bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroblastoma of unknown primary site with periorbital bone metastasis in a child
Authors: Salmi Darren , Patel Chirag , Imashuku Shinsaku , Shimada Hiroyuki , Satake Noriko
Published: April 2010

Neuroblastoma is the second most common solid tumor in children. Most tumors arise in the adrenal glands or paravertebral region. Rarely, patients present with metastatic disease but no primary site can be found despite extensive imaging. We report here a patient with a large periorbital bone metastasis and bone marrow involvement but with no known primary site. Pediatr Blood Cancer. © 2010 Wiley‐Liss, Inc.
Randomized trial to compare LSA2L2‐type maintenance therapy to daily 6‐mercaptopurine and weekly methotrexate with vincristine and dexamethasone pulse for children with acute lymphoblastic leukemia
Authors: Nagatoshi Yoshihisa , Matsuzaki Akinobu , Suminoe Aiko , Inada Hiroko , Ueda Kouichiro , Kawakami Kiyoshi , Yanai Fumio , Nakayama Hideki , Moritake Hiroshi , Itonaga Nobuyoshi , Hotta Noriko , Fujita Kyoko , Hidaka Yasufumi , Yamanaka Takeharu , Kawano Yoshifumi , Okamura Jun
Published: April 2010

Background

A total of 201 pediatric cases of acute lymphoblastic leukemia were treated with the ALL‐96 protocol by the Kyushu‐Yamaguchi Children's Cancer Study Group.

Procedure

Risk stratification was based on white cell counts, immunophenotype, the presence of central nervous system disease at diagnosis, organomegaly, and early treatment response (day 14 bone marrow status). All of the patients were classified into standard‐risk (SR) or high‐risk (HR) groups and were randomly assigned to receive maintenance therapy with either LSA2L2‐type or 6‐mercaptopurine (6‐MP)/methotrexate (MTX) with vincristine (VCR) and dexamethasone (DEX) pulse in both risk groups.

Results

The 7‐year event‐free survival (EFS) and overall survival (OS) rates in the entire study population were 72.1% (95% CI: 68.0–76.2%) and 84.8% (95% CI: 79.7–89.9%), respectively, and the EFS of the SR patients (85.3% [95% CI: 78.2–92.4%]) was significantly better than HR patients (62.4% [95% CI: 52.2–72.6%]) (P = 0.0007).

Conclusions

There were no differences in the EFS between the different maintenance therapies in each risk group; however, grade IV liver toxicity occurred more often in the patients receiving 6‐MP/MTX with VCR and DEX therapy than in patients receiving LSA2L2. Pediatr Blood Cancer. © 2010 Wiley‐Liss, Inc.
Review of polymer materials with low dielectric constant
Authors: Zhao Xiong‐Yan , Liu Hong‐Jie
Published: April 2010

One of the exciting and promising developments in material science today is the design and synthesis of novel low‐dielectric‐constant polymer materials, which are found to have potential applications in the field of ultralarge‐scale integration, capacitors and other electronic circuits as insulating and/or dielectric materials. In this article the new polymer dielectric materials reported in recent years are reviewed, including aromatic (heteroaromatic) polymers, silicon‐containing polymers, fluorinated polymers, porous polymers, etc. In summarizing the review, the development, potential applications and future directions of polymer materials with low dielectric constant are discussed. Copyright © 2010 Society of Chemical Industry
Differential proteomic analysis using isotope‐coded protein‐labeling strategies: Comparison, improvements and application to simulated microgravity effect on Cupriavidus metallidurans CH34
Authors: Leroy Baptiste , Rosier Caroline , Erculisse Vanessa , Leys Natalie , Mergeay Max , Wattiez Ruddy
Published: April 2010

Among differential proteomic methods based on stable isotopic labeling, isotope‐coded protein labeling (ICPL) is a recent non‐isobaric technique devised to label primary amines found in proteins. ICPL overcomes some of the disadvantages found in other chemical‐labeling techniques, such as iTRAQ or ICAT. However, previous analyses revealed that more than 30% of the proteins identified in regular ICPL generally remain unquantified. In this study, we describe a modified version of ICPL, named Post‐digest ICPL, that makes it possible to label and thus to quantify all the peptides in a sample (bottom–up approach). Optimization and validation of this Post‐digest ICPL approach were performed using a standard protein mixture and complex protein samples. Using this strategy, the number of proteins that were identified and quantified was greatly increased in comparison with regular ICPL and cICAT approaches. The pros and cons of this improvement are discussed. This complementary approach to traditional ICPL was applied to the analysis of modification of protein abundances in the model bacterium Cupriavidus metallidurans CH34 after cultivation under simulated microgravity. In this context, two different systems – a 2‐D clinorotation and 3‐D random positioning device – were used and the results were compared and discussed.
Protein reference mapping of dihydrofolate reductase‐deficient CHO DG44 cell lines using 2‐dimensional electrophoresis
Authors: Lee Jae Seong , Park Hyun Ju , Kim Young Hwan , Lee Gyun Min
Published: April 2010

Chinese hamster ovary (CHO) cells are the major mammalian host for producing various therapeutic proteins. Among CHO cells, the dihydrofolate reductase‐deficient CHO DG44 cell line has been used as a popular mammalian host because of the availability of a well‐characterized genetic selection and amplification system. However, this cell line has not been studied at the proteome level. Here, the first detailed proteome analysis of the CHO DG44 cell line is described. A protein reference map of the CHO DG44 cell line was established by analyzing whole cellular proteins using 2‐DE with various immobilized pH gradients (pHs 3–10, 5–8, and 3–6) in the first dimension and a 12% acrylamide gel in the second dimension. The map is composed of over 1400 silver‐stained protein spots. Among them, 179 protein spots, which represent proteins associated with various biological processes and cellular compartments, were identified based on MALDI‐TOF‐MS and MS/MS. This proteome database should be valuable for better understanding of CHO cell physiology and protein expression patterns which may lead to efficient therapeutic protein production.
Analysis of hepatic glycogen‐associated proteins
Authors: Stapleton David , Nelson Chad , Parsawar Krishna , McClain Donald , Gilbert‐Wilson Ryan , Barker Elizabeth , Rudd Brant , Brown Kevin , Hendrix Wayne , O'Donnell Paul , Parker Glendon
Published: April 2010

