice received PBS or GH for the 1-, 7-, and 28-day course of Sham operation or bile duct ligation (BDL). Proliferation-, metabolic-, and profibrotic-specific hepatic functions were assessed with a focus on candidate HNF-6 transcriptional target genes. Confirmation of HNF-6 regulation was done by analysis of target gene expression in liver infected with recombinant adenovirus AdHNF-6 expression vectors. GH administration upregulated HNF-6 expression throughout the course of liver injury. This was associated with increased expression of HNF-6 proliferative target genes cyclin D1 and metabolic gene Cyp7A1 and downregulation of profibrogenic TGFb2R. Hepatic function improved such as enhanced hepatocyte proliferation, higher cholesterol clearance throughout the course of injury, and attenuated fibrogenic response at day 28 of BDL. GH treatment also transcriptionally increased albumin expression in an HNF-6-independent manner. This was associated with enhanced serum albumin levels. In conclusion, the GH/HNF-6 axis is a potential in vivo mechanism underlying GH diverse function in the liver to modulate the liver repair response to BDL.
Alternans of cardiac calcium cycling in a cluster of ryanodine receptors: a simulation study
Authors: Tao T. , O'Neill S. C. , Diaz M. E. , Li Y. T. , Eisner D. A. , Zhang H.
Published: May 2008

Mechanical alternans in cardiac muscle is associated with intracellular Ca2+ alternans. Mechanisms underlying intracellular Ca2+ alternans are unclear. In previous experimental studies, we produced alternans of systolic Ca2+ under voltage clamp, either by partially inhibiting the Ca2+ release mechanism, or by applying small depolarizing pulses. In each case, alternans relied on propagating waves of Ca2+ release. The aim of this study is to investigate by computer modeling how alternans of systolic Ca2+ is produced. A mathematical model of a cardiac cell with 75 coupled elements is developed, with each element contains L-type Ca2+ current, a subspace into which Ca release takes place, a cytoplasmic space, sarcoplasmic reticulum (SR) release channels [ryanodine receptor (RyR)], and uptake sites (SERCA). Interelement coupling is via Ca2+ diffusion between neighboring subspaces via cytoplasmic spaces and network SR spaces. Small depolarizing pulses were simulated by step changes of cell membrane potential (20 mV) with random block of L-type channels. Partial inhibition of the release mechanism is mimicked by applying a reduction of RyR open probability in response to full stimulation by L-type channels. In both cases, systolic alternans follow, consistent with our experimental observations, being generated by propagating waves of Ca2+ release and sustained through alternation of SR Ca2+ content. This study provides novel and fundamental insights to understand mechanisms that may underlie intracellular Ca2+ alternans without the need for refractoriness of L-type Ca or RyR channels under rapid pacing.
Serological Diversity Demonstrable by a Set of Monoclonal Antibodies to Eight Serotypes of the Mutans Streptococci
Authors: Ota F. , Ota M. , Mahmud Z.H. , Mohammad A. , Yamato M. , Kassu A. , Kato Y. , Tomotake H. , Batoni G. , Campa M.
Published: May 2008

A set of monoclonal antibodies were prepared by the conventional cell fusion of myeloma cells (SP2/0-Ag14) with spleen cells from BALB/c mice immunised with whole cells of a strain of mutans streptococci. Their specificities were examined against 35 reference strains of mutans streptococci, 34 reference strains of other oral streptococci and 8 reference strains of other microorganisms often inhabiting the oral cavity. Specificity was examined by enzyme immunoassay using whole cells. A total of 52 strains, consisting of 19 strains isolated in Japan, 19 strains isolated in Italy and 14 strains isolated in England, were characterised by conventional physiological and biochemical tests and then serotyped by the use of 8 monoclonal antibodies with different specificities. They were also confirmed by guanine-plus-cytosine contents of their nucleic acid and DNA-DNA hybridisation test. The results indicated that all monoclonal antibodies are useful for identification of 8 serotypes of the mutans streptococci responsible for dental caries. They also suggest the existence of more serological varieties among mutans species.
A Rapid and Quantitative Detection System for Streptococcus mutans in Saliva Using Monoclonal Antibodies
Authors: Matsumoto Y. , Sugihara N. , Koseki M. , Maki Y.
Published: May 2008

A new semiquantitative enumeration system was developed to detect Streptococcus mutans in saliva. Using species-specific monoclonal antibodies, the system quickly detected salivary S. mutans in 30 min and classified the results into three levels. In this study, saliva samples collected from 28 young adults aged between 22 and 24 years were subjected to the monoclonal antibody-based detecting system and selective medium-based detecting methods. The results generated from the PCR-confirmed culture method indicated the mean salivary S. mutans counts at level 1, 2 and 3 were 5.7 × 104, 1.3 × 105 and 3.4 × 106 CFU/ml, respectively. The differences between level 3 and 1 and level 3 and 2 were statistically significant (one-way ANOVA; p < 0.01). The results generated from the system were consistent with the data generated from two culture-based commercial products.
Caries-Preventive Effect of a One-Time Application of Composite Resin and Glass Ionomer Sealants after 5 Years
Authors: Beiruti N. , Frencken J.E. , van’t Hof M.A. , Taifour D. , van Palenstein Helderman W.H.
Published: May 2008

