bluuebunny/crossref_metadata_2025 huggingface dataset:
Behaviour of flexible batter piles under inclined loads in layered soil
Authors: Meyerhof G. G. , Yalcin A. S.
Published: October 2009

The behaviour of single free-head model flexible vertical and batter piles under central inclined loads in two-layered soil is investigated. The bearing capacity of the piles is found to depend on the layered structure, load inclination, and pile batter. The theoretical estimates obtained from semiempirical relations agree well with the test results. Previous displacement equations for flexible batter piles in elastic isotropic soil are modified for piles in anisotropic layered soil using an effective embedment depth of equivalent rigid piles. Practical equations for horizontal and vertical displacements of flexible batter piles are presented on the basis of resultant influence factors that are related to the batter angle, load inclination, and distribution of soil modulus with depth. The observed horizontal and vertical displacements of the piles are in reasonable agreement with the theoretical estimates, which are also supported by the results of some field cases. Key words : bearing capacity, deformation, batter pile, inclination factor, inclined load, layered soil, model test, sand, clay.
The strength and deformation behaviour of model adfreeze and grouted piles in saline frozen soils
Authors: Biggar K. W. , Sego D. C.
Published: October 2009

The results of a laboratory study to determine the influence of soil salinity, pile surface treatment, pile backfill material, and temperature on the adfreeze bond strength and deformation of model piles are presented. The influence of salinity and temperature on the adfreeze strength is shown to be related through the unfrozen water, and similar strength results were obtained at similar unfrozen water contents. Salinity in the backfill material of 10 and 30 ppt caused reductions in the adfreeze bond strength of 80–99%. Similar salinities within the native soil reduced its shear strength causing the location of the failure to change from the pile–backfill interface to the backfill – native soil interface when nonsaline backfill was used. Sandblasting of the pile surface to remove any surface coating resulted in adfreeze bond strengths two to three times greater than those measured on nonsandblasted piles. The use of cementitious grout to replace the sand slurry backfill resulted in greater pile load carrying capacity as the failure surface was transferred to the grout (backfill) – native soil interface instead of the pile–backfill interface. Use of backfill made from saline native soil cutting should be discouraged because of the detrimental effects of pore-fluid salinity on the adfreeze bond strength. Key words : frozen soil, saline, model pile, adfreeze, strength, deformation, grout, temperature.
The effect of water seepage forces on the face stability of an experimental microtunnel
Authors: Pellet Frédéric , Descoeudres François , Egger Peter
Published: October 2009

The face heading stability of underground constructions remains quite difficult to assess, especially when groundwater is present. To investigate this, an experimental microtunnel was excavated at shallow depth in soft ground, below the water table. In agreement with field measurements of the piezometric level changes, a three-dimensional finite element analysis of groundwater flow shows that the head losses are concentrated in the close vicinity of the tunnel face. Both numerical equilibrium analysis and field measurements were used to show that the resulting seepage forces substantially increase the supporting pressure required to ensure face stability. Key words : microtunnel, shallow depth, soft ground, seepage forces, face stability, supporting pressure.
Flow field around a cylindrical pile during steady penetration
Authors: Silvestri V. , Tabib C.
Published: October 2009

An analytical solution is presented for the flow field around a cylindrical pile penetrating an inviscid and incompressible fluid. The problem is solved by using the theory of a complex variable and conformal mapping and by transforming the governing flow equation from cartesian to orthogonal curvilinear coordinates. The stream function, velocity field, and octahedral shear strain rates are fully determined and presented in graphical form. It is shown that the assumption of infinite extent of the pile results in the fluid velocity vanishing along the pile shaft. The flow field obtained is thought to represent a first approximation to in situ strains generated during the penetration of a cylindrical pile in very soft cohesive soils. Key words : flow field, cylindrical pile, soft cohesive soil, strain rates, velocity field.
THERMODYNAMICS OF THE UNIVERSE WITH MODIFIED CHAPLYGIN GAS
Authors: BANDYOPADHYAY TANWI , CHAKRABORTY SUBENOY
Published: October 2009

We investigate the thermodynamics of the universe filled with modified Chaplygin gas (MCG) considering the integrability condition of the laws of thermodynamics. In principle, all thermal variables can be expressed as functions of either volume or temperature. A new equation of state for MCG is obtained during thermal process. The asymptotic analysis shows that the thermal evolution of the universe is possible from radiation era to ΛCDM model, i.e. the thermal history of MCG gives a unified picture of dark matter and dark energy and as a result the universe cools down through expansion without any phase transition (no critical point).
INFLATION AS A RESPONSE TO PROTECT THE HOLOGRAPHIC PRINCIPLE
Authors: CÁRDENAS VÍCTOR H.
Published: October 2009

A model where the inflationary phase emerges as a response to protect the Fischler–Susskind holographic bound is described. A two-fluid model in a closed universe inflation picture is assumed, and a discussion on conditions under which it is possible to obtain an additional exponential expansion phase as those currently observed is given.
CONSTRAINTS ON PARAMETERS OF MODELS WITH EXTRA DIMENSION FROM PRIMORDIAL NUCLEOSYNTHESIS
Authors: IOFA MIKHAIL Z.
Published: October 2009