Glycogen particles are associated with a population of proteins that mediate its biological functions, including: management of glucose flux into and out of the glycogen particle, maintenance of glycogen structure and regulation of particle size, number, and cellular location. A survey of the glycogen‐associated proteome would be predicted to identify the relative representation of known members of this population, and associations with unexpected proteins that have the potential to mediate other functions of the glycogen particle. We therefore purified glycogen particles from both mouse and rat liver, using different techniques, and analyzed the resulting tryptic peptides by MS. We also specifically eluted glycogen‐binding proteins from the pellet using malto‐oligosaccharides. Comparison of the rat and mouse populations, and analysis of specifically eluted proteins allow some conclusions to be made about the hepatic glycogen sub‐proteome. With the exception of glycogen branching enzyme all glycogen metabolic proteins were detected. Novel associations were identified, including ferritin and starch‐binding domain protein 1, a protein that contains both a transmembrane endoplasmic reticulum signal peptide and a carbohydrate‐binding module. This study therefore provides insight into the organization of the glycogen proteome, identifies other associated proteins and provides a starting point to explore the dynamic nature and cellular distribution of this metabolically important protein population.
The essentiality of α‐2‐macroglobulin in human salivary innate immunity against new H1N1 swine origin influenza A virus
Authors: Chen Chao‐Hsuan , Zhang Xing‐Quan , Lo Chih‐Wei , Liu Pei‐Feng , Liu Yu‐Tsueng , Gallo Richard L. , Hsieh Ming‐Fa , Schooley Robert T. , Huang Chun‐Ming
Published: April 2010

A novel strain of influenza A H1N1 emerged in the spring of 2009 and has spread rapidly throughout the world. Although vaccines have recently been developed that are expected to be protective, their availability was delayed until well into the influenza season. Although anti‐influenza drugs such as neuraminidase inhibitors can be effective, resistance to these drugs has already been reported. Although human saliva was known to inhibit viral infection and may thus prevent viral transmission, the components responsible for this activity on influenza virus, in particular, influenza A swine origin influenza A virus (S‐OIV), have not yet been defined. By using a proteomic approach in conjunction with beads that bind α‐2,6‐sialylated glycoprotein, we determined that an α‐2‐macroglobulin (A2M) and an A2M‐like protein are essential components in salivary innate immunity against hemagglutination mediated by a clinical isolate of S‐OIV (San Diego/01/09 S‐OIV). A model of an A2M‐based “double‐edged sword” on competition of α‐2,6‐sialylated glycoprotein receptors and inactivation of host proteases is proposed. We emphasize that endogenous A2M in human innate immunity functions as a natural inhibitor against S‐OIV.
Proteomic analysis reveals novel binding partners of MIP‐T3 in human cells
Authors: Guo Chao‐Wan , Xiong Sheng , Liu Ge , Wang Yi‐Fei , He Qing‐Yu , Zhang Xian‐En , Zhang Zhi‐Ping , Ge Feng , Kitazato Kaio
Published: April 2010

MIP‐T3 (microtubule‐interacting protein associated with TRAF3) is a microtubule‐interacting protein that evolutionarily conserved from worms to humans, but whose cellular functions remains unknown. To get insight into the functions of MIP‐T3, we set out to identify MIP‐T3 interacting proteins by immunoprecipitation in human embryonic kidney 293 cells and MS analysis. As the results, a total of 34 proteins were identified and most of them were novel MIP‐T3 putative partners. The MIP‐T3‐associated proteins could be grouped into nine clusters based on their molecule functions, including cytoskeleton, chaperone, nucleic acid binding, kinase and so on. Three MIP‐T3‐interacted proteins – actin, HSPA8 and tubulin – were further confirmed by reciprocal coimmunoprecipitations and colocalization analysis. The interaction of MIP‐T3 with both actin filaments and microtubule suggested that MIP‐T3 may play an important role in regulation of cytoskeleton dynamics in cells. Our results therefore not only uncover a large number of MIP‐T3‐associated proteins that possess a variety of cellular functions, but also provide new research directions for the study of the functions of MIP‐T3.
Detection of respiratory events using pulse rate in children with and without obstructive sleep apnea
Authors: Noehren Anke , Brockmann Pablo E. , Urschitz Michael S. , Sokollik Christiane , Schlaud Martin , Poets Christian F.
Published: April 2010