The aim of the present trial was to (1) compare the caries-preventive effect of glass ionomer sealants, placed according to the atraumatic restorative treatment (ART) procedure, with composite resin sealants over time and (2) investigate the caries-preventive effect after complete disappearance of sealant material. Forty-six boys and 57 girls, mean age 7.8 years, were randomly divided into two treatment groups in a parallel-group study design. A light-polymerized composite resin sealant material and a high-viscosity glass ionomer were each placed in 180 fully erupted first molars in their respective treatment groups. Evaluation took place annually for 5 years by calibrated examiners. After 5 years, 86% composite resin and 88% glass ionomer sealants did not survive. Three categories of re-exposure periods for caries development in pits and fissures after complete loss of sealants were distinguished: 0–1, 1–2 and 2–3 years. In the 2- to 3-year group, 13 and 3% of pits and fissures previously sealed with composite resin and glass ionomer, respectively, were diagnosed as having developed a dentine lesion. The relative risks (95% CI) of dentine lesion development in surfaces sealed with glass ionomer compared to those sealed with composite resin after 3, 4 and 5 years were 0.22 (0.06–0.82), 0.32 (0.14–0.73) and 0.28 (0.13–0.61), respectively. The relative risks of dentine lesion development in pits and fissures previously sealed with glass ionomer compared with composite resin over re-exposure periods of 1–2 and 2–3 years were 0.26 (0.14–0.48) and 0.25 (0.09–0.68), respectively. We conclude that the caries-preventive effect of high-viscosity glass ionomer sealants, placed using the ART procedure, was between 3.1 and 4.5 times higher than that of composite resin sealants after 3–5 years. Furthermore, high-viscosity (ART) glass ionomer sealants appear to have a four times higher chance of preventing caries development in re-exposed pits and fissures of occlusal surfaces in first molars than light-cured composite resin sealant material over a 1- to 3-year period. A well-designed clinical trial using different types of oral health personnel should be implemented to confirm these initial results.
The Effects of Illumination and Focal Distance on Light-Induced Fluorescence Images in vitro
Authors: Pretty I.A. , Ellwood P.G. , Davies R.M. , Worthington H.W. , Ellwood R.P.
Published: May 2008

When using quantitative light-induced fluorescence a number of factors can influence illumination level. The purpose of this study was to investigate, using a high-resolution camera and fibre-optic light source, the impact of illumination level and focal distance on common quantitative light-induced fluorescence outcomes. Twenty-four extracted teeth were examined using 6 illumination levels and 4 focal distances. Analysis was conducted using multiple linear regression models fitted to log ΔQ, log ΔF and log area with clustering of teeth and robust standard errors. Separate models were used for the different light and focal levels. The regression coefficients were significant for both ΔQ and ΔF but not area. Despite the significant regressions the actual effect was very small, and unlikely to confound clinical trial or practice results.
Haplotype Association Analysis of AGT Variants with Hypertension-Related Traits: The HyperGEN Study
Authors: Gu C. Charles , Chang Yen-Pei C. , Hunt Steven C. , Schwander Karen , Arnett Donna , Djousse Luc , Heiss Gerardo , Oberman Al , Lalouel Jean-Marc , Province Mike , Chakravarti Aravinda , Rao D.C.
Published: May 2008

Objective: Function of the renin-angiotensin system is important to human hypertension, but its genetic etiology remains elusive. We set out to examine a hypothesis that multiple genetic variants in the system act together in blood pressure regulation, via intermediate phenotypes such as blood pressure reactivity. Methods: A sample of 531 hypertensive cases and 417 controls was selected from the HyperGEN study. Hypertension-related traits including blood pressure responses to challenges to math test, handgrip and postural change (mathBP, gripBP, and postBP), and body mass index (BMI) were analyzed for association with 10 single nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT) gene. Single-marker and haplotype analyses were performed to examine the effects of both individual and multiple variants. Multiple-trait profiling was used to assess interaction of latent intermediate factors with susceptible haplotypes. Results: In Blacks, two SNPs in exon 5 and 3′UTR showed significant association with gripBP, and two promoter SNPs were strongly associated with postBP. In Whites, only borderline association was found for 2 promoter SNPs with mathBP. Haplotype analyses in Blacks confirmed association with gripBP, and detected significant association of a haplotype to BMI (p =0.029). With the interactions modeled, haplotype associations found in Blacks remain significant, while significant associations to BMI (p = 0.009) and gripSBP emerged in Whites. Conclusion: Genetic variants in regulatory regions of AGT showed strong association with blood pressure reactivity. Interaction of promoter and genic SNPs in AGT revealed collective action of multiple variants on blood pressure reactivity and BMI both in Blacks and in Whites, possibly following different pathways.
On the Formula for Admixture Linkage Disequilibrium
Authors: Guo Wei , Fung Wing K. , Shi Ningzhong , Guo Jianhua
Published: May 2008

