bluuebunny/crossref_metadata_2025 huggingface dataset:
A Modular Synthesis of Functionalized Pyridines through Lewis‐Acid‐Mediated and Microwave‐Assisted Cycloadditions between Azapyrylium Intermediates and Alkynes
Authors: Linder Igor , Gerhard Markus , Schefzig Luise , Andrä Michal , Bentz Christoph , Reissig Hans‐Ulrich , Zimmer Reinhold
Published: September 2011

In this report we describe the synthesis of differentially functionalized pyridine derivatives 3 and the related 3‐bromo‐substituted pyridines 11. Dissociation of 6H‐1,2‐oxazine precursors (1a, 1b, 5, 6, or 12) in situ, mediated by boron trifluoride–diethyl ether, generates the azapyrylium intermediates A, which undergo hetero‐Diels–Alder reactions with various mono‐ and disubstituted alkynes 2. In general, these pyridine syntheses proceeded with high efficiencies and were very flexible with respect to all positions in the pyridine cores. For the 3‐phenyl‐substituted pyridine derivatives 3a–3j and 11a–11f the best results were obtained by a new microwave‐assisted protocol, which is clearly superior to the previously used conventional procedure at low temperature in dichloromethane. Furthermore, 3‐(trifluoromethyl)‐ and 3‐acryloyl‐substituted 6H‐1,2‐oxazines reacted cleanly under microwave irradiation conditions to furnish the expected pyridine derivatives 3k and 3l in respectable yields. The 3‐bromo‐substituted pyridines 11 were further functionalized through palladium‐catalyzed couplings such as Suzuki or Sonogashira reactions, which led smoothly to tri‐ or tetrasubstituted pyridine derivatives such as 19–21 and 23. Reductive debromination of 11e afforded the pyridine 17 in excellent yield, whereas oxidation of the pyridinyl thioether 3g with oxone led to the corresponding sulfoxide 24. Our method thus establishes a new and versatile approach to highly substituted pyridine derivatives.
Fluorescence Properties of 5‐(5,6‐Dimethoxybenzothiazol‐2‐yl)‐2′‐deoxyuridine (dbtU) and Oligodeoxyribonucleotides Containing dbtU
Authors: Hirose Wataru , Sato Kousuke , Matsuda Akira
Published: September 2011

We describe the synthesis and photophysical properties of 11 substituted 5‐(benzothiazol‐2‐yl)‐2′‐deoxyuridine derivatives and oligodeoxyribonucleotides (ODNs) containing 5‐(5,6‐dimethoxybenzothiazol‐2‐yl)‐2′‐deoxyuridine (dbtU), which was the strongest fluorescent derivative among those prepared. The fluorescence properties of dbtU itself and ODNs containing dbtU show the same tendency of being weaker in both neutral and acidic solution and stronger in basic solution. The ODNs (15mer) containing 16 combinations of 5′‐XbtU‐3′ and 5′‐btUY‐3′, where X, Y = A, T, G, or C, were synthesized, and their fluorescence intensity and quantum yield in basic solution were compared. On average, only the ODN with the 5′‐GbtU‐3′ sequence shows a 7.9‐fold lower fluorescence intensity than the other sequences. Ab initio calculations of 5′‐GbtU‐3′ and 5′‐btUG‐3′ as models under basic conditions suggest that the lower fluorescence of the ODN containing the 5′‐GbtU‐3′ sequence is caused by a wider overlap between stacked guanine (Gua) and btUra than that of the 5′‐btUG‐3′ sequence and that the HOMO is delocalized not only on btUra but also on Gua.
A Metal‐Free Approach Based on Graphene Oxide‐Modified Electrode for Monitoring the Photoelectrocatalytic Degradation of EDTA
Authors: Wei Lili , Yang Juan , Borowiec Joanna , Zhang Jingdong
Published: September 2011

A novel voltammetric method for the sensitive determination of ethylenediaminetetraacetic acid (EDTA) was developed based on a graphene oxide (GO) modified electrode. In acetate buffer solution, GO showed a voltammetric response composed of a sharp anodic peak and a weak cathodic peak. When EDTA was present in the solution, the voltammetric response of GO was suppressed. Under optimum conditions, the response of the GO‐modified electrode was inversely proportional to the concentration of EDTA from 6.0×10−7 to 1.0×10−4 mol/L. Using such a GO‐based voltammetry, the effective photoelectrocatalytic degradation of EDTA over a TiO2 film electrode was evaluated and some influencing factors were investigated.
Evaluation of the interaction between sitagliptin and cyclodextrin derivatives by capillary electrophoresis and nuclear magnetic resonance spectroscopy
Authors: Sohajda Tamás , Hu Wen Hui , Zeng Li Li , Li Hong , Szente Lajos , Noszál Béla , Béni Szabolcs
Published: September 2011

An aqueous capillary electrophoretic method was developed for chiral analysis of the novel anti‐diabetic drug, sitagliptin. The acid–base profiling of the analyte was carried out using both capillary electrophoresis and nuclear magnetic resonance pH titrations. The apparent complex stability and chiral separation properties were investigated with 30 different cyclodextrins under acidic conditions. The effect of concentration and pH of the BGE, temperature of the capillary, and the type and concentration of the chiral selector on the enantiomer resolution were thoroughly investigated. The effects of dual cyclodextrin systems on separation were also extensively studied. Complete separation of racemic sitagliptin with good resolution (RS=2.24) was achieved within a short time (15 min) with optimized parameters (10°C, pH=4.4, 40 mM phosphate buffer) of a sulfobutylether‐β‐cyclodextrin (averaged degree of substitution ∼4) and native β‐cyclodextrin dual system. The averaged stoichiometry of the inclusion complex was determined using the Job plot method with both 1H and 19F NMR experiments and resulted in a 1:1 complex. The structure of the inclusion complex was elucidated using 2‐D ROESY NMR experiments.
Cellular dielectrophoresis: Applications to the characterization, manipulation, separation and patterning of cells
Authors: Gagnon Zachary R.
Published: September 2011

