bluuebunny/crossref_metadata_2025 huggingface dataset:
Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule
Authors: Perry James R. , Rizek Philippe , Cashman Rosemary , Morrison Meredith , Morrison Tara
Published: August 2008

BACKGROUND.

Despite advances in first‐line therapy, there are few data on treatment of glioblastoma multiforme (GBM) at recurrence. Temozolomide (TMZ) is well tolerated and may have activity despite prior TMZ exposure if novel dose schedules are used.

METHODS.

The authors reviewed their experience with a continuous TMZ schedule (50 mg/m2 daily), given at progression after conventional 5‐day TMZ. Patients were reported in 3 groups: 1) GBM after progression on conventional TMZ; 2) GBM at first recurrence after completion of standard concomitant and adjuvant TMZ; and 3) patients with other anaplastic gliomas at second relapse on conventional TMZ.

RESULTS.

In Group 1, 21 patients with a median age of 54 years (range, 33 years‐68 years) received a median of 3 cycles (range, 2‐12 cycles) of continuous TMZ at 50 mg/m2. Overall clinical benefit (complete response, partial response, and stable disease) was 47%, with 6‐month progression‐free survival (PFS) of 17%. In Group 2, 14 patients with GBM, median age 52 years (range, 38 years‐62 years) received continuous TMZ at progression after initial TMZ/radiotherapy (RT) and adjuvant TMZ. The median interval after adjuvant TMZ was 3 months (range, 2 months‐10 months). A median of 5 cycles of TMZ was given, and 6‐month PFS was 57%. In Group 3, 14 patients with a median age of 49 years (range, 34 years‐56 years) received continuous TMZ; 2 partial responses and 6 with stable disease were seen, with a 6‐month PFS of 42%. Toxicities were mild and well tolerated; lymphopenia was common but no serious opportunistic infections were identified.

CONCLUSIONS.

Although retrospective, our results demonstrate that continuous daily administration of TMZ is an active regimen despite prior TMZ therapy. The excellent tolerability of this regimen may allow future combination with other alkylating agents or with novel therapies. Cancer 2008. © 2008 American Cancer Society.
The Preparation of α‐Alkylidene‐γ‐Butyrolactones Using a Telescoped Intramolecular Michael/Olefination (TIMO) Sequence: Synthesis of (+)‐Paeonilactone B
Authors: Edwards Michael G. , Kenworthy Martin N. , Kitson Russell R. A. , Perry Alexis , Scott Mark S. , Whitwood Adrian C. , Taylor Richard J. K.
Published: August 2008

A novel telescoped intramolecular Michael addition/proton transfer/HWE olefination sequence has been developed to provide rapid access to α‐alkylidene‐γ‐butyrolactones. This methodology has been applied to prepare a range of tetrahydrobenzofuran‐2,5‐diones, and related systems, and also utilised in an extremely short synthesis of the natural product (+)‐paeonilactone B in enantiomerically pure form. In addition, preliminary experiments are described that illustrate a palladium‐catalysed variant proceeding by way of a π‐allyl intermediate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Treatment of hepatocellular carcinoma by AdAFPep/rep, AdAFPep/p53, and 5-fluorouracil in mice
Authors: Sagawa Tamotsu , Yamada Yasuyuki , Takahashi Minoru , Sato Yasushi , Kobune Masayoshi , Takimoto Rishu , Fukaura Junki , Iyama Satoshi , Sato Tsutomu , Miyanishi Koji , Matsunaga Takuya , Takayama Tetsuji , Kato Junji , Sasaki Katsunori , Hamada Hirofumi , Niitsu Yoshiro
Published: August 2008

Although conditionally replicable adenovirus (CRAd) has been used in the clinical treatment of hepatocellular carcinoma (HCC), it suffers from the inherent drawback of having relatively low antitumor activity. Here, we have sought to overcome this drawback. First, we combined CRAd (AdAFPep/Rep) driven by α-fetoprotein enhancer/promoter (AFPep) with a replication-incompetent adenovirus carrying a p53 transgene that is also driven by AFPep. The synergism of this combination produced a significantly improved tumoricidal effect on the human HCC cell line Hep3B, which has a relatively short doubling time in comparison with other human HCC cell lines, through the transactivation of p53 by early region 1A transcribed by AdAFPep/Rep. This synergistic interaction was augmented by the addition of a subtumoricidal dose (0.5 μg/mL) of 5-fluorouracil (5-FU), which enhanced p53 expression and facilitated the release of virions from tumor cells. When relatively large (10-mm-diameter) Hep3B tumors grown in nude mice were injected with the two viruses in combination, they showed significantly impaired growth in comparison with those treated with each virus separately. The growth suppression effect of the virus combination was enhanced by a low dose (600 μg) of 5-FU. Survival of the tumor-bearing mice treated with these three agents was significantly longer than that of control mice. Moreover, the tumor completely disappeared with the repeated injection of these agents.

Conclusion:

This combination strategy holds promise for the treatment of relatively large and rapidly growing HCCs that may be encountered clinically. (Hepatology 2008;48:828–840.)
Of mice and molecular mimicry: Modeling autoimmune hepatitis
Authors: Bowen David G.
Published: August 2008

Holdener M, Hintermann E, Bayer M, Rhode A, Rodrigo E, Hintereder G, et al. Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection. J Exp Med 2008; 205:1409-1422. (Reprinted with permission.)

