bluuebunny/crossref_metadata_2025 huggingface dataset:
MUC1 Expression Is Repressed by Protein Inhibitor of Activated Signal Transducer and Activator of Transcription-y
Authors: Brayman Melissa Jo , Dharmaraj Neeraja , Lagow Errin , Carson Daniel D.
Published: August 2007

Mucin 1 (MUC1) is a transmembrane glycoprotein that modulates the interaction between the embryo and the uterine epithelial cell surface. MUC1 also is a tumor marker and has been implicated in the protection of cancer cells from immune cell attack as well as in cell signaling in some tumors. We and others have shown that MUC1 expression is activated by progesterone (P), TNF-α, and interferon-γ (IFN-γ). Here we demonstrate that MUC1 expression is down-regulated by overexpression of members of the protein inhibitor of activated signal transducer and activator of transcription (PIAS) family, PIAS1, PIAS3, PIASxα, PIASxβ, and PIASy, in human uterine epithelial cell lines HES and HEC-1A and in a breast cancer cell line, T47D. Treatments with P, TNF-α, and IFN-γ were unable to overcome the repression by PIASy. PIASy repression of basal, P-, and TNF-α-stimulated MUC1 promoter activity was not dependent on the PIASy sumoylation domain. In contrast, PIASy suppression of IFN-γ-activated MUC1 promoter activity was dependent on the PIASy sumoylation domain. PIASy and P receptor B were localized to the nucleus upon P treatment, and small interfering RNA knockdown of PIASy resulted in an increase in P-mediated stimulation of MUC1 protein expression. Overexpression of PIASy did not affect P receptor B binding to the MUC1 promoter but surprisingly led to a loss of nuclear receptor corepressor (NCoR), which was recruited to the promoter in response to P. Collectively, these data indicate that PIASy may be a useful target for down-regulation of MUC1 expression in various contexts.
Krüppel-Like Factor 9 Is a Negative Regulator of Ligand-Dependent Estrogen Receptor α Signaling in Ishikawa Endometrial Adenocarcinoma Cells
Authors: Velarde Michael C. , Zeng Zhaoyang , McQuown Jennelle R. , Simmen Frank A. , Simmen Rosalia C. M.
Published: August 2007

Estrogen and progesterone, acting through their respective receptors and other nuclear proteins, exhibit opposing activities in target cells. We previously reported that Krüppel-like factor 9 (KLF9) cooperates with progesterone receptor (PR) to facilitate P-dependent gene transcription in uterine epithelial cells. Here we evaluated whether KLF9 may further support PR function by directly opposing estrogen receptor (ER) signaling. Using human Ishikawa endometrial epithelial cells, we showed that 17β-estradiol (E2)-dependent down-regulation of ERα expression was reversed by a small interfering RNA to KLF9. Transcription assays with the E2-sensitive 4× estrogen-responsive element-thymidine kinase-promoter-luciferase reporter gene demonstrated inhibition of ligand-dependent ERα transactivation with ectopic KLF9 expression. E2 induced PR-A/B and PR-B isoform expression in the absence of effects on KLF9 levels. Addition of KLF9 small interfering RNA augmented E2 induction of PR-A/B while abrogating that of PR-B, indicating selective E2-mediated inhibition of PR-A by KLF9. Chromatin immunoprecipitation of the ERα minimal promoter demonstrated KLF9 promotion of E2-dependent ERα association to a region containing functional GC-rich motifs. KLF9 inhibited the recruitment of the ERα coactivator specificity protein 1 (Sp1) to the PR proximal promoter region containing a half-estrogen responsive element and GC-rich sites, but had no effect on Sp1 association to the PR distal promoter region containing GC-rich sequences. In vivo association of KLF9 and Sp1, but not of ERα with KLF9 or Sp1, was observed in control and E2-treated cells. Our data identify KLF9 as a transcriptional repressor of ERα signaling and suggest that it may function at the node of PR and ER genomic pathways to influence cell proliferation.
Importance of Constitutive Activity and Arrestin-Independent Mechanisms for Intracellular Trafficking of the Ghrelin Receptor
Authors: Holliday Nicholas D. , Holst Birgitte , Rodionova Elena A. , Schwartz Thue W. , Cox Helen M.
Published: August 2007

The ghrelin receptor (GhrelinR) and its related orphan GPR39 each display constitutive signaling, but only GhrelinRs undergo basal internalization. Here we investigate these differences by considering the roles of the C tail receptor domains for constitutive internalization and activity. Furthermore the interaction between phosphorylated receptors and β-arrestin adaptor proteins has been examined. Replacement of the FLAG-tagged GhrelinR C tail with the equivalent GPR39 domain (GhR-39 chimera) preserved Gq signaling. However in contrast to the GhrelinR, GhR-39 receptors exhibited no basal and substantially decreased agonist-induced internalization in transiently transfected HEK293 cells. Internalized GhrelinR and GhR-39 were predominantly localized to recycling compartments, identified with transferrin and the monomeric G proteins Rab5 and Rab11. Both the inverse agonist [d-Arg1, d-Phe5, d-Trp7,9, Leu11] substance P and a naturally occurring mutant GhrelinR (A204E) with eliminated constitutive activity inhibited basal GhrelinR internalization. Surprisingly, we found that noninternalizing GPR39 was highly phosphorylated and that basal and agonist-induced phosphorylation of the GhR-39 chimera was elevated compared with GhrelinRs. Moreover, basal GhrelinR endocytosis occurred without significant phosphorylation, and it was not prevented by cotransfection of a dominant-negative β-arrestin1(319–418) fragment or by expression in β-arrestin1/2 double-knockout mouse embryonic fibroblasts. In contrast, agonist-stimulated GhrelinRs recruited the clathrin adaptor green fluorescent protein-tagged β-arrestin2 to endosomes, coincident with increased receptor phosphorylation. Thus, GhrelinR internalization to recycling compartments depends on C-terminal motifs and constitutive activity, but the high levels of GPR39 phosphorylation, and of the GhR-39 chimera, are not sufficient to drive endocytosis. In addition, basal GhrelinR internalization occurs independently of β-arrestins.
Developing paediatric medicines: identifying the needs and recognizing the challenges
Authors: Ernest Terry B , Elder David P , Martini Luigi G , Roberts Matthew , Ford James L
Published: August 2007