Over the past decade, dielectrophoresis (DEP) has evolved into a powerful, robust and flexible method for cellular characterization, manipulation, separation and cell patterning. It is a field with widely varying disciplines, as it is quite common to see DEP integrated with a host of applications including microfluidics, impedance spectroscopy, tissue engineering, real‐time PCR, immunoassays, stem‐cell characterization, gene transfection and electroporation, just to name a few. The field is finally at the point where analytical and numerical polarization models can be used to adequately describe and characterize the dielectrophoretic behavior of cells, and there is ever increasing evidence demonstrating that electric fields can safely be used to manipulate cells without harm. As such, DEP is slowly making its way into the biological sciences. Today, DEP is being used to manipulate individual cells to specific regions of space for single‐cell assays. DEP is able to separate rare cells from a heterogeneous cell suspension, where isolated cells can then be characterized and dynamically studied using nothing more than electric fields. However, there is need for a critical report to integrate the many new features of DEP for cellular applications. Here, a review of the basic theory and current applications of DEP, specifically for cells, is presented.
Direct current insulator‐based dielectrophoretic characterization of erythrocytes: ABO‐Rh human blood typing
Authors: Srivastava Soumya K. , Artemiou Andreas , Minerick Adrienne R.
Published: September 2011

A microfluidic platform developed for quantifying the dependence of erythrocyte (red blood cell, RBC) responses by ABO‐Rh blood type via direct current insulator dielectrophoresis (DC‐iDEP) is presented. The PDMS DC‐iDEP device utilized a 400×170 μm2 rectangular insulating obstacle embedded in a 1.46‐cm long, 200‐μm wide inlet channel to create spatial non‐uniformities in direct current (DC) electric field density realized by separation into four outlet channels. The DC‐iDEP flow behaviors were investigated for all eight blood types (A+, A−, B+, B−, AB+, AB−, O+, O−) in the human ABO‐Rh blood typing system. Three independent donors of each blood type, same donor reproducibility, different conductivity buffers (0.52–9.1 mS/cm), and DC electric fields (17.1–68.5 V/cm) were tested to investigate separation dependencies. The data analysis was conducted from image intensity profiles across inlet and outlet channels in the device. Individual channel fractions suggest that the dielectrophoretic force experienced by the cells is dependent on erythrocyte antigen expression. Two different statistical analysis methods were conducted to determine how distinguishable a single blood type was from the others. Results indicate that channel fraction distributions differ by ABO‐Rh blood types suggesting that antigens present on the erythrocyte membrane polarize differently in DC‐iDEP fields. Under optimized conductivity and field conditions, certain blind blood samples could be sorted with low misclassification rates.
Electrochemical switchable protein‐based optical device
Authors: Frasca Stefano , Richter Claudia , von Graberg Till , Smarsly Bernd M. , Wollenberger Ulla
Published: September 2011

The present work contributes to the development of reusable sensing systems with a visual evaluation of the detection process related to an analyte. An electrochemical switchable protein‐based optical device was designed with the core part composed of cytochrome c immobilized in a mesoporous indium tin oxide film. A color‐developing redox‐sensitive dye was used as switchable component of the system. The cytochrome c‐catalyzed oxidation of the dye by hydrogen peroxide is spectroscopically investigated. When the dye is co‐immobilized with the protein, its redox state is easily controlled by application of an electrical potential at the supporting material. This enables to electrochemically reset the system to the initial state and repetitive signal generation. The implemented reset function of the color forming reaction will make calibration of small test devices possible. The principle can be extended to other color forming redox reactions and to coupled enzyme systems, such as rapid food testing and indication of critical concentrations of metabolites for health care.
EGFR mutations in non‐small‐cell lung cancer among smokers and non‐smokers: A meta‐analysis
Authors: Ren Jing‐Hua , He Wen‐Shan , Yan Guo‐Li , Jin Min , Yang Kun‐Yu , Wu Gang
Published: September 2011

Mounting evidence has suggested somatic mutations in the EGFR gene are associated with better responsiveness to EGFR tyrosine kinase inhibitors (TKIs) in patients with non‐small‐cell lung cancer (NSCLC). Some, but not all, studies have reported that the mutations were more frequently observed in patients without a smoking history. To comprehensively address this issue, we performed a meta‐analysis to evaluate the association between cigarette‐smoking history and mutation of the EGFR gene in NSCLC. Twenty‐six studies, involving 3,688 patients with NSCLC were included in the analysis. The pooled analysis shows that the incidence of EGFR mutations in NSCLC differs according to cigarette‐smoking history. The odds ratio (OR) for the EGFR mutation in non‐smokers relative to smokers was 4.829 (95% confidence interval [CI]: 3.598–6.482; P < 0.001). These data may assist clinicians in assessing the likelihood of EGFR mutations in patients with NSCLC when mutational analysis is not feasible. Environ. Mol. Mutagen. 2012. © 2011 Wiley Periodicals, Inc.
Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease
Authors: Valles‐Ortega Jordi , Duran Jordi , Garcia‐Rocha Mar , Bosch Carles , Saez Isabel , Pujadas Lluís , Serafin Anna , Cañas Xavier , Soriano Eduardo , Delgado‐García José M. , Gruart Agnès , Guinovart Joan J.
Published: September 2011