5D models with one 3D brane and one infinite extra dimension are studied. Matter is confined to the brane, gravity extends to the bulk. Models with positive and negative tension of the brane are studied. Cosmological solutions on the brane are obtained by solving the generalized Friedmann equation. As the input in cosmological solutions we use the present-time observational cosmological parameters. We find constraints on dimensionless combinations of scales of 5D models which follow from the requirement that the models reproduce the data on production of 4 He in primordial nucleosynthesis.
IMPROVING TARGET DETECTION IN REVERBERATION-LIMITED ENVIRONMENT VIA BISTABLE SYSTEM
Authors: ZHANG HUIQUAN , XU BOHOU , JIANG ZHONG-PING , LI JIANLONG
Published: October 2009

In this paper, we consider the problem of detecting the echo from a point target in the presence of reverberation. For its strong correlation to the transmitted signal and non-Rayleigh envelope arising from sparse distribution of scatterers, reverberation decreases the performance of the conventional matched filter (MF) receiver. We propose a nonlinear receiver using the bistable system with a discrete-time autoregressive model of order 1 [AR(1)]. The signals are pre-processed by bistable systems before the MF receiver. Numerical simulations are carried out to verify the performance of our proposed nonlinear receiver versus the conventional MF receiver. The reverberation is generated using the point-scatterer simulation method, and the results show that in reverberation-limited environment, our proposed nonlinear receiver may perform better and much more robust to the scatterer number than the conventional MF receiver.
PKCε-dependent and -independent effects of taurolithocholate on PI3K/PKB pathway and taurocholate uptake in HuH-NTCP cell line
Authors: Schonhoff Christopher M. , Yamazaki Ai , Hohenester Simon , Webster Cynthia R. L. , Bouscarel Bernard , Anwer M. Sawkat
Published: October 2009

The cholestatic bile acid taurolithocholate (TLC) inhibits biliary secretion of organic anions and hepatic uptake of taurocholate (TC). TLC has been suggested to induce retrieval of Mrp2 from the canalicular membrane via the phosphoinositide-3-kinase (PI3K)/PKB-dependent activation of novel protein kinase Cε (nPKCε) in rat hepatocytes. The aim of the present study was to determine whether TLC-induced inhibition of TC uptake may also involve PI3K-dependent activation of PKCε in HuH7 cells stably transfected with human Na+-dependent TC-cotransporting polypeptide (NTCP) (HuH-NTCP cells). To avoid direct competition for uptake, cells were pretreated with TLC, washed, and then incubated with3H-TC to determine TC uptake. TLC produced time- and dose-dependent inhibition of TC uptake. TLC inhibited TC uptake competitively without affecting NTCP membrane translocation. A PI3K inhibitor failed to reverse TLC-induced TC uptake inhibition and TLC-inhibited PKB phosphorylation. TLC did activate nPKCε as evidenced by increased membrane translocation and nPKCε-Ser729phosphorylation. Overexpression of dominant negative-nPKCε reversed TLC-induced inhibition of PKB phosphorylation but not of TC uptake. Finally, cAMP prevented TLC-induced inhibition of TC uptake via the PI3K pathway, and the prevention is due to the sum of cAMP-induced stimulation and TLC-induced inhibition of TC uptake. Taken together, these results suggest that TLC-induced inhibition of PKB, but not of TC uptake, is mediated via nPKCε. Activation of nPKCε and inhibition of TC uptake by TLC are not mediated via the PI3K/PKB pathway.
Gold Finger: Metal Jewellery as a Disease Modifying Antirheumatic Therapy!
Authors: Hlaing T. , Ramteke S. , Binymin K.
Published: October 2009

Polyarticular psoriatic arthritis is a chronic, progressive and disabling auto-immune disease often affecting the small joints of the hands in a symmetrical fashion. The disease can progress rapidly causing joint swelling and damaging cartilage and bone around the joints resulting in severe deformities. We report a very unusual case of a 49-year-old woman who presented with polyarticular psoriatic arthritis affecting all proximal interphalangeal (PIP) joints of both hands except the left ring finger PIP joint. On clinical examination there was no evidence of arthritis in the left ring finger PIP joint. We confirmed the paucity of joint damage in the PIP joint of the left ring finger using more modern imaging modalities such as musculoskeletal ultrasound and MRI scan of the small joints of the hands. All other PIP joints in both hands demonstrated advanced degrees of joint damage secondary to chronic psoriatic inflammatory arthritis. We postulated that wearing a gold wedding ring has helped protecting the PIP joint of the left ring finger from the damaging effect of inflammatory arthritis. The possible mechanisms by which metal jewellery (gold ring) confer protection to adjacent joints was discussed.
EBV-Induced Human CD8+ NKT Cells Suppress Tumorigenesis by EBV-Associated Malignancies
Authors: Yuling He , Ruijing Xiao , Li Li , Xiang Ji , Rui Zhou , Yujuan Wang , Lijun Zhang , Chunxian Du , Xinti Tan , Wei Xiao , Lang Chen , Yanping Jiang , Tao Xiong , Mengjun Wu , Jie Xiong , Youxin Jin , Jinquan Tan
Published: October 2009

