bluuebunny/crossref_metadata_2025 huggingface dataset:
No clear genetic influences on the association between dyslexia and anxiety in a population‐based sample of female twins
Authors: Whitehouse Andrew J.O. , Spector Tim D. , Cherkas Lynn F.
Published: November 2008

Individuals with dyslexia are at an increased risk for anxiety disorders (e.g. generalized anxiety disorder, stress disorders, panic disorder). The extent to which this association is mediated by genetic and/or environmental influences is unclear. The current study explored the relationship between these two phenotypes using a large population‐based twin sample. In total, 940 monozygotic and 903 dizygotic female twin pairs were included in the analyses. The presence of dyslexia and anxiety was determined by self‐report of diagnosis by a health professional. Tetrachoric correlations confirmed an association between the two phenotypes, but suggested that there was no evidence for shared genetic risks. Bivariate twin modelling corroborated this finding and indicated the relationship between dyslexia and anxiety is mediated by shared environmental factors. Future research should seek to identifying the environmental factors that increase the vulnerability of individuals with dyslexia to emotional problems should be a priority for future research. Copyright © 2008 John Wiley & Sons, Ltd.
Amperometric Determination of Aminobiphenyls Using HPLC‐ED with Boron‐Doped Diamond Electrode
Authors: Pecková Karolina , Jandová Kateřina , Maixnerová Lucie , Swain Greg M. , Barek Jiří
Published: November 2008

Amino derivatives of biphenyl have been proven to be genotoxic and/or carcinogenic, thus they are widely monitored in the environment as well as in biological liquids. This study was devoted to HPLC determination of 2‐aminobiphenyl, 3‐aminobiphenyl, and 4‐aminobiphenyl in model drinking and river water samples using amperometric detection in a thin layer cell with boron doped diamond thin film electrode. Satisfactory separation of studied analytes was achieved at a ChiraDex column (Merck, Germany) with chemically bonded β‐cyclodextrin in a mobile phase aqueous buffer/acetonitrile/methanol (40/30/30, v/v/v) with total separation time of six minutes. The highest detector response with satisfactory repeatability (relative standard deviation <2.9% for all aminobiphenyls) was obtained using 0.01 mol L−1 acetate buffer at pH 5.0 as an aqueous component of the mobile phase. For direct determination of aminobiphenyls in drinking and river water model samples limits of quantitation ca. 4×10−7 mol L−1 were achieved. Applying off‐line solid phase extraction using Lichrolut EN (Merck, Germany) cartridges and elution by diethyl ether, limits of quantitation were lowered down to the 10−9 mol L−1 concentration range.
Electrochemical Determination of Manganese Solubility in Mercury via Amalgamation and Stripping in the Room Temperature Ionic Liquid n‐Hexyltriethylammonium Bis(trifluoromethanesulfonyl)imide, [N6,2,2,2][NTf2]
Authors: Rogers Emma I. , Šljukić Biljana , Hardacre Christopher , Compton Richard G.
Published: November 2008

The solubility of manganese in mercury was determined electrochemically via amalgamation and stripping in the room temperature ionic liquid n‐hexyltriethylammonium bis(trifluoromethanesulfonyl)imide, [N6,2,2,2][NTf2]. A hemispherical mercury electrode was made by electrodepositing mercury onto a planar platinum microelectrode. Cyclic voltammetry of Mn2+ in [N6,2,2,2][NTf2] at the mercury microhemisphere electrode was investigated at temperatures of 298, 303 and 313 K. The solubility of Mn in Hg was determined on the basis of the charge under the reduction peak (Mn2+→Mn0) and the corresponding reoxidation.
Construction of L‐Lysine Sensor by Layer‐by‐Layer Adsorption of L‐Lysine 6‐Dehydrogenase and Ferrocene‐Labeled High Molecular Weight Coenzyme Derivative on Gold Electrode
Authors: Zheng Haitao , Zhou Jingli , Okezaki Yosuke , Suye Shin‐ichiro
Published: November 2008

A ferrocene‐labeled high molecular weight coenzyme derivative (PEI‐Fc‐NAD) and a thermostable NAD‐dependent L‐lysine 6‐dehydrogenase (LysDH) from thermophile Geobacillus stearothermophilus were used to fabricate a reagentless L‐lysine sensor. Both LysDH and PEI‐Fc‐NAD were immobilized on the surface of a gold electrode by consecutive layer‐by‐layer adsorption (LBL) technique. By the simple LBL method, the reagentless L‐lysine sensor, with co‐immobilization of the mediator, coenzyme, and enzyme was obtained, which exhibited current response to L‐lysine without the addition of native coenzyme to the analysis system. The amperometric response of the sensor was dependent on the applied potential, bilayer number of PEI‐Fc‐NAD/LysDH, and substrate concentration. A linear current response, proportional to L‐lysine concentration in the range of 1–120 mM was observed. The response of the sensor to L‐lysine was decreased by 30% from the original activity after one month storage.
Comparison of the analytical performance of electrophoresis microchannels fabricated in PDMS, glass, and polyester‐toner
Authors: Coltro Wendell Karlos Tomazelli , Lunte Susan M. , Carrilho Emanuel
Published: November 2008

This paper compares the analytical performance of microchannels fabricated in PDMS, glass, and polyester‐toner for electrophoretic separations. Glass and PDMS chips were fabricated using well‐established photolithographic and replica‐molding procedures, respectively. PDMS channels were sealed against three different types of materials: native PDMS, plasma‐oxidized PDMS, and glass. Polyester‐toner chips were micromachined by a direct‐printing process using an office laser printer. All microchannels were fabricated with similar dimensions according to the limitations of the direct‐printing process (width/depth 150 μm/12 μm). LIF was employed for detection to rule out any losses in separation efficiency due to the detector configuration. Two fluorescent dyes, coumarin and fluorescein, were used as model analytes. Devices were evaluated for the following parameters related to electrophoretic separations: EOF, heat dissipation, injection reproducibility, separation efficiency, and adsorption to channel wall.
Impact of laser excitation intensity on deep UV fluorescence detection in microchip electrophoresis
Authors: Schulze Philipp , Ludwig Martin , Belder Detlev
Published: November 2008