Autoimmune liver diseases, such as autoimmune hepatitis (AIH) and primary biliary cirrhosis, often have severe consequences for the patient. Because of a lack of appropriate animal models, not much is known about their potential viral etiology. Infection by liver-tropic viruses is one possibility for the breakdown of self-tolerance. Therefore, we infected mice with adenovirus Ad5 expressing human cytochrome P450 2D6 (Ad-2D6). Ad-2D6-infected mice developed persistent autoimmune liver disease, apparent by cellular infiltration, hepatic fibrosis, “fused” liver lobules, and necrosis. Similar to type 2 AIH patients, Ad-2D6-infected mice generated type 1 liver kidney microsomal-like antibodies recognizing the immunodominant epitope WDPAQPPRD of cytochrome P450 2D6 (CYP2D6). Interestingly, Ad-2D6-infected wild-type FVB/N mice displayed exacerbated liver damage when compared with transgenic mice expressing the identical human CYP2D6 protein in the liver, indicating the presence of a stronger immunological tolerance in CYP2D6 mice. We demonstrate for the first time that infection with a virus expressing a natural human autoantigen breaks tolerance, resulting in a chronic form of severe, autoimmune liver damage. Our novel model system should be instrumental for studying mechanisms involved in the initiation, propagation, and precipitation of virus-induced autoimmune liver diseases.
Polymorphisms of fibroblast growth factor receptor 4 have association with the development of prostate cancer and benign prostatic hyperplasia and the progression of prostate cancer in a Japanese population
Authors: Ma Zhiyong , Tsuchiya Norihiko , Yuasa Takeshi , Inoue Takamitsu , Kumazawa Teruaki , Narita Shintaro , Horikawa Yohei , Tsuruta Hiroshi , Obara Takashi , Saito Mitsuru , Satoh Shigeru , Ogawa Osamu , Habuchi Tomonori
Published: August 2008

Fibroblast growth factor receptor 4 (FGFR4) is a member of a family of transmembrane receptors with ligand‐induced tyrosine kinase activity. The Glycine (Gly) to Arginine (Arg) polymorphism at codon 388 (Gly388Arg), which encodes an amino acid in the transmembrane part of the FGFR4 gene, was reported to be associated with an increased risk in some carcinomas. We investigated the association between the Gly388Arg polymorphism or the G or A polymorphism at intron 11 (rs2011077) of FGFR4, which was located 1,213 base pairs apart from the Gly388Arg polymorphism, and the risk of prostate cancer or benign prostate hyperplasia (BPH), and the prostate cancer disease status in Japanese men. Genotypes of Gly388Arg and rs2011077 polymorphisms of FGFR4 were determined in 492 patients with prostate cancer, 165 patients with BPH and 179 male controls. Regarding the Gly388Arg polymorphism, individuals with the ArgArg genotype had a 2.207‐ and 1.958‐fold increased risk of prostate cancer and BPH, and a 1.804‐fold increased risk of metastatic prostate cancer compared with those with the GlyGly genotype. Regarding the rs2011077 polymorphism, individuals with the GG genotype had a 6.260‐ and 3.033‐fold increased risk of prostate cancer and BPH, and a 5.550‐fold increased risk of metastatic prostate cancer compared with those with the AA genotype. Our results indicate that the FGFR4 Arg allele of the Gly388Arg polymorphism and the G allele of the rs2011077 polymorphism have a significant impact on the development of prostate cancer and BPH, and the progression of prostate cancer in a Japanese population. © 2008 Wiley‐Liss, Inc.
Hesperidin, an antioxidant flavonoid, prevents acrylonitrile‐induced oxidative stress in rat brain
Authors: El‐Sayed El‐Sayed M. , Abo‐Salem Osama M. , Abd‐Ellah Mohamed F. , Abd‐Alla Gamil M.
Published: August 2008

Acrylonitrile (ACN) is a volatile, toxic liquid used as a monomer in the manufacture of synthetic rubber, styrene plastics, acrylic fiber, and adhesives. ACN is a potent neurotoxin. A role for free radical mediated lipid peroxidation in the toxicity of ACN has been suggested. We examined the ability of hesperidin, an antioxidant flavonoid, to attenuate ACN‐induced alterations in lipid peroxidation in rat brains. The daily oral administration of ACN to male albino rats in a dose of 50 mg/kg bwt for a period of 28 days produced a significant elevation in brain lipid peroxides measured as malondialdehyde (MDA) amounting to 107%, accompanied by a marked decrease in brain‐reduced glutathione (GSH) content reaching 63%. In addition, ACN administration resulted in significant reductions in the enzymatic antioxidant parameters of brain; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‐Px), and glutathione‐S‐transferase (GST) recording 43%, 64%, 52%, and 43%, respectively. On the other hand, pretreatment with hesperidin and its coadministration with ACN once daily in a dose of 200 mg/kg bwt i.p. for 28 days ameliorated ACN‐induced alterations in brain lipid peroxidation. These results suggest that hesperidin may have a beneficial role against ACN‐induced oxidative stress in the brain; an effect that is mainly attributed to the antioxidant property of hesperidin. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:268–273, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20237
Translation elongation factor eEF1A binds to a novel myosin binding protein‐C‐like protein
Authors: Mansilla Francisco , Dominguez Carlota A.G. , Yeadon James E. , Corydon Thomas J. , Burden Steven J. , Knudsen Charlotte R.
Published: August 2008