Admixture linkage disequilibrium (ALD), a phenomenon created by gene flow between genetically distinct populations, has for some time been used as a tool in gene mapping. It is therefore important to analyze the pattern of ALD over generations. In this study we explore two models of admixture: the gradual admixture (GA) model, in which admixture occurs at a variable rate in every generation; and the immediate admixture (IA) model, a special case of the GA model, in which admixture occurs in a single generation. In the case of ALD, the well-known formula of linkage disequilibrium (Δ(t) = (1 – r)t Δ(0)) is not applicable under these two models. We note the effect of a random mating population (RMP) to the gametic frequencies from the parental population to the offspring population, and provide the correct formula for ALD.
Phylogenetic Analysis of General Bacterial Porins: A Phylogenomic Case Study
Authors: Nguyen Thai X. , Alegre Eric R. , Kelley Scott T.
Published: May 2008

Bacterial porin proteins allow for the selective movement of hydrophilic solutes through the outer membrane of Gram-negative bacteria. The purpose of this study was to clarify the evolutionary relationships among the Type 1 general bacterial porins (GBPs), a porin protein subfamily that includes outer membrane proteins ompC and ompF among others. Specifically, we investigated the potential utility of phylogenetic analysis for refining poorly annotated or mis-annotated protein sequences in databases, and for characterizing new functionally distinct groups of porin proteins. Preliminary phylogenetic analysis of sequences obtained from GenBank indicated that many of these sequences were incompletely or even incorrectly annotated. Using a well-curated set of porins classified via comparative genomics, we applied recently developed bayesian phylogenetic methods for protein sequence analysis to determine the relationships among the Type 1 GBPs. Our analysis found that the major GBP classes (ompC, phoE, nmpC and ompN) formed strongly supported monophyletic groups, with the exception of ompF, which split into two distinct clades. The relationships of the GBP groups to one another had less statistical support, except for the relationships of ompC and ompN sequences, which were strongly supported as sister groups. A phylogenetic analysis comparing the relationships of the GenBank GBP sequences to the correctly annotated set of GBPs identified a large number of previously unclassified and mis-annotated GBPs. Given these promising results, we developed a tree-parsing algorithm for automated phylogenetic annotation and tested it with GenBank sequences. Our algorithm was able to automatically classify 30 unidentified and 15 mis-annotated GBPs out of 78 sequences. Altogether, our results support the potential for phylogenomics to increase the accuracy of sequence annotations.
MdfA from Escherichia coli, a Model Protein for Studying Secondary Multidrug Transport
Authors: Sigal Nadejda , Cohen-Karni Devora , Siemion Shira , Bibi Eitan
Published: May 2008

MdfA is a prototypic secondary multidrug transporter from Escherichia coli, which recognizes and exports a broad spectrum of structurally and electrically dissimilar toxic compounds. Here we review recent studies of MdfA, which, on the one hand, provide advanced understanding of certain aspects of secondary multidrug transport, and, on the other, address major mechanistic questions, some of which remain to be elucidated. Using biochemical, genetic, and physiological approaches, we have revealed several surprisingly promiscuous properties of MdfA including its multidrug recognition capacity, proton recognition determinants, aspects of energy utilization, and physiological role.
Calcium Channel Auxiliary Subunits
Authors: Tseng Tsai-Tien , McMahon Allison M. , Zahm Robert J. , Pacold Mary E. , Jakobsson Eric
Published: May 2008

Many channels and carriers associate with auxiliary subunits which modify their activities and facilitate biogenesis. Advances in genome sequencing as well as biochemical, molecular genetic, and physiological experimentation have allowed for the discovery of many transport auxiliary subunits. Recent interests in the pharmacology of the calcium auxiliary subunits prompted a large amount of effort in deciphering their specific role in the conductance of calcium ions. In this review, we evaluate the functions of the ‘extra’ subunits of the voltage-gated calcium channels in animals as an example of auxiliary subunits of transporters in general. We discuss the functional data available for each of these subunits, present phylogenetic analyses, and discuss their potential evolutionary origins. Our analyses also reveal novel homologues of these subunits which might be of interest to the community.
Characterization of Ectomesenchymal Cells Isolated from the First Branchial Arch during Multilineage Differentiation
Authors: Yan Zhengbin , Lin Yunfeng , Jiao Xiaohui , Li Zhiyong , Wu Ling , Jing Wei , Qiao Ju , Liu Lei , Tang Wei , Zheng Xiaohui , Tian Weidong
Published: May 2008