A high intensity 266 nm continuous wave (cw‐) laser developed for material processing was utilised as an excitation source for sensitive native fluorescence detection of unlabelled compounds in MCE. This 120 mW laser was attached via an optical fibre into a commercial epifluorescence microscope. With this MCE set‐up we evaluated the impact of laser power on the S/N of aromatic compounds as well as of proteins. Compared with a previous work which used a 4 mW pulsed laser for excitation, improved S/N for small aromatics and to a lesser extent for proteins could be attained. The LOD of the system was determined down to 24 ng/mL for serotonin (113 nM), 24 ng/mL for propranolol (81 nM), 80 ng/mL for tryptophan (392 nM) and 80 ng/mL for an aromatic diol (475 nM). Sensitive protein detection was obtained at concentrations of 5 μg/mL for lysocyme, trypsinogen and chymotrypsinogen (340, 208 and 195 nM, respectively). Finally, a comparison of the cw‐ with a pulsed 266 nm laser, operating at the same average power, showed a higher attainable sensitivity of the cw‐laser. This can be attributed to fluorescence saturation and photobleaching effects of the pulsed laser at high pulse energies.
Mutational analysis of the mitochondrial tRNA genes and flanking regions in umbilical cord tissue from uninfected infants receiving AZT‐based therapies for prophylaxis of HIV‐1
Authors: Torres Salina M. , Walker Dale M. , McCash Consuelo L. , Carter Meghan M. , Ming Jessica , Cordova Edmund M. , Pons Rachel M. , Cook Dennis L. , Seilkop Steven K. , Copeland William C. , Walker Vernon E.
Published: November 2008

A sensitive vertical denaturing gradient gel electrophoresis (DGGE) method, using 13 unipolar psoralen‐clamped PCR primer pairs, was developed for detecting sequence variants in the 22 tRNA genes and flanking regions (together spanning ∼21%) of the human mitochondrial genome. A study was conducted to determine (i) if mitochondrial DNA (mtDNA) polymorphisms and/or mutations were detectable in healthy newborns and (ii) if prepartum 3′‐azido‐2′,3′‐dideoxythymidine (AZT) based HIV‐1 prophylaxis was associated with significant increases in mtDNA mutations and changes in the degree of heteroplasmy of sequence variants in uninfected infants born to HIV‐1‐infected mothers. DGGE analysis of umbilical cord tissue (where vascular endothelium and smooth muscle cells are the major source of mtDNA) showed that mtDNA sequence variants were significantly elevated by threefold in AZT‐treated infants compared with unexposed controls (P < 0.001), with 24 changes observed in 19/52 (37%) treated newborns (averaging 0.46 changes/subject) versus only eight changes found in 7/55 (13%) unexposed newborns (averaging 0.15 changes/subject). Six distinct sequence variants occurring in unexposed controls were predominately synonymous and homoplasmic, representing previously reported polymorphisms. Uninfected infants exposed to a combination of AZT and 2′,3′‐dideoxy‐3′‐thiacytidine and “maternal HIV‐1” had a significant shift in the spectrum of mutations (P = 0.04) driven by increases in nonsynonymous heteroplasmic sequence variants at polymorphic sites (10 distinct variants) and novel sites (four distinct variants). While the weight of evidence suggests that prepartum AZT‐based prophylaxis produces mtDNA mutations, additional research is needed to determine the degree to which fetal responses to maternal HIV‐1 infection, in the absence of antiretroviral treatment, contribute to prenatal mtDNA mutagenesis. Environ. Mol. Mutagen., 2009. © 2008 Wiley‐Liss, Inc.
Procedure to predict the storey where plastic drift dominates in two‐storey building under strong ground motion
Authors: Hibino Yo , Ichinose Toshikatsu , Domingues Costa J. L. , Nielsen M. P.
Published: November 2008

A procedure is presented to predict the storey where plastic drift dominates in two‐storey buildings under strong ground motion. The procedure utilizes the yield strength and the mass of each storey as well as the peak ground acceleration. The procedure is based on two different assumptions: (1) the seismic force distribution is of inverted triangular form and (2) the rigid‐plastic model represents the system. The first and the second assumptions, respectively, lead to lower and upper estimates of the base shear coefficient under which the drift of the first storey exceeds that of the second storey. The efficiency of the procedure is verified by dynamic response analyses using elasto‐plastic model. Copyright © 2008 John Wiley & Sons, Ltd.
Hysteretic energy dissipation capacity and the cyclic to monotonic drift ratio for rectangular RC columns in flexure
Authors: Poljanšek Karmen , Peruš Iztok , Fajfar Peter
Published: November 2008

Predictions of energy dissipation capacity and of the deterioration of deformation capacity due to cumulative damage have been made by means of a non‐parametric empirical approach, called the conditional average estimator method, using empirical data on rectangular reinforced concrete columns that failed in flexure. Five input parameters were used: axial load index, index related to confinement, shear span index, concrete compressive strength, and longitudinal reinforcement index. The energy capacity was expressed in three different normalized forms and the deterioration of deformation capacity was defined as the ratio of the cyclic to the monotonic ultimate drift. The longitudinal reinforcement index, the index related to confinement, and the axial load index are the most influential input parameters in the case of energy capacity, whereas the latter two indices exhibit the most significant influence in the case of the drift ratio. Energy capacity decreases with an increasing axial load index, whereas it increases with increasing longitudinal reinforcement and with better confinement. In the case of the shear span index, the trend is more complex. Normal concrete has a higher energy dissipation capacity than high‐strength concrete. Similar trends are observed for the drift ratio, with the exception of the influence of the axial load index, where the trend is opposite. The dispersion of the results is high. Copyright © 2008 John Wiley & Sons, Ltd.
Aroma‐impact compounds in Lysimachia foenum‐graecum extracts
Authors: Shu Na , Shen Hong
Published: November 2008