There is a significant need for research and development into paediatric medicines. Only a small fraction of the drugs marketed and utilized as therapeutic agents in children have been clinically evaluated. The majority of marketed drugs are either not labelled, or inadequately labelled, for use in paediatric patients. The absence of suitable medicines or critical safety and efficacy information poses significant risks to a particularly vulnerable patient population. However, there are many challenges associated with developing medicines for the paediatric population and this review paper is intended to highlight these. The paediatric population is made up of a wide range of individuals of substantially varied physical size, weight and stage of physiological development. Experimentation on children is considered by many to be unethical, resulting in difficulties in obtaining critical safety data. Clinical trials are subject to detailed scrutiny by the various regulatory bodies who have recently recognized the need for pharmaceutical companies to invest in paediatric medicines. The costs associated with paediatric product development could result in poor or negative return on investment and so incentives have been proposed by the EU and US regulatory bodies. Additionally, some commonly used excipients may be unsuitable for use in children; and some dosage forms may be undesirable to the paediatric population.
A novel synthetic oleanolic acid derivative with amino acid conjugate suppresses tumour growth by inducing cell cycle arrest
Authors: Lu Xiao-Min , Yi Hong-Wei , Xu Jian-Liang , Sun Yang , Li Jian-Xin , Cao Shao-Xian , Xu Qiang
Published: August 2007

Oleanolic acid (3β-hydroxy-olean-12-en-28-oic acid; OA) has a wide variety of bioactivities and is used for medicinal purposes in many Asian countries. Various derivatives of OA have been synthesized in attempts to improve the potency. Here we describe the anti-tumour activity of a novel OA derivative, N-[(3β)-3-(acetyloxy)-28-oxoolean-12-en-28-yl]-glycine methyl ester (AOA-GMe). AOA-GMe was a more potent inhibitor of the growth of B16 melanoma cells than its parent compound OA, both in-vitro and in-vivo. AOA-GMe also exhibited dose-dependent inhibition of human K562 leukaemia cells, but had almost no toxicity in normal human peripheral blood mononuclear cells. AOA-GMe induced cell cycle arrest in G0/G1 and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D, cyclin-dependent kinase CDK4 and phosphorylated retinoblastoma protein, and increases in the cyclin-dependent kinase inhibitor p15. OA did not show such activities. These results suggest that AOA-GMe may induce growth arrest in tumour cells through regulation of proteins involved in the cell cycle.
Effects of low oxygen levels on the expression and function of transporter OCTN2 in BeWo cells
Authors: Rytting Erik , Audus Kenneth L
Published: August 2007

Although hypoxia is normal in early pregnancy, low placental oxygen concentrations later in pregnancy are often linked to complications such as pre-eclampsia and intrauterine growth restriction. The effects of low oxygen levels on drug and nutrient uptake via the organic cation transporter OCTN2 has been studied in BeWo cells, an in-vitro model of human trophoblast. BeWo cells were cultured under 20% (control) or 2% O2 (hypoxia) for 48 h before each experiment. In-vitro hypoxia was also simulated by the addition of CoCl2 to the cell culture medium. RT-PCR indicated increased transcription of OCTN2 in BeWo cells cultured under hypoxia, but Western blots did not show a corresponding increase in the amount of OCTN2 protein in the hypoxic cells compared with control. Hypoxia resulted in significant reductions in OCTN2-mediated carnitine uptake. Decreased placental transport of carnitine may lead to symptoms of carnitine deficiency in infants from hypoxic pregnancies, whether caused by high altitude, pre-eclampsia or other factors. The OCTN1 substrate ergothioneine reversed the effects of hypoxia on carnitine transport, but identical concentrations of N-acetylcysteine, another water-soluble intracellular antioxidant, did not have the same effect.
Protective effect of (+)-catechin against gastric mucosal injury induced by ischaemia-reperfusion in rats
Authors: Rao Ch V , Vijayakumar M
Published: August 2007

Ischaemia and reperfusion are known to induce gastric lesions, predominantly due to excessive formation of reactive oxygen metabolites, adhesion of neutrophils to endothelial cells, microvascular dysfunction, gastric acid secretion, endogenous histamine and gastrin release. We have studied the effect of (+)-catechin on a gastric ulcer model involving damage to gastric injury by ischaemia-reperfusion (I/R) in rats. (+)-Catechin 50 mg kg−1 administered orally, once daily for three days after the initiation of I/R injury showed a significant (P < 0.001) anti-ulcer activity against mucosal damage. However, (+)-catechin significantly decreased the lipid peroxidation and increased the level of catalase in the I/R condition. Elevated levels of alkaline phosphatase in the I/R group was significantly lowered (P < 0.01) by (+)-catechin. The amount of H+K+ATPase was significantly decreased (P < 0.001) in (+)-catechin-treated as compared with I/R rats. (+)-Catechin significantly decreased elevated plasma histamine (P < 0.05) and corticosterone (P < 0.05). The results suggested that (+)-catechin protected gastric mucosa against ischaemia-reperfusion-induced gastric ulcers by its antioxidant activity and mucus protection.
Involvement of kappa opioid receptors in formalin-induced inhibition of analgesic tolerance to morphine in mice
Authors: Tokuyama Shogo , Nagae Ryuji , Mashida Emiko , Hamabe Wakako
Published: August 2007

