bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting AML through DR4 with a novel variant of rhTRAIL
Authors: Szegezdi Eva , Reis Carlos R. , Sloot Almer M. van der , Natoni Alessandro , O’Reilly Aoife , Reeve Janice , Cool Robbert H. , O’Dwyer Michael , Knapper Steven , Serrano Luis , Quax Wim J. , Samali Afshin
Published: November 2010

Despite progress in the treatment of acute myelogenous leukaemia (AML) the outcome often remains poor. Tumour necrosis factor related apoptosis‐inducing ligand (TRAIL) is a promising therapeutic agent in many different types of tumours, but AML cells are relatively insensitive to TRAIL‐induced apoptosis. Here we show that TRAIL‐induced apoptosis in AML cells is predominantly mediated by death receptor 4 (DR4) and not DR5. Therefore, we constructed a variant of TRAIL (rhTRAIL‐C3) that is a strong inducer of DR4‐mediated apoptosis. TRAIL‐C3 demonstrated much stronger pro‐apoptotic activity than wild‐type (WT) TRAIL in a panel of AML cell lines as well as in primary AML blasts. The higher pro‐apoptotic potential was further enhanced when the TRAIL mutant was used in combination with BMS‐345541, a selective inhibitor of inhibitor‐κB kinases. It illustrates that combination of this TRAIL variant with chemotherapeutics or other targeted agents can kill AML with high efficacy. This may represent a major advantage over the currently used therapies that have serious toxic side effects. The high efficacy of rhTRAIL‐C3 containing therapies may enable the use of lower drug doses to reduce the toxic side effects and improve patient outcome. Our findings suggest that the rational design of TRAIL variants that target DR4 potentiate the death‐inducing activity of TRAIL and offer a novel therapeutic strategy for the treatment of AML.
Down‐regulated miR‐331–5p and miR‐27a are associated with chemotherapy resistance and relapse in leukaemia
Authors: Feng Dan‐Dan , Zhang Hua , Zhang Peng , Zheng Yu‐Sheng , Zhang Xing‐Ju , Han Bo‐Wei , Luo Xue‐Qun , Xu Ling , Zhou Hui , Qu Liang‐Hu , Chen Yue‐Qin
Published: November 2010

Multidrug resistance (MDR) and disease relapse are challenging clinical problems in the treatment of leukaemia. Relapsed disease is frequently refractory to chemotherapy and exhibits multiple drug resistance. Therefore, it is important to identify the mechanism by which cancer cells develop resistance. In this study, we used microRNA (miRNA) microarray and qRT‐PCR approaches to investigate the expression of miRNAs in three leukaemia cell lines with different degrees of resistance to doxorubicin (DOX) compared with their parent cell line, K562. The expression of miR‐331–5p and miR‐27a was inversely correlated with the expression of a drug‐resistant factor, P‐glycoprotein (P‐gp), in leukaemia cell lines with gradually increasing resistance. The development of drug resistance is regulated by the expression of the P‐gp. Transfection of the K562 and, a human promyelocytic cell line (HL) HL60 DOX‐resistant cells with miR‐331–5p and miR‐27a, separately or in combination, resulted in the increased sensitivity of cells to DOX, suggesting that correction of altered expression of miRNAs may be used for therapeutic strategies to overcome leukaemia cell resistance. Importantly, miR‐331–5p and miR‐27a were also expressed at lower levels in a panel of relapse patients compared with primary patients at diagnosis, further illustrating that leukaemia relapse might be a consequence of deregulation of miR‐331–5p and miR‐27a.
Melatonin, a novel Sirt1 inhibitor, imparts antiproliferative effects against prostate cancer in vitro in culture and in vivo in TRAMP model
Authors: Jung‐Hynes Brittney , Schmit Travis L. , Reagan‐Shaw Shannon R. , Siddiqui Imtiaz A. , Mukhtar Hasan , Ahmad Nihal
Published: November 2010

Abstract:  We recently demonstrated that Sirt1, a NAD+‐dependent histone deacetylase, was overexpressed in prostate cancer (PCa) and its inhibition resulted in a significant antiproliferative response in human PCa cells. Studies have suggested a link between Sirt1 and circadian rhythms, the disruption of which has been linked to cancer. Interestingly, a decreased production of the pineal melatonin has been shown to deregulate the circadian rhythm machinery and increase cancer risk. Furthermore, disruption in melatonin production and circadian rhythmicity has been associated with aging. Here, we challenged our hypothesis that melatonin will impart antiproliferative response against PCa via inhibiting Sirt1. We demonstrated that melatonin significantly inhibited Sirt1 protein and activity in vitro in multiple human PCa cell lines, and melatonin‐mediated Sirt1 inhibition was accompanied with a significant decrease in the proliferative potential of PCa cells, but not of normal cells. Forced overexpression of Sirt1 partially rescued the PCa cells from melatonin’s antiproliferative effects, suggesting that Sirt1 is a direct target of melatonin. Employing transgenic adenocarcinoma of mouse prostate (TRAMP) mice, we also demonstrated that oral administration of melatonin, at human‐achievable doses, significantly inhibited PCa tumorigenesis as shown by decreases in (i) prostate and genitourinary weight, (ii) serum insulin‐like growth factor‐1 (IGF‐1)/IGF‐binding protein‐3 (IGFBP3) ratio, (iii) mRNA and protein levels of the proliferation markers (PCNA, Ki‐67). This anti‐PCa response was accompanied with a significant decrease in Sirt1 in TRAMP prostate. Our data identified melatonin as a novel inhibitor of Sirt1 and suggest that melatonin can inhibit PCa growth via Sirt1 inhibition.
Association of RNA with the uracil‐DNA‐degrading factor has major conformational effects and is potentially involved in protein folding
Authors: Bekesi Angela , Pukancsik Maria , Haasz Peter , Felfoldi Lilla , Leveles Ibolya , Muha Villo , Hunyadi‐Gulyas Eva , Erdei Anna , Medzihradszky Katalin F. , Vertessy Beata G.
Published: November 2010