Ectomesenchymal cells isolated from the first branchial arch have the potential to differentiate into a variety of cell lineages both in vitro and in vivo. This study was aimed to confirm the plasticity of multilineage differentiation with molecular and cellular characterization. Monolayer cultures of ectomesenchymal cells harvested from the first branchial arch primordia in embryonic day 9.5 BALB/c mice were passaged 3 times before analysis. Staining with antibodies against S-100, p75 and vimentin suggested that the population of stem cells originated from ectomesenchyme, with few contaminating cells stained for cytokeratin. Then, cells were transferred to adipogenic, osteogenic, chondrogenic and odontogenic media. The initiation of controlled differentiation was determined with histological assays, and the expression of tissue-specific genes was detected using immunocytochemical staining and reverse transcription polymerase chain reaction. The adipogenic ectomesenchymal cells showed accumulation of lipid vacuoles and expression of lipoprotein lipase and peroxisome proliferator-activated receptor γ2. Following osteoinduction, the fibroblast-like cells became cuboidal and formed mineralized nodules. In addition, the expression of mRNA encoding osteocalcin and osteopontin proved osteogenesis at the molecular level. Chondrogenic lineage expressed collagen type II, aggrecan and Sox9 with a low level of collagen type I in monolayer culture. Odontogenesis was determined by dentin sialophosphoprotein, collagen type I and dentin matrix protein 1 expression. Therefore, we have demonstrated that ectomesenchymal cells from the first branchial arch are capable of extensive multilineage differentiation in vitro, controllable by the culture environment. This makes them a relevant and valuable source of stem cells for research of craniofacial development and tissue engineering of restoration.
Adipose Tissue Engineering by Human Adipose-Derived Stromal Cells
Authors: Hong Liu , Peptan Ioana A. , Colpan Aylin , Daw Joseph L.
Published: May 2008

Tissue engineering has emerged as a promising alternative approach to current clinical treatments for restoration of soft tissue defects. The purpose of this study was to investigate adipose tissue formation in vitro and in vivo by using human adipose-derived stromal cells (ADSCs) utilizing a gelatin sponge (Gelform®) as a scaffold. Adipogenic potentials of human ADSCs were demonstrated by Oil-O-red staining and cellular morphology. After seeding human ADSCs in a density of 3 × 106 cells/ml on three-dimensional gelatin sponges, tissue-engineered constructs were exposed to adipogenic differentiation medium for in vitro studies and implanted in the backs of severe combined immunodeficient (SCID) mice for in vivo adipose regeneration. Adipogenesis of ADSC-seeded gelatin sponges was confirmed by Oil-O-red staining after 4 weeks of in vitro incubation. The optical density of the elution from Oil-O-red staining of adipogenic constructs is significantly higher than that of the control group (p < 0.05, n = 4). With short-term in vitro differentiation, adipogenic constructs turned into fat tissue 4 weeks after in vivo implantation, confirmed by biochemical and immunohistochemical examination. No adipogenic-morphological change or fat formation was observed in in vitro or in vivo studies when ADSCs were exposed to a control medium without adipogenic stimulation. These results indicate that engineered adipose tissue can be achieved using human ADSCs and biocompatible and degradable gelatin sponges.
Structure of the Midterm Placenta of the Spotted Hyena, Crocuta crocuta, with Emphasis on the Diverse Hemophagous Regions
Authors: Enders Allen C. , Blankenship Thomas N. , Conley Alan J. , Jones Carolyn J.P.
Published: May 2008

The hyena placenta is unique among carnivores in being hemochorial. It also has areas of erythrocyte uptake that differ from those seen in more commonly studied carnivores. The availability of timed midterm pregnancies made it possible to examine the organization of the placenta, the distribution of regions of columnar trophoblast and the nature of the heterophagous and hemophagous regions in well-preserved material. The labyrinth of the placenta is orderly arranged with periodic primary villi that have a surface of syncytial trophoblast. Secondary projections from the primary villi anastomose extensively. The junctional extreme of each primary villus forms an expanded tip covered by columnar trophoblast cells. Marginal to the hemochorial placenta, the paraplacenta is exposed to varying amounts of extravasated maternal blood which the cytotrophoblast cells ingest and destroy. Columnar trophoblast cells at the tips of the primary villi, in the villi of paraplacental margins of the labyrinth, in isolated patches within the labyrinth and beneath the allantochorionic plate are all capable of and are variably involved in erythrophagocytosis. Variations in the structure and the lectin histochemistry of the columnar trophoblast cells indicate variation depending on the exposure of these cells to erythrocytes and/or other histotrophic materials. The widespread distribution of the hemophagous regions suggests a nutritive function in addition to an iron transfer function of the columnar cytotrophoblast.
Direct Magnetic Tubular Cell Seeding: A Novel Approach for Vascular Tissue Engineering
Authors: Perea Héctor , Aigner Joachim , Hopfner Ursula , Wintermantel Erich
Published: May 2008