The underlying mechanism of the protective and suppressive role of NKT cells in human tumor immunosurveillance remains to be fully elucidated. We show that the frequencies of CD8+ NKT cells in patients with EBV-associated Hodgkin's lymphoma or nasopharyngeal carcinoma are significantly lower than those in healthy EBV carriers. These CD8+ NKT cells in tumor patients are also functionally impaired. In human-thymus-severe combined immunodeficient (hu-thym-SCID) chimeras, EBV challenge efficiently promotes the generation of IFN-γ–biased CD8+ NKT cells. These cells are strongly cytotoxic, drive syngeneic T cells into a Th1 bias, and enhance T-cell cytotoxicity to EBV-associated tumor cells. Interleukin-4–biased CD4+ NKT cells are predominately generated in unchallenged chimeras. These cells are noncytotoxic, drive syngeneic T cells into a Th2 bias, and do not affect T-cell cytotoxicity. In humanized xenogeneic tumor-transplanted hu-thym-SCID chimeras, adoptive transfer with EBV-induced CD8+ NKT cells significantly suppresses tumorigenesis by EBV-associated malignancies. EBV-induced CD8+ NKT cells are necessary and sufficient to enhance the T-cell immunity to EBV-associated malignancies in the hu-thym-SCID chimeras. CD4+ NKT cells are synergetic with CD8+ NKT cells, leading to a more pronounced T-cell antitumor response in the chimeras cotransferred with CD4+ and CD8+ NKT cells. Thus, immune reconstitution with EBV-induced CD8+ NKT cells could be a useful strategy in management of EBV-associated malignancies. [Cancer Res 2009;69(20):7935–44]
A Modified Sleeping Beauty Transposon System That Can Be Used to Model a Wide Variety of Human Cancers in Mice
Authors: Dupuy Adam J. , Rogers Laura M. , Kim Jinsil , Nannapaneni Kishore , Starr Timothy K. , Liu Pentao , Largaespada David A. , Scheetz Todd E. , Jenkins Nancy A. , Copeland Neal G.
Published: October 2009

Recent advances in cancer therapeutics stress the need for a better understanding of the molecular mechanisms driving tumor formation. This can be accomplished by obtaining a more complete description of the genes that contribute to cancer. We previously described an approach using the Sleeping Beauty (SB) transposon system to model hematopoietic malignancies in mice. Here, we describe modifications of the SB system that provide additional flexibility in generating mouse models of cancer. First, we describe a Cre-inducible SBase allele, RosaSBaseLsL, that allows the restriction of transposon mutagenesis to a specific tissue of interest. This allele was used to generate a model of germinal center B-cell lymphoma by activating SBase expression with an Aid-Cre allele. In a second approach, a novel transposon was generated, T2/Onc3, in which the CMV enhancer/chicken β-actin promoter drives oncogene expression. When combined with ubiquitous SBase expression, the T2/Onc3 transposon produced nearly 200 independent tumors of more than 20 different types in a cohort of 62 mice. Analysis of transposon insertion sites identified novel candidate genes, including Zmiz1 and Rian, involved in squamous cell carcinoma and hepatocellular carcinoma, respectively. These novel alleles provide additional tools for the SB system and provide some insight into how this mutagenesis system can be manipulated to model cancer in mice. [Cancer Res 2009;69(20):8150–6]
Structural Basis for the Binding of the Anticancer Compound 6-(7-Nitro-2,1,3-Benzoxadiazol-4-Ylthio)Hexanol to Human Glutathione S-Transferases
Authors: Federici Luca , Lo Sterzo Carlo , Pezzola Silvia , Di Matteo Adele , Scaloni Flavio , Federici Giorgio , Caccuri Anna Maria
Published: October 2009

Glutathione S-transferases (GST) constitute a superfamily of enzymes with diversified functions including detoxification from xenobiotics. In many human cancers, Pi class GST (GSTP1-1) is overexpressed and contributes to multidrug resistance by conjugating chemotherapeutics. In addition, GSTP1-1 displays antiapoptotic activity by interacting with c-Jun NH2-terminal kinase, a key regulator of apoptosis. Therefore, GSTP1-1 is considered a promising target for pharmaceutical treatment. Recently, a potent inhibitor of GSTs, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), was identified and tested on several tumor cell lines demonstrating high antiproliferative activity. To establish the structural basis of NBDHEX activity, we determined the crystal structure of NBDHEX bound to either GSTP1-1 or GSTM2-2 (mu class). NBDHEX in both cases binds to the H-site but occupies different positions. Furthermore, the compound is covalently attached to the GSH sulfur in the GSTM2-2 crystal, forming a σ-complex, although it is bound but not conjugated in the GSTP1-1 crystal. Several differences in the H-sites of the two isozymes determine the higher affinity of NBDHEX for GSTM2-2 with respect to GSTP1-1. One such difference is the presence of Ile104 in GSTP1-1 close to the bound NBDHEX, whereas the corresponding position is occupied by an alanine in GSTM2-2. Mutation of Ile104 into valine is a frequent GSTP1-1 polymorphism and we show here that the Ile104Val and Ile104Ala variants display a 4-fold higher affinity for the compound. Remarkably, the GSTP1-1/Ile104Ala structure in complex with NBDHEX shows a considerable shift of the compound inside the H-site. These data might be useful for the development of new anticancer compounds. [Cancer Res 2009;69(20):8025–34]
Differences in Tumor Regulatory T-Cell Localization and Activation Status Impact Patient Outcome
Authors: Ménétrier-Caux Christine , Gobert Michael , Caux Christophe
Published: October 2009

The presence of regulatory T cells (Treg) has been described in a large panel of solid tumors. However, their impact on tumor progression differs according to the tumor type analyzed. We recently obtained evidence in breast carcinoma that Treg localized within lymphoid aggregates, but not in the tumor bed, have a negative impact on patients' survival. Moreover, we showed selective Treg recruitment through CCR4/CCL22 in the lymphoid aggregates upon contact with dendritic cells (DC), where they became strongly and selectively activated (ICOShigh) and block conventional T-cell response. Here, we discuss the meaning and potential implication of these novel findings. [Cancer Res 2009;69(20):7895–8]
Revving the Throttle on an Oncogene: CDK8 Takes the Driver Seat
Authors: Firestein Ron , Hahn William C.
Published: October 2009