Recently, a novel uracil‐DNA‐degrading factor protein (UDE) was identified in Drosophila melanogaster, with homologues only in pupating insects. Its unique uracil‐DNA‐degrading activity and a potential domain organization pattern have been described. UDE seems to be the first representative of a new protein family with unique enzyme activity that has a putative role in insect development. In addition, UDE may also serve as potential tool in molecular biological applications. Owing to lack of homology with other proteins with known structure and/or function, de novo data are required for a detailed characterization of UDE structure and function. Here, experimental evidence is provided that recombinant protein is present in two distinct conformers. One of these contains a significant amount of RNA strongly bound to the protein, influencing its conformation. Detailed biophysical characterization of the two distinct conformational states (termed UDE and RNA–UDE) revealed essential differences. UDE cannot be converted into RNA–UDE by addition of the same RNA, implying putatively joint processes of RNA binding and protein folding in this conformational species. By real‐time PCR and sequencing after random cloning, the bound RNA pool was shown to consist of UDE mRNA and the two ribosomal RNAs, also suggesting cotranslational RNA‐assisted folding. This finding, on the one hand, might open a way to obtain a conformationally homogeneous UDE preparation, promoting successful crystallization; on the other hand, it might imply a further molecular function of the protein. In fact, RNA‐dependent complexation of UDE was also demonstrated in a fruit fly pupal extract, suggesting physiological relevance of RNA binding of this DNA‐processing enzyme.
Boar Taint Detection Using Parasitoid Biosensors
Authors: Wäckers Felix , Olson Dawn , Rains Glen , Lundby Frank , Haugen John‐Erik
Published: November 2010

Abstract:  The off‐flavor boar taint associated with the substances skatole, androstenone, and possibly indole represents a significant problem in the pig husbandry industry. Boar taint may occur in meat from uncastrated sexually mature male pigs; consumers commonly show a strong aversion to tainted meat. Consequently, there is a need for rapid methods to sort out and remove tainted carcasses at the slaughterline. We tested the ability of wasps, Microplitis croceipes to perceive and learn the 3 boar taint compounds both individually and in combination using classical conditioning paradigms. We also established the effectiveness and reliability of boar taint odor detection when wasps were used as biosensors in a contained system called the “wasp hound” using a cohort of trained wasps. We found that the wasps are able to successfully learn indole, skatole and to also detect them when presented a 1: 1: 1 mixture of all 3 compounds. This was shown for both a single hand‐manipulated wasp bioassay and when using the “wasp hound” detector device. In contrast, the wasps showed a weak conditioned response to androstenone at the concentration tested. The estimated gas phase concentrations that the wasps perceived during training were in the range of 10 ± 0.4 pg/s for skatole and indole, and 2 ± 0.5 pg/s for androstenone. We conclude that use of these wasps as biosensors presents a promising method for boar taint detection and discuss future training paradigms that may improve their responses to compounds such as androstenone.

Practical Application:  The development of a perceptive, inexpensive, and reliable means of detecting boar taint before the product is presented to sensitive consumers.
The cell biology of human hair follicle pigmentation
Authors: Tobin Desmond J.
Published: November 2010

Although we have made significant progress in understanding the regulation of the UVR‐exposed epidermal‐melanin unit, we know relatively little about how human hair follicle pigmentation is regulated. Progress has been hampered by gaps in our knowledge of the hair growth cycle’s controls, to which hair pigmentation appears tightly coupled. However, pigment cell researchers may have overly focused on the follicular melanocytes of the nocturnal and UVR‐shy mouse as a proxy for human epidermal melanocytes. Here, I emphasize the epidermis‐follicular melanocyte pluralism of human skin, as research models for vitiligo, alopecia areata and melanoma, personal care/cosmetics innovation. Further motivation could be in finding answers to why hair follicle and epidermal pigmentary units remain broadly distinct? Why melanomas tend to originate from epidermal rather than follicular melanocytes? Why multiple follicular melanocyte sub‐populations exist? Why follicular melanocytes are more sensitive to aging influences? In this perspective, I attempt to raise the status of the human hair follicle melanocyte and highlight some species‐specific issues involved which the general reader of the pigmentation literature (with its substantial mouse‐based data) may not fully appreciate.
Evaluation of phacoemulsification‐induced oxidative stress and damage of cultured human corneal endothelial cells in different solutions using redox fluorometry microscopy
Authors: Nishi Yutaro , Engler Christoph , Na Dae Ro , Kashiwabuchi Renata T. , Shin Young Joo , Cano Marisol , Jun Albert S. , Chuck Roy S.
Published: November 2010

Acta Ophthalmol. 2010: 88: e323–e327

Purpose:  To describe the basic concept of redox fluorometry microscopy and investigate its efficacy in evaluating the state of cultured human corneal endothelial cells in different solutions when ultrasonic energy was applied in vitro.