This study examined the role of kappa opioid receptors (KOR) in the mechanism underlying tolerance to the analgesic effects of morphine induced by chronic pain. The analgesic effect of morphine (10 mg kg−1), estimated by the tail-flick test in mice, gradually decreased during repeated daily morphine treatment. A significant decrease in the analgesic effect of morphine was seen on the fifth day of repeated morphine treatment compared with the first day. Chronic pain was induced by subcutaneous administration of 2% formalin into the dorsal part of the left hind paw, which significantly inhibited development of tolerance to morphine analgesia. The effect of formalin-induced pain on inhibition of morphine tolerance was reversed by the KOR antagonist nor-binaltorphimine. Furthermore, an antisense oligodeoxynucleotide, but not a missense oligodeoxynucleotide, against KOR completely suppressed the inhibitory effect of formalin-induced pain on morphine tolerance. Naltrindole, an antagonist of delta opioid receptor, did not affect chronic-pain-induced tolerance to morphine. Our findings show that the inhibitory effect of chronic pain on analgesic tolerance to morphine is mediated by KOR rather than delta opioid receptors.
Effects of water-soluble low-molecular-weight β-1, 3-D-glucan (branch β-1, 6) isolated from Aureobasidium pullulans 1A1 strain black yeast on restraint stress in mice
Authors: Kimura Yoshiyuki , Sumiyoshi Maho , Suzuki Takahiro , Suzuki Toshio , Sakanaka Masahiro
Published: August 2007

It is well known that different stress paradigms are able to rapidly induce corticosterone production and immune function through the activation of the hypothalamic-pituitary-adrenal axis. It has been reported that glucocorticoids suppress natural killer (NK) activity and interleukin (IL)-1 production and, on the other hand, that IL-1 and IL-6 stimulate the release of corticotrophin-releasing-hormone from the rat hypothalamus. Moreover, it has been reported that IL-12 plays a central role in the initiation of cell-mediated immunity, directly and via its induction of interferon (IFN)-γ and activation of NK cells. In this study, we examined the effects of water-soluble low-molecular-weight β-glucan isolated from Aureobasidium pullulans 1A1 strain on the corticosterone levels and immune function, such as NK activity and IL-6 and IL-12 production, using a restraint stress-induced mouse model. The water-soluble low-molecular-weight β-glucan at a dose of 50 or 100 mg kg−1 inhibited the increases in the blood corticosterone level and the reduction of NK activity induced by restraint stress. Furthermore, the water-soluble low-molecular-weight β-glucan (100 mg kg−1) prevented the reduction of IL-6 and IL-12 production by splenocytes caused by restraint stress. These findings suggest that the inhibitory actions of water-soluble low-molecular-weight β-glucan on the increase in corticosterone level and reduction of NK activity induced by restraint stress may be associated with the abrogation of the IL-6 and IL-12 reduction caused by the stress. Thus, water-soluble low-molecular-weight β-glucan may be an effective dietary supplement for the prevention of stress.
Lipoproteins and their receptors in embryonic development: more than cholesterol clearance
Authors: Willnow Thomas E. , Hammes Annette , Eaton Suzanne
Published: August 2007

Previously, the relevance of lipoproteins and their receptors has mainly been discussed in terms of cholesterol clearance in the adult organism. Now,findings from nematodes to fruit flies to mammals all point towards novel and unexpected roles for lipoprotein metabolism in the control of key regulatory pathways in the developing embryo, including signaling through steroid hormones and throughout the hedgehog and Wnt signaling pathways. Here, we discuss the emerging view of how lipoproteins and their receptors regulate embryogenesis.
SULF1 and SULF2 regulate heparan sulfate-mediated GDNF signaling for esophageal innervation
Authors: Ai Xingbin , Kitazawa Toshio , Do Anh-Tri , Kusche-Gullberg Marion , Labosky Patricia A. , Emerson Charles P.
Published: August 2007

Heparan sulfate (HS) plays an essential role in extracellular signaling during development. Biochemical studies have established that HS binding to ligands and receptors is regulated by the fine 6-O-sulfated structure of HS;however, mechanisms that control sulfated HS structure and associated signaling functions in vivo are not known. Extracellular HS 6-O-endosulfatases, SULF1 and SULF2, are candidate enzymatic regulators of HS 6-O-sulfated structure and modulate HS-dependent signaling. To investigate Sulf regulation of developmental signaling, we have disrupted Sulf genes in mouse and identified redundant functions of Sulfs in GDNF-dependent neural innervation and enteric glial formation in the esophagus, resulting in esophageal contractile malfunction in Sulf1-/-;Sulf2-/- mice. SULF1 is expressed in GDNF-expressing esophageal muscle and SULF2 in innervating neurons,establishing their direct functions in esophageal innervation. Biochemical and cell signaling studies show that Sulfs are the major regulators of HS 6-O-desulfation, acting to reduce GDNF binding to HS and to enhance GDNF signaling and neurite sprouting in the embryonic esophagus. The functional specificity of Sulfs in GDNF signaling during esophageal innervation was established by showing that the neurite sprouting is selectively dependent on GDNF, but not on neurotrophins or other signaling ligands. These findings provide the first in vivo evidence that Sulfs are essential developmental regulators of cellular HS 6-O-sulfation for matrix transmission and reception of GDNF signal from muscle to innervating neurons.
FoxFis essential for FGF-induced migration of heart progenitor cells in the ascidianCiona intestinalis
Authors: Beh Jeni , Shi Weiyang , Levine Mike , Davidson Brad , Christiaen Lionel
Published: August 2007