Lafora disease (LD) is caused by mutations in either the laforin or malin gene. The hallmark of the disease is the accumulation of polyglucosan inclusions called Lafora Bodies (LBs). Malin knockout (KO) mice present polyglucosan accumulations in several brain areas, as do patients of LD. These structures are abundant in the cerebellum and hippocampus. Here, we report a large increase in glycogen synthase (GS) in these mice, in which the enzyme accumulates in LBs. Our study focused on the hippocampus where, under physiological conditions, astrocytes and parvalbumin‐positive (PV+) interneurons expressed GS and malin. Although LBs have been described only in neurons, we found this polyglucosan accumulation in the astrocytes of the KO mice. They also had LBs in the soma and some processes of PV+ interneurons. This phenomenon was accompanied by the progressive loss of these neuronal cells and, importantly, neurophysiological alterations potentially related to impairment of hippocampal function. Our results emphasize the relevance of the laforin–malin complex in the control of glycogen metabolism and highlight altered glycogen accumulation as a key contributor to neurodegeneration in LD.
Nutrient loss with runoff from fairway turf: An evaluation of core cultivation practices and their environmental impact
Authors: Rice Pamela J , Horgan Brian P
Published: September 2011

The presence of excess nutrients in surface waters can result in undesirable environmental and economic consequences, including nuisance algal blooms and eutrophication. Fertilizer use in highly managed turf systems has raised questions concerning the contribution of nutrients to surrounding surface waters. Experiments were designed to quantify phosphorus and nitrogen transport with runoff from turf plots maintained as a golf course fairway to identify which cultural practice, solid tine (ST) or hollow tine (HT) core cultivation, maximized phosphorus and nitrogen retention at the site of fertilizer application. Simulated precipitation and collection of resulting runoff were completed 26 ± 13 h following granular fertilizer application (18-3-18: N-P2O5-K2O) and 63 d and 2 d following core cultivation. Runoff volumes were reduced in fairway turf plots aerated with HT relative to ST (63 d: 10%, 2 d: 55% reduction). Analysis of the runoff revealed a reduction in soluble phosphorus, ammonium nitrogen, and nitrate nitrogen losses with runoff from plots managed with HT; a 5 to 27% reduction after 63 d; and a 39 to 77% reduction at 2 d. Golf course runoff-to-surface water scenarios were used to calculate estimated environmental concentrations (EECs) of nitrogen and phosphorus in surface water receiving runoff from turf managed with ST or HT core cultivation. Surface water concentrations of phosphorus remained above the U.S. Environmental Protection Agency's water quality criteria to limit eutrophication, with the exception of concentrations associated with HT core cultivation at 2 d. Regardless of management practice (ST or HT) and time between core cultivation and runoff (63 d or 2 d), all EECs of nitrogen were below levels associated with increased algal growth. Understanding nutrient transport with runoff and identifying strategies that reduce off-site transport will increase their effectiveness at intended sites of application and minimize undesirable effects to surrounding surface water resources. Environ. Toxicol. Chem. 2011;30:2473–2480. © 2011 SETAC
Vitellogenin induction by 17β-estradiol and 17α-ethynylestradiol in male Murray rainbowfish (Melanotaenia fluviatilis)
Authors: Woods Marianne , Kumar Anupama
Published: September 2011

Hepatic vitellogenin (VTG) mRNA and plasma protein assays were developed for the Murray rainbowfish (Melanotaenia fluviatilis), a native freshwater fish species in Australia. Adult male Murray rainbowfish were exposed to 17β-estradiol (E2) or 17α-ethynylestradiol (EE2) at 0, 1, 5, 10, 50, or 100 ng/L in a semistatic system for 7 d. Vitellogenin mRNA was quantified by quantitative polymerase chain reaction, and VTG protein was semiquantified in plasma using an enzyme-linked immunosorbent assay. Water concentrations were quantified by liquid chromatography coupled with tandem mass spectrometry and were on average 110% and 85% nominal concentrations for E2 and EE2, respectively. Vitellogenin transcripts and protein were upregulated in male Murray rainbowfish exposed to either E2 or EE2 in a dose–responsive manner, with calculated 10% effective concentration (EC10) values for E2 of 3.71 ng/L and 11.6 ng/L for VTG mRNA and protein, respectively, and for EE2 of 2.77 ng/L and 8.47 ng/L for VTG mRNA and protein, respectively. Comparisons of these responses with responses of commonly used test species, including zebrafish (Danio rerio), fathead minnow (Pimephales promelas), and Japanese medaka (Oryzias latipes), revealed the Murray rainbowfish to be a sensitive test species for estrogenic effects via the estrogen receptor pathway. The present study suggests that the Murray rainbowfish would be a suitable candidate for future field studies designed for assessing estrogenic effects of effluent discharges in the Australian freshwater environment. Environ. Toxicol. Chem. 2011;30:2620–2627. © 2011 SETAC
The feasibility of using mosquitofish (Gambusia affinis) for detecting endocrine-disrupting chemicals in the freshwater environment
Authors: Kamata Ryo , Itoh Keisuke , Nakajima Daisuke , Kageyama Shiho , Sawabe Akiyoshi , Terasaki Masanori , Shiraishi Fujio
Published: September 2011