Eukaryotic translation elongation factor 1A (eEF1A) is a guanine‐nucleotide binding protein, which transports aminoacylated tRNA to the ribosomal A site during protein synthesis. In a yeast two‐hybrid screening of a human skeletal muscle cDNA library, a novel eEF1A binding protein, immunoglobulin‐like and fibronectin type III domain containing 1 (IGFN1), was discovered, and its interaction with eEF1A was confirmed in vitro. IGFN1 is specifically expressed in skeletal muscle and presents immunoglobulin I and fibronectin III sets of domains characteristic of sarcomeric proteins. IGFN1 shows sequence and structural homology to myosin binding protein‐C fast and slow‐type skeletal muscle isoforms. IGFN1 is substantially upregulated during muscle denervation. We propose a model in which this increased expression of IGFN1 serves to down‐regulate protein synthesis via interaction with eEF1A during denervation. J. Cell. Biochem. 105: 847–858, 2008. © 2008 Wiley‐Liss, Inc.
Involvement of AMP‐activated protein kinase and p38 mitogen‐activated protein kinase in 8‐Cl‐cAMP‐induced growth inhibition
Authors: Han Jee Hae , Ahn Young‐Ho , Choi Ki‐Young , Hong Seung Hwan
Published: August 2008

8‐Cl‐cAMP (8‐chloro‐cyclic AMP), which induces differentiation, growth inhibition and apoptosis in various cancer cells, has been investigated as a putative anti‐cancer drug. Although we reported that 8‐Cl‐cAMP induces growth inhibition via p38 mitogen‐activated protein kinase (MAPK) and a metabolite of 8‐Cl‐cAMP, 8‐Cl‐adenosine mediates this process, the action mechanism of 8‐Cl‐cAMP is still uncertain. In this study, it was found that 8‐Cl‐cAMP‐induced growth inhibition is mediated by AMP‐activated protein kinase (AMPK). 8‐Cl‐cAMP was shown to activate AMPK, which was also dependent on the metabolic degradation of 8‐Cl‐cAMP. A potent agonist of AMPK, 5‐aminoimidazole‐4‐carboxamide ribonucleoside (AICAR) could also induce growth inhibition and apoptosis. To further delineate the role of AMPK in 8‐Cl‐cAMP‐induced growth inhibition and apoptosis, we used two approaches: pharmacological inhibition of the enzyme with compound C and expression of a dominant negative mutant (a kinase‐dead form of AMPKα2, KD‐AMPK). AICAR was able to activate p38 MAPK and pre‐treatment with AMPK inhibitor or expression of KD‐AMPK blocked this p38 MAPK activation. Cell growth inhibition was also attenuated. Furthermore, p38 MAPK inhibitor attenuated 8‐Cl‐cAMP‐ or AICAR‐induced growth inhibition but had no effect on AMPK activation. These results demonstrate that 8‐Cl‐cAMP induced growth inhibition through AMPK activation and p38 MAPK acts downstream of AMPK in this signaling pathway. J. Cell. Physiol. 218: 104–112, 2009. © 2008 Wiley‐Liss, Inc.
Targeted overexpression of BSP in osteoclasts promotes bone metastasis of breast cancer cells
Authors: Tu Qisheng , Zhang Jin , Fix Amanda , Brewer Erika , Li Yi‐Ping , Zhang Zhi‐yuan , Chen Jake
Published: August 2008

Bone is one of the most common sites of breast cancer metastasis while bone sialoprotein (BSP) is thought to play an important role in bone metastasis of malignant tumors. The objective of this study is to determine the role of BSP overexpression in osteolytic metastasis using two homozygous transgenic mouse lines in which BSP expression is elevated either in all the tissues (CMV‐BSP mice) or only in the osteoclasts (CtpsK‐BSP mice). The results showed that skeletal as well as systemic metastases of 4T1 murine breast cancer cells were dramatically increased in CMV‐BSP mice. In CtpsK‐BSP mice, it was found that targeted BSP overexpression in osteoclasts promoted in vitro osteoclastogenesis and activated osteoclastic differentiation markers such as Cathepsin K, TRAP and NFAT2. MicroCT scan demonstrated that CtpsK/BSP mice had reduced trabecular bone volume and bone mineral density (BMD). The real‐time IVIS Imaging System showed that targeted BSP overexpression in osteoclasts promoted bone metastasis of breast cancer cells. The osteolytic lesion area was significantly larger in CtpsK/BSP mice than in the controls as demonstrated by both radiographic and histomorphometric analyses. TRAP staining demonstrated a twofold increase in the number of osteoclasts in the bone lesion area from CtpsK/BSP mice compared with that from wild type mice. We conclude that host tissue‐derived BSP also plays important roles in breast cancer metastasis through inducing tumor cell seeding into the remote host tissues. Furthermore, osteoclast‐derived BSP promotes osteoclast differentiation in an autocrine manner and consequently promotes osteolytic bone metastasis of breast cancer. J. Cell. Physiol. 218: 135–145, 2009. © 2008 Wiley‐Liss, Inc.
Temporal predictability in food availability: effects upon the reproductive axis in Scrub‐Jays
Authors: Bridge Eli S. , Schoech Stephan J. , Bowman Reed , Wingfield John C.
Published: August 2008