Heart development requires precise coordination of morphogenetic movements with progressive cell fate specification and differentiation. In ascidian embryos, FGF/MAPK-mediated activation of the transcription factor Ets1/2 is required for heart tissue specification and cell migration. We found that FoxF is one of the first genes to be activated in heart precursors in response to FGF signaling. We identified the FoxF minimal heart enhancer and used a cis-trans complementation test to show that Ets1/2 can interact with the FoxF enhancer in vivo. Next, we found that FoxF function is required downstream and in parallel to the FGF/MAPK/Ets cascade for cell migration. In addition, we demonstrated that targeted expression of a dominant-negative form of FoxF inhibits cell migration but not heart differentiation, resulting in a striking phenotype: a beating heart at an ectopic location within the body cavity of juveniles. Taken together, our results indicate that FoxF is a direct target of FGF signaling and is predominantly involved in the regulation of heart cell migration.
Porcupine-mediated lipid-modification regulates the activity and distribution of Wnt proteins in the chick neural tube
Authors: Galli Lisa M. , Barnes Tiffany L. , Secrest Stephanie S. , Kadowaki Tatsuhiko , Burrus Laura W.
Published: August 2007

A long-term goal of developmental biology is to understand how morphogens establish gradients that promote proper tissue patterning. A number of reports describe the formation of the Wg (Wnt1) gradient in Drosophila and have shown that Porcupine, a predicted membrane-bound O-acyl transferase, is required for the correct distribution of Wg protein. The discovery that Wnts are palmitoylated on a conserved cysteine residue suggests that porcupine activity and Wnt palmitoylation are important for the generation of Wnt gradients. To establish the role of porcupine in Wnt gradient formation in vertebrates, we tested the role of porcupine/Wnt palmitoylation in human embryonic kidney 293T cells and in the chick neural tube. Our results lead us to conclude that: (1) vertebrate Wnt1 and Wnt3a possess at least one additional site for porcupine-mediated lipid-modification; (2)porcupine-mediated lipid-modification of Wnt proteins promotes their activity in 293T cells and in the chick neural tube; and (3) porcupine-mediated lipid-modification reduces the range of activity of Wnt1 and Wnt3a in the chick neural tube. These findings highlight the importance of porcupine-mediated lipid modifications in the formation of vertebrate Wnt activity gradients.
Requirements for smart materials
Authors: Lloyd P A
Published: August 2007

Smart materials obtain their unique properties by the deliberate introduction of multi-functionality. This can enable the material, or the structure fromwhich it is made, to diagnose its condition or environment, change shape, self-repair, or other functions as developing technology allows. It is argued that any of these functions are only viable if both the costs and benefits are considered on a system-wide basis. Some of the particular requirements and challenges for a number of example applications are considered and some general requirements suggested. It is concluded that such system-wide approach to optimization is a challenge for both designers and for those developing smart materials but it is necessary if the full advantages of smart materials are to be realized.
Some Decomposition Methods for Revenue Management
Authors: Cooper William L. , Homem-de-Mello Tito
Published: August 2007

Working within a Markov decision process (MDP) framework, we study revenue management policies that combine aspects of mathematical programming approaches and pure MDP methods by decomposing the problem by time, state, or both. The “time decomposition” policies employ heuristics early in the booking horizon and switch to a more-detailed decision rule closer to the time of departure. We present a family of formulations that yield such policies and discuss versions of the formulation that have appeared in the literature. Subsequently, we describe sampling-based stochastic optimization methods for solving a particular case of the formulation. Numerical results for two-leg problems suggest that the policies perform well. By viewing the MDP as a large stochastic program, we derive some structural properties of two-leg problems. We show that these properties cannot, in general, be extended to larger networks. For such larger networks we also present a “state-space decomposition” approach that partitions the network problem into two-leg subproblems, each of which is solved. The solutions of these subproblems are then recombined to obtain a booking policy for the network problem.
Pricing in Dynamic Vehicle Routing Problems
Authors: Figliozzi Miguel Andres , Mahmassani Hani S. , Jaillet Patrick
Published: August 2007

The principal focus of this paper is to study carrier pricing decisions for a type of vehicle routing problems defined in a competitive and dynamic environment. This paper introduces the vehicle routing problem in a competitive environment (VRPCE) as an extension of the traveling-salesman problem with profits (TSPP) to a dynamic competitive auction environment. In the VRPCE, the carrier must estimate the incremental cost of servicing new service requests as they arrive dynamically. The paper presents a rigorous and precise treatment of the sequential pricing and costing problem that a carrier faces in such an environment. The sequential pricing problem presented here is an intrinsic feature of a sequential auction problem. In addition to introducing the formulation of this class of problems and discussing the main sources of difficulty in devising a solution, a simple example is constructed to show that carriers’ prices under first-price auction payment rules do not necessarily reflect the cost of servicing transportation requests. An approximate solution approach with a finite rolling horizon is presented and illustrated through numerical experiments, in competition with a static approach with no look-ahead.
TSL Dissertation Abstracts—2006 Transportation Science and Logistics Society Dissertation Prize Competition
Authors: Mark Hickman
Published: August 2007

The Transportation Science and Logistics (TSL) Society Dissertation Prize Competition is the oldest and most prestigious competition for doctoral dissertations in the field. The 2006 TSL dissertation prize committee consisted of Professor Michel Bierlaire (École Polytechnique Fédérale de Lausanne), Professor Ann Campbell (University of Iowa), Professor Alan Erera (Georgia Institute of Technology), Professor Donald Hearn (University of Florida), and Professor Mark Hickman (University of Arizona).