Optimizing seeding efficiency, reducing delayed culture periods and mimicking native tissue architecture are crucial requirements for the development of seeding procedures in tissue engineering. In vascular applications, the tubular geometry of the grafts further hampers the efficient delivery of cells onto the scaffold. To overcome these limitations, a novel technology based upon the use of magnetic fields is presented in this study: a radial magnetic force drives the cells immediately onto the luminal surface of a tubular scaffold and immobilizes the cells on the substrate’s surface promoting cell attachment. Human smooth muscle cells (SMCs) labeled with CD44 magnetic Dynabeads® were successively seeded onto the luminal surface of a tubular shaped collagen membrane. After 5 h, one additional layer of human umbilical vein endothelial cells (HUVECs) labeled with CD31 magnetic Dynabeads® was seeded onto the luminal SMCs. The co-culture was incubated during 5 days prior to analysis. Cell viability and expression profiles were preserved during the entire seeding process. Histological examination of the constructs highlighted densely packed multilayers of SMCs covered by a monolayer of endothelial cells. SEM inspection confirmed a heterotypic multilayer assembly formed by multiple layers of elongated SMCs covered by a single layer of endothelial cells. Seeding kinetics of HUVECs and SMCs showed over 90% seeding efficiency after 20 and 40 min magnetic exposure respectively. Magnetically induced cell seeding provides a valuable tool for rapid seeding procedures of tubular scaffolds while complying with the histological architecture of tissue.
Hemoglobin Changes at the Initiation of High-Flux Hemodialysis
Authors: Sombolos K. , Christidou F. , Bamichas G. , Gionanlis L. , Karagianni A. , Fytili C. , Natse T.
Published: May 2008

Background: The aim of the present study was to assess hemoglobin changes occurring at the beginning of high-flux hemodialysis (HD). Methods: In a group of 20 chronic HD patients (group A), total hemoglobin (tHb), hematocrit (Hct) and total serum proteins (TP) were measured in blood samples drawn from an arterial fistula needle before the initiation of high-flux HD, and from an arterial line 5 min after HD with the dialysate in the bypass mode. 31 chronic stable HD patients (group B) served as controls. In group B patients, tHb was measured in blood samples drawn from an arterial fistula needle before the initiation of high-flux HD, and from arterial and venous lines simultaneously 5 min later. Blood flow rates in groups A and B were set from the beginning of the study to 300 ml/min, while the bicarbonate dialysate flow rate and ultrafiltration rate in group B patients was set to 700 ml/min and zero, respectively. The same high-flux dialyzer was used for all patients (FLX-18, membrane PEPA 1.8 m2). Results: A comparison of baseline (pre-dialysis) values with those derived from an analysis of the arterial line in groups A and B at 5 min revealed that tHb decreased by 0.6 ± 0.2 g/dl (5.2 ± 1.7%, p < 0.001) and 0.7 ± 0.7 g/dl (5.4 ± 6.2%, p < 0.001), respectively. At the same time, Hct and TP in group A decreased by 1.32 ± 0.7% (3.8 ± 2.0%, p <0.001) and 0.3 ± 0.1 g/dl (4.8 ± 1.4%, p < 0.001), respectively. Blood volume (BV) and plasma volume (PV) in group A patients at 5 min as calculated from tHb and TP values increased by 5.6 ± 1.9 and 5.2 ± 1.7%, respectively, while BV in group B patients increased by 6.1 ± 7.0% (not significant when compared to group A). tHb did not change significantly in 14 patients (group C) studied immediately after adopting the supine position and 5 min later in the absence of HD. Conclusion: A 5% decrease in tHb was observed 5 min after the initiation of high-flux HD with a zero ultrafiltration rate, and was due to an increase in BV.
Safety and Efficacy of Juniperus ashei Sublingual-Swallow Ultra-Rush Pollen Immunotherapy in Cypress Rhinoconjunctivitis
Authors: Vervloet D. , Birnbaum J. , Laurent P. , Hugues B. , Fardeau M.F. , Massabie-Bouchat Y.P. , Aferiat-Derome A. , André C.
Published: May 2008