Two different extraction methods were used to obtain representative extracts from stems and leaves of Lysimachia foenum‐graecum, a Chinese plant with a smoky, spicy, green, woody and caramel aroma. An extract was obtained by steam distillation followed by pentane back‐extraction. Plants were also extracted with dichloromethane, and the non‐volatile compounds were separated from volatiles by high‐vacuum distillation (SAFE). Compared to the steam distillate extract, the SAFE‐distilled extract was judged to be more similar to the aroma of the starting materials. The aroma‐impact compounds of the SAFE extract were then determined using multidimensional GC. From the detection frequencies and the intensities of the peaks, 47 peaks with odour‐activity were determined, using an adaptation of the GC–SNIFF method, to have an impact on the overall aroma of the extract. Fifty‐four compounds responsible for the peaks presenting odour‐activity were identified from mass spectral data, retention indices, olfactory character and co‐injection of authentic standards. Copyright © 2008 John Wiley & Sons, Ltd.
Failure of Ca2+‐activated, CREB‐dependent transcription in astrocytes
Authors: Murray Peter D. , Kingsbury Tami J. , Krueger Bruce K.
Published: November 2008

Astrocytes participate in signaling via Ca2+ transients that spread from cell to cell across a multicellular syncytium. The effect, if any, of these Ca2+ waves on the transcription of Ca2+/cAMP‐regulatory element binding protein (CREB)‐dependent genes is not known. We report here that, unlike neurons, increasing intracellular Ca2+ in cultured mouse cortical astrocytes failed to activate CREB‐dependent transcription, even though CREB was phosphorylated at serine 133. In contrast, both CREB phosphorylation and CREB‐dependent transcription were robustly stimulated by increasing cAMP. The failure of Ca2+‐activated transcription in astrocytes was correlated with the absence of CaMKIV, a Ca2+‐dependent protein kinase required for Ca2+‐stimulated gene transcription in neurons. The inability of Ca2+ to signal via CaMKIV may insulate CREB‐dependent gene transcription in astrocytes from activation by Ca2+ waves. © 2008 Wiley‐Liss, Inc.
Reduced nicotinamide adenine dinucleotide phosphate oxidase mediates fibrotic and inflammatory effects of leptin on hepatic stellate cells
Authors: De Minicis Samuele , Seki Ekihiro , Oesterreicher Christoph , Schnabl Bernd , Schwabe Robert F. , Brenner David A.
Published: November 2008

Although leptin induces fibrotic activity in hepatic stellate cells (HSCs), the mechanisms are not entirely understood. To investigate the potential role of reduced nicotinamide adenine dinucleotide phosphate oxidase (NADPH) and reactive oxygen species (ROS) in leptin signaling in HSCs, we analyzed leptin-induced intracellular signaling pathways in primary wild-type (WT), p47
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, and signal transducer and activator of transcription protein 3 (STAT3)-deleted HSCs. Leptin-stimulated ROS production was attenuated in human and mouse HSCs by the NADPH oxidase inhibitor diphenylene-iodonium (DPI) and in HSCs lacking the NADPH component p47phox. Leptin-induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT, but not of STAT3, was blocked by NADPH oxidase inhibition. Moreover, leptin-induced ROS production was inhibited by the Janus kinase (JAK) inhibitor, AG490, but normal ROS production was observed in STAT3-deleted HSCs. Pharmacologic or genetic inhibition of NADPH in HSCs not only resulted in a reduction of leptin-mediated HSC proliferation but also reduced the leptin-mediated up-regulation of the fibrogenic markers collagen α1(I) and α-smooth muscle actin and of the inflammatory mediators monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein 1 (MIP-1), and macrophage inflammatory protein 2 (MIP-2).

In vivo

, leptin enhanced chemokine expression induced by chemokine (C-C motif) ligand 4 (CCl4) in WT mice, but a blunted response was observed in p47phox−/− mice. In conclusion, NADPH oxidase is a crucial mediator of proliferative, fibrogenic, and inflammatory actions of leptin. Leptin-induced NADPH oxidase acts downstream of JAK activation but is independent of STAT3. Our results, in conjunction with previous studies on angiotensin II and platelet-derived growth factor (PDGF), place NADPH in the center of the fibrogenic signaling response in HSCs and demonstrate its potential role as a pharmacological target for antifibrotic therapies. (Hepatology 2008;48:2016–2026.)
Human reach envelope and zone differentiation for ergonomic design
Authors: Yang Jingzhou (James) , Abdel‐Malek Karim
Published: November 2008

In human‐centric design, the human reach envelope is one of the most important components to help layout design for workstations, vehicles, and aircrafts. It also can help people to study the range of motion of different body segments. Various methods have been developed to determine human reach envelopes. This article presents different methods and common challenges. Human reach envelopes only give feedback concerning whether a point is reachable. This is not enough for the designers. The more important information the designers need to know is the zones with different discomfort levels. This capability is a powerful tool for ergonomic designers. In addition, a methodology for workspace solid zone differentiation or surface zone differentiation in the three‐dimensional space is presented. © 2008 Wiley Periodicals, Inc.
Potent antitumor effect of SN‐38‐incorporating polymeric micelle, NK012, against malignant glioma
Authors: Kuroda Jun‐ichiro , Kuratsu Jun‐ichi , Yasunaga Masahiro , Koga Yoshikatsu , Saito Yohei , Matsumura Yasuhiro
Published: November 2008