The Wnt/β-catenin pathway plays an important role in initiation in most, if not all, colon cancers. Prior work has provided important insights into the regulation of β-catenin stability in the cytoplasm; however, relatively little is known about the mechanism by which β-catenin activates gene transcription in the nucleus. Using genetic approaches, studies in human colon cancers and Drosophila have identified CDK8 as a colon cancer oncogene that regulates β-catenin transcriptional activity. These convergent observations provide new insights into the regulation of nuclear β-catenin activity and identify a novel therapeutic target for β-catenin-driven malignancies. [Cancer Res 2009;69(20):OF7899–901]
The Cytoskeleton Protein Filamin-A Is Required for an Efficient Recombinational DNA Double Strand Break Repair
Authors: Yue Jingyin , Wang Qin , Lu Huimei , Brenneman Mark , Fan Feiyue , Shen Zhiyuan
Published: October 2009

The human actin-binding protein filamin-A (also known as ABP-280) cross-links actin into a dynamic three-dimensional structure. It interacts with >45 proteins of diverse functions, serving as the scaffold in various signaling networks. BRCA2 is a protein that regulates RAD51-dependent recombinational repair of DNA double strand breaks (DSB). Proximate to the COOH terminus of the BRCA2 protein, a conserved and DNA binding domain (BRCA2-DBD) interacts with filamin-A and BCCIP. In this study, we sought to test the hypothesis that filamin-A influences homologous recombinational repair of DSB and the maintenance of genomic stability. We used three pairs of cell lines with normal and reduced filamin-A expression, including breast cancer and melanoma cells. We found that lack or reduction of filamin-A sensitizes cells to ionizing radiation, slows the removal of DNA damage–induced γH2AX nuclear foci, reduces RAD51 nuclear focus formation and recruitment to chromatin in response to irradiation, and results in a 2-fold reduction of homologous recombinational repair of DSB. Furthermore, filamin-A–deficient cells have increased frequencies of micronucleus formation after irradiation. Our data illustrate the importance of the cytoskeleton structure in supporting the homologous recombinational DNA repair machinery and genome integrity, and further implicate a potential of filamin-A as a marker for prognosis in DNA damage–based cancer therapy. [Cancer Res 2009;69(20):7978–85]
BH3-only proteins Mcl-1 and Bim as well as endonuclease G are targeted in spongistatin 1–induced apoptosis in breast cancer cells
Authors: Schneiders Uta M. , Schyschka Lilianna , Rudy Anita , Vollmar Angelika M.
Published: October 2009

Spongistatin 1, a marine experimental substance with chemotherapeutic potential, induces apoptosis and inhibits clonogenic survival of MCF-7 cells. Regarding the apoptotic signaling pathways of spongistatin 1, we present two major facts. Firstly, spongistatin 1–induced cell death, mainly caspase-independent, involves the proapoptotic proteins apoptosis-inducing factor and endonuclease G. Both proteins translocate from mitochondria to the nucleus and contribute to spongistatin 1–mediated apoptosis as shown via gene silencing. Secondly, spongistatin 1 acts as a tubulin depolymerizing agent and is able to free the proapoptotic Bcl-2 family member Bim from its sequestration both by the microtubular complex and by the antiapoptotic protein Mcl-1. Silencing of Bim by small interfering RNA leads to a diminished translocation of apoptosis-inducing factor and endonuclease G to the nucleus and subsequently reduces apoptosis rate. Thus, we identified Bim as an important factor upstream of mitochondria executing a central role in the caspase-independent apoptotic signaling pathway induced by spongistatin 1. Taken together, spongistatin 1 is both a valuable tool for the characterization of apoptotic pathways and a promising experimental anticancer drug. [Mol Cancer Ther 2009;8(10):2914–25]
Management of Spontaneous Coronary Artery Dissection: Review of the Literature and Discussion Based on a Series of 12 Young Women with Acute Coronary Syndrome
Authors: Motreff P. , Souteyrand G. , Dauphin C. , Eschalier R. , Cassagnes J. , Lusson J.R.
Published: October 2009

Spontaneous coronary artery dissection (SCAD) is a rare pathology, principally affecting young women free of atheroma risk factors. Its physiopathology remains little understood, and the prognosis for such acute coronary syndromes is poor, as they occur suddenly. Management is often difficult, and no guidelines exist. The present single-center retrospective study concerns 12 cases of SCAD occurring between 2001 and 2008 in female patients under the age of 60. Eleven patients survived, with a favorable long-term evolution. Only 2 had conservative medical therapy, the other 10 undergoing percutaneous coronary intervention (2 procedures involving a coronary artery bypass graft). On the basis of this series and data from the literature, we suggest a strategy to improve the often dire prognosis of SCAD. Emergency angiography to confirm diagnosis is essential. Treatment should be guided by the extent of the lesions, the myocardial ischemia and the hemodynamic status. Conservative medical therapy is a reasonable approach in the case of distal dissection or conserved coronary flow. Percutaneous coronary intervention is feasible in the acute phase to restore coronary perfusion and hemodynamic stability. Surgery – emergency bypass or assisted circulation – should be restricted to cases where percutaneous coronary intervention has failed or is impossible.
Sodium Load Combined with Low Doses of Exogenous Angiotensin II Upregulate Intrarenal Angiotensin II
Authors: Rosón María Inés , Cao Gabriel , Della Penna Silvana , Gorzalczany Susana , Pandolfo Marcela , Medici Cecilia , Fernández Belisario E. , Toblli Jorge E.
Published: October 2009