Florida Scrub‐Jays (Aphelocoma coerulescens) in a suburban environment with year‐round access to multiple sources of abundant, human‐source foods consistently breed earlier each year and have lower baseline levels of circulating corticosterone (CORT) than jays in a nearby wildland setting. These findings suggest that food supplies influence CORT levels, which in turn may partially determine the timing of reproduction. However, wildland birds with access to high‐quality supplemental foods did not advance breeding or lower CORT levels to the degree observed in the suburbs. Therefore, rather than quality or quantity of food consumed, the perception of a reliable and predictable food supply may be an important factor in determining laying dates. If a predictable food supply accelerates the reproductive process, it follows that food provided on an unpredictable schedule may slow reproduction. We subjected captive Western Scrub‐Jays (A. californica) to a 30‐day photoperiod transition from short‐ to long‐days and tested whether birds with access to food on an unpredictable schedule exhibited delayed or reduced production of reproductive hormones compared with birds given food on a predictable schedule. Baseline CORT concentrations increased slightly during the experiment, but did not differ between treatment groups. Birds with unpredictable food had slightly lower testosterone levels relative to controls, but there was no effect on estradiol or luteinizing hormone. Our findings offer weak support for the hypothesis that an unpredictable food supply will delay the onset of reproduction; however, the artificial lab environment may limit the application of these findings to free‐living populations. J. Exp. Zool. 311A:35–44, 2009. © 2008 Wiley‐Liss, Inc.
Discourses, dynamics and disquiet: Multiple knowledges in science, society and development
Authors: Leach Melissa , Sumner Andy , Waldman Linda
Published: August 2008

The links between science, society and development are attracting research and policy attention as never before. Rapid advances in science and technology, whether in the fields of health, agriculture, information and communication, industrial production or environment offer, it seems, an array of new promises and opportunities in meeting development challenges. As we approach the end of the new Millennium's first decade, ‘science, technology and development’ have become a firmly embedded part of the international scene, attracting the attention of donors, intergovernmental and ministerial initiatives, NGOs and business corporations alike. This editorial for our special issue reflects on the fact that the emerging relationships between science, technology and processes of social change are providing a fertile field for analysts and practitioners engaged in the diversity of what we might define as ‘development studies’, yet also challenge them to engage more effectively with complex dynamics and multiple knowledges. Copyright © 2008 John Wiley & Sons, Ltd.
Reframing expert support for development management
Authors: Reynolds Martin
Published: August 2008

Three critiques of participatory development (PD) and their respective challenges for expert support are discussed—(i) the masking of ideological imperatives behind PD, (ii) the depoliticising practice of policy language and (iii) the restrictive space for enabling responsible support from different fields of expertise including science. Drawing on the experience of two interventions—one Guyana based and one European based—three conceptual tools are suggested for dealing with these issues, respectively. First, systems thinking is described from a critical systems perspective, interrogating the legitimacy of boundaries that we use to frame reality. Second, social learning is considered as a complementary policy instrument in which language and communication are regarded as integral to development. Third, critical space for systems thinking and social learning is examined with reference to the limitations of space provided by conventional project management. Copyright © 2008 John Wiley & Sons, Ltd.
Developing a regional drought climatology for the Czech Republic
Authors: Trnka M. , Dubrovský M. , Svoboda M. , Semerádová D. , Hayes M. , Žalud Z. , Wilhite D.
Published: August 2008

This study presents a methodology for the analysis of a drought climatology within a particular region that enables a user to define drought areas at a high spatial resolution. It is suitable for quantifying the relative differences in the intensity of drought spells, and the frequency and duration between individual stations within an area of interest. The methodology is based on the Standardized Precipitation Index (SPI), the Palmer Drought Severity Index (PDSI) and the Palmer Z‐index (Z‐index). However, the climatological parameters needed to process and calculate the indices were not derived separately for each site as is usually done, but were based on a set of all available weather stations in the studied region. This approach was utilized in the case study including all of the Czech Republic using 233 climatological stations with monthly records of mean temperature and precipitation for the period 1961–2000. The study is also focussed on the development of more efficient ways of communicating results to the stakeholders. Therefore, a method allowing for an integration of several drought indices into a single indicator called the Integrated Climatological Drought Indicator (ICDI) was developed. The newly developed method allowed for an objective identification of the drought‐prone regions of the country that were defined as areas with a chance (higher than 50 and 60% respectively) of moderate or extreme drought. We have found that 12.3 and 3% of the country area, respectively, belong within these categories and that these regions also happen to be prime agricultural areas. The conclusions were supported by the results of a cluster analysis. Finally, the analysis of time trends was conducted, which showed that the majority of 233 stations had grown significantly drier during the studied period. The main driving force behind this development was found to be an increase of temperature, especially in the 1990s. Copyright © 2008 Royal Meteorological Society
Outcomes of Living Donor Liver Transplantation for Acute Liver Failure: the Adult-to-Adult Living Donor Liver Transplantation Cohort Study
Authors: Campsen Jeffrey , Blei Andres T. , Emond Jean C. , Everhart James E. , Freise Chris E. , Lok Anna S. , Saab Sammy , Wisniewski Karen A. , Trotter James F.
Published: August 2008

For acute liver failure (ALF), living donor liver transplantation (LDLT) may reduce waiting time and provide better timing compared to deceased donor liver transplantation (DDLT). However, there are concerns that a partial graft would result in reduced survival of critically ill LDLT recipients and that the rapid evolution of ALF would lead to selection of inappropriate donors. We report outcomes for ALF patients (and their donors) evaluated for LDLT between 1998 and April 2007 from the Adult-to-Adult Living Donor Liver Transplantation Cohort. Of the 1201 potential LDLT recipients, 14 had ALF, only 6 of whom had an identified cause. The median time from listing to first donor evaluation was 1.5 days, and the median time from evaluation to transplantation was 1 day. One patient recovered without liver transplant, 3 of 10 LDLT recipients died, and 1 of 3 DDLT recipients died. Five of the 10 living donors had a total of 7 posttransplant complications. In conclusion, LDLT is rarely performed for ALF, but in selected patients it may be associated with acceptable recipient mortality and donor morbidity.
Improvement of Impaired Albumin Binding Capacity in Acute-on-Chronic Liver Failure by Albumin Dialysis
Authors: Klammt Sebastian , Mitzner Steffen R. , Stange Jan , Loock Jan , Heemann Uwe , Emmrich Jörg , Reisinger Emil C. , Schmidt Reinhard
Published: August 2008