We evaluated the utility of gene-transcriptional responses in the liver of mosquitofish (Gambusia affinis), a species introduced to many countries and therefore widely available, for detecting endocrine-disrupting activity in water. Exposure to β-naphthoflavone, an aryl hydrocarbon receptor (AhR) agonist, significantly increased the transcript of the cytochrome P4501A gene (cyp1a), peaking at 24 h, in both sexes at concentrations of 10 µg/L or more. 17β-Estradiol (E2) at 500 ng/L increased the number of males showing gene transcription of precursors of yolk protein, vitellogenin (Vtga, Vtgb, and Vtgc), at 24, 48, and 72 h. Exposure for 48 h to bisphenol A (BPA), an estrogen mimic, also increased vtg-positive males at 1 mg/L or more. Leachate from a Japanese stable-type landfill significantly increased vtg-positive males after 48 h exposure, and the in vitro activity of the leachate against the estrogen receptor (ER) was estimated as an E2 equivalent of 240 ng/L by yeast transfected with the ER. Chemical analysis showed that major contributors to the ER activation were BPA and 4-tert-octylphenol. This leachate and drainage water from a control-type landfill had AhR activities, estimated by yeast with the AhR, but had no significant effect on cyp1a transcription. These results showed that mosquitofish are suitable for detecting in vivo AhR and ER effects, but are insensitive to E2. Environ. Toxicol. Chem. 2011;30:2778–2785. © 2011 SETAC
Development of two indices based on discrete wavelet transform for transformer differential protection
Authors: Zendehdel Mohammad Hossein , Sanaye‐Pasand Majid
Published: September 2011

This paper proposes an algorithm for transformer differential protection. The paper presents the development of two indices based on discrete wavelet transform to discriminate between internal faults and inrush currents. Each of the proposed indices, that is, the retained energy and the number of zeros can be used individually for the suggested algorithm. The proposed technique consists of decomposition of differential current signals up to a specific level and compression by level thresholding. Various simulations and analysis have been performed to determine the best compression ratio to distinguish between transformer inrush and fault currents. The performance of these indices is demonstrated by simulation of different faults and switching conditions on a modeled power system. Obtained results show that the proposed scheme is robust and reliable. Copyright © 2011 John Wiley & Sons, Ltd.
Proportionally fair scheduler for heterogeneous wireless systems
Authors: Calabuig Daniel , Monserrat Jose F. , Cardona Narcís
Published: September 2011

The proportional fair allocation depends firstly upon the priority weights given to users and secondly upon the proportional distribution of resources according to these weights. This distribution is trivial in single‐technology systems but remains unresolved for heterogeneous wireless systems. This letter addresses this allocation problem not paying attention to the weights calculation, because this issue has been widely studied in the past. The novel proportionally fair scheduler for heterogeneous wireless systems (PFS‐H) is based on linear programming and allocates any arbitrary resource quantity to users that are simultaneously served by several technologies. Given a priority list, the solution of the optimisation problem divides users and technologies into clusters to perform the fairest allocation of resources among users while maximising its usage. Results show that the PFS‐H improves fairness up to 60% as compared with a single‐technology policy. Copyright © 2011 John Wiley & Sons, Ltd.
Transport Properties of Zeolite Na‐X–Nafion Membranes: Effect of Zeolite Loadings and Particle Size
Authors: Lavorgna M. , Sansone L. , Scherillo G. , Gu R. , Baker A. P.
Published: September 2011

Na‐X zeolites particles, synthesized in two size ranges, namely 200–300 nm and 30–100 nm, were used to prepare Nafion/Na‐X zeolite composite membranes by recast method. The physical, chemical, and morphological properties of the zeolite powders and composite membranes were examined by XRD, N2 adsorption isotherms, FTIR, SEM, and SAXS analysis. Furthermore, the effect of zeolite particles size and loadings (i.e., 5 and 10% w/w) on the water, methanol, and proton transport properties was investigated.

It has been found that the size of the Na‐X zeolite particles plays a key role in the proton and methanol transport behavior since it rules the zeolite hydrophilic behavior, the morphology of polymer–filler interphase, and also the nature of water established in the composite membrane.

The results show that the membranes loaded with a 5% w/w of submicron‐sized Na‐X zeolite exhibit a proton conductivity and selectivity significantly higher than Nafion. In particular the proton conductivity at 120 °C is around eight times and the selectivity at 25 °C is around 40% higher than those exhibited by recast Nafion.
Common colorectal cancer risk variants in SMAD7 are associated with survival among prediagnostic nonsteroidal anti‐inflammatory drug users: A population‐based study of postmenopausal women
Authors: Passarelli Michael N. , Coghill Anna E. , Hutter Carolyn M. , Zheng Yingye , Makar Karen W. , Potter John D. , Newcomb Polly A.
Published: September 2011