Oximetry is a simple but insensitive diagnostic test modality for obstructive sleep apnea (OSA) in children. Sensitivity for OSA may be enhanced if pulse rate is analyzed in conjunction with oxygen saturation. We analyzed 25 ambulatory polysomnographic recordings obtained from children with (n = 5) and without (n = 20) OSA. To assess sensitivity and specificity, pulse rate increases were determined during respiratory (i.e., apneas and hypopneas; n = 965) and non‐respiratory sleep events (i.e., body movements; n = 1,197), and contrasted to baseline fluctuations (n = 209). The absolute pulse rate increase (APRI) was the parameter that differentiated best between baseline fluctuations and sleep events (area under the receiver operating characteristic curve [AUC]: 0.88). At a cutoff value of 12 beats per minute, APRI showed a sensitivity and specificity for detecting sleep events of 0.81 each. However, AUC was lower for the differentiation between respiratory and non‐respiratory sleep events (0.77) and between central and obstructive respiratory events (0.68). In OSA cases, influencing factors for APRI following respiratory events were age, occurrence of a body movement, and severity of concomitant oxygen desaturation. We conclude that pulse rate analysis may be used to detect respiratory events in oximetry recordings in children. Pediatr Pulmonol. 2010; 45:459–468. © 2010 Wiley‐Liss, Inc.
A comparison of parent‐reported wheezing or shortness of breath among infants as assessed by questionnaire and physician‐interview: The Generation R study
Authors: Mohangoo Ashna D. , de Koning Harry J. , Hafkamp‐de Groen Esther , van der Wouden Johannes C. , Jaddoe Vincent W.V. , Moll Henriette A. , Hofman Albert , Mackenbach Johan P. , de Jongste Johan C. , Raat Hein
Published: April 2010

Purpose

The prevalence of asthma symptoms among preschool children is difficult to determine with accuracy because no gold standard is available for diagnosis. The aim of this study was to compare parent‐reported wheezing or shortness of breath among infants as assessed by questionnaire and physician‐interview.

Methods

We studied 1,202 children participating in the Generation R study. Their parents completed a written questionnaire at home when the infant was 12 months old, including items on wheezing or shortness of breath. During the regular free‐of‐charge youth healthcare visit at age 14 months, the physician interviewed the parents to assess the presence of wheezing or shortness of breath.

Results

The prevalence of wheezing or shortness of breath estimated from questionnaire was significantly higher than from physician‐interview (36% vs. 20%; P < 0.001): observed agreement 73% (kappa 0.36). Only 41% of questionnaire‐reported symptoms were assessed through the physician‐interview, while 73% of physician‐interviewed symptoms were reported in the questionnaire. Compared with infants in the subgroup with agreement on the presence of wheezing or shortness of breath, the infants in the subgroups without agreement significantly less often received anti‐asthma medication and significantly less often had abnormal respiratory sounds or bronchiolitis or croup, and their mothers were significantly less often working. The proportion of infants receiving anti‐asthma medication was higher in interview‐data compared with questionnaire‐data (22.7% vs. 3.9%; P < 0.001).

Conclusions

Questionnaire yielded higher prevalence rates for wheezing or shortness of breath than physician‐interview. Physician‐reported symptoms are associated with a higher proportion of infants receiving anti‐asthma medication. Parent‐reported asthma symptoms should be confirmed by pediatricians whenever possible. Pediatr Pulmonol. 2010; 45:500–507. © 2010 Wiley‐Liss, Inc.
The electroweak symmetry breaking riddle
Authors: Altarelli G.
Published: April 2010

I present a concise review of the Higgs problem which plays a central role in particle physics today. The Higgs of the minimal Standard Model is so far just a conjecture that needs to be verified or discarded at the LHC. Probably the reality is more complicated. I will summarize the motivation for New Physics that should accompany or even replace the Higgs discovery and a number of its possible forms that could be revealed by the LHC.
Neutrino physics beyond neutrino masses
Authors: del Aguila F. , de Blas J. , Carmona A. , Santiago J.
Published: April 2010

We briefly summarise the current status of neutrino masses and mixing, paying special attention to the prospects for observing new leptonic interactions.
Detection of organophosphate and pyrethroid resistance alleles in Czech Leptinotarsa decemlineata (Coleoptera: Chrysomelidae) populations by molecular methods
Authors: Zichová Tereza , Kocourek František , Salava Jaroslav , Nad'ová Kateřina , Stará Jitka
Published: April 2010

BACKGROUND:

Pyrethroids and organophosphates are the most frequently used insecticides for Colorado potato beetle, Leptinotarsa decemlineata (Say), control in the Czech Republic. Based on molecular methods, organophosphate and pyrethroid resistance alleles have been detected in samples from three sites. The accuracy of restriction fragment length polymorphism (RFLP) and bidirectional polymerase chain reaction amplification of specific alleles (Bi‐PASA) for detection of resistance alleles is compared.

RESULTS:

Leptinotarsa decemlineata from three sites showed higher frequencies of resistance alleles to organophosphates than to pyrethroids. The rates of occurrence of individuals homozygous resistant (RR) to pyrethroids ranged from 20.0 to 22.9%, while the rates of occurrence of individuals RR to organophosphates ranged from 52.9 to 66.7%. The incidences of individuals with resistance alleles to both organophosphates and pyrethroids ranged from 8.6 to 13.6%. No relationship was found between incidence of the pyrethroid resistance allele and site, while incidence of the organophosphate resistance allele differed significantly according to site.

CONCLUSION:

Both RFLP and Bi‐PASA were suitable for detecting resistance alleles to pyrethroids, and in most cases also for detecting resistance alleles to organophosphates. In contrast to Bi‐PASA, RFLP was also suitable for samples with lower DNA quality when testing for the resistance allele to pyrethroids. On the other hand, RFLP was not as accurate as Bi‐PASA in detection of the organophosphate resistance allele. Copyright © 2010 Society of Chemical Industry
Cross‐resistance between azinphos‐methyl and acetamiprid in populations of codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae), from Washington State
Authors: Knight Alan L
Published: April 2010

BACKGROUND: Codling moth, Cydia pomonella (L.), has been intensely managed with the organophosphate insecticide azinphos‐methyl for 50 years, and populations have developed resistance. New management programs have been developed and implemented that rely more heavily on other classes of insecticides. A prerequisite for developing effective resistance management strategies for these compounds is to establish their current levels of effectiveness. Adult and neonate larval assays were conducted to assess the response of field‐collected codling moth populations from apple in Washington State.