Methods:  Human corneal endothelial cells from human donor tissue not suitable for transplantation were cultured. A phacoemulsification probe with a 30° round, 1.1‐ mm TurboSonics® ABS™ Tip (Alcon, Fort Worth, Texas) was introduced into culture dishes filled with balanced salt solution (BSS) and BSS plus (Alcon, Fort Worth, Texas). Cellular autofluorescence images were obtained using a Zeiss inverted microscope. The redox fluorometric ratio, which can be related to cellular metabolism, mitochondrial distribution patterns, which can shift in reaction to environmental changes, and cell size were analysed with a software program.

Results:  Human corneal endothelial cells exposed to increasing phacoemulsification times and ultrasonic energy displayed dose‐dependent decreases in redox ratios. At a lower ultrasonic power and time, BSS plus showed significantly less change in redox ratio than BSS and control (p < 0.05, Mann–Whitney test). As ultrasonic power and time increased, BSS plus had no more significance.

Conclusion:  Redox fluorometry, with further technological improvement, might be an interesting and potentially useful tool for evaluation of phacoemulsification‐induced corneal endothelial damage and screening of protective agents in vitro.
The effects of hyperoxic ventilation in the treatment of myocardial infarction
Authors: CONTI C. RICHARD
Published: November 2010

Everyone supports the use of oxygen therapy to treat hypoxia secondary to acute myocardial infarction. However, the literature is confusing on the subject of supplemental oxygenation of patients with normal oxygen saturation and uncomplicated acute myocardial infarction, despite the fact that controlled randomized human studies have failed to support the need for supplemental oxygen in the uncomplicated patient. Both normobaric and hyperbaric oxygen must be recognized as a vasoactive substance and thus be considered a drug to which the patient may have an adverse response, particularly in patients whose oxygen saturation is 95% or greater, for example, coronary vasoconstriction.

The level of evidence for the use of normobaric oxygenation in uncomplicated acute myocardial infarction patients who were not hypoxemic is based on expert opinion, case studies and ‘standard of care’. Hyperbaric oxygen therapy has not been shown to be beneficial in human studies.

Most studies of the use of supplemental oxygen in humans with acute myocardial infarction were performed prior to modern aggressive medical therapy and current thrombolytic or percutaneous coronary intervention therapy. Perhaps a randomized clinical trial in patients with normal oxygen saturations and modern therapy will shed some light on the subject.
Parallel Dynamic Optimization of Steel Risers
Authors: Tanaka Rafael L. , Martins Clóvis de A.
Published: November 2010

This paper addresses the use of optimization techniques in the design of a steel riser. Two methods are used: the genetic algorithm, which imitates the process of natural selection, and the simulated annealing, which is based on the process of annealing of a metal. Both of them are capable of searching a given solution space for the best feasible riser configuration according to predefined criteria. Optimization issues are discussed, such as problem codification, parameter selection, definition of objective function, and restrictions. A comparison between the results obtained for economic and structural objective functions is made for a case study. Optimization method parallelization is also addressed.
Fabrication of three-dimensional structures for the assessment of cell mechanical interactions within cell monolayers
Authors: Fuard David , Moussus Michel , Tomba Caterina , Peyrade David , Nicolas Alice
Published: November 2010

The measurement of the forces at play in cell/cell adhesion uses a cell monolayer plated onto two-dimensional substrate like arrays of elastomeric microfabricated pillars. Unfortunately, the few attempts that have been done in this direction do not mimic the extracellular environment and lack knowledge on the correlation between the various types of cellular adhesions. Here, the authors suggest using a new experimental setup that more accurately simulates the three-dimensional (3D) environment of cells in tissues, using stretchable hexagonal monocellular 3D structures. The present article shows a way of fabricating these hexagonal biosensors, which are open structures made of biocompatible elastomeric polydimethylsiloxane (PDMS). The novelty of the whole fabrication process of these 3D PDMS structures consists in the use of a sacrificial silicon mold. An original mechanical PDMS planarization process is proposed. This article also describes a strategy for a selective functionalization of the 3D structure sidewalls where the cells must adhere.
Development of a high density integrated reference genetic linkage map for the multinational Brassica rapa Genome Sequencing ProjectThis article is one of a selection of papers from the conference “Exploiting Genome-wide Association in Oilseed Brassicas: a model for genetic improvement of major OECD crops for sustainable farming”.
Authors: Li Xiaonan , Ramchiary Nirala , Choi Su Ryun , Van Nguyen Dan , Hossain Md. Jamil , Yang Hyeon Kook , Lim Yong Pyo
Published: November 2010

We constructed a high-density Brassica rapa integrated linkage map by combining a reference genetic map of 78 doubled haploid lines derived from Chiifu-401-42 × Kenshin (CKDH) and a new map of 190 F2lines derived from Chiifu-401-42 × rapid cycling B. rapa (CRF2). The integrated map contains 1017 markers and covers 1262.0 cM of the B. rapa genome, with an average interlocus distance of 1.24 cM. High similarity of marker order and position was observed among the linkage groups of the maps with few short-distance inversions. In total, 155 simple sequence repeat (SSR) markers, anchored to 102 new bacterial artificial chromosomes (BACs) and 146 intron polymorphic (IP) markers were mapped in the integrated map, which would be helpful to align the sequenced BACs in the ongoing multinational Brassica rapa Genome Sequencing Project (BrGSP). Further, comparison of the B. rapa consensus map with the 10 B. juncea A-genome linkage groups by using 98 common IP markers showed high-degree colinearity between the A-genome linkage groups, except for few markers showing inversion or translocation. Suggesting that chromosomes are highly conserved between these Brassica species, although they evolved independently after divergence. The sequence information coming out of BrGSP would be useful for B. juncea breeding. and the identified Arabidopsis chromosomal blocks and known quantitative trait loci (QTL) information of B. juncea could be applied to improve other Brassica crops including B. rapa.
Future tools for association mapping in crop plantsThis article is one of a selection of papers from the conference “Exploiting Genome-wide Association in Oilseed Brassicas: a model for genetic improvement of major OECD crops for sustainable farming”.
Authors: Duran Chris , Eales Dominic , Marshall Daniel , Imelfort Michael , Stiller Jiri , Berkman Paul J. , Clark Terry , McKenzie Megan , Appleby Nikki , Batley Jacqueline , Basford Kaye , Edwards David
Published: November 2010