Background: The safety and efficacy of high-dose sublingual-swallow immunotherapy (SLIT) has been established in pollen rhinoconjunctivitis. This treatment has now been evaluated using an ultra-rush incremental dose regimen with a Juniperus ashei allergen extract in patients allergic to Cupressus sempervirens and Cupressus arizonica. Methods: Patients received either placebo or SLIT. Evaluation of safety was based on the frequency of adverse events during the incremental dose period (half a day) and during maintenance therapy (4 months). Evaluation of efficacy was based on symptom and medication scores at the pollen peak. Results: Seventy of the 76 patients included completed the study. There were no drop-outs during the rush procedure. One patient in the active group dropped out during the maintenance therapy due to adverse events: gastric pain and vomiting. There was also 1 drop-out in the placebo group due to pregnancy. Adverse events were infrequent, local and mild. Symptom scores for rhinitis and conjunctivitis were not statistically different between groups, but there was a marked and significant (p < 0.03) decrease of the medication score (about 50%) and nasal steroid consumption (about 75%) in the active treatment group. An increase from baseline of serum IgE and IgG4 J. ashei-specific antibodies was only observed in actively treated patients (p < 0.04 and p < 0.01, respectively). Conclusions: The tolerability and safety of high-dose ultra-rush SLIT were comparable to those reported in previous SLIT studies. SLIT with J. ashei extract, due to its high Jun a 1 content, significantly reduced nasal steroid consumption in patients allergic to European cypress.
Differential Inhibition of Primary versus Preactivated T Cells by Pimecrolimus but Not by Tacrolimus in vitro
Authors: Kalthoff Frank S. , Winiski Anthony , Fichtinger Petra , Schwendinger Brigitte , Wang Shirley , Weishaeupl Cordula , Stuetz Anton
Published: May 2008

Background: Recent studies in murine models of allergic contact dermatitis have shown that systemic treatment with pimecrolimus in contrast to tacrolimus did not inhibit the sensitization phase, whereas both compounds equivalently suppressed the inflammatory response in sensitized animals. This finding indicated a differential sensitivity of antigen-naïve and primed T cells towards pimecrolimus and tacrolimus. Methods: T cells obtained from healthy and allergic donors were subjected to primary and secondary stimulation by allogeneic or staphylococcal superantigen-presenting dendritic cells (DC). Human skin-derived, allergen-specific T cell clones from an atopic dermatitis patient were activated by anti-CD3 antibodies or by specific allergen-presenting DC. The inhibition of T cell proliferation and cytokine release by graded doses of calcineurin inhibitors was evaluated. Results: Primary stimulation of T cells was inhibited by pimecrolimus with an approximately 8-fold lower potency as compared with tacrolimus. In contrast, the secondary response of ex vivo expanded T cells activated by allogeneic or staphylococcal superantigen-presenting DC was inhibited by both compounds with equivalent potency. Likewise, both drugs showed very similar potency to inhibit the proliferation and cytokine synthesis from antigen- stimulated T cell clones and the induction of cytokines in Jurkat T cells. Conclusion: These data indicate that pimecrolimus has a selectivity for antigen-primed memory T cells not seen with tacrolimus.
Fluoxetine Is Not Effective in the Treatment of Poststroke Fatigue: A Double-Blind, Placebo-Controlled Study
Authors: Choi-Kwon Smi , Choi Jimi , Kwon Sun U. , Kang Dong-Wha , Kim Jong S.
Published: May 2008

Background and Purpose: Although poststroke fatigue (PoSF) is common, pharmacological interventions to improve PoSF have rarely been carried out. The purpose of the present study was to evaluate the therapeutic effect of fluoxetine on PoSF. Methods: We studied 83 consecutive outpatients with PoSF at an average of 14 months after the onset of stroke. The presence of poststroke depression, poststroke emotional incontinence and poststroke anger proneness was also evaluated with the use of a standardized questionnaire. The presence of PoSF and prestroke fatigue was assessed. The visual analogue scale (VAS) and Fatigue Severity Score (FSS) were used to assess PoSF. The subjects were given either 20 mg/day of fluoxetine (n = 40) or placebo (n = 43) for 3 months. Follow-up evaluations were done 3 and 6 months after the beginning of the treatment. Results: The initial mean fatigue VAS score and the mean overall FSS score were 5.4 ± 2.0 and 4.4 ± 1.2, respectively. There were no differences in the number of patients with PoSF between the fluoxetine group and the placebo group at 3 and 6 months after the treatment. The percent changes in VAS scores and FSS at all follow-up assessments were not significantly different either. However, fluoxetine significantly improved poststroke emotional incontinence (p < 0.05) and poststroke depression (p = 0.05) in the patients with PoSF. Conclusions: Fluoxetine does not improve PoSF, although some concomitant emotional disturbances improved significantly. Our results suggest that PoSF may be associated with diverse etiologies but not closely related to serotonergic dysfunction. Further studies are required to elucidate the causative factors and to find an appropriate treatment for PoSF.
Microcirculatory Dysfunction in the Brain Precedes Changes in Evoked Potentials in Endotoxin-Induced Sepsis Syndrome in Rats
Authors: Rosengarten Bernhard , Hecht Mirko , Auch Dieter , Ghofrani Hossein Ardeschir , Schermuly Ralf Theo , Grimminger Friedrich , Kaps Manfred
Published: May 2008