Background/Aims: The present study was designed to evaluate the effects of a salt load combined with exogenous low nonhypertensive angiotensin II (Ang II) doses on Ang II intrarenal regulation. Methods: Sprague-Dawley rats were infused with Ang II nonhypertensive doses (0.1 μg·kg–1·h–1 and 5 μg·kg–1·h–1) and saline overload (Na 0.5 M, Na 1.0 M and Na 1.5 M) for 2 h (0.04 ml·min–1). Sodium tubular reabsorption, sodium urinary excretion and mean arterial pressure (MAP) were measured. Ang II was evaluated in the kidneys by immunohistochemistry. Results: Ang II levels in glomeruli and vessels were exacerbated when sodium load and Ang II were given simultaneously, independently of MAP elevation. In tubules, Ang II staining in the presence of sodium overload was greater in the Ang 0.1 groups than in the Ang 5 groups. Compared with the controls, sodium tubular reabsorption rose in the Ang 0.1-Na 0.5 and Ang 0.1-Na 1 groups and sodium urinary excretion decreased in the Ang 5-Na 0.5 and Ang 5-Na 1 groups. MAP increased in the Ang 5-Na 1 and Ang 5-Na 1.5 groups. Conclusion: We conclude that local renal Ang II levels were upregulated when acute sodium overload and nonhypertensive Ang II doses were administered simultaneously in normal rats, independently from blood pressure and glomerular function changes.
Gonadectomy Influences Blood Pressure through the Kallikrein-Kinin System
Authors: Azurmendi Pablo J. , Oddo Elisabet M. , Obika Leonard F. , Corbera Natalia L. , Martín Rodolfo S. , Ibarra Fernando R. , Arrizurieta Elvira E.
Published: October 2009

The kallikrein-kinin system (KKS) appears to be involved in blood pressure regulation. We showed that ovariectomy (oVx) stimulates urinary kallikrein activity (UKa). So, we test whether gonadectomy (Gx) would affect blood pressure through an increase in KKS activity and which mechanism(s) were involved. We studied adult Wistar rats of either sex, with and without Gx. At baseline all groups were normotensive although the oVx mean arterial pressure (MAP) was lower than female MAP (p < 0.05). KKS blockade by aprotinin increased MAP (p < 0.05) exclusively in the oVx group. The probably mechanism(s) involved in KKS regulation (synthesis, renal content and UKa) were also studied. Previous Gx, kallikrein content (nkat/g kidney weight) and UKa (nkat/g kidney weight/day) were higher in female than in male rats: 12 ± 1.1 versus 6 ± 0.7 and 40 ± 6.8 versus 26 ± 3.4, respectively. After Gx, kallikrein content increased significantly in both orchiectomized (oRx) and oVx rats, and UKa showed a similar tendency (NS). Kallikrein synthesis did not show gender difference in non-Gx rats, but an increase after oVx was observed. KKS was found to be involved in blood pressure regulation in oVx animals. oVx may trigger the increase in kallikrein synthesis and content and UKa to act upon blood pressure.
Assessment and Reproducibility of Non-Eosinophilic Asthma Using Induced Sputum
Authors: Simpson Jodie L. , McElduff Patrick , Gibson Peter G.
Published: October 2009

Background: The assessment of eosinophilic airway inflammation using induced sputum identifies a corticosteroid-responsive subtype that can be used to guide anti-inflammatory therapy. The stability of airway inflammation in asthma over time is not known, yet this information is crucial to inflammation-based patient management. Objective: The aim of this study was to determine the reproducibility of non-eosinophilic asthma. Methods: Participants with stable asthma (n = 26) underwent a sputum induction each month for 5 months. Sputum was dispersed and differential cell counts were performed. The reproducibility of inflammatory subtype with different eosinophil cut points (starting at 1% eosinophils) was examined and the minimum number of visits required to determine inflammatory subtype was calculated. Results: One hundred and twenty- two sputum samples were obtained (success 94%). All cut points greater than 2% eosinophils were reproducible and a 3% cut point resulted in the highest agreement with a κ statistic of 0.538. Specificity and sensitivity were high for determining inflammatory subtype after 1 or 3 sputum samples. Conclusions: A cut point of 3% eosinophils should be used to distinguish eosinophilic from non-eosinophilic airway inflammation in asthma. This allows a single sputum sample to be used to reliably determine the presence of eosinophilia.
Alzheimer Disease–Associated Peptide, Amyloid β40, Inhibits Vascular Regeneration With Induction of Endothelial Autophagy
Authors: Hayashi Shin-ichiro , Sato Naoyuki , Yamamoto Akitsugu , Ikegame Yuka , Nakashima Shigeru , Ogihara Toshio , Morishita Ryuichi
Published: October 2009

Objective—

Although the majority of cases of Alzheimer disease (AD) are known to be attributable to the sporadic (nongenetic) form of the disease, the mechanism underlying its cause and progression still remains unclear.

Methods and Results—

We found that vascular β-amyloid (Aβ), Aβ40, inhibited the proliferative activity of human brain vascular endothelial cells (HBECs) without toxic effects on them. This peptide also inhibited tube formation and migration of HBECs. Moreover, Aβ40 inhibited ex vivo hippocampal revascularization, reendothelialization, and the differentiation of adult endothelial progenitor cells. Importantly, Aβ40 suppressed the proliferative activity of HBECs through the induction of “self-digesting” autophagy. This induction involved the intracellular regulation of class 3 phosphatidylinositol 3-kinase (PI3K) as well as Akt signaling in HBECs. Furthermore, tissue culture of murine brain sections from GFP-LC3 transgenic mice revealed that Aβ40 not only reduced the vessel density in hippocampal lesions, but also induced autophagy in neurovascular ECs.