Association mapping currently relies on the identification of genetic markers. Several technologies have been adopted for genetic marker analysis, with single nucleotide polymorphisms (SNPs) being the most popular where a reasonable quantity of genome sequence data are available. We describe several tools we have developed for the discovery, annotation, and visualization of molecular markers for association mapping. These include autoSNPdb for SNP discovery from assembled sequence data; TAGdb for the identification of gene specific paired read Illumina GAII data; CMap3D for the comparison of mapped genetic and physical markers; and BAC and Gene Annotator for the online annotation of genes and genomic sequences.
(k, s)-POSITIVITY AND VANISHING THEOREMS FOR COMPACT KÄHLER MANIFOLDS
Authors: YANG QILIN
Published: November 2010

We study the (k, s)-positivity for holomorphic vector bundles on compact complex manifolds. (0, s)-positivity is exactly the Demailly s-positivity and a (k, 1)-positive line bundle is just a k-positive line bundle in the sense of Sommese. In this way we get a unified theory for all kinds of positivities used for semipositive vector bundles. Several new vanishing theorems for (k, s)-positive vector bundles are proved and the vanishing theorems for k-ample vector bundles on projective algebraic manifolds are generalized to k-positive vector bundles on compact Kähler manifolds.
GRÖBNER–SHIRSHOV BASES AND EMBEDDINGS OF ALGEBRAS
Authors: BOKUT L. A. , CHEN YUQUN , MO QIUHUI
Published: November 2010

In this paper, by using Gröbner–Shirshov bases, we show that in the following classes, each (respectively, countably generated) algebra can be embedded into a simple (respectively, two-generated) algebra: associative differential algebras, associative Ω-algebras, associative λ-differential algebras. We show that in the following classes, each countably generated algebra over a countable field k can be embedded into a simple two-generated algebra: associative algebras, semigroups, Lie algebras, associative differential algebras, associative Ω-algebras, associative λ-differential algebras. We give another proofs of the well known theorems: each countably generated group (respectively, associative algebra, semigroup, Lie algebra) can be embedded into a two-generated group (respectively, associative algebra, semigroup, Lie algebra).
ON LABEL INFORMATION INCORPORATED METRIC LEARNING FOR REGRESSIONS
Authors: JIN CHENG , LONG YANGJING
Published: November 2010

We present a distance metric learning algorithm for regression problems, which incorporates label information to form a biased distance metric in the process of learning. We use Newton's optimization method to solve an optimization problem for the sake of learning this biased distance metric. Experiments show that this method can find the intrinsic variation trend of data in a regression model by a relative small amount of samples without any prior assumption of the structure or distribution of data. In addition, the test sample data can be projected to this metric by a simple linear transformation and it is easy to be combined with manifold learning algorithms to improve the performance. Experiments are conducted on the FG-NET aging database, the UIUC-IFP-Y aging database, and the CHIL head pose database by Gaussian process regression based on the learned metric, which shows that our method is competitive among the start-of-art.
DIFFERENT MORPHOLOGIES OFTiO2NANOSTRUCTURES IN ACIDIC AND BASIC SOL–GEL METHOD
Authors: IMANIEH M. H. , VAHIDSHAD Y. , NOURPOUR P. , SHAKESI S. , SHABANI K.
Published: November 2010

In this research, nanocrystalline titanium dioxide (TiO2) particles were prepared by a modified alkoxide technique under basic and acidic conditions at room temperatures. A simple method for preparing different morphology of TiO2has been developed. The reaction condition was used to control the crystalline size, phase and morphology of the TiO2nanostructures. In this process by adjusting the Rw(water to precursor ratio) and pH value the hydrolysis and condensation reactions were controlled. This led to the development of a new process to produce TiO2nanorod (for the first time by sol–gel method) at high pH value (basic) while the water content was sufficient whereas at low pH value (acidic) nanosphere TiO2were obtained. The powders were characterized by DTA, XRD, FE-SEM and UV–vis techniques and their physical properties were compared.
LIGHT PROPAGATING IN METAL SUB-WAVELENGTH-HOLE ARRAYS
Authors: TANG YONGAN , VLAHOVIC BRANISLAV , BRADY DAVID J.
Published: November 2010

We investigate the light propagating through a sub-wavelength-hole array in a thin gold film. The extraordinary light transmission (ELT) of the metallic array is observed. This ELT is due to the localized plasmon polaritons, whose production are dependent on the polarization of the light, the periodicity of the array, the features of the hole, and the thickness of the gold film. These parameters of the metallic structures are investigated through the finite difference time domain method. It is possible to obtain a desired transmission spectrum from the sub-wavelength-hole array by designing these parameters.
Pathogen-induced heart rate changes associated with cholinergic nervous system activation
Authors: Fairchild Karen D. , Srinivasan Varadamurthy , Randall Moorman J. , Gaykema Ronald P. A. , Goehler Lisa E.
Published: November 2010