Eligibility was limited to doctoral dissertations completed between June 1, 2005, and May 31, 2006, in the general area of transportation science and logistics. To be considered, a dissertation must have been nominated by the author’s thesis supervisor. This year we received 26 nominations from 24 universities and 10 countries, representing such diverse areas as vehicle routing, vehicle scheduling, traveler behavior, activity analysis, logistics, and supply chain management.

This year’s pool of dissertations was exceptional in both its breadth and depth, showing remarkable theoretical and practical insights into many very interesting problems in transportation and logistics. With the large number of submissions and their exceptional quality, it was not easy for the committee to select a first place winner and an honorable mention. I would like to thank the authors, their advisors, and the prize committee for their part in this effort to recognize and honor the field’s outstanding doctoral researchers. Awards were announced at the TSL meeting at the 2006 INFORMS meeting in Pittsburgh.

Perhaps without saying, the theses nominated for the TSL Dissertation Prize are distinguished by the fact that they were nominated for the award. Each dissertation makes a unique and valuable contribution to transportation science and logistics, and all entrants and their advisors deserve our sincere congratulations.

Abstracts for the 26 dissertations follow; awardees are listed first, and finalists’ abstracts follow in alphabetical order by author.

First Place: Christian Liebchen, Technische Universität Berlin, Germany. Advisors: Rolf H. Möhring and Karl Nachtigall. Title: “Periodic Timetable Optimization in Public Transport”.

Honorable Mention: Anne Goodchild, University of California, Berkeley. Advisor: Carlos Daganzo. Title: “Crane Double Cycling in Container Ports: Algorithms, Evaluation, and Planning”.
Unlabeled Probes for the Detection and Typing of Herpes Simplex Virus
Authors: Dames Shale , Pattison David C , Bromley L Kathryn , Wittwer Carl T , Voelkerding Karl V
Published: August 2007

Background: Unlabeled probe detection with a double-stranded DNA (dsDNA) binding dye is one method to detect and confirm target amplification after PCR. Unlabeled probes and amplicon melting have been used to detect small deletions and single-nucleotide polymorphisms in assays where template is in abundance. Unlabeled probes have not been applied to low-level target detection, however.

Methods: Herpes simplex virus (HSV) was chosen as a model to compare the unlabeled probe method to an in-house reference assay using dual-labeled, minor groove binding probes. A saturating dsDNA dye (LCGreen® Plus) was used for real-time PCR. HSV-1, HSV-2, and an internal control were differentiated by PCR amplicon and unlabeled probe melting analysis after PCR.

Results: The unlabeled probe technique displayed 98% concordance with the reference assay for the detection of HSV from a variety of archived clinical samples (n = 182). HSV typing using unlabeled probes was 99% concordant (n = 104) to sequenced clinical samples and allowed for the detection of sequence polymorphisms in the amplicon and under the probe.

Conclusions: Unlabeled probes and amplicon melting can be used to detect and genotype as few as 10 copies of target per reaction, restricted only by stochastic limitations. The use of unlabeled probes provides an attractive alternative to conventional fluorescence-labeled, probe-based assays for genotyping and detection of HSV and might be useful for other low-copy targets where typing is informative.
Introduction
Authors: BORITZ J. EFRIM
Published: August 2007

Afin de stimuler la réflexion et la discussion, le groupe de travail d'experts sur les marchés financiers (Capital Markets Leadership Task Force — CMLTF) a commandé un document de travail brossant le tableau de l'environnement actuel et approfondissant les questions clés que soulève le maintien de la qualité des marchés financiers canadiens. Ce document de travail porte sur la nature des marchés financiers canadiens, l'analyse des principaux éléments de l'environnement informationnel dans lequel ils évoluent et l'examen de la façon dont les principales parties prenantes contribuent à cet environnement. Il contient des suggestions quant aux mesures à prendre pour maintenir et améliorer l'attrait de ces marchés, en réduisant les risques inutiles d'une information erronée et, ce faisant, en s'assurant que les entreprises canadiennes ont accès aux capitaux au coût le plus bas, toutes choses étant égales. Le CMLTF a accepté le document de travail lors de sa réunion du 5 avril 2006, bien que les opinions qui y sont exprimées soient strictement celles de l'auteur et qu'elles puissent ne pas représenter celles des membres du groupe de travail. La version intégrale du document peut être téléchargée à partir du site Web du CMLTF, http:www.cmltf.ca. Puisque le document de travail avait pour but de stimuler la réflexion et la discussion, trois professeurs bien connus ont été invités à le commenter à la lumière des points de vue exprimés lors du congrès de décembre 2005 par les participants issus des principaux groupes de parties prenantes.
Improving Interim Reporting/L'Amélioration de L'Information Financière Intermédiaire
Authors: Wiedman Christine I.
Published: August 2007

This paper is based on the Interim Reporting session of the Maintaining Quality Capital Markets through Quality Information Conference. Several significant initiatives relating to interim reporting were introduced and debated, including moving to a mandatory review regime in Canada and requiring firms to issue a review engagement report on the interim financial statements to the public. Conference participants were asked to vote on seven questions relating to these initiatives. This paper summarizes the results of the voting and discussion from the conference. Related academic research is also presented.