Extracorporeal albumin dialysis (ECAD) enables the elimination of albumin bound substances and is used as artificial liver support system. Albumin binding function for the benzodiazepine binding site specific marker Dansylsarcosine was estimated in plasma samples of 22 patients with cirrhosis and hyperbilirubinaemia (ECAD: n = 12; control: n = 10) during a period of 30 days in a randomized controlled clinical ECAD trial. Albumin Binding Capacity (ABiC) at baseline was reduced to 31.8% (median; range 24%-74%) and correlated to the severity of liver disease. Within two weeks a significant improvement of ABiC and a reduction of the albumin bound markers bilirubin and bile acids were observed in the ECAD group. During single treatments a significant decrease of albumin bound substances (bilirubin and bile acids) as well as an increase in ABiC was observed. In the control group, baseline ABiC was significantly lower in patients who died during study period (34.2% vs. 41.7%; P < 0.028), whereas no significant differences were observed for CHILD, coagulation factors, albumin, bile acids nor bilirubin. At baseline 13 patients had a severely impaired ABiC (<40%), improvement of ABiC was more frequent in the ECAD group (5/6) than in the SMT group (2/7). Reduced albumin binding function is present in decompensated liver failure and is related to severity and 30 day survival. ABiC can be improved by ECAD. The beneficial effect of this treatment may be related to the improvement of albumin binding function more than to the elimination of specific substances. Characterization of albumin function by the ABiC test may help to evaluate different liver support systems and other therapeutic measures.
Chickenpox-Associated Fulminant Hepatitis That Led to Liver Transplantation in a 63-Year-Old Woman
Authors: Roque-Afonso Anne-Marie , Bralet Marie-Pierre , Ichai Philippe , Desbois Delphine , Vaghefi Parissa , Castaing Denis , Samuel Didier , Dussaix Elisabeth
Published: August 2008

A 63-year-old woman treated with prednisone for sinusitis developed fulminant liver failure due to a clinically unsuspected primary varicella zoster virus infection. The diagnosis of herpetic hepatitis was made from a liver biopsy, and varicella zoster virus viremia was detected by polymerase chain reaction. She was treated successfully with transplantation and perioperative administration of acyclovir.
Macromol. Chem. Phys. 17/2008
Authors: Su Hung‐Wen , Chen Wen‐Chang
Published: August 2008

Cover: The cover shows the variation in refractive index of acrylic polymer‐titania hybrid films as a function of the titania content, along with a high‐resolution TEM image of the nanocrystalline domain in the hybrid film. Further details can be found in the article by H.‐W. Su and W.‐C. Chen on page 1778.
Proteomics study of medullary thyroid carcinomas expressing RET germ‐line mutations: Identification of new signaling elements
Authors: Gorla L. , Mondellini P. , Cuccuru G. , Miccichè F. , Cassinelli G. , Cremona M. , Pierotti M.A. , Lanzi C. , Bongarzone I.
Published: August 2008

Proteomics may help to elucidate differential signaling networks underlying the effects of compounds and to identify new therapeutic targets. Using a proteomic‐multiplexed analysis of the phosphotyrosine signaling together with antibody‐based validation techniques, we identified several candidate molecules for RET (rearranged during transfection) tyrosine kinase receptor carrying mutations responsible for the multiple endocrine neoplasia type 2A and 2B (MEN2A and MEN2B) syndromes in two human medullary thyroid carcinoma (MTC) cell lines, TT and MZ‐CRC‐1, which express the RET‐MEN2A and RET‐MEN2B oncoproteins, respectively. Signaling elements downstream of these oncoproteins were identified after treating cells with the indolinone tyrosine kinase inhibitor RPI‐1 to knock down RET phosphorylation activity. We detected 23 and 18 affinity‐purified phosphotyrosine proteins in untreated TT and MZ‐CRC‐1 cells, respectively, most of which were shared and sensitive to RPI‐1 treatment. However, our data clearly point to specific signaling features of the RET‐MEN2A and RET‐MEN2B oncogenic pathways. Moreover, the detection of high‐level expression of minimally phosphorylated epidermal growth factor receptor (EGFR) in both TT and MZ‐CRC‐1 cells, together with our data on the effects of EGF stimulation on the proteomic profiles and the response to Gefitinib treatment, suggest the relevance of EGFR signaling in these cell lines, especially since analysis of 14 archival MTC specimens revealed EGFR mRNA expression in all samples. Together, our data suggest that RET/EGFR multi‐target inhibitors might be beneficial for therapy of MTC. © 2008 Wiley‐Liss, Inc.
MnSOD deficiency has a differential effect on disease progression in two different ALS mutant mouse models
Authors: Muller Florian L. , Liu Yuhong , Jernigan Amanda , Borchelt David , Richardson Arlan , Van Remmen Holly
Published: August 2008