The autonomic nervous system plays a central role in regulation of host defense and in physiological responses to sepsis, including changes in heart rate and heart rate variability. The cholinergic anti-inflammatory response, whereby infection triggers vagal efferent signals that dampen production of proinflammatory cytokines, would be predicted to result in increased vagal signaling to the heart and increased heart rate variability. In fact, decreased heart rate variability is widely described in humans with sepsis. Our studies elucidate this apparent paradox by showing that mice injected with pathogens demonstrate transient bradyarrhythmias of vagal origin in a background of decreased heart rate variability (HRV). Intraperitoneal injection of a large inoculum of Gram-positive or Gram-negative bacteria or Candida albicans rapidly induced bradyarrhythmias of sinus and AV nodal block, characteristic of cardiac vagal firing and dramatically increased short-term HRV. These pathogen-induced bradycardias were immediately terminated by atropine, an antagonist of muscarinic cholinergic receptors, demonstrating the role of vagal efferent signaling in this response. Vagal afferent signaling following pathogen injection was demonstrated by intense nuclear c-Fos activity in neurons of the vagal sensory ganglia and brain stem. Surprisingly, pathogen-induced bradycardia demonstrated rapid and prolonged desensitization and did not recur on repeat injection of the same organism 3 h or 3 days after the initial exposure. After recovery from the initial bradycardia, depressed heart rate variability developed in some mice and was correlated with elevated plasma cytokine levels and mortality. Our findings of decreased HRV and transient heart rate decelerations in infected mice are similar to heart rate changes described by our group in preterm neonates with sepsis. Pathogen sensing and signaling via the vagus nerve, and the desensitization of this response, may account for periods of both increased and decreased heart rate variability in sepsis.
Surface-Immobilized Aptamers for Cancer Cell Isolation and Microscopic Cytology
Authors: Wan Yuan , Kim Young-tae , Li Na , Cho Steve K. , Bachoo Robert , Ellington Andrew D. , Iqbal Samir M.
Published: November 2010

Exposing rare but highly malignant tumor cells that migrate from the primary tumor mass into adjacent tissue(s) or circulate in the bloodstream is critical for early detection and effective intervention(s). Here, we report on an aptamer-based strategy directed against epidermal growth factor receptor (EGFR), the most common oncogene in glioblastoma (GBM), to detect these deadly tumor cells. GBMs are characterized by diffuse infiltration into normal brain regions, and the inability to detect GBM cells renders the disease surgically incurable with a median survival of just 14.2 months. To test the sensitivity and specificity of our platform, anti-EGFR RNA aptamers were immobilized on chemically modified glass surfaces. Cells tested included primary human GBM cells expressing high levels of the wild-type EGFR, as well as genetically engineered murine glioma cells overexpressing the most common EGFR mutant (EGFRvIII lacking exons 2–7) in Ink4a/Arf-deficient astrocytes. We found that surfaces functionalized with anti-EGFR aptamers could capture both the human and murine GBM cells with high sensitivity and specificity. Our findings show how novel aptamer substrates could be used to determine whether surgical resection margins are free of tumor cells, or more widely for detecting tumor cells circulating in peripheral blood to improve early detection and/or monitoring residual disease after treatment. Cancer Res; 70(22); 9371–80. ©2010 AACR.
Liver Transplantation for Congenital Biliary Dilatation: A Single-Center Experience
Authors: Hori Tomohide , Oike Fumitaka , Ogura Yasuhiro , Ogawa Kohei , Hata Koichiro , Yonekawa Yukihide , Ueda Mikiko , Sakamoto Seisuke , Kasahara Mureo , Egawa Hiroto , Takada Yasutsugu , Kaido Toshimi , Hatano Etsuro , Nguyen Justin H. , Chen Feng , Baine Ann-Marie T. , Uemoto Shinji
Published: November 2010

Background: Congenital biliary dilatation is a rare disease. Although the possibility of refractory cholangitis and/or the frequency of malignant tumors legitimize hepatobiliary surgery, repeated cholangitis and biliary obstruction result in secondary liver cirrhosis even after polysurgery. There are no definitive guidelines on liver transplantation for congenital biliary dilatation. Patients: A total of 1,101 liver transplantation recipients were enrolled in this study. Eleven patients with congenital biliary dilatation including 5 patients with Caroli’s disease were retrospectively analyzed in detail. Results: Nine of 11 patients underwent initial operations before liver transplantation while 2 patients with Caroli’s disease received liver transplantation as initial surgery, with good outcomes. All patients had intractable symptoms caused by liver cirrhosis, and growth delay was considerable in patients aged <20 years. Histopathological analysis of the native liver revealed hepatic fibrosis (≧F2). One patient with ABO incompatibility died. One patient with Caroli’s disease accompanied with intrahepatic carcinoma survives 11.8 years after liver transplantation without any recurrences. Conclusions: Patients with congenital biliary dilatation with refractory symptoms and complications secondary to liver failure are appropriate candidates for liver transplantation. We suggest that liver transplantation is an effective therapeutic option for patients with congenital biliary dilatation with due consideration to many accompanying factors, such as clinical course, growth delay, image findings and histopathological analysis.
Knockout of Angiotensin 1–7 Receptor Mas Worsens the Course of Two-Kidney, One-Clip Goldblatt Hypertension: Roles of Nitric Oxide Deficiency and Enhanced Vascular Responsiveness to Angiotensin II
Authors: Rakušan Dan , Bürgelová Marcela , Vaněčková Ivana , Vaňourková Zdeňka , Husková Zuzana , Škaroupková Petra , Mrázová Iveta , Opočenský Martin , Kramer Herbert J. , Netuka Ivan , Malý Jan , Alenina Natalia , Bader Michael , Santos Robson A.S. , Červenka Luděk
Published: November 2010