Background: During sepsis progression microcirculatory dysfunction precedes macrocirculatory failure, partly explaining the occurrence of early organ dysfunction. The matter concerning microcirculatory dysfunction in the brain under septic conditions is less clear. We investigated the integrity of the activation flow coupling during sepsis progression in a rat model of septic shock. Methods: Chloralose-anesthetized rats (n = 30) were subjected to electric forepaw stimulation. Over the somatosensory cortex electrical activity and hemodynamic responses were recorded with surface electrodes and laser Doppler. After baseline recordings, vehicle, 1 or 5 mg/kg lipopolysaccharide (LPS) from Escherichia coli was given intravenously, and activation flow coupling, blood pressure and blood gases were investigated at regular time points up to 270 min. In the end lactate, glucose, neuron-specific enolase (NSE) and S-100B protein levels were measured. Results: Besides stable data from the control group, all LPS-treated rats developed signs of septic shock, which were more pronounced in the 5 mg/kg LPS group. Cerebral hyperemia occurred and was similar between the sepsis groups despite lower blood pressure levels in the 5 mg/kg LPS group. While the activation flow coupling remained intact in the 1 mg/kg LPS group, an uncoupling occurred in the 5 mg/kg group. First, the evoked flow velocity responses dropped 60 min after sepsis induction before the somatosensory amplitudes also decreased 120 min later. From similar NSE levels we suggest a functional rather than structural deficit explaining the difference in evoked potentials. Conclusions: For the first time we demonstrate microcirculatory dysfunction in the activation flow coupling of the brain. Inappropriate blood supply of neurons might explain the disturbance of neuronal function.
Anandamide Inhibits Endothelin-1 Production by Human Cultured Endothelial Cells: A New Vascular Action of This Endocannabinoid
Authors: Ronco Ana María , Llanos Miguel , Tamayo Daniela , Hirsch Sandra
Published: May 2008

The endogenous cannabinoid receptor agonist anandamide (AEA) exerts vascular effects such as vasodilatation and hypotension. In this study, we determined the effect of AEA on endothelin-1 production by cultured human umbilical vein endothelial cells. Anandamide (≧5 µmol/l) significantly decreased endothelin-1 production in a dose-dependent manner, a response not affected by the specific CB1 receptor antagonist/inverse agonist SR-141716A. Adenosine, via activation of adenosine receptors (also targets for SR-141716A), was not involved in these effects. Conversely, AEA increased nitric oxide (NO) production, an effect inhibited by SR-141716A, indicating the involvement of CB1 receptors. Therefore, we hypothesize that AEA effects on endothelial cells may lead to vasodilatation through independent concerted mechanisms, involving a non-CB1 receptor-dependent inhibition of endothelin-1 production and a CB1-mediated increase of NO.
Preliminary Assessment of Cognitive Function in Older Adults by Clock Drawing, Box Copying and Narrative Writing
Authors: Paganini-Hill Annlia , Clark Linda J.
Published: May 2008

Objective: To examine 3 cognitive screening tasks in older adults and determine which demographic, medical and lifestyle variables obtained 13–17 years previously predicted cognitive performance. Design: Population-based longitudinal cohort study begun in 1981. Setting: Leisure World Laguna Hills, a California retirement community. Participants: The cohort is predominantly white, well educated, upper-middle class; two thirds are women. Data from 1,744 participants (mean age 83 years, range 57–103) were analyzed. Measurements: The baseline postal survey (1981–1985) asked demographic information, medical history, selected drug use and personal habits. The 1998 follow-up included 3 tasks to assess cognitive function: (1) clock drawing, (2) copying a box drawing and (3) narrative writing to describe a pictured scene. Results: Within age groups, women tended to have lower scores than men on box copying, similar scores on clock drawing, but higher informational and complexity scores on narrative writing. Performance decreased with increasing age and was poorest in individuals ≧90 years old. In addition to age, sex and education, significant predictors of performance were: exercise, body mass index and cataract surgery (clock); vitamin E supplements, daily aspirin use and gallbladder surgery (box); vitamin A supplements (narrative writing). Mean scores on all tasks were lower in those later identified as demented compared with nondemented but significantly different only for clock and box drawings. Conclusion: Performance on 3 cognitive tests showed significant effects of age, sex and education and was related to later dementia. Better performance by users of antioxidant supplements and aspirin suggests that these drugs may maintain cognitive function in later life.
Genetic Variants of Y Chromosome Are Associated With a Protective Lipid Profile in Black Men
Authors: Russo Paola , Siani Alfonso , Miller Michelle A. , Karanam Sharada , Esposito Teresa , Gianfrancesco Fernando , Barba Gianvincenzo , Lauria Fabio , Strazzullo Pasquale , Cappuccio Francesco P.
Published: May 2008

Objective—

Gender and ethnicity modulate the phenotypic expression of cardiovascular risk factors. In particular, men are at higher risk of developing cardiovascular diseases compared to women, whereas black populations of African origin display reduced mortality from coronary heart disease (CHD) as compared to both whites and South Asians. Because the male-specific region (MSY) of the human Y chromosome is an obvious candidate for gender-related differences in the development of cardiovascular diseases, we aimed to identify genetic variants of MSY influencing cardiovascular risk profile in different ethnic groups.