Mitochondrial dysfunction and oxidative stress are thought to participate in the pathogenesis of amyotrophic lateral sclerosis (ALS). The purpose of this study was to determine the effect of reduced mitochondrial antioxidant defense on lifespan and disease progression in two mouse models of familial ALS (G93A and H46R/H48Q mutant lines) that represent pseudo‐wildtype and metal‐deficient ALS mutants, respectively. The metal‐deficient H46R/H48Q mutant differs from the G93A mutant in that it cannot bind copper in the active site and thus lacks SOD activity. We crossed each of these mutant lines with mice deficient in the mitochondrial matrix antioxidant enzyme MnSOD (Sod2+/− mice). In both high (G93A1Gur) and low (G93ADL) copy G93A strains, MnSOD deficiency caused a decrease in lifespan that was associated with a reduced disease duration rather than earlier disease onset. In contrast, MnSOD deficiency had no effect on lifespan or disease parameters of H46R/H48Q mutant mice. MnSOD deficiency thus has a differential effect on disease progression in different mutant SOD1 ALS mouse models, suggesting that different ALS‐causing mutations in SOD1 result in disease progression by at least proximally different mechanisms/pathways. Muscle Nerve 38: 1173–1183, 2008
Statins may aggravate myasthenia gravis
Authors: Oh Shin J. , Dhall Rohit , Young Angela , Morgan Marla B. , Lu Liang , Claussen Gwendolyn C.
Published: August 2008

Statin‐induced myopathy is well‐known, but the effect of cholesterol‐lowering agents on myasthenia gravis (MG) has not been studied in detail. We investigated statin use and its effects on MG among patients with this disease. Statin information was systemically obtained from 170 patients being treated at the Neuromuscular Disease Clinic at the University of Alabama at Birmingham. When a new myalgic syndrome or worsening of MG developed within 4 months after statin treatment, no other likely cause was found, and clinical improvement occurred either with or without discontinuation of the statin, we considered these symptoms to be statin‐induced. Fifty‐four patients (31%) were on statins. The statin group had proportionally more males, and older patients compared with the non‐statin group. A myalgic syndrome was noted in 7 (13%) patients, but it resolved without any sequelae after withdrawal of the statin. MG worsening occurred in 6 (11%) patients without regard to type of MG or brand of statin. MG worsening occurred independently of myalgic syndrome and involved predominantly oculobulbar symptoms within 1–16 weeks of statin treatment. In 4 patients, additional treatment was needed to reverse MG worsening. Statins are safe in the majority of MG patients, but their use must be accompanied by close observation for possible MG worsening. Muscle Nerve 38: 1101–1107, 2008
The scaled boundary finite element method in structural dynamics
Authors: Song Chongmin
Published: August 2008

The scaled boundary finite element method is extended to solve problems of structural dynamics. The dynamic stiffness matrix of a bounded (finite) domain is obtained as a continued fraction solution for the scaled boundary finite element equation. The inertial effect at high frequencies is modeled by high‐order terms of the continued fraction without introducing an internal mesh. By using this solution and introducing auxiliary variables, the equation of motion of the bounded domain is expressed in high‐order static stiffness and mass matrices. Standard procedures in structural dynamics can be applied to perform modal analyses and transient response analyses directly in the time domain. Numerical examples for modal and direct time‐domain analyses are presented. Rapid convergence is observed as the order of continued fraction increases. A guideline for selecting the order of continued fraction is proposed and validated. High computational efficiency is demonstrated for problems with stress singularity. Copyright © 2008 John Wiley & Sons, Ltd.
Rheological and thermal properties of ethylene–styrene copolymers
Authors: Marques Maria de Fátima Vieira , de Moraes Luanda Silva
Published: August 2008

The metallocene compounds Ph2C(Flu,Cp)ZrCl2 (cat 1) and Et(Flu)2ZrCl2 (cat 2) activated with methylaluminoxane (MAO) were evaluated on ethylene and styrene copolymerization. The comonomer concentration (2.2 M), polymerization temperature (80°C), and ethylene concentration (0.135 M) were maintained constant in the reaction medium. The materials were evaluated in a differential scanning calorimeter (DSC), in a rheometer with parallel plate geometry, and their specific gravities were determined. The copolymer obtained with the catalyst 1 was amorphous; however, that obtained with the catalyst 2 at the same reaction conditions presented melting temperature lower than that of polyethylene. For the rheological measurements, the TA Instruments Rheometer AR 2000 employing dynamic experiments at 190°C was used. The rheological analyses indicated that the obtained polymers presented pseudoplastic behavior in the whole studied frequency range. The behavior of the synthesized copolymers was compared with that of the polyethylene obtained at the same reaction conditions. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Intra‐ versus intermolecular hydrogen bonding equilibrium in 2‐hydroxy‐N,N‐diethylbenzamide
Authors: Majewska P. , Pająk J. , Rospenk M. , Filarowski A.
Published: August 2008

Complex studies of the intramolecular versus intermolecular hydrogen bond equilibrium and internal rotation of the N,N‐diethylamine group in 2‐hydroxy‐N,N‐diethylbenzamide were conducted. The intramolecular versus intermolecular process in 2‐hydroxy‐N,N‐diethylbenzamide was studied by UV–Vis, NMR, IR and Vapour Pressure Osmometric (VPO) methods as a function of temperature and concentration in non‐polar, basic and protic solvents. The unequal positions of the ethyl groups were analysed and the energy barrier to the re‐orientation was defined by the NMR method. This paper presents a study into a complicated nature of competitive interaction 2‐hydroxy‐N,N‐diethylbenzamide with the environment by means of the aforesaid methods. Copyright © 2008 John Wiley & Sons, Ltd.
Improving the effectiveness of process safety management in small companies
Authors: Louvar Joseph F.
Published: August 2008

Major accidents are continuing to injure people, and damage facilities and the environment. About 50% of these accidents are in plants that are covered by process safety management (PSM) and 50% are in smaller plants that are not covered. However, the damage is the same. Clearly the OSHA PSM regulation and recommendations by CSB, CCPS, PSP, etc. are not being used as specified. The objective of this paper is to express an enthusiastic support for these major excellent recommendations and to make a few additional recommendations that should enhance those previously listed. This article describes (a) specifically designed methods to improve the implementation of PSM and the above‐mentioned recommendations and (b) additional plant practices for preventing accidents. The methods and practices presented in this article are especially important for smaller plants; most of the larger companies already have good systems to prevent accidents. However, since many of the large accidents are in PSM‐covered plants, some of these larger plants may also benefit from these additional recommendations.