Aims: The present study was performed to evaluate the effects of target disruption of the G-protein-coupled receptor Mas for angiotensin 1–7 [Ang(1–7)] in knockout mice on the course of two-kidney, one-clip (2K1C) Goldblatt hypertension. Methods: Knockout and wild-type mice underwent clipping of one renal artery. Blood pressure (BP) was monitored by radiotelemetry. The mice were either untreated or chronically treated with the superoxide (O2–) scavenger tempol (400 mg/l) or the inhibitor of NADPH oxidase apocynin (1 g/l) administered in drinking water. Results: Knockout mice responded to clipping by accelerated increases in BP and the final BP was significantly higher than that in wild-type mice. Chronic treatment with tempol or apocynin elicited similar antihypertensive effects in 2K1C/knockout as in 2K1C/wild-type mice. Acute nitric oxide synthase inhibition caused greater BP increases in 2K1C/wild-type than in 2K1C/knockout mice. Conclusion: Our present findings support the notion that the angiotensin-converting enzyme 2-Ang(1–7)-Mas axis serves as an important endogenous physiological counterbalancing mechanism that partially attenuates the hypertensinogenic actions of the activated renin-angiotensin system. The impairment in this axis may contribute to the deterioration of the course of 2K1C Goldblatt hypertension.
Glycated Hemoglobin Predicts Mortality in Nondiabetic Patients Receiving Chronic Peritoneal Dialysis
Authors: Chen Kuan-Hsing , Lin Ja-Liang , Lin-Tan Dan-Tzu , Hsu Ching-Wei , Huang Wen-Hung , Yen Tzung-Hai , Weng Shu-Man , Hung Cheng-Chieh
Published: November 2010

Background: Patients with chronic peritoneal dialysis (CPD) use glucose-based dialysate to maintain their life; however, whether the glycemic status influences outcome of these patients without diabetes remains unknown. Methods: We conducted a cross-sectional and 18-month prospective study, and 269 nondiabetic patients with CPD were enrolled in a medical center. Glycated hemoglobin (HbA1c) levels were measured at baseline and categorized in tertiles of HbA1c: high (>5.4%), middle (5.1–5.4%) and low normal (<5.1%). Mortality and cause of death were recorded for longitudinal analyses. Results: The study results showed high HbA1c group patients had a trend of being older and having higher body mass index (BMI) than other group patients. Stepwise multiple linear regression analysis showed HbA1c was positively related to age, BMI and the peritoneal solute transport rate. After 18 months of follow-up, Cox multivariate analysis showed that HbA1c (HR: 4.114; 95% CI: 1.426–11.872; p = 0.009) was the significant risk factor for all-cause mortality after relating variables were adjusted. Moreover, high HbA1c (HR: 3.892; 95% CI: 1.273–11.959; p = 0.026) and low HbA1c (HR: 1.179; 95% CI: 1.160–1.198; p = 0.039), with middle HbA1c group as the reference, also significantly predicted for mortality in these patients. Conclusions: HbA1c levels, or presence of low or high HbA1c, are associated with 18-month all-cause mortality in nondiabetic patients with CPD.
Diminished Antioxidant Activity of High-Density Lipoprotein–Associated Proteins in Systolic Heart Failure
Authors: Tang W.H. Wilson , Wu Yuping , Mann Shirley , Pepoy Michael , Shrestha Kevin , Borowski Allen G. , Hazen Stanley L.
Published: November 2010

Background—

Diminished serum arylesterase activity, catalyzed by the high-density lipoprotein–associated paraoxonase-1, is associated with heightened systemic oxidative stress and atherosclerosis risk. In the present study, we sought to determine the prognostic role of serum arylesterase activity in subjects with systolic heart failure, particularly in relation to established cardiac biomarkers.

Methods and Results—

We measured serum arylesterase activity in 760 subjects with impaired left ventricular systolic function (left ventricular ejection fraction <50%), and prospectively followed major adverse cardiac events (including death, nonfatal myocardial infarction, and stroke) for 3 years. In our study cohort (mean age, 64±11 years; 74% men; median left ventricular ejection fraction, 35%; median creatinine clearance, 96 mg/dL), mean serum arylesterase activity (98±25 μmol/L/min/mL) was lower compared with that in healthy control subjects (mean, 115±26 μmol/L/min/mL,
P
<0.01) but higher compared with advanced decompensated heart failure subjects (mean, 69±22 μmol/L/min/mL,
P
<0.01). Within our cohort, there was modest correlation between serum arylesterase activity and high-density lipoprotein cholesterol (
r
=0.33,
P
<0.01) as well as B-type natriuretic peptide (
r
=−0.23,
P
<0.01). Lower serum arylesterase activity was a strong predictor of poorer outcomes (hazard ratio, 2.94; 95% confidence interval, 1.54, 5.62;
P
<0.001). After adjusting for traditional risk factors, medication use, B-type natriuretic peptide, and creatinine clearance, lower serum arylesterase still conferred an increased risk of major adverse cardiac events at 3 years (hazard ratio, 2.69; 95% confidence interval, 1.37 to 5.28;
P
=0.004).