RESULTS: Male codling moth populations exhibited a range of responses to a discriminating concentration of azinphos‐methyl in a survey of 20 populations. Populations from certified organic orchards were more susceptible than those from conventional orchards. Mean fecundity was inversely related to azinphos‐methyl tolerance. Male responses to azinphos‐methyl and acetamiprid varied significantly among populations and were correlated. The residual effectiveness of field applications of both insecticides varied significantly against neonate larvae. Neonate bioassays with insecticide‐dipped fruit found significant differences among populations with azinphos‐methyl, acetamiprid, methoxyfenozide and spinosad, but not with esfenvalerate.

CONCLUSION: These results support a concern that alternation of insecticides with different modes of action may not be a sufficient strategy to avoid the evolution of broad‐spectrum insecticide resistance by codling moth. Published 2010 by John Wiley & Sons, Ltd.
Characteristics of ZnO thin film transistor prepared by two different methods
Authors: Haga Koichi , Sakuma Mio , Takizawa Yoshihiro , Seki Shigeyuki
Published: April 2010

We succeeded the fabrication of bottom gate ZnO‐TFT on thermal oxidized n‐type Si substrate with the high‐resistivity ZnO active layer which was prepared by two different methods. The first preparation methods was LP‐CVD using the fibrous bis(acetylacetonato)‐zinc(II) (Zn(C5H7O2)2) and ozone(O3). The second one was RF(13.56 MHz) sputtering using a ceramic oxide target ZnO with a purity of 99.99% and 2 in. diameter. For all the ZnO films prepared by different methods, the ZnO (0001) peak at 2θ ≈ 34.4° was mainly observed. The films are polycrystalline with a hexagonal structure and a preferred orientation with the c‐axis perpendicular to the substrate.The ZnO‐TFT prepared by LP‐CVD shows electrical properties with a field effect mobility of 6 cm2/V s, an on to off ratio greater than 106, the off current of less than 10‐10A. Zn, O, Si elerment in the interface of ZnO and SiO2gate insulator were analyzed by using X‐ray photoelectron spectroscopy. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dependence of electron spin relaxation times on the crystal orientation of CdTe grown on (100)ZnSe/GaAs substrates
Authors: Zhang Qiang , Li Yunpu , Liu Xuejun , Pagliero Daniela , Shen Aidong , Meriles Carlos A. , Tamargo Maria C.
Published: April 2010

Depending on the shutter sequence used to initiate CdTe deposition, either (100) or (111) CdTe layers can be reproducibly grown on (100) ZnSe/GaAs substrates. Using a hexagonal surface model for (111) CdTe we propose a mechanism for the crystalline orientation selectivity. We use time‐resolved Kerr rotation to monitor the electron spin dynamics in these films. While the spin lifetime is found to depend on material quality, only (100) films show a clear temperature dependence, a peculiar feature we believe to arise from different residual strains in the layers with the two different orientations. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Mistletoe lectin‐I augments antiproliferative effects of the PPARγ agonist rosiglitazone on human malignant melanoma cells
Authors: Freudlsperger Christian , Dahl Anka , Hoffmann Juergen , Reinert Siegmar , Schumacher Udo
Published: April 2010

As malignant melanoma cells are highly resistant to conventional chemotherapy, survival rates after tumor spread remain poor and hence there is an urgent need for new therapeutic options. For both mistletoe lectin‐I (ML‐I) and the thiazolidinediones as synthetic ligands of the peroxisome proliferator‐activated receptor γ (PPARγ) an antiproliferative effect on malignant melanoma cells has previously been shown. Hence, the aim of this study was to investigate whether the combination of ML‐I and the PPARγ ligand rosiglitazone is more efficacious in the treatment of malignant melanoma cells than either agent alone. Proliferation of three human melanoma cell lines treated with ML‐I, rosiglitazone and the combination of both was measured in a broad concentration range (0.0001–100 μg/mL) using the XTT cell proliferation assay. Combined application tremendously increased the antiproliferative effect on all three melanoma cell lines compared with single agent treatment. In comparison with the single use of rosiglitazone, the combination with ML‐I significantly increased the inhibition of cell growth by 51–79% and in comparison with the single use of ML‐I by 9–32%, respectively. In conclusion, this study shows that the combination of ML‐I with rosiglitazone significantly augments their antiproliferative effect on malignant melanoma cells in comparison with their single agent application, which might be a promising tool for further therapeutic studies. Copyright © 2010 John Wiley & Sons, Ltd.
Fatty acid synthase inhibitory activity of dibenzocyclooctadiene lignans isolated from Schisandra chinensis
Authors: Na MinKyun , Hung Tran Manh , Oh Won Keun , Min Byung Sun , Lee Seung Ho , Bae KiHwan
Published: April 2010

Inhibition of fatty acid synthase (FAS) has been proposed to be a new therapeutic target for the treatment of cancer and obesity. In our preliminary screening study on the FAS inhibitory activity, a n‐hexane soluble fraction prepared from the fruit of Schisandra chinensis (Schisandraceae) was found to inhibit FAS activity at 100 μg/mL. Nine dibenzocyclooctadiene lignans were isolated from the active fraction and were evaluated for their inhibitory effect on FAS for the first time. The compounds possessing a benzoyl or tigloyl group in the dibenzocyclooctadiene skeleton entirely inhibited the FAS activity in a dose dependent manner. The findings may be partially related to the anticancer effect of the medicinal plant, suggesting a further study on the anticancer potential of dibenzocyclooctadiene derivatives. Copyright © 2010 John Wiley & Sons, Ltd.
Wound healing effects of noni (Morinda citrifoliaL.) leaves: a mechanism involving its PDGF/A2A receptor ligand binding and promotion of wound closure
Authors: Palu Afa , Su Chen , Zhou Bing‐Nan , West Brett , Jensen Jarakae
Published: April 2010