Conclusions—

Our present findings indicate that the initial progression of AD might be in part driven by Aβ40-induced endothelial autophagy and impairment of neurovascular regeneration, suggesting important implications for therapeutic approaches to AD.
A Randomized Clinical Trial to Reduce Patient Prehospital Delay to Treatment in Acute Coronary Syndrome
Authors: Dracup Kathleen , McKinley Sharon , Riegel Barbara , Moser Debra K. , Meischke Hendrika , Doering Lynn V. , Davidson Patricia , Paul Steven M. , Baker Heather , Pelter Michele
Published: October 2009

Background—

Delay from onset of acute coronary syndrome (ACS) symptoms to hospital admission continues to be prolonged. To date, community education campaigns on the topic have had disappointing results. Therefore, we conducted a clinical randomized trial to test whether an intervention tailored specifically for patients with ACS and delivered one-on-one would reduce prehospital delay time.

Methods and Results—

Participants (n=3522) with documented coronary heart disease were randomized to experimental (n=1777) or control (n=1745) groups. Experimental patients received education and counseling about ACS symptoms and actions required. Patients had a mean age of 67±11 years, and 68% were male. Over the 2 years of follow-up, 565 patients (16.0%) were admitted to an emergency department with ACS symptoms a total of 842 times. Neither median prehospital delay time (experimental, 2.20 versus control, 2.25 hours) nor emergency medical system use (experimental, 63.6% versus control, 66.9%) was different between groups, although experimental patients were more likely than control to call the emergency medical system if the symptoms occurred within the first 6 months following the intervention (
P
=0.036). Experimental patients were significantly more likely to take aspirin after symptom onset than control patients (experimental, 22.3% versus control, 10.1%,
P
=0.02). The intervention did not result in an increase in emergency department use (experimental, 14.6% versus control, 17.5%).

Conclusions—

The education and counseling intervention did not lead to reduced prehospital delay or increased ambulance use. Reducing the time from onset of ACS symptoms to arrival at the hospital continues to be a significant public health challenge.

Clinical Trial Registration—

clinicaltrials.gov. Identifier NCT00734760.
Impact of Transradial Coronary Procedures on Radial Artery
Authors: Zhenxian Yan  , Yujie Zhou  , Yingxin Zhao  , Zhiming Zhou  , Shiwei Yang  , Zhijian Wang
Published: October 2009

Objective: We evaluated the impact of transradial coronary procedures on the radial artery (RA). Methods: A total of 355 patients who underwent the transradial coronary procedures including transradial coronary angiography (CAG) and percutaneous coronary intervention (PCI) were enrolled. The right RA (RRA) was examined by ultrasound. Results: The mean RRA diameter was 2.37 ± 0.57, 1.95 ± 0.50, and 2.23 ± 0.41 mm, respectively, before the procedure, 1 day, and 1 month after the procedures (P < .01 at 1 day, P < .05 at 1 month). The mean intima-media thickness of RRA was 0.25 ± 0.12, 0.69 ± 0.31, and 0.38 ± 0.17 mm, respectively, before the procedure, 1 day and 1 month after the procedure (P < .01 at 1 day, P < .05 at 1 month). The incidence of RRA stenosis was 0%, 15.7%, and 7.6%, respectively; the incidence of RRA occlusion was 0%, 2.8%, and 1.7%, respectively, before the procedure,1 day and 1 month after the procedure. Conclusions: Transradial coronary procedures can lead to early RA injury, but this repairs later.
The Contested Politics of Corporate Governance
Authors: Levy David L. , Szejnwald Brown Halina , de Jong Martin
Published: October 2009

The Global Reporting Initiative (GRI) has successfully become institutionalized as the preeminent global framework for voluntary corporate environmental and social reporting. Its success can be attributed to the “institutional entrepreneurs” who analyzed the reporting field and deployed discursive, material, and organizational strategies to change it. GRI has, however, fallen short of the aspirations of its founders to use disclosure to empower nongovernmental organizations (NGOs). The authors argue that its trajectory reflects the power relations between members of the field, their strategic choices and compromises, their ability to mobilize alliances and resources, and constraints imposed by the broader institutions of financial and capital markets. The authors draw three notable implications from this study. First, institutional theory needs to pay more attention to economic structures, strategies, and resources. Second, institutional entrepreneurship by relatively weak societal groups such as NGOs is inherently constrained by the structural power of wider institutions and by the compromises required to initiate change. Third, the strategies of NGOs represent a form of power capable of shifting, if not transforming, the field of corporate governance.
Thermal Conductivity of Carbon-filled Polypropylene-based Resins
Authors: King Julia A. , Lopez Gaxiola Daniel , Johnson Beth A. , Keith Jason M.
Published: October 2009