One recommendation is that small companies, although not covered by PSM, should practice the intent of the regulation. At a minimum, companies should develop a document that is at least similar to the PSM documentation. However, this article emphasizes that this documentation is not enough because the management of the requirements is extremely difficult. Companies need to have a system that includes the PSM documents, communication, delegation, and follow‐up to insure that the requirements are practiced as intended.

Based on the author's experience, the use of additional plant practices such as an effective management system, internal audits, walk‐the‐line, and checklists will enhance the utilization of PSM. These practices are easy to use and will prevent accidents. More of these methods and practices are needed and should be shared between companies. © 2008 American Institute of Chemical Engineers Process Saf Prog, 2008
MOVPE and photoluminescence of narrow band gap (0.77 eV) InN on GaN/sapphire by pulsed growth mode
Authors: Jamil Muhammad , Zhao Hongping , Higgins John B. , Tansu Nelson
Published: August 2008

This paper reports the metalorganic vapor phase epitaxy (MOVPE) of InN on GaN/sapphire templates by pulsed growth mode. Photoluminescence analysis of the films has been performed both at room temperature (T = 300 K) and low temperature (T = 77 K). At room temperature, the band gap of InN is measured as 0.77 eV which is observed to have strong dependence on the growth temperature of the film. The appearance of otherwise less dominant transitions is associated to defects related luminescence from the films grown at relatively low growth temperatures. The electron mobility of 681 cm2/(V s) is obtained for InN alloy grown under optimal condition. The X‐ray diffraction (XRD) analysis, structural quality and the evolution of the surface morphology of thin InN films have also been studied in the context of the given growth conditions. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Determination of critical thickness for defect formation of CdSe/ZnSe heterostructures by transmission electron microscopy and photoluminescence spectroscopy
Authors: Litvinov D. , Schowalter M. , Rosenauer A. , Daniel B. , Fallert J. , Löffler W. , Kalt H. , Hetterich M.
Published: August 2008

We report on the investigation of CdSe/ZnSe heterostructures by transmission electron microscopy (TEM) and photoluminescence spectroscopy (PL). CdSe layers with nominal thicknesses tCdSe between 0.5 and 8 monolayers (ML) were embedded in a ZnSe matrix and grown on a GaAs(001) substrate by molecular‐beam epitaxy at 280 °C. The Cd‐distribution was obtained from high‐resolution TEM lattice fringe images using composition evaluation by lattice fringe analysis technique. The measured minimum, average and maximum Cd‐concentrations and the overall CdSe contents in the layers increase with the nominal CdSe layer thickness and reach a constant value at tCdSe = 4 ML. The measured CdSe content in the regions with the maximal Cd‐concentration continues to increase for tCdSe ≥ 5 ML. The increasing of measured Cd‐concentrations/CdSe contents is correlated with a red shift of PL spectra. In the CdSe layers with tCdSe ≥ 5 ML, formation of defects is observed. The increasing density of defects and decreasing intensity of PL spectra with tCdSe suggest that the critical thickness for defect formation during CdSe growth on the ZnSe(001) is between 4 ML and 5 ML. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Plasmonic nanostructures in aperture‐less scanning near‐field optical microscopy (aSNOM)
Authors: Vogelgesang Ralf , Dorfmüller Jens , Esteban Ruben , Weitz R. Thomas , Dmitriev Alexandre , Kern Klaus
Published: August 2008

Apertureless scanning near‐field optical microscopy offers superb spatial resolution, but interpreting the recorded signal can still be a challenge. Especially images of eigenmodes in plasmonic nanostructures are very often obscured by concurrent scattering from the tip and/or coupling effects in the tip‐sample system. We show here how the use of orthogonal polarizations in excitation and detection affords us with an elegant method to map near‐fields of plasmonic eigenmodes and other optical phenomena. We demonstrate with a variety of samples possible applications of this cross‐polarization scheme, such as verification of functional nanooptical structures, systematic studies of localized and propagating plasmonic eigenmodes, and their susceptibility to disturbance from structural defects. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electronic properties of chemically modi.ed graphene ribbons
Authors: Cervantes‐Sodi F. , Csányi G. , Piscanec S. , Ferrari A. C.
Published: August 2008

We compare the electronic properties of graphene nanoribbons, with either bulk or edge substitutions, edge functionalization, or chemisorption. Chemical modifications can cause semiconductor‐metal transitions, lifting of spin degeneracy, widening of bandgap, or appearance of non‐dispersive impurity bands and doping. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Pre‐study analytical method validation: comparison of four alternative approaches based on quality‐level estimation and tolerance intervals
Authors: Govaerts Bernadette , Dewé Walthère , Maumy Myriam , Boulanger Bruno
Published: August 2008