Common single nucleotide polymorphisms (SNPs) in SMAD7 (18q21) have been linked to colorectal cancer (CRC) risk in genome‐wide association studies, but little is known about their effects on survival. SMAD7 regulates gastrointestinal inflammation by inhibiting transforming growth factor‐β (TGFB), which can act as both a tumor suppressor and a promoter of metastasis. Regular use of cyclooxygenase‐2 (COX2) inhibitors, such as nonsteroidal anti‐inflammatory drugs (NSAIDs), reduces the risk of developing CRC. Because COX2 overexpression reduces the growth suppressing effects of TGFB, we hypothesized that survival may depend on both SMAD7 genotype and prediagnostic NSAID use. Postmenopausal women, ages 50–74, diagnosed with incident invasive CRC from 1997 to 2002 were identified using the Seattle‐Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. Information on prediagnostic NSAID use and other risk factors was ascertained by interview, and women were followed‐up for survival through December 31, 2009. Seven hundred and twenty‐seven cases were genotyped for two GWAS hits in SMAD7 with minor allele frequency > 30%, one with minor allele associated with decreased risk (rs4939827) and one with minor allele associated with increased risk (rs4464148). Two hundred and forty‐two deaths occurred, 160 attributable to CRC. Among those without distant disease at diagnosis, CRC‐specific survival differed by genotype only for NSAID users: each minor allele of rs4939827 was associated with worse survival [hazard ratio (HR) = 2.67, 95% confidence interval (CI): 1.33–5.37] and each minor allele of rs4464148 was associated with better survival (HR = 0.41, CI 0.18–0.94). SMAD7 variants known to be important for CRC risk were associated with disease‐specific survival among prediagnostic NSAID users. © 2011 Wiley‐Liss, Inc.
t(4;8)(q27;q24) in Hodgkin lymphoma cells targets phosphodiesterase PDE5A and homeobox gene ZHX2
Authors: Nagel Stefan , Schneider Björn , Rosenwald Andreas , Meyer Corinna , Kaufmann Maren , Drexler Hans G. , MacLeod Roderick A. F.
Published: September 2011

Hodgkin/Reed–Sternberg (HRS) cells represent the malignant fraction of infiltrated lymph nodes in Hodgkin lymphoma (HL). Although HRS cells display multiple chromosomal aberrations, few are recurrent and the targeted genes unknown. However, understanding the pathology of HL and developing rational therapies may well require identifying putative deregulated genes. Here, we analyzed the karyotype of the well‐defined HL cell line L‐1236 by spectral karyotyping and identified multiple abnormalities, therein, notably t(4;8)(q27;q24) which includes two breakpoint regions previously highlighted in HL. Target genes at 4q27 and 8q24 were shortlisted by high density genomic arrays and fluorescence in situ hybridization. Expression analysis of candidate target genes revealed conspicuous activation of phosphodiesterase PDE5A at 4q27 and inhibition of homeobox gene ZHX2 at 8q24. Treatment of L‐1236 with PDE5A‐inhibitor sildenafil or with siRNA directed against PDE5A and concomitant stimulation with cyclic guanosine monophosphate (cGMP) resulted in enhanced apoptosis, indicating PDE5A as an oncogene. Expression profiling of L‐1236 cells following siRNA‐mediated knockdown of ZHX2 showed inhibition of genes regulating differentiation and apoptosis, suggesting tumor suppressor activity of ZHX2. Downstream genes included STAT1 and several STAT1‐target genes, indicating activation of STAT1‐signaling by ZHX2 as analyzed by RQ‐PCR and western blot. Taken together, we have identified a novel aberration with recurrent breakpoints in HL, t(4;8)(q27;q24), which activate PDE5A and repress ZHX2, deregulating apoptosis, differentiation, and STAT1‐signaling in HL cells. © 2011 Wiley Periodicals, Inc.
Promoter methylation‐mediated inactivation of PCDH10 in acute lymphoblastic leukemia contributes to chemotherapy resistance
Authors: Narayan Gopeshwar , Freddy Allen J. , Xie Dongxu , Liyanage Hema , Clark Lorraine , Kisselev Sergey , Un Kang Ji , Nandula Subhadra V. , McGuinn Catherine , Subramaniyam Shivakumar , Alobeid Bachir , Satwani Prakash , Savage David , Bhagat Govind , Murty Vundavalli V.
Published: September 2011

PCDH10 has been implicated as a tumor suppressor, since epigenetic alterations of this gene have been noted in multiple tumor types. However, to date, studies regarding its role in acute and chronic leukemias are lacking. Here, we have investigated the presence of promoter hypermethylation of two CpG islands of the PCDH10 gene by methylation‐specific PCR in 215 cases of various subsets of myeloid‐ and lymphoid‐lineage leukemias. We found that PCDH10 promoter hypermethylation was frequent in both B‐cell (81.9%) and T‐cell (80%) acute lymphoblastic leukemia (ALL), while it was present in low frequency in most subtypes of myeloid leukemias (25.9%) and rare in chronic myeloid leukemia (2.2%). PCDH10 expression was downregulated via promoter hypermethylation in primary ALL samples (N = 4) and leukemia cell lines (N = 11). The transcriptional repression caused by PCDH10 methylation could be restored by pharmacologic inhibition of DNA methyltransferases. ALL cell lines harboring methylation‐mediated inactivation of PCDH10 were less sensitive to commonly used leukemia‐specific drugs suggesting that PCDH10 methylation might serve as a biomarker of chemotherapy response. Our results demonstrate that PCDH10 is a target of epigenetic silencing in ALL, a phenomenon that may impact lymphoid‐lineage leukemogenesis, serve as an indicator of drug resistance and may also have potential implications for targeted epigenetic therapy. © 2011 Wiley Periodicals, Inc.
CNS live imaging reveals a new mechanism of myelination: The liquid croissant model
Authors: Sobottka Bettina , Ziegler Urs , Kaech Andres , Becher Burkhard , Goebels Norbert
Published: September 2011