Le présent article s'inspire de la séance du congrès sur le rôle de la qualité de l'information dans le maintien de la qualité des marchés financiers ayant porté sur l'information financière intermédiaire. Plusieurs projets importants relatifs à l'information financière intermédiaire ont été présentés et débattus, notamment la perspective du passage à un régime d'examen obligatoire au Canada et de l'obligation pour les entreprises de produire un rapport de mission d'examen des états financiers intermédiaires à l'intention du public. Les participants au congrès ont été appelés à voter sur sept questions relatives à ces projets. Le présent article résume les résultats du vote et les discussions tenues dans le cadre du congrès. Des recherches universitaires connexes sont également présentées.
Die Gestalt im Gesicht. Zur Figur Don Quijotes und zu den Strukturen literarischer Reputation
Authors: Witthaus Jan-Henrik
Published: August 2007

The central issue in the self-reflexive development of Don Quijote is an episode in Part I, 19, in which Sancho Panza names his master “Caballero de la Triste Figura.” The early German Quijote-translators Joachim Caesar, Friedrich Justin Bertuch, and Ludwig Tieck rendered the phrase as “Ritter (von) der traurigen Gestalt,” which has been repeatedly criticized. But we may ask whether the alleged mistranslation Gestalt does not have an impact on Cervantes's phrase and not, perhaps, disclose something in it. It may be argued that Figura anticipates the status of the knight as a literary figure. The premise of the second part of the novel is the popularity of the protagonist. The sobriquet that Sacho Panza gives to Don Quijote actually serves as a promise that is fulfilled in the second part of the novel.

Für Siegfried Jüttner zum 66. Geburtstag
Gotische Capricen. Zur Aufnahme François Villons durch Heinrich Heine, Théophile Gautier und Gérard de Nerval
Authors: Häfner Ralph
Published: August 2007

The works of François Villon had a remarkable impact on nineteenth-century literature. In Gérard de Nerval's novella “La Main enchantée” Villon is a “gallant outlaw” (Walter Scott), a favorite figure of the actual protagonist Godinot Chevassut. Nerval himself admired Villon's bohemianism. Théophile Gautier wrote a highly appreciative article on Villon in 1834, which became part of his collection “Les Grotesques” (1844). Heinrich Heine doesn't mention Villon, but four of his poems, “Testament,” “Vermächtniß,” “Der Philanthrop,” and “Rhampsenit,” seem to adopt Villon's legacy for Heine's own age. In the story of the Egyptian king Rhampsenit, Heine incorporates Villon's social and political critique, but in an orientalist perspective dear to the generation of 1830.
Laokoons ältester Sohn. Gewalt und Bildlichkeit bei Peter Weiss
Authors: Buch Robert
Published: August 2007

Peter Weiss' longstanding fascination with images of violence and pain is from the very beginning accompagnied by a certain anxiety and even a sense of guilt. These conflicting attitudes relate not only to descriptions of artworks in “The Aesthetics of Resistance,” but also to the author's two best-known dramatic productions. While the late novelistic trilogy stages the confrontation with iconic representations of violence and pain as one of overwhelming immediacy and presence, “Marat/Sade” effectively dismantles one such icon, David's famous portrait of the revolutionary slain in his bathtub. The other play, The Investigation, programmatically rejects the idea of representing atrocities committed in the concentration camps, but, paradoxically, the self-imposed proscription on images proves to be no less evocative than the ekphrastic ‘image-effects’ of the other two works.
Strain Hardening During Mechanical Twinning and Dislocation Channeling in Irradiated 316 Stainless Steels
Authors: Byun T. S. , Hashimoto N.
Published: August 2007

Localized deformation mechanisms and strain-hardening behaviors in irradiated 316 and 316LN stainless steels were investigated, and a theoretical model was proposed to explain the linear strain-hardening behavior during the localized deformation. After low temperature irradiation to significant doses, the deformation microstructure changed from dislocation tangles to channels or mechanical twins. It was also observed that irradiation hardening straightened gliding dislocations and increased the tendency for forming pileups. Regardless of these microstructural changes, the strain-hardening behavior was relatively insensitive to the irradiation. This dose-independent strain-hardening rate resulted in dose independence of the true stress parameters, such as the plastic instability stress and true fracture stress. In the proposed model, the long-range back stress was formulated as a function of the number of pileup dislocations per slip band and the number of slip bands in a grain. The calculation results confirmed the experimental observation that strain-hardening rate was insensitive to the change in deformation mechanism because the long-range back stress hardening became as high as the hardening by tangled dislocations.
LOX Compatible Toughened Bismaleimide Matrix Thermally Conductive Fiber Composites Part I: Composite Fabrication Viability And Thermal Conductivity Measurement
Authors: Gerzeski Roger
Published: August 2007