Conclusions—

In patients with systolic heart failure, decreased serum arylesterase activity, a measure of diminished antioxidant properties of high-density lipoprotein, predicts higher risk of incident long-term adverse cardiac event independent of established clinical and biochemical risk factors.
Six-Month Results of the NEVO RES-ELUTION I (NEVO RES-I) Trial
Authors: Ormiston John A. , Abizaid Alexandre , Spertus John , Fajadet Jean , Mauri Laura , Schofer Joachim , Verheye Stefan , Dens Joseph , Thuesen Leif , Dubois Christophe , Hoffmann Rainer , Wijns William , Fitzgerald Peter J. , Popma Jeffrey J. , Macours Nathalie , Cebrian Ana , Stoll Hans-Peter , Rogers Campbell , Spaulding Christian ,   on behalf of the NEVO ResElution-I Investigators
Published: November 2010

Background—

Drug-eluting stents reduce restenosis and reintervention rates but are complicated by stent thrombosis, which may be related to polymer coating. The NEVO sirolimus-eluting coronary stent (NEVO SES) is designed to improve long-term percutaneous coronary intervention safety by combining sirolimus release from reservoirs with bioabsorbable polymer to reduce spatial and temporal polymer exposure.

Methods and Results—

NEVO ResElution-I was a prospective randomized study in 394 patients with coronary artery disease comparing the NEVO SES with the TAXUS Liberté paclitaxel-eluting coronary stent (TAXUS Liberté PES) stent. The primary end point was in-stent angiographic late loss at 6 months. Six months after percutaneous coronary intervention (PCI), the primary end point favored NEVO SES (0.13±0.31 mm versus 0.36±0.48 mm,
P
<0.001 for noninferiority and superiority). The study was not powered for clinical end points and showed no significant difference for NEVO SES versus TAXUS Liberté PES: death: 0.5 versus 1.6%,
P
=0.36; myocardial infarction: 2.0 versus 2.6%,
P
=0.75; target lesion revascularization: 1.5 versus 3.2%,
P
=0.33; major adverse cardiac events: 4.0 versus 7.4%,
P
=0.19. No stent thrombosis was observed with NEVO SES, whereas 2 cases occurred in TAXUS Liberté PES. Intravascular ultrasound showed lower percent volume obstruction for NEVO SES (5.5±11% versus 11.5±9.7%,
P
=0.016).

Conclusions—

This trial proved the superiority of NEVO SES over TAXUS Liberté PES for the primary angiographic end point of in-stent late loss. No stent thrombosis occurred in the NEVO SES group.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00606333.
Weight Approximation in Stroke Before Thrombolysis
Authors: Breuer Lorenz , Nowe Tim , Huttner Hagen B. , Blinzler Christian , Kollmar Rainer , Schellinger Peter D. , Schwab Stefan , Köhrmann Martin
Published: November 2010

Background and Purpose—

Because of the narrow therapeutic range for thrombolysis in stroke, accurate weight-based dosing is essential for efficacy and safety. Stroke patients are frequently incapable to communicate their correct body weight (BW). Thus, dosing is often based on BW estimation, which may lead to dosing errors. The aim of our study was to evaluate availability of BW information, accuracy of estimations, and final dosing of Alteplase (tissue plasminogen activator [tPA]) in a routine clinical setting.

Methods—

A total of 109 consecutive intravenous thrombolysis patients were prospectively included in the study. Recruitment concluded with 100 complete data sets. Before therapy, BW was estimated independently by 2 physicians, 2 emergency nurses, and a neuroradiological technical assistant. Patients were weighed, and anthropometric measurements for BW approximation were taken. Dosing errors were assessed. Clinical outcome was evaluated at 90 days.

Results—

Of 109 patients, 55 (50.5%) were unable to provide information on their BW. Of those, 11 (20%) were accompanied by relatives able to give BW information. For all patients, estimation errors rates ranged from 20.8% (patient’s own estimation) up to 38.2% (treating physician) and 42.2% (emergency nurse). Finally, 29 patients received an Alteplase dosage diverging >10% from the optimal dose. Twelve were under- and 17 overdosed. Underdosage was an independent predictor for worse outcome in multivariate analysis.

Conclusions—

Our study shows that reliable BW data are missing for a majority of intravenous thrombolysis patients. Measuring BW before administering Alteplase remains challenging. Given dosing errors in one-third of patients and the observed impact on outcome, standardized weighing before thrombolysis should be considered.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006434.
Whistle Pig Saloon: Performing Technologies
Authors: Ferguson John Robert , van Heumen Robert
Published: November 2010

The authors discuss their practice of technologically mediated improvisation while exploring questions about the relationship of performers to technology.
Montanism and Present Day “Prophets”
Authors: Robeck Cecil M.
Published: November 2010