The overall morphology and with it associated the formation of myelin is generally thought to be resolved. Based on electron microscopic findings more than half a century ago, the current model of myelination describes all myelin membranes to run in parallel with the longitudinal axis of the axon and to form a smooth surface, reminiscent of a rolled up carpet. However, different studies in the past demonstrated a distinct myelin morphology with an uneven myelin surface contour that challenges the established concept. Even though the current model of myelination has since been recognized as insufficient, CNS myelin formation has not yet been investigated in real‐time with the requisite technique and resolution. We therefore traced myelin growth in murine organotypic cerebellar slice cultures using high‐resolution confocal live imaging, light and electron microscopy and assessed myelin morphology in young and adult mice by confocal microscopy. Our data verify that the myelin surface is indeed not smooth but runs in a bidirectional, regularly spaced coil along the axon in both young and adult mice. Time‐lapse imaging revealed that the growth of coiled myelin turns emerges during myelin formation. We therefore propose the “liquid croissant” model as a new concept of myelination that overcomes not only some of the incongruences of previous myelination theories, but potentially also explains the development of certain myelin pathologies observed in remyelination and axonopathies. © 2011 Wiley‐Liss, Inc.
The dual role of CXCL8 in human CNS stem cell function: Multipotent neural stem cell death and oligodendrocyte progenitor cell chemotaxis
Authors: Kelland Eve E. , Gilmore Wendy , Weiner Leslie P. , Lund Brett T.
Published: September 2011

Research into multiple sclerosis (MS) has shown that cells purportedly important to myelin repair within the CNS, namely neural stem cells (NSC) and oligodendrocyte progenitor cells (OPC), are recruited to active lesion sites during the course of the disease. However, over time these cells appear to become depleted or functionally blocked in and around lesions, accompanied by a failure of repair mechanisms. We have previously demonstrated elevated CXCL8 in patients with MS, and hypothesized that this chemokine may play a role in the pathology of this disease. Using NSC and OPC derived in vitro from human embryonic stem cells (hESC) we demonstrate here that CXCL8 has a dual role on stem cell biology in vitro. CXCL8 caused CXCR1‐mediated death of NSC, but not OPC, whilst also acting as a potent chemoattractant for both cell types. These data support a context‐dependent role for CXCL8 expression in the CNS in which it may drive recruitment of NSC and OPC to sites of inflammation, but as a side‐effect could also contribute to the failure of myelin repair in MS. © 2011 Wiley‐Liss, Inc.
Efficacy of memantine in delaying clinical worsening in Alzheimer's disease (AD): responder analyses of nine clinical trials with patients with moderate to severe AD
Authors: Hellweg Rainer , Wirth Yvonne , Janetzky Wolfgang , Hartmann Susanne
Published: September 2011

Objective

Responder analyses are of relevance to evaluate the benefits of a medical treatment. The aim of the current paper is to analyse the response of patients with moderate to severe Alzheimer's disease (AD) to memantine, and clinical relevant response is defined as a delay of clinical worsening.

Methods

Post hoc analyses were performed over the results of nine individual clinical trials including 2506 study patients. Overall, estimates of the odds ratio (OR) and corresponding confidence intervals were based upon a random‐effect model for three individual domains (cognition, activities of daily living and clinical global impression). In addition, a combined responder criterion (triple response) includes all three individual domains.

Results

Responder analyses have shown that AD patients treated with memantine benefited from a significant delay of clinical worsening compared with placebo‐treated patients, and fewer patients faced clinical worsening in the relevant domains cognition (24.6% vs 36.2%, p < 0.001), activities of daily living (56.2% vs 61.6%, p < 0.05) and global impression of change (40.9% vs 49.8, p < 0.001). In addition, response to treatment on the combined domains (triple response) was significantly in favour of memantine compared with placebo, with fewer patients showing clinical worsening (11.0% vs 20.4%, p < 0.001).

Conclusions

Treatment with memantine delays clinical worsening in patients with moderate to severe AD when compared with placebo. This effect was seen in single domains (cognition, functional abilities and clinical global impression) as well as in the combination of these domains. The consistent results prove the beneficial effects of memantine in moderate to severe AD patients. Copyright © 2011 John Wiley & Sons, Ltd.
Diagnosing different binge‐eating disorders based on reward‐related brain activation patterns
Authors: Weygandt Martin , Schaefer Axel , Schienle Anne , Haynes John‐Dylan
Published: September 2011