Morinda citrifoliaL. (Rubiaceae) commonly known as noni, has been used in Polynesia by traditional healers for the treatment of cuts, bruises and wounds. Our objective was to investigate the wound‐healing mechanisms of the noni leaf. The investigations of its wound‐healing mechanisms were carried out using fresh noni leaf juice (NLJ), noni leaf ethanol extract (NLEE) and its methanol (MFEE) and hexane (HFEE) fractions on the PDGF and A2Areceptorsin vitroand topically in mice. Fresh noni leaf juice showed significant affinity to PDGF receptors, and displayed 166% binding inhibition of the ligand binding to its receptors, while at the same concentration, it only had 7% inhibition of the ligand binding to the A2Areceptors. NLEE, HFEE and MFEE showed significant affinity to A2Areceptors, concentration dependently, with IC50values of 34.1, 42.9 and 86.7 μg/mL, respectively. However, MFEE significantly increased wound closure and reduced the half closure time in mice with a CT50of 5.4 ± 0.2 days compared with control (p< 0.05). These results suggest that noni leaf significantly accelerated wound healing in mice via its ligand binding to the PDGF and A2Areceptors as its probable mechanisms of wound‐healing and also support its traditional usage for wound‐healing in Polynesia. Copyright © 2010 John Wiley & Sons, Ltd.
Pharmacokinetics of valerenic acid after single and multiple doses of valerian in older women
Authors: Anderson Gail D. , Elmer Gary W. , Taibi Diana M. , Vitiello Michael V. , Kantor Eric , Kalhorn Thomas F. , Howald William N. , Barsness Suzanne , Landis Carol A.
Published: April 2010

Insomnia is a commonly reported clinical problem with as many as 50% of older adults reporting difficulty in falling and/or remaining asleep. Valerian (Valeriana officinalis) is a commonly used herb that has been advocated for promoting sleep. Valerenic acid is used as a marker for quantitative analysis of valerian products with evidence of pharmacological activity relevant to the hypnotic effects of valerian. The objective of this study was to determine the pharmacokinetics of valerenic acid in a group of elderly women after receiving a single nightly valerian dose and after 2 weeks of valerian dosing. There was not a statistically significant difference in the average peak concentration (Cmax), time to maximum concentration (Tmax) area under the time curve (AUC), elimination half‐life (T1/2) and oral clearance after a single dose compared with multiple dosing. There was considerable inter‐ and intra‐subject variability in the pharmacokinetic parameters. Cmax and AUC deceased and T1/2 increased with increased body weight. The variability between the capsules was extremely low: 2.2%, 1.4% and 1.4%, for hydroxyvalerenic acid, acetoxyvalerenic acid and valerenic acid, respectively. In conclusion, large variability in the pharmacokinetics of valerenic acid may contribute to the inconsistencies in the effect of valerian as a sleep aid. Copyright © 2010 John Wiley & Sons, Ltd.
The impact of mesoscale convective systems on the surface and boundary‐layer structure in West Africa: Case‐studies from the AMMA campaign 2006
Authors: Schwendike Juliane , Kalthoff Norbert , Kohler Martin
Published: April 2010

Within the framework of the AMMA project, atmospheric, surface and soil observations were performed during the pre‐onset phase of the monsoon (Special Observing Period SOP 1) and during the summer monsoon (SOP 2) in 2006. Based on several case‐studies the paper investigates the impact of mesoscale convective systems (MCSs) on the surface and boundary layer (PBL), the recovery time of the surface and the PBL after MCS passages, and the differences between the two monsoon phases.

In the pre‐MCS environment the mean conditional and convective instabilities were higher in SOP 1 than in SOP 2 (e.g. CAPE = 1815 J kg−1 and CAPE = 1295 J kg−1, respectively). In both monsoon phases these instabilities, which were strongly reduced by MCSs, recovered within less than 2 days. Precipitation of the MCSs and the resulting soil moisture increase caused a significant decrease in the surface temperature by up to 10 K and an increase in evapotranspiration by up to 2.5 mm d−1. In both phases of the monsoon, these surface anomalies and, hence, the conditions favourable for triggering MCSs by thermally induced circulation systems, diminished largely within 2 to 3 days. Due to the repeated passage of the first MCSs at intervals of a few days during SOP 1, the surface properties exhibited trends towards higher soil moisture, evapotranspiration and humidity, and lower albedo, temperature and Bowen ratio. After two weeks only, the mean conditions present in the summer monsoon were reached. In SOP 2 no significant trends could be detected. Copyright © 2010 Royal Meteorological Society
On random sampling in uniform hypergraphs
Authors: Czygrinow Andrzej , Nagle Brendan
Published: April 2010