ASTM D2512 is the standard test used to determine if a material is liquid oxygen (LOX) compatible. To date all composites considered for use in making a LOX component have failed to pass this test due to their very low in-plane thermal conductivity (K). Since a higher K is usually a hallmark of a LOX compatible material, adequately increasing the in-plane K of a composite will render it D2512 LOX compatible. Good 66.0, 63.2, and 63.1 % fiber volume composites have been fabricated for the first time out of baseline T650-35-UC309 and thermally conductive YSH50A and YSH60A fibers using the toughened bismaleimide matrix 5250-4 RTM. The in-plane K of the thermally conductive fibered composites is within the estimated ∼30 to ∼70 W/mK range that a composite will require to pass D2512.
Cattle in Hawai'i: Biological and Cultural Exchange
Authors: FISCHER JOHN RYAN
Published: August 2007

Capt. George Vancouver fifirst introduced cattle to the Hawaiian Islands in 1793, and the animals rapidly multiplied, roaming wild and causing environmental destruction for decades. In 1832 the Hawaiian monarch imported Mexican vaqueros to train Native Hawaiians in the skills necessary to manage and control the wild livestock, which led to the development of Hawaiian cowboys, known as paniolos, with a unique and locally celebrated cowboy culture that mixes Native Hawaiian elements with vaquero influences. This study of biotic and cultural exchange and native adaptation complicates and adds to our understanding of Hawai‘i’s place in the American West and the cultural factors that encourage and mediate biological invasions.
Wallace Stegner's Arabian Discovery: Imperial Blind Spots in a Continental Vision
Authors: VITALIS ROBERT
Published: August 2007

In 1956 Wallace Stegner wrote a history of the Arabian American Oil Company (Aramco), but it was only published fifteen years later—in Beirut. The book complicates the view of Stegner as a destroyer of American western myths and a forerunner of the social and environmental turn in western history. Stegner shared with those who bought his services some problematic ideas about American identity and history in the context of the Cold War. His forgotten history of oil exploration in Saudi Arabia reveals the blind spots in his “continental vision,” an inability or unwillingness to see the moment as part of the long, unbroken past of the U.S. West. Stegner's journey, from chronicler of the despoiling of the West by eastern oil and copper barons to defender of cultural diversity and the collective commons, stopped, as it has for many other Americanists, at the water's edge.
Segregationists Confront American Empire: The Conservative White South and the Question of Hawaiian Statehood, 1947–1959
Authors: ZIKER ANN K.
Published: August 2007

Legislative and public debate over Hawai‘i”s proposed statehood coincided with the intensification of the African American freedom struggle in the U.S. South as well as the post-World War II rise of anti-colonial nationalism in Africa and Asia. To white racial conservatives, these were interrelated threats; each challenged the once-dominant association of whiteness and access to democracy. This article uncovers and analyzes the widespread grass-roots opposition to Hawaiian statehood among white Southerners. In doing so, it casts post-World War II racial conservatism in a new light: by illustrating how segregationists turned their attention to places far beyond the borders of the U.S. South to defend the ideology that legitimated Jim Crow; by highlighting the persistence of a race-based anti-imperialist sentiment; and by exploring segregationist ideas about race, religion, and the right to self-rule.
Endotoxins do not influence transplacental transmission of lymphotropic human herpesviruses and human papillomaviruses into amniotic fluid taken from healthy mothers before parturition in Hungary
Authors: Younes S. , Csire Márta , Pályi Bernadett , Mikala G. , Vályi-Nagy I. , Cseh I. , Benczik Márta , Jeney Cs. , Takács T. , Simon Éva , Fülöp V. , Berencsi G. , Fekete Gy. , Visy Mária
Published: August 2007

Pregnant women were examined following healthy pregnancies at term. Amniotic fluids were sampled before arteficial rupture of membranes using closed vacutainer system. Blood samples were also taken from the pregnants simultaneously.Endotoxin concentrations of amniotic fluids were tested by the semiquantitative Limulus amebocyte lysate. Both amniotic fluids and blood samples were tested for the presence of DNA of lymphotropic human herpesviruses. The DNA of human papillomaviruses were tested only in the amniotic fluid samples.One-third of the amniotic fluids tested were found to contain measurable amounts of endotoxin. Lymphotropic herpesvirus DNA was deteced in every fourth amniotic fluid sample and in every 8
th
blood sample. The prevalence of papillomaviruses was 7 of 96 samples.No significant correlation was found between the presence of endotoxin and viruses in the amniotic fluids. Epstein-Barr virus, human cytomegalovirus and human herpesvirus type 7 were found more frequently in the amniotic fluids than in blood samples (7 to 1). The prevalence of human herpesvirus 6 and 8 was higher in the blood samples than that in the amniotic fluids.The mean weight of the neonates were not impaired significantly by the presence of either viruses or endotoxin. Possible post partum consequences, i.e. partial immunotolerance to viruses is discussed.
Structural transformation of the capital stock and capital-saving technical change
Authors: Szalavetz A.
Published: August 2007

We argue that the information technology revolution has brought about the differentiation of secular capital-using and labour-saving direction of technical change. Based on the example of the US manufacturing industry, asset and sector specific differences in the bias of technical change are documented. While the clear ICT- and intangible capital-using bias of technical change is well-documented in the literature, this paper provides evidence for the non-ICT capital-saving bias of technical change in the fifth Kondratieff cycle. In the past decade the US manufacturing sector displayed a noticeable deceleration of capital accumulation and capital intensity increase, a trend that diverges from the one observed in the other two sectors of the economy: in agriculture and in services. Non-ICT capital-saving technical change provokes increasing divergence between the development strategies of technological followers (characterised by tangible investment-led growth, and increasing capital-output ratios), and of technological leaders (marked by increasing intangible capital-intensity and diminishing tangible capital-intensity).
Development of silent gastric carcinoid in a type 1 diabetic patient with primer hypothyreosis
Authors: Somogyi Anikó , Ruzicska Éva , Varga Timea , Rácz Károly , Nagy Géza
Published: August 2007