This study addresses how visual food cues are encoded in reward related brain areas and whether this encoding might provide information to differentiate between patients suffering from eating disorders [binge‐eating disorder (BED) and bulimia nervosa (BN)], overweight controls (C‐OW), and normal‐weight controls (C‐NW). Participants passively viewed pictures of food stimuli and neutral stimuli in a cue reactivity design. Two classification analyses were conducted. First, we used multivariate pattern recognition techniques to decode the category of a currently viewed picture from local brain activity patterns. In the second analysis, we applied an ensemble classifier to predict the clinical status of subjects (BED, BN, C‐OW, and C‐NW) based on food‐related brain response patterns. The left insular cortex separated between food and neutral contents in all four groups. Patterns in the right insular cortex provided a maximum diagnostic accuracy for the separation of BED patients and C‐NW (86% accuracy, P < 10−5, 82% sensitivity, and 90% specificity) as well as BN patients and C‐NW (78% accuracy, P = 0.001, 86% sensitivity, and 70% specificity). The right ventral striatum separated maximally between BED patients and C‐OW (71% accuracy, P = 0.013, 59% sensitivity, and 82% specificity). The right lateral orbitofrontal cortex separated maximally between BN patients and C‐OW (86% accuracy, P < 10−4, 79% sensitivity, and 94% specificity). The best differential diagnostic separation between BED and BN patients was obtained in the left ventral striatum (84% accuracy, P < 10−3, 82% sensitivity, and 86% specificity). Our results indicate that pattern recognition techniques are able to contribute to a reliable differential diagnosis of BN and BED. Hum Brain Mapp 33:2135–2146, 2012. © 2011 Wiley Periodicals, Inc.
Comparing ERCC1 protein expression, mRNA levels, and genotype in squamous cell carcinomas of the head and neck treated with concurrent chemoradiation stratified by HPV status
Authors: Hao Desirée , Lau Harold Y. , Eliasziw Misha , Box Alan , Diaz Román , Klimowicz Alexander C. , Shin Brian , Lees‐Miller Susan P. , Magliocco Anthony M.
Published: September 2011

Background

Previous studies examining excision repair cross‐complementation group 1 (ERCC1) in squamous cell carcinoma of the head and neck (SCCHN) have not compared methods of ERCC1 testing nor been stratified by human papillomavirus (HPV) status.

Methods

ERCC1 protein expression, mRNA, and genotype were retrospectively evaluated from pretreatment biopsies in 55 patients with SCCHN treated with chemoradiation.

Results

In all, 50% of patients had high ERCC1 protein expression, 28.2% had low mRNA levels, and genotype frequencies were C/C = 17.1%, C/T = 43.9%, and T/T = 39.0%. No correlations were found among protein expression, mRNA, or genotype. With a median follow‐up of 54 months, the 5‐year overall survival was 57.7%. After adjusting for known prognostic factors, ERCC1 protein level and genotype resulted in hazard ratios indicating an increased risk of death of 4.4‐fold (p = .004) and 4.2‐fold (p = .044), respectively. An exploratory analysis suggested a differential prognostic effect in HPV‐negative SCCHN.

Conclusions

ERCC1 protein expression using the FL297 antibody warrants further study as a potential prognostic marker in SCCHN. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
Management of complete esophageal stricture after treatment of head and neck cancer using combined anterograde retrograde esophageal dilation
Authors: Fowlkes Jonathan , Zald Philip B. , Andersen Peter
Published: September 2011

Background

Complete esophageal stricture is a difficult problem to manage. There is limited literature to support clinical decision‐making. To evaluate outcomes and efficacy, we performed a retrospective medical chart review of patients who received combined anterograde retrograde esophageal dilation (CARD) between 2002 and 2009 at our institution.

Methods

Fifteen patients were identified who developed a stricture requiring CARD after treatment for head and neck cancers. Outcomes were pretreatment and posttreatment diet, gastrostomy tube status, and operative complications.

Results

Six of 15 patients were gastrostomy tube‐free at last follow‐up and 11 of 15 patients were taking oral nutrition. There were 4 complications. One patient died. Two gastrostomy tube site complications occurred. One patient sustained a dental injury.

Conclusion

CARD offers benefit to most patients. Despite risks associated with the procedure, CARD should be considered by the clinician and patient in management of complete esophageal stricture. © 2011 Wiley Periodicals, Inc. Head Neck, 2011
The relationship between sap flow of intercropped young poplar trees (Populus×euramericana cv. N3016) and environmental factors in a semiarid region of northeastern China
Authors: Guan De‐Xin , Zhang Xiao‐Jing , Yuan Feng‐Hui , Chen Ni‐Na , Wang An‐Zhi , Wu Jia‐Bing , Jin Chang‐Jie
Published: September 2011

Estimating transpiration of the trees in agroforestry system is important in water management of the site. Sap flow of intercropped fast‐growing young poplar trees and microclimate factors in semiarid northeastern China was measured in two growing seasons (2008 and 2009). Sapwood growth and water storage of wood and leaf increment during the growing season were involved in the calculation of sap flow. The results showed that diurnal variation of sap flow followed to that of short wave solar radiation. Sap flows both in 10 min mean and daily gross values mainly depended on solar radiation and vapor pressure deficit, and the relations well fit hyperbolic function. The regression coefficients of monthly window data indicated that the seasonal variation of sap flow capacities decreased gradually from June to September. Moderate soil water stress of upper soil layer (0–50 cm) did not constrain the sap flow because the trees could use the water at deeper soil layer. The daily sap flow per tree ranged 0.8 to 18.1 and 3.7 to 23.8 kg d−1 tree−1, with averages of 8.7 and 14.3 kg d−1 tree−1 in 2008 and 2009 respectively. An empirical model was established to estimate the sap flow of the poplar trees by solar radiation, vapor pressure deficit, leaf area index and Julian days. Copyright © 2011 John Wiley & Sons, Ltd.
Spatial variability of hydraulic conductivity and bulk density along a blanket peatland hillslope
Authors: Lewis Ciaran , Albertson John , Xu Xianli , Kiely Ger
Published: September 2011