A k‐graph
\documentclass{article} \usepackage{amsmath,amsfonts,mathrsfs,amssymb}\pagestyle{empty}\begin{document} ${\mathcal{G}}^{(k)}$ \end{document}
on vertex set [n] = {1,…,n} is said to be (ρ,ζ)‐uniform if every S ⊆ [n] of size s = |S| > ζn spans (ρ ± ζ)\documentclass{article} \usepackage{amsmath,amsfonts,mathrsfs,amssymb}\pagestyle{empty}\begin{document} $\binom{s}{k}$ \end{document}
edges. A ‘grabbing lemma’ of Mubayi and Rödl shows that this property is typically inherited locally: if \documentclass{article} \usepackage{amsmath,amsfonts,mathrsfs,amssymb}\pagestyle{empty}\begin{document} ${\mathcal{G}}^{(k)}$ \end{document}
is (ρ,ζ)‐uniform, then all but exp{−s1/k/20}\documentclass{article} \usepackage{amsmath,amsfonts,mathrsfs,amssymb}\pagestyle{empty}\begin{document} $\binom{n}{s}$ \end{document}
sets \documentclass{article} \usepackage{amsmath,amsfonts,mathrsfs,amssymb}\pagestyle{empty}\begin{document} $ S \in \binom{[n]}{s}$ \end{document}
span (ρ,ζ′)‐uniform subhypergraphs \documentclass{article} \usepackage{amsmath,amsfonts,mathrsfs,amssymb}\pagestyle{empty}\begin{document} ${\mathcal{G}}^{(k)}\lbrack S\rbrack$ \end{document}, where ζ′→ 0 as ζ → 0, s ≥ s0(ζ′) and n is sufficiently large. In this article, we establish a grabbing lemma for a different concept of hypergraph uniformity, and infer the result above as a corollary. In particular, we improve, in the context above, the error exp{−s1/k/20} to exp{−cs}, for a constant c = c(k,ζ′) > 0. © 2011 Wiley Periodicals, Inc. Random Struct. Alg., 38, 422–440, 2011
VAMAS interlaboratory study on organic depth profiling. Part I: Preliminary report
Authors: Shard A. G. , Foster R. , Gilmore I. S. , Lee J. L. S. , Ray S. , Yang L.
Published: April 2010

We present preliminary results of a VAMAS interlaboratory study on organic depth profiling, TWA2, sub‐project A3 (d). A layered organic system was used to assess the repeatability and comparability of organic depth profiling. Nineteen respondents have provided sufficient data to demonstrate that the coefficients of variation for depth resolution, sputtering yield and relative secondary ion intensities are typically 5–10%. This can be as good as 2–3% with modern instruments, when using a stable sputtering ion current and careful procedures, which approaches the limits set by the samples themselves. The respondents have also demonstrated three methods to improve the quality of depth profiling for this system, namely, sample rotation, cooling to at least − 80 °C and grazing incidence angles for the sputtering ion. Copyright © 2010 John Wiley & Sons, Ltd.
Composition of plasma‐sprayed tungsten coatings on CuCrZr alloy
Authors: Kaciulis S. , Mezzi A. , Montanari R. , Ucciardello N. , Volterri R.
Published: April 2010

Mock‐ups for the International Thermonuclear Experimental Reactor(ITER) were manufactured by depositing W coatings on tubular substrates of CuCrZr alloy via plasma spraying. An appropriate interlayer (of Ni, Al and Si) was optimised to increase the adhesion of W on the Cu alloy and to provide a soft interface with intermediate thermal expansion coefficient for better thermo‐mechanical compatibility.

The distribution of chemical elements in the layered interface and in the coating was investigated by energy dispersive spectroscopy (EDS), XPS and AES in the as‐prepared material and after heat treatment of 24 h at 823 K. Moreover, the external W layer was examined by inductively coupled plasma emission spectrometry(ICP‐ES).

The results showed that the as‐prepared material does not exhibit macro‐porosity. The layers forming the interface do not exhibit any long‐range diffusion of the chemical species from layer to layer during the deposition process. The heat treatment does not seem to cause long‐range migration of Al and Ni into the W coating.

The presence of Ni (0.4 wt%) in the as‐deposited external W layer as shown by ICP‐ES is only due to the low purity (commercial grade) of W powders used in spraying operations. It can be eliminated by using W powders of higher purity in the deposition process. Copyright © 2010 John Wiley & Sons, Ltd.
Molecular events involved in ochratoxin A induced mitochondrial pathway of apoptosis, modulation by Bcl‐2 family members
Authors: Bouaziz Chayma , Sharaf el dein Ossama , Martel Cécile , Golli Emna El , Abid‐Essefi Salwa , Brenner Catherine , Lemaire Christophe , Bacha Hassen
Published: April 2010

In this study, we looked for the role of the mitochondrion in the cytotoxicity of ochratoxin A (OTA), which is one of the most abundant food‐contaminating mycotoxins in the world. In different human carcinoma cell lines, OTA triggered a mitochondria‐dependent apoptotic process, which is characterized by opening of the mitochondrial permeability transition pore (PTPC), loss of mitochondrial transmembrane potential (ΔΨm), increase in O2[chemp]– production, mitochondrial relocalization of Bax, release of cytochrome c, and caspase activation. However, studies performed on purified organelles suggested that OTA does not directly target the mitochondrion. In addition, we showed that mitochondrial alterations induced by this mycotoxin are favored by the proapoptotic protein Bax, but not Bak. These alterations are prevented by the antiapoptotic proteins, Bcl‐2 and to a lesser degree by Bcl‐XL. Taken together, these data indicate that although mitochondria, PTPC members and proteins of Bcl‐2 family play a pivotal role in OTA‐induced apoptosis, they do not constitute real targets to overcome its toxicity. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2011.
Application of microbial assay for risk assessment biotest in evaluation of toxicity of human and veterinary antibiotics
Authors: Nałȩcz‐Jawecki G. , Wadhia K. , Adomas B. , Piotrowicz‐Cieślak A.I. , Sawicki J.
Published: April 2010