Methods and Results—

We genotyped 4 polymorphisms of MSY (
Hind
III±, rs768983 of
TBL1Y
, rs3212292 of
USP9Y
, and rs9341273 of
UTY
genes) in 579 men of different ethnic groups (blacks, South Asians, and whites) from UK and in 301 whites in Italy. We found that the
TBL1Y
A
USP9Y
A
haplotype, present only in blacks in whom it represents the most frequent allelic combinations (AA: n=125; all other combinations: n=45), was associated with lower levels of triglycerides (
P
=0.025) and higher levels of HDL-cholesterol (
P
=0.005) as compared to the other haplotypes.

Conclusion—

The
TBL1Y
A
USP9Y
A
haplotype of the Y chromosome, present only in black people of African origin, attributes a favorable lipoprotein pattern, likely to contribute to their reduced susceptibility to coronary heart disease.
Direct Treatment of Mouse or Human Blood With Soluble 5′-Nucleotidase Inhibits Platelet Aggregation
Authors: Hart Melanie L. , Köhler David , Eckle Tobias , Kloor Doris , Stahl Gregory L. , Eltzschig Holger K.
Published: May 2008

Objective—

Adenosine signaling is known to inhibit platelet aggregation. Extracellular adenosine mainly stems from enzymatic phosphohydrolysis of precursor nucleotides via ecto-5′-nucleotidase. Previous studies suggest that soluble 5′-nucleotidase (5′-NT) derived from
Crotalus atrox
venom may be clinically beneficial in vascular leakage, myocardial, renal, and intestinal ischemia, or acute lung injury. However, the effects of 5′-NT treatment on platelet aggregation remain unknown. We examined the direct effects of 5′-NT treatment on platelet aggregation in vivo and ex vivo using a whole blood aggregation method.

Methods and Results—

Platelet aggregation in whole human blood was completely inhibited by 5′-NT. When 5′-[αβ-methylene] diphosphate (APCP), a specific 5′-ecto-nucleotidase inhibitor, was added together with 5′-NT, APCP fully restored collagen- or ADP-induced aggregation. Adenosine levels in whole blood were significantly increased after 5′-NT treatment compared to controls and inhibition of platelet aggregation by 5′-NT was completely reversed by pretreatment with the nonspecific adenosine receptor antagonist 8-(p-sulfophenyl)theophylline hydrate (8-SPT), suggesting that 5′-NT inhibits aggregation via increased adenosine signaling. Administration of 5′-NT to mice in vivo abolished ADP- and collagen-induced platelet aggregation and increased adenosine concentrations and tail bleeding time.

Conclusions—

5′-NT treatment inhibits platelet aggregation via generation of increased levels of extracellular adenosine and subsequent adenosine receptor signaling.
Prospects of the EPS GRAS Mission For Operational Atmospheric Applications
Authors: Luntama Juha-Pekka , Kirchengast Gottfried , Borsche Michael , Foelsche Ulrich , Steiner Andrea , Healy Sean , von Engeln Axel , O'Clerigh Eoin , Marquardt Christian
Published: May 2008

Global Navigation Satellite System (GNSS) Receiver for Atmospheric Sounding (GRAS) is a radio occupation instrument especially designed and built for operational meteorological missions. GRAS has been developed by the European Space Agency (ESA) and the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT) in the framework of the EUMETSAT Polar System (EPS). The GRAS instrument is already flying on board the first MetOp satellite (.MetOp-A) that was launched in October 2006. It will also be on board two other MetOp satellites (MetOp-B and MetOp-C) that will successively cover the total EPS mission lifetime of over 14 yr. GRAS provides daily about 600 globally distributed occultation measurements and the GRAS data products are disseminated to the users in near-real time (NRT) so that they can be assimilated into numerical weather prediction (NWP) systems. All GRAS data and products are permanently archived and made available to the users for climate applications and scientific research through the EUMETSAT Unified Meteorological Archive and Retrieval Facility (U-MARF) and the GRAS Meteorology Satellite Application Facility (SAF) Archive and Retrieval Facility (GARF). The GRAS navigation data can be used in space weather applications.