This article presents the results of a field investigation of saturated hydraulic conductivity Ksat and bulk density (ρbd) in an Atlantic blanket bog in the southwest of Ireland. Starting at a peatland stream and moving along an uphill transect toward the peatland interior, ρbd and Ksat were examined at regular intervals. Saturated horizontal hydraulic conductivity (Khsat) and vertical (Kvsat) was estimated at two depths: 10–20 and 30–40 cm below the peat surface, whereas ρbd was estimated for the full profile. We consider two separate zones, one a riparian zone extending 10 m from the stream and a second zone in the bog interior. We found that the Ksat was higher (~10–5 m s–1) in the bog interior than that in the riparian zone (~10–6 m s–1), whereas the converse applied to bulk density, with lowest density (~0.055 g cm–3) at the interior and highest (~0.11 g cm–3) at the riparian zone. In general, we found Khsat to be approximately twice the Kvsat. These results support the idea that the lower Ksat at the margins control the hydrology of blanket peatlands. It is therefore important that the spatial variation of these two key properties be accommodated in hydrological models if the correct rainfall runoff characteristics are to be correctly modelled. Stream flow analysis over 3 years at the peatland catchment outlet showed that the stream runoff was composed of 8% base flow and 92% flood flow, suggesting that this blanket peatland is a source rather than a sink for floodwaters. Copyright © 2011 John Wiley & Sons, Ltd.
Annual estimates of water and solute export from 42 tributaries to the Yukon River
Authors: Frederick Zanden A. , Anderson Suzanne P. , Striegl Robert G.
Published: September 2011

Annual export of 11 major and trace solutes for the Yukon River is found to be accurately determined based on summing 42 tributary contributions. These findings provide the first published estimates of tributary specific distribution of solutes within the Yukon River basin. First, we show that annual discharge of the Yukon River can be computed by summing calculated annual discharges from 42 tributaries. Annual discharge for the tributaries is calculated from the basin area and average annual precipitation over that area using a previously published regional regression equation. Based on tributary inputs, we estimate an average annual discharge for the Yukon River of 210 km3 year–1. This value is within 1% of the average measured annual discharge at the U.S. Geological Survey gaging station near the river terminus at Pilot Station, AK, for water years 2001 through 2005. Next, annual loads for 11 solutes are determined by combining annual discharge with point measurements of solute concentrations in tributary river water. Based on the sum of solutes in tributary water, we find that the Yukon River discharges approximately 33 million metric tons of dissolved solids each year at Pilot Station. Discharged solutes are dominated by cations calcium and magnesium (5.65 × 109 and 1.42 × 109 g year–1) and anions bicarbonate and sulphate (17.3 × 109 and 5.40 × 109 g year–1). These loads compare well with loads calculated independently at the three continuous gaging stations along the Yukon River. These findings show how annual solute yields vary throughout a major subarctic river basin and that accurate estimates of total river export can be determined from calculated tributary contributions. Copyright © 2011. This article is a U.S. Government work and is in the public domain in the USA.
Towards a better understanding of riparian zone water table response to precipitation: surface water infiltration, hillslope contribution or pressure wave processes?
Authors: Vidon Philippe
Published: September 2011

Determining how riparian zone hydrological conditions may change in response to precipitation in various geomorphic settings is critical to determine the occurrence of hot moments of biogeochemical transformations for phosphorus, nitrogen, sulfate, mercury and greenhouse gases in these systems. The author investigate water table response to precipitation at a high temporal resolution (15 min) in a riparian zone located in a deeply incised glacial till valley (20 m) with approximately 2 m of alluvium over a confining layer, in Indiana, USA. During storms, larger water table fluctuations (approximately 100 cm) occurred near the stream than near the toe slope (10–25 cm). A quick rise in water table near the stream occurred for all storms, with partial flow reversals occurring for three of seven storms. The quick rise of the water table near the stream was associated with a decrease in hillslope water contributions to the stream during storms and the development of a water table down valley gradient for most storms. Water table fluctuations, groundwater flow velocities and electrical conductivity data indicated that riparian zone water table response to precipitation was primarily regulated by pressure wave processes. Regardless of the storm, high water tables persisted for at least 2 days after the cessation of precipitation. Although this suggests that high‐resolution precipitation data may be useful to quantify hot moments of biogeochemical transformation associated with high water tables in riparian zones, precipitation data alone are not sufficient to correctly estimate the magnitude of riparian water table level changes during storms. Copyright © 2011 John Wiley & Sons, Ltd.
A synergetic use of satellite imagery from SAR and optical sensors to improve coastal flood mapping in the Gulf of Mexico
Authors: Chaouch Naira , Temimi Marouane , Hagen Scott , Weishampel John , Medeiros Stephen , Khanbilvardi Reza
Published: September 2011

This work proposes a method for detecting inundation between semi‐diurnal low and high water conditions in the northern Gulf of Mexico using high‐resolution satellite imagery. Radarsat 1, Landsat imagery and aerial photography from the Apalachicola region in Florida were used to demonstrate and validate the algorithm. A change detection approach was implemented through the analysis of red, green and blue (RGB) false colour composites image to emphasise differences in high and low tide inundation patterns. To alleviate the effect of inherent speckle in the SAR images, we also applied ancillary optical data. The flood‐prone area for the site was delineated a priori through the determination of lower and higher water contour lines with Landsat images combined with a high‐resolution digital elevation model. This masking technique improved the performance of the proposed algorithm with respect to detection techniques using the entire Radarsat scene. The resulting inundation maps agreed well with historical aerial photography as the probability of detection reached 83%. The combination of SAR data and optical images, when coupled with a high‐resolution digital elevation model, was shown to be useful for inundation mapping and have a great potential for evaluating wetting/drying algorithms of inland and coastal hydrodynamic models. Copyright © 2011 John Wiley & Sons, Ltd.