In industry and in laboratories, it is crucial to continuously control the validity of the analytical methods used to follow the products' quality characteristics. Validity must be assessed at two levels. The ‘pre‐study’ validation aims at demonstrating before use that the method will be able to achieve its objectives. The ‘in‐study’ validation is intended to verify, by inserting quality control (QC) samples in routine runs, that the method remains valid over time. At these two levels, the analytical method will be claimed valid if it is possible to prove that a sufficient proportion of analytical results is expected to lie within given acceptance limits [−λ,λ] around the nominal value. This paper presents and compares four approaches to checking the validity of a measurement method at the pre‐study level. They can be classified into two categories. In the first, a lower confidence bound for the estimated probability π of a result lying within the acceptance limits is computed and compared with a given acceptance level. Maximum likelihood and delta methods are used to estimate the quality level π and the corresponding estimator variance. Two approaches are then proposed to derive the confidence bound: the asymptotic maximum likelihood approach and a method proposed by Mee (Commun. Stat. Theory Methods 1988; 17(5):1465–1479). The second category of approaches checks whether a tolerance interval for hypothetical future measurements lies within the predefined acceptance limits [−λ,λ]. β‐expectation and β–γ‐content tolerance intervals are investigated and compared in this context. These four approaches are illustrated on a bioanalytical HPLC‐UV analytical process and compared through simulations. Copyright © 2008 John Wiley & Sons, Ltd.
Case‐based reasoning and the statistical challenges
Authors: Perner Petra
Published: August 2008

Case‐based reasoning (CBR) solves problems using the already stored knowledge and captures new knowledge, making it immediately available for solving the next problem. Therefore, CBR can be seen as a method for problem solving and also as a method to capture new experience and make it immediately available for problem solving. The CBR paradigm has been originally introduced by the cognitive science community. The CBR community aims at developing computer models that follow this cognitive process. Up to now many successful computer systems have been established on the CBR paradigm for a wide range of real‐world problems. In this paper we will review the CBR process and the main topics within the CBR work. Hereby we try bridging between the concepts developed within the CBR community and the statistics community. The CBR topics we describe are similarity, memory organization, CBR learning and case‐base maintenance. Then we will review, based on applications, the open problems that need to be solved. The applications we focus on are meta‐learning for parameter selection, image interpretation, incremental prototype‐based classification and novelty detection and handling. Finally, we summarize our concept on CBR. Copyright © 2008 John Wiley & Sons, Ltd.
Recommendations on the use of Bayesian optimal designs for choice experiments
Authors: Kessels Roselinde , Jones Bradley , Goos Peter , Vandebroek Martina
Published: August 2008

In this paper, we argue that some of the prior parameter distributions used in the literature for the construction of Bayesian optimal designs are internally inconsistent. We provide practical advice on how to properly specify the prior parameter distribution. Also, we present an example to illustrate that Bayesian optimal designs generally outperform utility‐neutral optimal designs that are based on linear design principles. Copyright © 2008 John Wiley & Sons, Ltd.
A transmission capacity enhancement of the CDM‐based satellite DMB system
Authors: Lee Ho‐Jin , Lee In‐Ki , Chang Dae‐Ig , Kim Tae‐Hoon
Published: August 2008

After the launch of Satellite Digital Multimedia Broadcasting (S‐DMB) service in Korea, there was a requirement to have more channels to accommodate more bandwidth‐requiring applications. We designed a new architecture to provide the system with more channel capacity while maintaining the current performance as much as possible. We took a hierarchical modulation technology used for the DVB‐S2 standard. A number of combinations of modulation parameters and FEC modes have been simulated for the evaluation of technical feasibility of the proposed structure. Also investigations were carried out to assess the impact to current service performance. It was found that a 16200‐bit LDPC with hierarchical modulation could give additional channel capacity while keeping the current quality of service for selected CODEC and code rates (Int. J. Satellite Commun. Networks 2004; 22). Though 1ldB degradation of BER to the existing service was resulted by this approach, but no perceptional service degradation was expected since current link margin is larger than 3ldB. We found that about 36% of capacity enhancement can be achievable by the hierarchical modulation with proper CODEC selection. Additional degradation, however, may be encountered in mobile environment due to the multipath channel in spite of its performance immunity to the Doppler effect. Copyright © 2008 John Wiley & Sons, Ltd.
Satellite digital multimedia mobile broadcasting (S‐DMB) system
Authors: Suenaga Masashi
Published: August 2008

The MBSAT spacecraft was lunched in March 2004 and has been in service for the world first satellite base multimedia service for mobile users in Japan and Korea. The service is based on the unique hybrid system named satellite digital multimedia mobile broadcasting (S‐DMB). The system consists of sophisticated high‐power satellite and ground base repeaters called gap filler (GF). The satellite MBSAT has unique features such as 12 m unfurlable mesh reflector antenna, the use of stationary plasma thruster for north–south stationkeeping and ring laser gyro for attitude control references. The MBSAT provides more than 57 dBW equivalent isotropic radiated power over Japan and Korea coverage area. The S‐DMB service has started using MBSAT in Japan and Korea. People can enjoy video, audio and data broadcasting services with mobile handy terminal in outdoor, in high‐speed moving vehicle, in commuter train and even in airplane. This system is also useful as an emergency media for disaster prevention such as tsunami warns or earthquake alarming. As S‐DMB is a flexible hybrid system, the service could be initiated by using only GF system in urban area. This approach enables launching mobile TV service fast and efficiently. Copyright © 2008 John Wiley & Sons, Ltd.