The microbial assay for risk assessment (MARA) is a multispecies, growth inhibition microplate toxicity test with 11 microorganisms individually lyophilized in microplate wells. The microbial species representing wide diversity, generated 11 microbial toxic concentration (MTC) values were obtained giving a unique “toxic fingerprint” profile of the test sample. The toxicity of 14 antibiotics was evaluated with the MARA test. The fingerprints for each group of antibiotics differ, indicating a particular toxic profile. Tetracyclines were the most toxic antibacterials with the minimum MTC value of 3.6 μg L−1. In the group of tetracyclines the order of the three most sensitive microbial strains was the same 2 > 6 > 7. Quinolones affected the most sensitive strain(s) at concentrations of 12–75 μg L−1. The MARA bioassay exhibited different spectra of toxic responses to microbial strains for the first and second generation quinolones. However, for first generation quinolones strain 6 was substantially more sensitive than the other microorganisms, while second generation quinolones were most toxic to strain 3, followed by 6 then 4. In this instance, the three strains belong to two different phylogenetic groups–strain 3 is γ‐proteotype and strains 4 and 6 are β‐proteotype. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.
Early defense responses in the freshwater bivalve Corbicula fluminea exposed to copper and cadmium: Transcriptional and histochemical studies
Authors: Bigot Aurélie , Minguez Laëtitia , Giambérini Laure , Rodius François
Published: April 2010

The aim of the present study was to measure the early effects of copper (10 and 50 μg L−1), cadmium (2, 10, and 50 μg L−1) and mixtures of these metals in the freshwater bivalve Corbicula fluminea exposed for 12 h in laboratory. Transcription levels of superoxide dismutase (SOD), catalase (CAT), selenium‐dependent glutathione peroxidase (Se‐GPx), pi‐class glutathione S‐transferase (pi‐GST), metallothionein (MT) in digestive gland and gills, and response of lysosomal system and neutral lipids in digestive gland were determined after the exposure period. Results showed that lysosomal system, neutral lipids content, and mRNA levels were modified, suggesting their early response against oxidative stress and their important role in cell integrity. The integrated biomarker response was calculated and showed that the effects of the combinations of Cu and Cd on the biomarker responses are additive. MT and pi‐GST mRNA expression correspond to the largest ranges of response. As efficient biomarkers should have an early warning capacity, SOD, CAT, Se‐GPx, pi‐GST, MT transcripts levels, lysosomal system, and neutral lipids could be used as biomarkers of metal contamination in the aquatic environment. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2011.
Attitudes of Genetic Counselors Towards Genetic Susceptibility Testing in Children
Authors: Mackoff Rishona L. , Iverson Ellen F. , Kiekel Preston , Dorey Frederick , Upperman Jeffrey S. , Metzenberg Aida B.
Published: April 2010

Genetic susceptibility research and testing is leading to an era of personalized medicine. Genetic counselors act as liaisons between the medical genetics community and the public. Understanding the opinions of genetic counselors will be important in developing testing guidelines. Attitudes towards genetic susceptibility testing in children were assessed for 216 NSGC members. Genetic counselors were likely to support testing if the results would determine: disease progression or prognosis, likelihood of survival after a specific treatment, or risk for an adverse drug reaction. Genetic counselors were unlikely to support testing to determine susceptibility to later disease development or in the absence of available intervention. There was a strong positive correlation between attitudes associated with desire to test their own child, if at risk and their support for genetic testing in any child at risk. Respondents strongly favored parent/guardian and child's rights over doctor or insurance rights. They indicated assent should be obtained prior to testing, when appropriate, and that a copy of results should be kept in a permanent medical record. Respondents expressed concerns about insurance discrimination, testing in the absence of medical necessity, and taking away a child's autonomy.
Computed tomography of complicated Meckel’s diverticulum in adults: a pictorial review
Authors: Platon Alexandra , Gervaz Pascal , Becker Christoph D. , Morel Philippe , Poletti Pierre-Alexandre
Published: April 2010

Objective

To show various CT aspects of complicated Meckel’s diverticulum in adult patients to facilitate the preoperative diagnosis of this rare pathology in emergency settings.

Methods

A computer search of medical records over a 15 year period identified 23 adult patients who underwent surgery for acute abdomen generated by a complicated Meckel’s diverticulum. CT images available for review were analyzed, and some specific patterns leading to the diagnosis of complicated Meckel’s diverticulum are presented in this review.

Results

Complications were related to inflammation (14 patients), bleeding (5 patients), intestinal obstruction (3 patients), and penetrating foreign body (1 patient). The presence of a Meckel’s diverticulum was usually suggested at CT scan by an abnormal outpouching, blind-ending digestive structure connected to the terminal ileum by a neck of variable caliber. Depending on the type of complications, the diverticulum was surrounded by mesenteric inflammatory changes, or presented as a localized fluid or air-fluid collection contiguous with the terminal ileum. The diverticulum was also the source of active bleeding or acted as the lead point to intestinal obstruction or intussusception.

Conclusion

CT findings of complicated Meckel’s diverticulum are polymorphic and should be considered in the evaluation of adult patients with acute abdomen.
Single‐molecule analysis of the Escherichia coli replisome and use of clamps to bypass replication barriers
Authors: Georgescu Roxana E. , Yao Nina Y. , O'Donnell Mike
Published: April 2010

The process of chromosome duplication faces many obstacles. One way to circumvent blocks is to hop over them by placing a new clamp on a downstream primer. This resembles lagging strand synthesis, where the tight grip of polymerase to the clamp and DNA must be overcome upon completing each Okazaki fragment so it can transfer to new primed sites. This review focuses on recent single‐molecule studies showing that Escherichia coli Pol III can hop from one clamp to another without leaving the replication fork. This capability provides a means to circumvent obstacles like transcription or DNA lesions without fork collapse.
Salicylate‐induced translocation of prestin having mutation in the GTSRH sequence to the plasma membrane
Authors: Kumano Shun , Iida Koji , Ishihara Kenji , Murakoshi Michio , Tsumoto Kouhei , Ikeda Katsuhisa , Kumagai Izumi , Kobayashi Toshimitsu , Wada Hiroshi
Published: April 2010