Recent published reports on clinical trials of CPT‐11 indicate the effectiveness of this compound, a prodrug of SN‐38, against malignant glioma in combination with anti‐vascular endothelial growth factor antibody. Here, we determined if NK012, and SN‐38 incorporating micelle, can be an appropriate formulation for glioblastoma treatment compared with CPT‐11.In vitrocytotoxicity was evaluated against several glioma lines with NK012, CPT‐11, SN‐38, ACNU, CDDP and etoposide. For thein vivotest, a human glioma line (U87MG) transfected with theluciferasegene was inoculated into nude mice brain for pharmacokinetic analysis by fluorescence microscopy and high‐performance liquid chromatography after intravenous injection of NK012 and CPT‐11.In vivoantitumor activity of NK012 and CPT‐11 was evaluated by bioluminescence image and Kaplan‐Meier analyses. The growth‐inhibitory effects of NK012 were 34‐ to 444‐fold more potent than those of CPT‐11. Markedly enhanced and prolonged distribution of free SN‐38 in the xenografts was observed after NK012 injection compared with CPT‐11. NK012 showed significantly potent antitumor activity against an orthotopic glioblastoma multiforme xenograft and significantly longer survival rate than CPT‐11 (p= 0.0014). This implies that NK012 can pass through the blood brain tumor barrier effectively. NK012, which combines enhanced distribution with prolonged sustained release, may be ideal for glioma treatment. Currently, a phase I study of NK012 is almost complete in Japan and the US. The present translational study warrants the clinical phase II study of NK012 in patients with malignant glioma. © 2008 Wiley‐Liss, Inc.
Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study
Authors: Wilson Kathryn M. , Bälter Katarina , Adami Hans‐Olov , Grönberg Henrik , Vikström Anna C. , Paulsson Birgit , Törnqvist Margareta , Mucci Lorelei A.
Published: November 2008

Acrylamide, a probable human carcinogen, is formed during the cooking of many commonly consumed foods. Data are scant on whether dietary acrylamide represents an important cancer risk in humans. We studied the association between acrylamide and prostate cancer risk using 2 measures of acrylamide exposure: intake from a food frequency questionnaire (FFQ) and acrylamide adducts to hemoglobin. We also studied the correlation between these 2 exposure measures. We used data from the population‐based case‐control study Cancer of the Prostate in Sweden (CAPS). Dietary data was available for 1,499 cases and 1,118 controls. Hemoglobin adducts of acrylamide were measured in blood samples from a subset of 170 cases and 161 controls. We calculated odds ratios (ORs) for the risk of prostate cancer in high versus low quantiles of acrylamide exposure using logistic regression. The correlation between FFQ acrylamide intake and acrylamide adducts in non‐smokers was 0.25 (95% confidence interval: 0.14–0.35), adjusted for age, region, energy intake, and laboratory batch. Among controls the correlation was 0.35 (95% CI: 0.21–0.48); among cases it was 0.15 (95% CI: 0.00–0.30). The OR of prostate cancer for the highest versus lowest quartile of acrylamide adducts was 0.93 (95% CI: 0.47–1.85, p‐value for trend = 0.98). For FFQ acrylamide, the OR of prostate cancer for the highest versus lowest quintile was 0.97 (95% CI: 0.75–1.27, p trend = 0.67). No significant associations were found between acrylamide exposure and risk of prostate cancer by stage, grade, or PSA level. Acrylamide adducts to hemoglobin and FFQ‐measured acrylamide intake were moderately correlated. Neither measure of acrylamide exposure—hemoglobin adducts or FFQ—was associated with risk of prostate cancer. © 2008 Wiley‐Liss, Inc.
A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays
Authors: Charpin Colette , Secq Véronique , Giusiano Sophie , Carpentier Séverine , Andrac Lucile , Lavaut Marie‐Noëlle , Allasia Claude , Bonnier Pascal , Garcia Stéphane
Published: November 2008

Quantitative immunocytochemical assays of 1,200 breast carcinomas were assessed after construction of tissue microarrays. A total of 42 markers were evaluated for prognostic significance by univariate log rank test (mean follow‐up, 79 months), using quantitative scoring by an image analysis device and specific software. Complete data were obtained for 924 patients, for whom 27 of the 42 markers proved to be significant prognostic indicators. Analysis of these 27 markers by logistic regression showed that 18 (cMet, CD44v6, FAK, moesin, caveolin, c‐Kit, CK14, CD10, P21, P27, pMAPK, pSTAT3, STAT1, SHARP2, FYN, ER, PgR and c‐erb B2), and 15 when ER, PgR and c‐erb B2 were excluded, were 80.52% and 78.9% predictive of disease outcome, respectively. The immunocytochemical assays on 4 micron thick sections of fixed tissue are easy to handle in current practice and are cost‐effective. Quantitative densitometric measurement of immunoprecipitates by computer‐assisted devices from digitized microscopic images allows standardized high‐throughput “in situ” molecular profiling within tumors. It is concluded that this 15 marker immunohistochemical signature is suitable for current practice, since performed on paraffin sections of fixed tumor samples, and can be used to select patients needing more aggressive therapy, since this signature is about 80% predictive of poor clinical outcome. Also, the markers included in the signature may be indicative of tumor responsiveness to current chemotherapy or suggest new targets for specific therapies. © 2008 Wiley‐Liss, Inc.
Recurrent chemical reactivations of EBV promotes genome instability and enhances tumor progression of nasopharyngeal carcinoma cells
Authors: Fang Chih‐Yeu , Lee Chia‐Huei , Wu Chung‐Chun , Chang Yu‐Ting , Yu Shu‐Ling , Chou Sheng‐Ping , Huang Ping‐Ting , Chen Chi‐Long , Hou Jia‐Woei , Chang Yao , Tsai Ching‐Hwa , Takada Kenzo , Chen Jen‐Yang
Published: November 2008