Over the past decade and a half, William Tabbernee, the world’s leading authority on Montanism or the New Prophecy, has written four major works on the subject. Three of them are reviewed in this article. One looks at Montanism through the eyes of church and state; a second provides documentation for the identification of the headquarters city of the Montanists; and the third puts the two together in a creative narrative. These three volumes are placed within the context of larger issues surrounding the history of this powerful prophetic movement that originated in late second-century Asia Minor and subsequently spread throughout the Roman Empire up until the sixth century. The reactions and responses of various orthodox Christian leaders and secular government officials to the claims of this highly independent prophetic movement, which called for more reliance upon the spontaneity of the Holy Spirit and a more conservative personal ethic, suggest strong parallels between Montanism and what might be found in today’s Charismatic, New Apostolic, and Emerging Church movements.
Behold Adam: A Reading of John 19:5
Authors: Litwa M. David
Published: November 2010

This essay offers a theological interpretation of Pilate’s famous phrase “Behold the man!” (δο νρωπος, John 19:5) in light of two proposed intertextual echoes: Genesis 3:22 and Vita Adae et Evae 13:3. Both texts feature the phrase “Behold the man/Adam.” In each case, the phrase prima facie highlights Adam’s divinity, but ironically underscores the frailty of his humanity. In John 19:5, however, the phrase “Behold the man” functions in the opposite manner. Although on the surface it highlights Jesus’ ridiculousness and misery, it ironically manifests his divine sovereignty. The essay concludes by suggesting that the Fourth Evangelist echoes the earlier phrase “Behold the man/Adam” to generate a contrast between Adam and Christ.
Arab Women Bloggers: The Emergence of Literary Counterpublics
Authors: Elsadda Hoda
Published: November 2010

Cyberspace as a forum for expression, mobilization, dissent and the organization of alternative social and political networks has been a distinct feature of the new global order since the 1990s. Cyberspace as a forum for alternative expression is also making inroads in the Arabic literary establishment. In 2008, Dar al-Shorouq, an established privately-owned Egyptian publishing house, published three collections of short stories by three women bloggers, Ghada 'Abd al-'Aal, Rihab Bassam and Ghada Mohamed Mahmoud. In this article, I argue that cyberspace, particularly the noted proliferation of literary blogs and blogging among Arab youth, has created new literary public spheres, or 'competing counterpublics', that are breaking the monopoly of mainstream literary spaces and changing tastes. I also argue that cyberspace has been particularly conducive to the participation of women in the literary field, and pose questions about the implications of the emergence of cyber counterpublics on the Arab literary establishment and the canon of Arabic literature.
Discourse Prominence and Pe-marking in Romanian
Authors: von Heusinger Klaus , Chiriacescu Sofiana
Published: November 2010

Referential expressions are used to introduce and continue reference to entities with particular referential properties, but also with particular discourse properties. In this paper we investigate the referential and discourse properties of pe-marked indefinite direct objects in Romanian, which are an instance of Diff erential Object Marking (DOM). Pe-marking is generally obligatory for definite noun phrases but optional for indefinite ones. The optionality of pe marking with indefinite descriptions constitutes the focus of the present article. We will show that, on the one hand, pe with indefinite descriptions allows the realization of referential properties such as specific or wide scope readings, but that on the other hand, pe also signals discourse prominence, in particular in such contexts where referential properties are neutralized. We assume three parameters for discourse prominence, namely referential persistence, the topic-shift potential and the type of anaphoric referring expressions. We used these three parameters in a web-based story continuation experiment. The findings of the experiment revealed several interesting patterns: (i) that pe -marked direct objects are referentially more persistent than their unmarked counterparts, (ii) that pe -marked direct objects show a systematic preference to become topics two or three sentences after being introduced in the discourse, and (iii) that (modified) definite NPs were chosen to refer back to the referent of the marked as well as to the referent of the unmarked direct object. On the basis of the first two parameters we conclude that the relevant discourse contribution of pe is to signal to the hearer that subsequent information about that referent will follow, whereas the third parameter indicates that the referent of the pe -marked indefinite is not necessarily associated with a high level of activation. The general findings of the experiment support Kehler et al.'s (2008) intuition to differentiate between referential persistence and the activation level of the referent.
An Estimation of Turbulent Characteristics in the Low-Level Region of Intense Hurricanes Allen (1980) and Hugo (1989)
Authors: Zhang Jun A. , Marks Frank D. , Montgomery Michael T. , Lorsolo Sylvie
Published: November 2010

This study analyzes the flight-level data collected by research aircraft that penetrated the eyewalls of category 5 Hurricane Hugo (1989) and category 4 Hurricane Allen (1980) between 1 km and the sea surface. Estimates of turbulent momentum flux, turbulent kinetic energy (TKE), and vertical eddy diffusivity are obtained before and during the eyewall penetrations. Spatial scales of turbulent eddies are determined through a spectral analysis. The turbulence parameters estimated for the eyewall penetration leg are found to be nearly an order of magnitude larger than those for the leg outside the eyewall at similar altitudes. In the low-level intense eyewall region, the horizontal length scale of the dominant turbulent eddies is found to be between 500 and 3000 m, and the corresponding vertical length scale is approximately 100 m. The results suggest also that it is unwise to include eyewall vorticity maxima (EVM) in the turbulence parameter estimation because the EVMs are likely to be quasi-two-dimensional vortex structures that are embedded within the three-dimensional turbulence on the inside edge of the eyewall.

This study is a first attempt at estimating the characteristics of turbulent flow in the low-level troposphere of an intense eyewall using in situ aircraft observations. The authors believe that the results can offer useful guidance in numerical weather prediction efforts aimed at improving the forecast of hurricane intensity. Because of the small sample size analyzed in this study, further analyses of the turbulent characteristics in the high-wind region of hurricanes are imperative.