Az 1-es típusú cukorbetegség gyakran társul egyéb autoimmun kórképekkel. A parietalis sejtellenes antitestek (PCA), melyek az 1-es típusú cukorbetegek mintegy 20%-ában megtalálhatók, autoimmun gastritis és anaemia perniciosa jelenlétére figyelmeztetnek. A PCA-k a gyomor-H
+
/K
+
ATP-ázt károsítják, és hypo-/achlorhydriát, hypergastrinaemiát okozhatnak. Ennek következtében az enterochromaffin-szerű (ECL) sejtek hyper-/dysplasiaja alakulhat ki, mely carcinoid gyomortumor kialakulására hajlamosít. Az ECL-sejtek hyperplasiájából fejlődő gyomorcarcinoidok az autoimmun gastritises vagy anaemia perniciosában szenvedő betegek 4–9%-ában alakulnak ki. A 29 éves, 6 éve 1-es típusú diabéteszben szenvedő, 8 éves kora óta primer hypothyreosis miatt pajzsmirigyhormon-szubsztitúcióban részesülő nőbetegünknél gyomorpanaszok miatt felső panendoszkópia és biopsziás vizsgálat történt. Az endoszkópia többszörös kicsi polipokat mutatott a fundus területén nonantral hypergastrinaemiás (A-típusú) atrophiás gastritissel. A parietalis sejtantitest-vizsgálat pozitív volt, a szérum-chromogranin-A koncentrációja (CgA) 289,7 ng/ml (norm: 98 ng/ml alatt), a TSH-szint 9,93 mIU/L volt. A szövettani vizsgálat carcinoid tumort igazolt. Octreotidterápiát követően parciális gastrectomiát végeztek. Műtét után a szérum-chromogranin-A-szint normalizálódott. A nonatral, többszörös polipok néma neuroendocrin tumort takarhatnak, melyek rendszerint lassan növekvő, benignus viselkedésű endokrin daganatok, de magas malignitású endokrin karcinómák is lehetnek. A specifikus szérum- vagy szöveti chromogranin-A (CgA) és egyéb endokrin tumorra utaló markerek mérésének elérhetővé válásával e tumorok könnyen felismerhetők lehetnek a klinikus számára.
Self-Renewal of Murine Embryonic Stem Cells Is Supported by the Serine/Threonine Kinases Pim-1 and Pim-3
Authors: Aksoy Irène , Sakabedoyan Caline , Bourillot Pierre-Yves , Malashicheva Anna B. , Mancip Jimmy , Knoblauch Kenneth , Afanassieff Marielle , Savatier Pierre
Published: August 2007

pim-1 and pim-3 encode serine/threonine kinases involved in the regulation of cell proliferation and apoptosis in response to cytokine stimulation. We analyzed the regulation of pim-1 and pim-3 by the leukemia inhibitory factor (LIF)/gp130/signal transducer and activator of transcription-3 (STAT3) pathway and the role of Pim-1 and Pim-3 kinases in mouse embryonic stem (ES) cell self-renewal. Making use of ES cells expressing a granulocyte colony-stimulating factor:gp130 chimeric receptor and a hormone-dependent signal transducer and activator of transcription-3 estrogen receptor (STAT3-ERT2), we showed that expression of pim-1 and pim-3 was upregulated by LIF/gp130-dependent signaling and the STAT3 transcription factor. ES cells overexpressing pim-1 and pim-3 had a greater capacity to self-renew and displayed a greater resistance to LIF starvation based on a clonal assay. In contrast, knockdown of pim-1 and pim-3 increased the rate of spontaneous differentiation in a self-renewal assay. Knockdown of pim-1 and pim-3 was also detrimental to the growth of undifferentiated ES cell colonies and increased the rate of apoptosis. These findings provide a novel role of Pim-1 and Pim-3 kinases in the control of self-renewal of ES cells.

Disclosure of potential conflicts of interest is found at the end of this article.
The autocyclic nature of glaciations
Authors: Van Vliet-Lanoë Brigitte
Published: August 2007

The maximum extent of a glaciation is often confused with the coldest part of a glaciation. During the Last Glaciation, the date of the Last Ice Maximum Extent (LIME) is diachronous very early at high latitudes close to the traditional date in the intertropical mountains. The classical Last Glacial Maximum (LGM) never corresponds to the LIME with the exception of intertropical regions. At middle and high latitudes advances of the LGM only correspond to surges of a lately thickened ice sheet. The same structure also exists at the level of the entire Cenozoic of a whole glaciation or of much shorter events as the scale of a whole Bond’s cycle. For each type of event the reactional sequence is autocyclic: a rapid warming ends a slowly cooling trend due to the higher susceptibility of lower latitudes to external forcing (orbital and solar activity). Moisture supply from an ice-free ocean is the sine qua non to build glaciers. The syngenetic extent of the cold desert toward the equator is the limiting factor for ice volume: when glaciations develop in intertropical mountains with the development of sea ice in the polar zones, glaciers recede by precipitation starvation with restricted sedimentation. During a glacial era in parallel with ice cap building, the progressive sea level lowering and the subsequent enhanced aridity counterbalance the generalization of a world-scale glaciation. This concept could be also valid for the Neoproterozoic Glacial era and should probably invalidate the snowball hypothesis.