Nasopharyngeal carcinoma (NPC) is an endemic malignancy prevalent in South East Asia. Epidemiological studies have associated this disease closely with Epstein‐Barr virus (EBV) infection. Previous studies also showed that EBV reactivation is implicated in the progression of NPC. Thus, we proposed that recurrent reactivations of EBV may be important for its pathogenic role. In this study, NPC cell lines latently infected with EBV, NA and HA, and the corresponding EBV‐negative NPC cell lines, NPC‐TW01 (TW01) and HONE‐1, were treated with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and sodium n‐butyrate (SB) for lytic cycle induction. A single treatment with TPA/SB revealed that DNA double‐strand breaks and formation of micronuclei (a marker for genome instability) were associated with EBV reactivation in NA and HA cells. Examination of EBV early genes had identified several lytic proteins, particularly EBV DNase, as potent activators that induced DNA double‐strand breaks and contribute to genome instability. Recurrent reactivations of EBV in NA and HA cells resulted in a marked increase of genome instability. In addition, the degree of chromosomal aberrations, as shown by chromosome structural variants and DNA copy‐number alterations, is proportional to the frequency of TPA/SB‐induced EBV reactivation. Whereas these DNA abnormalities were limited in EBV‐negative TW01 cells with mock or TPA/SB treatment, and were few in mock‐treated NA cells. The invasiveness and tumorigenesis assays also revealed a profound increase in both characteristics of the repeatedly reactivated NA cells. These results suggest that recurrent EBV reactivations may result in accumulation of genome instability and promote the tumor progression of NPC. © 2008 Wiley‐Liss, Inc.
Minimizing misclassification of hormone users at mammography screening
Authors: Njor Sisse Helle , Pedersen Anette Tønnes , Schwartz Walter , Hallas Jesper , Lynge Elsebeth
Published: November 2008

The aim of the study was to retrospectively determine the impact of comparing current mammograms with prior mammograms on risk of misclassification especially for hormone users. Data on mammography screening were retrieved for 1993–2005 from Fyn, Denmark. At first screen, two projections were made; at subsequent screens, one projection for fatty and two projections for mixed/dense breasts. Until June 3, 2002, 2‐year‐old mammograms were used for comparison, and later 4‐year‐old mammograms. Prescription drug data were used to identify hormone, hormone therapy (HT), use. False positive risk and interval cancer proportion dependency on age, hormone use, screen number, projection and prior mammogram were tested with logistic regression. Controlled for breast density, current HT‐users had a lower risk of a false positive test 0.69 (95%CI 0.55–0.86) and a lower interval cancer proportion 0.66 (95%CI 0.45–0.99) when 4‐year‐old instead of 2‐year‐old mammograms were used for comparison. The use of 4‐year‐old instead of 2‐year‐old mammograms for comparison lowered the risk of false positive test in never users, but otherwise age of comparison mammogram had no impact on classification of never and past users of HT. The study indicated that misclassification at screening mammography in current users of HT can be reduced considerably, when the screening mammograms are viewed with the mammograms taken 4 years earlier. It should be stressed that these results come from a single clinic, and replication in other observational and/or experimental studies is warranted. © 2008 Wiley‐Liss, Inc.
Inducible NO synthase confers chemoresistance in head and neck cancer by modulating survivin
Authors: Fetz Verena , Bier Carolin , Habtemichael Negusse , Schuon Robert , Schweitzer Andrea , Kunkel Martin , Engels Knut , Kovács Adorján F. , Schneider Sandra , Mann Wolf , Stauber Roland H. , Knauer Shirley K.
Published: November 2008

The dual role of the inducible NO synthase (iNOS) and NO signaling in head and neck squamous cell carcinoma (HNSCC) is a complex and can both promote or inhibit tumor progression. However, the underlying molecular mechanisms are not yet resolved in detail. We show for the first time that conditions, favoring low NO levels conferred resistance against cisplatin/taxol‐induced apoptosis in HNSCC cell lines. Cytoprotection was mediated by survivin, because we observed its upregulation subsequent to low doses of the NO donors S‐nitroso‐N‐acetyl‐penicillamine (SNAP) and sodium nitroprusside (SNP) or ectopic expression of physiologic amounts of iNOS. Also, RNAi‐mediated depletion of survivin blocked NOs anti‐apoptotic effects. Induction of survivin involves activation of the phosphatidylinositol‐3‐kinase/Akt (PI3K/Akt) pathway, which was antagonized by the PI3K‐inhibitor LY294002. Importantly, application of the iNOS‐specific inhibitor 1400W combined with RNAi‐mediated downregulation of survivin cooperatively enhanced drug‐induced cell death. The iNOS/survivin‐axis appears to be also of clinical relevance since immunohistochemistry revealed that iNOS expression correlated with enhanced survivin levels in HNSCC specimens. In contrast, high NO concentrations suppressed survivin levels in HNSCC but also in non‐malignant cells resulting in apoptosis. Cell death induced by high amounts of SNAP/SNP or by strong overexpression of iNOS involved activation of p38MAP‐kinase, which was counteracted by the p38MAP‐kinase inhibitor SB202190. Here, we provide evidence for a novel molecular mechanism how NO signaling may contribute to therapy resistance in HNSCC by modulating survivin expression. Our data further suggest pursuing pharmacogenetic iNOS/survivin‐targeting approaches as potential therapeutic strategies in head and neck cancer. © 2008 Wiley‐Liss, Inc.
Fabrication, characterization, and in vitro evaluation of poly(lactic acid glycolic acid)/nano‐hydroxyapatite composite microsphere‐based scaffolds for bone tissue engineering in rotating bioreactors
Authors: Lv Qing , Nair Lakshmi , Laurencin Cato T.
Published: November 2008