Prestin is a key molecule for mammalian hearing. The present study investigated changes in characteristics of prestin by culturing prestin‐transfected cells with salicylate, an antagonist of prestin. As a result, the plasma membrane localization of prestin bearing a mutation in the GTSRH sequence, which normally accumulates in the cytoplasm, was recovered. Moreover, the nonlinear capacitance of the majority of the mutants, which is a signature of prestin activity, was also recovered. Thus, the present study discovered a new effect of salicylate on prestin, namely, the promotion of the plasma membrane expression of prestin mutants in an active state.
Avt5p is required for vacuolar uptake of amino acids in the fission yeast Schizosaccharomycespombe
Authors: Chardwiriyapreecha Soracom , Mukaiyama Hiroyuki , Sekito Takayuki , Iwaki Tomoko , Takegawa Kaoru , Kakinuma Yoshimi
Published: April 2010

We identified SPBC1685.07c of Schizosaccharomyces pombe as a novel vacuolar protein, Avt5p, with similarity to vacuolar amino acid transporters Avt5p from Saccharomyces cerevisiae. Avt5p localizes to the vacuolar membrane and upon disruption of avt5, uptake of histidine, glutamate, tyrosine, arginine, lysine or serine was impaired. During nitrogen starvation, the transient increase of vacuolar lysine transport observed for wild‐type cells still occurred in the mutant cells, however, uptake of glutamate did not significantly increase in response to nitrogen starvation. Our results show that under diverse growth conditions Avt5p is involved in vacuolar transport of a selective set of amino acids.
Oncogenic mutant forms of EGFR: Lessons in signal transduction and targets for cancer therapy
Authors: Pines Gur , Köstler Wolfgang J. , Yarden Yosef
Published: April 2010

The EGF‐receptor is frequently mutated in a large variety of tumors. Here we review the most frequent mutations and conclude that they commonly enhance the intrinsic tyrosine kinase activity, or they represent loss‐of‐function of suppressive regulatory domains. Interestingly, the constitutive activity of mutant receptors translates to downstream pathways, which are subtly different from those stimulated by the wild‐type receptor. Cancer drugs intercepting EGFR signaling have already entered clinical application. Both kinase inhibitors specific to EGFR, and monoclonal antibodies to the receptor are described, along with experimental approaches targeting the HSP90 chaperone. Deeper understanding of signaling pathways downstream to mutant receptors will likely improve the outcome of current EGFR‐targeted therapies, as well as help develop new drugs and combinations.
Hare's Utilitarianism and the Free-Rider Problem
Authors: Kornegay R. Jo
Published: April 2010

Cet essai se concentre sur les tentatives de Hare de résoudre le problème du profiteur (free-rider) dans les termes de la théorie où il distingue les niveaux intuitif et critique de la pensée morale. Hare fait valoir que la pensée critique correcte en utilitarisme des actes endosse les règles qui serviront à la pensée intuitive, règles enjoignant à un individu de s'acquitter de ses responabilités sociales, par exemple voter ou recycler ses ordures. Je fais valoir que Hare propose ou suggère implicitement divers entères de sélection des règies, critères que j'entreprends de désambiguïser. Je soutiens en outre qu'aucun de ces critères n'arrive à résoudre complètement le problème du profiteur.
Y a-t-il des sentiments moraux?
Authors: Dumouchel Paul
Published: April 2010

A quick survey of the literature reveals that authors disagree as to which sentiments are moral and which are not, they disagee as to how to distinguish between moral and other sentiments, and finally that often the same author will claim a sentiment is moral at some times but not at others. These difficulties arise, I argue, from an underlying concept of emotion that I call atomism. Viewing emotions as means of coordination among agents, rather than as psychic atoms, suggests a radically different approach to the question of morality and affects, one where emotions pave the way for normative expectations.
Platonism, Metaphor, and Mathematics
Authors: Parsons Glenn G. , Brown James Robert
Published: April 2010

Dans leur livre récent, George Lakoff et Rafael Núñez se livrent à une critique naturaliste soutenue du platonisme traditionnel concernant les entités mathématiques. Ils affirment que des résultats récents en sciences cognitives démontrent qu'il est faux. En particulier, ils estiment que la découverte que la cognition mathématique s'appuie pour une large part sur les métaphores conceptuelles est incompatible avec le platonisme. Nous montrons ici que tel n'est pas le cas. Nous examinons et rejetons également quelques arguments philosophiques que formulent Lakoff et Núñez contre le platonisme. Enfin, nous lions leur hostilité au platonisme à certaines opinions sur les ramifications politiques de celui-ci. Pour conclure, nous faisons valoir que ces opinions sont sans fondements et présentent une image distordue des dimensions politiques du platonisme.
Extrinsic Denominations and Universal Expression in Leibniz
Authors: Maunu Ari
Published: April 2010

Cet article discute de la théorie des dénominations, expression et notions individuelles de Leibniz. Son point central est que la clé pour élucider plusieurs thèses fondamentales de Leibniz est de se pencher sur son argumentation, en commençant par sa théorie de la vérité (voulant qu'un énoncé vrai soit un énoncé dont la notion du prédicat est comprise dans celle du sujet), laquelle s'oppose à l'idée de dénominations purement extrinsèques. Cet argument montre pourquoi il y a un fondement interne à toutes les dénominations, pourquoi tout dans le monde est interrelié, pourquoi chaque substance exprime toutes les autres et pourquoi chaque changement dans le monde se reflète par un changement véritable, interne, en chaque substance.