Varying amounts of three different carbons (carbon black, synthetic graphite particles, and carbon nanotubes) were added to polypropylene, and the resulting single-filler composites were tested for thermal conductivity using the nanoflash test method. In addition, the effects of single fillers and combinations of different carbon fillers were studied via a factorial design. Each single filler caused a statistically significant increase in through-plane thermal conductivity at the 95% confidence level, with synthetic graphite causing the largest increase, followed by carbon nanotubes, and then carbon black. The synthetic graphite/carbon nanotube formulations, followed by the carbon black/synthetic graphite formulations also caused a statistically significant increase in composite through-plane thermal conductivity. Composites containing 75 and 80 wt% synthetic graphite in polypropylene had an in-plane thermal conductivity of 24 and 34 W/m·K, respectively. This meets the thermal conductivity target of >20 W/m·K for fuel cell bipolar plates.
Conservative Design Optimization of Laminated Composite Structures Using Genetic Algorithms and Multiple Failure Criteria
Authors: Satheesh R. , Narayana Naik G. , Ganguli Ranjan
Published: October 2009

This article analyzes the effect of devising a new failure envelope by the combination of the most commonly used failure criteria for the composite laminates, on the design of composite structures. The failure criteria considered for the study are maximum stress and Tsai—Wu criteria. In addition to these popular phenomenological-based failure criteria, a micromechanics-based failure criterion called failure mechanism-based failure criterion is also considered. The failure envelopes obtained by these failure criteria are superimposed over one another and a new failure envelope is constructed based on the lowest absolute values of the strengths predicted by these failure criteria. Thus, the new failure envelope so obtained is named as most conservative failure envelope. A minimum weight design of composite laminates is performed using genetic algorithms. In addition to this, the effect of stacking sequence on the minimum weight of the laminate is also studied. Results are compared for the different failure envelopes and the conservative design is evaluated, with respect to the designs obtained by using only one failure criteria. The design approach is recommended for structures where composites are the key load-carrying members such as helicopter rotor blades.
The Principal’s Role in Professional Development for Social Justice
Authors: Kose Brad W.
Published: October 2009

Literature on principal leadership in professional development offers important but underdeveloped conceptions of how school principals promote professional development for social justice. This article offers an empirically-based framework of the principal’s role in professional development for social justice. An in-depth qualitative multicase study design was used to examine how three school principals for social justice influenced professional learning in their schools. Data collection included 5 months of field work and more than 40 semistructured interviews with principals, teachers, specialists, and other personnel. Data suggest five principal roles worked together to optimize professional learning: transformative visionary, transformative learning leader, transformative structural leader, transformative cultural leader, and transformative political leader.
Applying Expenditure-based Segmentation on Special-Interest Tourists: The Case of Golf Travelers
Authors: Shani Amir , Youcheng Wang  , Hutchinson Joe , Fujun Lai
Published: October 2009

Given the growing competition among golf travel destinations and the increasing costs of managing and maintaining related facilities, it is important to investigate and understand the expenditure patterns of golf travelers. The results of this research provide useful information for golf destination marketers in the development of strategies to attract and retain golf travelers. This study uses an expenditure-based segmentation of golf travelers visiting a Southern Gulf region in the United States. The findings indicate that the heavy spenders exhibit clear spending patterns and are responsible for most of the sample’s total expenditures. The heavy spenders also are well differentiated along golfographic and tripographic measures, but not along sociodemographics and information sources used prior to the vacation. The article ends with an assessment of the contributions of the findings both to the literature on travel expenditure and to golf destination marketers.
Measuring Residents’ Emotional Solidarity with Tourists: Scale Development of Durkheim’s Theoretical Constructs
Authors: Woosnam Kyle M. , Norman William C.
Published: October 2009

While it can prove easy to conceptualize of the relationship between residents and tourists as “us versus them,” it devalues the potential for intimate relationships to exist, whereby residents and tourists have many things in common. The theory of emotional solidarity can aid in explaining such an intimate relationship. Developing the framework from previous qualitative work, the purpose of this study is to formulate and validate scales corresponding to the constructs in Durkheim’s theoretical framework of emotional solidarity. Following two initial stages of pilot testing, each scale is included in an onsite self-administered survey instrument, with 455 heads of household completing the instrument in a coastal South Carolina county. Psychometric properties are assessed and each scale is found to be high in internal consistency and construct validity (i.e., convergent and discriminant validity). Implications as well as potential research opportunities concerning emotional solidarity are discussed.
Question Order and Interviewer Effects in CATI Scale-up Surveys
Authors: Snidero Silvia , Zobec Federica , Berchialla Paola , Corradetti Roberto , Gregori Dario
Published: October 2009

The scale-up estimator is a network-based estimator for the size of hidden or hard to count subpopulations. Several issues arise in the public health context when the aim is the estimation of injuries occurring in a certain population, where two common problems are present: (a) Small injuries are usually difficult to observe and rarely reported in the official data and (b) people are not always compliant in giving information about some specific injuries, in particular when children are involved. This study checked the methodological issues arising from using a computer-assisted telephone interview (CATI) survey using the scale-up methodology for detecting the number of injuries due to choking in children ages 0 to 14 in Italy. For this purpose, 1,000 CATI interviews were conducted during a week using a questionnaire based on 33 questions about populations of known size according to census data. Then, each respondent was asked about other questions related to the main target population (e.g., number of children known to suffer from a choking accident). A sensitivity analysis was conducted for estimating the effect of varying subpopulations, order of the questions, and interviewer effects on the resulting estimates. For the interviewer effect, no particular differences were observed in the overall estimates of injuries. The conclusion is the scale-up estimator in association with CATI methodology shows a high potential in the field of injury prevention, being accurate and robust, but particular attention should be given to the training of the interviewers to improve stability of the estimates.
A Phase I Study to Characterize the Safety, Tolerability, and Pharmacokinetics of Topotecan at 4 mg/m2Administered Weekly as a 30‐Minute Intravenous Infusion in Patients With Cancer
Authors: Curtis Kelly K. , Hartney Jean T. , Jewell Roxanne C. , Park Jung W. , Lebowitz Peter F. , Griffin Pamela P. , Borad Mitesh J. , Fitch Tom R. , Northfelt Donald W.
Published: October 2009