Dynamic flow culture bioreactor systems have been shown to enhance in vitro bone tissue formation by facilitating mass transfer and providing mechanical stimulation. Our laboratory has developed a biodegradable poly (lactic acid glycolic acid) (PLAGA) mixed scaffold consisting of lighter‐than‐water (LTW) and heavier‐than‐water (HTW) microspheres as potential matrices for engineering tissue using a high aspect ratio vessel (HARV) rotating bioreactor system. We have demonstrated enhanced osteoblast differentiation and mineralization on PLAGA scaffolds in the HARV rotating bioreactor system when compared with static culture. The objective of the present study is to improve the mechanical properties and bioactivity of polymeric scaffolds by designing LTW polymer/ceramic composite scaffolds suitable for dynamic culture using a HARV bioreactor. We employed a microsphere sintering method to fabricate three‐dimensional PLAGA/nano‐hydroxyapatite (n‐HA) mixed scaffolds composed of LTW and HTW composite microspheres. The mechanical properties, pore size and porosity of the composite scaffolds were controlled by varying parameters, such as sintering temperature, sintering time, and PLAGA/n‐HA ratio. The PLAGA/n‐HA (4:1) scaffold sintered at 90°C for 3 h demonstrated the highest mechanical properties and an appropriate pore structure for bone tissue engineering applications. Furthermore, evaluation human mesenchymal stem cells (HMSCs) response to PLAGA/n‐HA scaffolds was performed. HMSCs on PLAGA/n‐HA scaffolds demonstrated enhanced proliferation, differentiation, and mineralization when compared with those on PLAGA scaffolds. Therefore, PLAGA/n‐HA mixed scaffolds are promising candidates for HARV bioreactor‐based bone tissue engineering applications. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Different hatching strategies in embryos of two species, pacific herring Clupea pallasii and Japanese anchovy Engraulis japonicus, that belong to the same order Clupeiformes, and their environmental adaptation
Authors: Kawaguchi Mari , Fujita Hideaki , Yoshizaki Norio , Hiroi Junya , Okouchi Hiroyuki , Nagakura Yoshitomo , Noda Tsutomu , Watanabe Satoshi , Katayama Satoshi , Iwamuro Shawichi , Nishida Mutsumi , Iuchi Ichiro , Yasumasu Shigeki
Published: November 2008

Pacific herring Clupea pallasii and Japanese anchovy Engraulis japonicus, which belong to the same order Clupeiformes, spawn different types of eggs: demersal adherent eggs and pelagic eggs, respectively. We cloned three cDNAs for Pacific herring hatching enzyme and five for Japanese anchovy. Each of them was divided into two groups (group A and B) by phylogenetic analysis. They were expressed specifically in hatching gland cells (HGCs), which differentiated from the pillow and migrated to the edge of the head in both species. HGCs of Japanese anchovy stopped migration at that place, whereas those of Pacific herring continued to migrate dorsally and distributed widely all over the head region. During evolution, the program for the HGC migration would be varied to adapt to different hatching timing. Analysis of the gene expression revealed that Pacific herring embryos synthesized a large amount of hatching enzyme when compared with Japanese anchovy. Chorion of Pacific herring embryo was about 7.5 times thicker than that of Japanese anchovy embryo. Thus, the difference in their gene expression levels between two species is correlated with the difference in the thickness of chorion. These results suggest that the hatching system of each fish adapted to its respective hatching environment. Finally, hatching enzyme genes were cloned from each genomic DNA. The exon–intron structure of group B genes basically conserved that of the ancestral gene, whereas group A genes lost one intron. Several gene‐specific changes of the exon–intron structure owing to nucleotide insertion and/or duplication were found in Japanese anchovy genes. J. Exp. Zool. (Mol. Dev. Evol.) 312B:95–107, 2009. © 2008 Wiley‐Liss, Inc.
Potential of magnetization transfer MRI for target volume definition in patients with non‐small‐cell lung cancer
Authors: Arnold Johannes F.T. , Kotas Markus , Pyzalski Robert W. , Pracht Eberhard D. , Flentje Michael , Jakob Peter M.
Published: November 2008

Purpose

To develop a magnetization transfer (MT) module in conjunction with a single‐shot MRI readout technique and to investigate the MT phenomenon in non‐small‐cell lung cancer (NSCLC) as an adjunct for radiation therapy planning.

Materials and Methods

A total of 10 patients with inoperable NSCLC were investigated using a 1.5T MR scanner. MT ratio (MTR) maps of several slices throughout the tumor were assessed. Each MTR‐map was acquired within a short breathhold. Fluorodeoxyglucose positron emission tomography (FDG‐PET) investigations were performed in addition to the MRI protocol. A total of 60 structures appearing conspicuous in FDG‐PET were compared with structures appearing conspicuous in corresponding MTR maps. Quantification of similarity between both modalities was performed using similarity index calculation.

Results

MTR‐maps showed different contrast than FDG‐PET images. However, structures that appeared conspicuous in FDG‐PET images, either by a marked signal enhancement or signal decrease, were found to be similarly present in MTR maps. A mean similarity index of 0.65 was calculated. MTR values of suspected atelectasis were on average lower than MTR values of tumor tissue.

Conclusion

The proposed MT‐MRI technique provides a high MT efficiency, while being robust and fast enough for breathhold acquisition. The results obtained encourage for further exploration of MT‐MRI as an adjunct for radiotherapy planning in NSCLC. J. Magn. Reson. Imaging 2008;28:1417–1424. © 2008 Wiley‐Liss, Inc.
Conjunction analysis and propositional logic in fMRI data analysis using Bayesian statistics
Authors: Rudert Thomas , Lohmann Gabriele
Published: November 2008

Purpose

To evaluate logical expressions over different effects in data analyses using the general linear model (GLM) and to evaluate logical expressions over different posterior probability maps (PPMs).

Materials and Methods

In functional magnetic resonance imaging (fMRI) data analysis, the GLM was applied to estimate unknown regression parameters. Based on the GLM, Bayesian statistics can be used to determine the probability of conjunction, disjunction, implication, or any other arbitrary logical expression over different effects or contrast. For second‐level inferences, PPMs from individual sessions or subjects are utilized. These PPMs can be combined to a logical expression and its probability can be computed. The methods proposed in this article are applied to data from a STROOP experiment and the methods are compared to conjunction analysis approaches for test‐statistics.

Results

The combination of Bayesian statistics with propositional logic provides a new approach for data analyses in fMRI. Two different methods are introduced for propositional logic: the first for analyses using the GLM and the second for common inferences about different probability maps.

Conclusion

The methods introduced extend the idea of conjunction analysis to a full propositional logic and adapt it from test‐statistics to Bayesian statistics. The new approaches allow inferences that are not possible with known standard methods in fMRI. J. Magn. Reson. Imaging 2008;28:1533–1539. © 2008 Wiley‐Liss, Inc.
Perfusion imaging of the pancreas using an arterial spin labeling technique
Authors: Schraml Christina , Schwenzer Nina F. , Martirosian Petros , Claussen Claus D. , Schick Fritz
Published: November 2008

Purpose

To investigate the feasibility of perfusion imaging of the pancreas using an arterial spin labeling (ASL) technique.

Materials and Methods

An adapted flow‐sensitive alternating inversion recovery (FAIR)‐TrueFISP ASL technique was implemented on a 1.5T scanner. Anatomical and perfusion imaging in three different parts of the pancreas were performed in 10 healthy volunteers. Quantitative perfusion values were calculated using the extended Bloch equations.

Results

Perfusion images of all subjects showed diagnostic image quality in the pancreatic tail and the head. Assessment of pancreatic tissue perfusion was possible in all organ parts. Mean perfusion values were 271 ± 79 mL/100g/min in the head, 351 ± 112 mL/100g/min in the body, and 243 ± 55 mL/100g/min in the tail of the pancreas. Total examination time for perfusion imaging of the entire organ was 15.4 minutes.

Conclusion

FAIR‐TrueFISP permits analysis of pancreatic tissue perfusion with good image quality in a clinically applicable measuring time. Assessment of perfusion disorders may be useful in the diagnosis of inflammatory pancreatic pathologies, endocrine and exocrine pancreatic disorders, and in monitoring of pancreatic transplants. J. Magn. Reson. Imaging 2008;28:1459–1465. © 2008 Wiley‐Liss, Inc.
Head‐to‐head comparison between delayed enhancement and percent infarct mapping for assessment of myocardial infarct size in a canine model
Authors: Ruzsics Balázs , Surányi Pál , Kiss Pál , Brott Brigitta C. , Elgavish Ada , Simor Tamas , Elgavish Gabriel A.
Published: November 2008

Purpose

To compare a novel method, percent‐infarct‐mapping (PIM), with conventional delayed enhancement (DE) of contrast for accurate myocardial viability assessment. Contrary to signal intensity (SI), the longitudinal relaxation‐rate enhancement (ΔR1) is an intrinsic parameter linearly proportional to the concentration of contrast agent (CA). Determining ΔR1 voxel‐by‐voxel, after administering an infarct‐avid CA, allows determination of per‐voxel percentage of infarcted tissue. The feasibility of generating PIM is demonstrated in canine reperfused infarction using an infarct‐avid, persistent‐CA (PCA), (Gd)(ABE‐DTTA). PIM is compared to the DE method using Gd(DTPA), and both to triphenyltetrazolium chloride (TTC) staining histochemistry.

Materials and Methods

In six dogs, 48 hours following closed‐chest, 180‐minute coronary occlusion, DE imaging was carried out. PCA was administered immediately thereafter. Pixel‐by‐pixel R1 maps of the entire left ventricle (LV) were generated 48 hours after PCA using inversion‐recovery with multiple inversion times. R1, ΔR1, and percent‐infarct values were calculated voxel‐by‐voxel.

Results

Significant correlations (P < 0.01, R ≥ 0.8) were obtained for percent‐infarct‐per‐slice (PIS) determined by DE or PIM vs. those from corresponding TTC‐stained slices. Compared to TTC, DE overestimated PIS by 32 ± 18%. PIM underestimated PIS by 2.5 ± 4.9%. Infarction fraction overestimation was 29 ± 6% of LV by DE, but only 1.0 ± 2.3% by PIM. Errors with PIM were significantly smaller than those with DE. Infarct area determined by signal intensity was similarly overestimated whether using Gd(DTPA) or Gd(ABE‐DTTA).

Conclusion

The ΔR1‐based PIM method is highly reproducible and more accurate than DE for quantifying myocardial viability in vivo. J. Magn. Reson. Imaging 2008;28:1386–1392. © 2008 Wiley‐Liss, Inc.
Comparison of 2D and multislab 3D magnetic resonance techniques for measuring carotid wall volumes
Authors: Keenan Niall G. , Grasso Agata , Locca Didier , Roughton Michael , Gatehouse Peter D. , Firmin David N. , Pennell Dudley J.
Published: November 2008

Purpose

To compare a multislab three‐dimensional volume‐selective fast spin‐echo (FSE) magnetic resonance (MR) sequence with a routine two‐dimensional FSE sequence for quantification of carotid wall volume.