Topotecan pharmacokinetics at higher infusion rates (4 mg/m2over 30 minutes) have not been studied. The authors report a pharmacokinetics and safety study of this dose in advanced cancer patients. Sixteen patients were given a 4‐mg/m2topotecan infusion intravenously (IV) over 30 minutes weekly for 3 weeks, repeated every 28 days. Pharmacokinetics were determined after the first dose. Plasma concentrations of total topotecan were measured to derive CL, Vss, Cmax, tmax, t1/2, AUC0‐t, and AUC0–∞. Plasma total topotecan concentrations decreased biexponentially, with a mean CL value of 20.6 L/h, Vssvalue of 101 L, and t1/2value of 5.0 h. Nine significant adverse events (all hematologic) were topotecan related. Grade 3 or less adverse events included anemia, thrombocytopenia, leukopenia, and fatigue. Pharmacokinetics of the 4‐mg/m2infusion of topotecan over 30 minutes are comparable to findings from studies of lower and higher doses. Toxicities are similar to previous reports.
Clinical Trials of Herbal Treatments
Authors: Turner Ronald B.
Published: October 2009

The deregulation of the marketing of dietary supplements with health claims has increased interest in evaluating the clinical effectiveness of these products. Clinical trials of herbal treatments pose challenges of limited preclinical data, lack of product standardization and characterization, and difficulties of blinding, which are substantially different from those in studies of conventional medications. These issues must be recognized and addressed if studies of herbal remedies are to provide useful information.
Uncertainty Assessment of Input Parameters for Economic Evaluation: Gauss’s Error Propagation, an Alternative to Established Methods
Authors: Stollenwerk Björn , Stock Stephanie , Siebert Uwe , Lauterbach Karl W. , Holle Rolf
Published: October 2009

In decision modeling for health economic evaluation, bootstrapping and the Cholesky decomposition method are frequently used to assess parameter uncertainty and to support probabilistic sensitivity analysis. An alternative, Gauss’s error propagation law, is rarely known but may be useful in some settings. Bootstrapping, the Cholesky decomposition method, and the error propagation law were compared regarding standard deviation estimates of a hypothetic parameter, which was derived from a regression model fitted to simulated data. Furthermore, to demonstrate its value, the error propagation law was applied to German administrative claims data. All 3 methods yielded almost identical estimates of the standard deviation of the target parameter. The error propagation law was much faster than the other 2 alternatives. Furthermore, it succeeded the claims data example, a case in which the established methods failed. In conclusion, the error propagation law is a useful extension of parameter uncertainty assessment.
Landfilling of waste: accounting of greenhouse gases and global warming contributions
Authors: Manfredi Simone , Tonini Davide , Christensen Thomas H. , Scharff Heijo
Published: October 2009

Accounting of greenhouse gas (GHG) emissions from waste landfilling is summarized with the focus on processes and technical data for a number of different landfilling technologies: open dump (which was included as the worst-case-scenario), conventional landfills with flares and with energy recovery, and landfills receiving low-organic-carbon waste. The results showed that direct emissions of GHG from the landfill systems (primarily dispersive release of methane) are the major contributions to the GHG accounting, up to about 1000 kg CO2-eq. tonne—1for the open dump, 300 kg CO2-eq. tonne—1for conventional landfilling of mixed waste and 70 kg CO2-eq. tonne—1for low-organic-carbon waste landfills. The load caused by indirect, upstream emissions from provision of energy and materials to the landfill was low, here estimated to be up to 16 kg CO2-eq. tonne—1. On the other hand, utilization of landfill gas for electricity generation contributed to major savings, in most cases, corresponding to about half of the load caused by direct GHG emission from the landfill. However, this saving can vary significantly depending on what the generated electricity substitutes for. Significant amounts of biogenic carbon may still be stored within the landfill body after 100 years, which here is counted as a saved GHG emission. With respect to landfilling of mixed waste with energy recovery, the net, average GHG accounting ranged from about —70 to 30 kg CO2-eq. tonne— 1, obtained by summing the direct and indirect (upstream and downstream) emissions and accounting for stored biogenic carbon as a saving. However, if binding of biogenic carbon was not accounted for, the overall GHG load would be in the range of 60 to 300 kg CO2-eq. tonne—1. This paper clearly shows that electricity generation as well as accounting of stored biogenic carbon are crucial to the accounting of GHG of waste landfilling.
Global warming factor of municipal solid waste management in Europe
Authors: Gentil Emmanuel , Clavreul Julie , Christensen Thomas H.
Published: October 2009

The global warming factor (GWF; CO2-eq. tonne—1 waste) performance of municipal waste management has been investigated for six representative European Member States: Denmark, France, Germany, Greece, Poland and the United Kingdom. The study integrated European waste statistical data for 2007 in a life-cycle assessment modelling perspective. It is shown that significant GWF benefit was achieved due to the high level of energy and material recovery substituting fossil energy and raw materials production, especially in Denmark and Germany. The study showed that, despite strong regulation of waste management at European level, there are major differences in GWF performance among the member states, due to the relative differences of waste composition, type of waste management technologies available nationally, and the average performance of these technologies. It has been demonstrated through a number of sensitivity analyses that, within the national framework, key waste management technology parameters can influence drastically the national GWF performance of waste management.