Materials and Methods

One hundred normal subjects (50 men, mean age 44.6 years) underwent carotid vessel wall MR using 2D and 3D techniques. Carotid artery total vessel volume, lumen volume, wall volume, and wall/outer wall (W/OW) ratio were measured over 20 contiguous slices. Two‐ (2D) and three‐dimensional (3D) results were compared.

Results

The mean difference between 2D and 3D datasets (as a percentage of the mean absolute value) was 1.7% for vessel volume, 4.9% for lumen volume, 4.7% for wall volume, and 5.8% for W/OW ratio. There was good correlation between 2D and 3D models for total vessel volume (R2 = 0.93, P < 0.001), lumen area (R2 = 0.92, P < 0.001), and wall volume (R2 = 0.77, P < 0.001). The correlation for the W/OW ratio was weaker (R2 = 0.30; P < 0.001). The signal‐to‐noise ratio (SNR) for the 3D technique was 2.1‐fold greater than for the 2D technique (P < 0.001). When using the 3D sequence, scan time was reduced by 63%.

Conclusion

Multislab volume selective 3D FSE carotid arterial wall imaging performs similarly to a conventional 2D technique, but with over twice the SNR and substantially reduced scan time. J. Magn. Reson. Imaging 2008;28:1476–1482. © 2008 Wiley‐Liss, Inc.
J‐difference lactate editing at 3.0 Tesla in the presence of strong lipids
Authors: Smith Mari A. , Koutcher Jason A. , Zakian Kristen L.
Published: November 2008

Purpose

To implement in vivo detection of lactate in the presence of lipids by proton magnetic resonance spectroscopy at a 3 Tesla (T) field strength for potential applications in human tumors outside of the brain.

Materials and Methods

The BASING J‐difference sequence was implemented in the presence of high lipid concentrations in phantoms and in vivo at 3 Tesla.

Results

The effectiveness of the lactate editing scheme is demonstrated in phantoms containing both lactate and lipids and in vivo in ischemic induced human muscle.

Conclusion

The ability of the BASING J‐difference technique to detect lactate in the presence of strong lipid signals outside the brain at 3T is feasible. This robust technique should permit noninvasive lactate measurements in human tumors to investigate its potential as a prognostic indicator. J. Magn. Reson. Imaging 2008;28:1492–1498. © 2008 Wiley‐Liss, Inc.
Left ventricle segmentation using graph searching on intensity and gradient and a priori knowledge (lvGIGA) for short‐axis cardiac magnetic resonance imaging
Authors: Lee Hae‐Yeoun , Codella Noel , Cham Matthew , Prince Martin , Weinsaft Jonathan , Wang Yi
Published: November 2008

Purpose

To develop and evaluate an automated left ventricle (LV) segmentation algorithm using Graph searching based on Intensity and Gradient information and A priori knowledge (lvGIGA).

Materials and Methods

The lvGIGA algorithm was implemented with coil sensitivity correction and polar coordinate transformation. Graph searching and expansion were applied for extracting myocardial endocardial and epicardial borders. LV blood and myocardium intensities were estimated for accurate partial volume calculation of blood volume and myocardial mass. Cardiac cine SSFP images were acquired from 38 patients. The lvGIGA algorithm was used to measure blood volume, myocardial mass, and ejection fraction, and compared with clinical manual tracing and the commercial MASS software.

Results

The success rate for segmenting both endocardial and epicardial borders was 95.6% slices for lvGIGA and 37.8% for MASS (excluding basal slices that required manual enclosure of ventricle blood). The lvGIGA segmentation result agreed well with manual tracing, within −2.9 ± 4.4 mL, 2.1 ± 2.2%, and −9.6 ± 13.0 g, for blood volume, ejection fraction, and myocardial mass, respectively.

Conclusion

The lvGIGA algorithm substantially improves the robustness of LV segmentation automation over the commercial MASS software, agrees well with clinical manual tracing, and may be a useful tool for clinical practice. J. Magn. Reson. Imaging 2008;28:1393–1401. © 2008 Wiley‐Liss, Inc.
Erythrocyte‐shape evolution recorded with fast‐measurement NMR diffusion–diffraction
Authors: Pages Guilhem , Szekely David , Kuchel Philip W.
Published: November 2008

Purpose

To monitor red blood cell (RBC) shape evolution by 1H2O diffusion–diffraction NMR in time steps comparable to those required for the acquisition of a 31P NMR spectrum; thus, to correlate RBC mean diameter with ATP concentration after poisoning with NaF.

Materials and Methods

Pulsed‐field gradient‐stimulated echo (PFGSTE) diffusion experiments were recorded on 1H2O in RBC suspensions. Under conditions of restricted diffusion, q‐space experiments report on mean RBC diameter. To decrease experiment time, the phase cycling of radiofrequency (RF) pulses was cut to two transients by using unbalanced pairs of gradient pulses. Data processing used a recent digital filter. Differential interference contrast (DIC) light microscopy also recorded shape changes. 31P NMR spectroscopy gave estimates of mean ATP concentration.

Results

NaF caused RBC‐shape evolution from discocytes, through various forms of echinocytes, to spherocytes, over ∼6 h and ∼10 h at 37°C and 25°C, respectively. ATP declined to ∼0.5 its normal concentration before the first stage of discocyte transformation; the concentration was 0.0 after ∼1.5 h and 3.0 h, respectively, at the two temperatures.

Conclusion

RBC shape was readily monitored by NMR with a temporal resolution that was useful for correlations with both DIC microscopy and 31P NMR spectra. J. Magn. Reson. Imaging 2008;28:1409–1416. © 2008 Wiley‐Liss, Inc.