bluuebunny/crossref_metadata_2025 huggingface dataset:
Two Methods for the Determination of Enantiomeric Excess and Concentration of a Chiral Sample with a Single Spectroscopic Measurement
Authors: Zhu Lei , Shabbir Shagufta H. , Anslyn Eric V.
Published: October 2006

The previously established enantioselective indicator–displacement assays (eIDAs) for the determination of concentration and enantiomeric excess (ee) require two spectroscopic measurements for each chiral sample. To further simplify the operation of eIDAs, we now introduce two innovative analytical methods, both of which utilize a dual‐chamber quartz cuvette, which reduces the number of spectroscopic measurements from two to one. An attractive feature of this cuvette is that the concentration‐ and ee‐dependent absorption data can be collected at the isosbestic points or transparent regions of the spectra recorded in each individual chamber, thereby reflecting optical changes that occur in the other chamber. Therefore, two independent equations, which are needed to solve the values of the two independent variables—concentration and ee—can be established with only a single spectroscopic measurement. The first method takes advantage of this feature in conjunction with a judicious choice of indicator/host combinations to generate concentration‐ and ee‐dependent calibration curves. Our second method removes the requirement to measure equilibrium constants and molar absorptivities altogether through the use of artificial neural networks (ANNs). The most frequently used three‐layer feed‐forward network is generated, which relates the absorption data to concentration and ee of the samples by training with a back propagation procedure. Here, the data collection is not limited to the isosbestic points or transparent regions. Both approaches enabled accurate and rapid determination of concentration and ee of chiral samples. The technology removes the relative difficulty, which is the need for two separate measurements for concentration and ee respectively, of analyzing chiral samples compared to achiral samples. When implemented in a high‐throughput format, this technology should greatly facilitate the discovery of asymmetric catalysts in the same way as conventional high‐throughput screening assays.
Accuracy of lymphatic mapping and sentinel lymph node biopsy after previous wide local excision in patients with primary melanoma
Authors: Gannon Christopher J. , Rousseau Dennis L. , Ross Merrick I. , Johnson Marcella M. , Lee Jeffrey E. , Mansfield Paul F. , Cormier Janice N. , Prieto Victor G. , Gershenwald Jeffrey E.
Published: October 2006

BACKGROUND.

Sentinel lymph node (SLN) status is the most important prognostic factor with respect to the survival of patients with primary cutaneous melanoma. However, lymphatic mapping and SLN biopsies (LM/SLNBs) performed in patients who have had a wide local excision (WLE) may not accurately reflect the pathologic status of the draining lymph node basins. The purpose of this study was to assess the feasibility and accuracy of LM/SLNB in patients who have had a previous WLE.

METHODS.

A single‐institution database was examined to identify patients who had a WLE before LM/SLNB and patients who had a concomitant LM/SLNB. Primary clinicopathologic features (age, tumor thickness, and ulceration), SLN identification rate, SLN pathologic status, and the incidence and sites of recurrences were compared between patients with and without prior WLE.

RESULTS.

Of the 1395 patients identified, 104 had WLE before LM/SLNB. The mean preoperative WLE radial margin was 1.4 cm (median, 1.0 cm). LM/SLNB was successful in 103 of 104 (99%) patients. Age, tumor thickness, incidence of ulceration, and incidence of SLN positivity in the group with prior WLE were similar to those of the cohort of patients who had concomitant LM/SLNB and WLE (n = 1291). In 97 (93%) of the 104 prior‐WLE patients, the surgical defects were closed by either primary closure or skin graft; 7 patients (7%) had rotational flaps. The median follow‐up of these 104 patients was 51 months. Among the prior‐WLE group, 19 patients (18%) had a positive SLNB; of these 19 patients, 4 (21%) had recurrences (3 distant failures and 1 local and distant failure). There were no lymph node recurrences—in a mapped or unmapped basin—in these 104 patients with a negative or positive SLNB.

CONCLUSIONS.

SLNs can be successfully identified and accurately reflect the status of the regional lymph node basin in carefully selected melanoma patients with a previous WLE. Prior WLE does not appear to adversely impact the ability to detect lymphatic metastases, although the utility of LM/SLNB in patients who have undergone extensive reconstruction of the primary excision site remains to be defined. Because more extensive surgery may be required to accomplish accurate lymph node staging in patients who have undergone prior WLE—including the possible removal of SLNs from additional lymph node basins and an additional surgical procedure—to minimize morbidity and cost, concomitant WLE and LM/SLNB is strongly preferred whenever possible. Cancer 2006. © 2006 American Cancer Society.
Simultaneous quantification of oxidative stress and cell spreading using 5‐(and‐6)‐chloromethyl‐2′,7′‐dichlorofluorescein
Authors: Koopman Werner J. H. , Verkaart Sjoerd , van Emst‐de Vries Sjenet E. , Grefte Sander , Smeitink Jan A. M. , Willems Peter H. G. M.
Published: October 2006

Background:

Mitochondrial dysfunction may lead to increased oxidative stress and consequent changes in cell spreading. Here, we describe and validate a novel method for simultaneous quantification of these two parameters.

Methods:

Human skin fibroblasts were loaded with 5‐(and‐6)‐chloromethyl‐2′,7′‐dichlorodihydrofluorescein (CM‐H2DCF), and its oxidative conversion into CM‐DCF was monitored as a function of time by video‐rate confocal microscopy and real‐time image averaging. Cell size was determined after binarization of the acquired images.

Results:

At the lowest practical laser output, CM‐DCF formation occurred with zero order kinetics, indicating that [CM‐H2DCF] was not rate‐limiting and that the rate of [CM‐DCF] formation (VCM‐DCF) was a function of the cellular oxidant level. Analysis of fibroblasts of a healthy control subject and a patient with a deficiency of NADH:ubiquinone oxidoreductase, the first complex of the oxidative phosphorylation system, revealed a significant increase in cellular oxidant level in the latter cells that was, however, not accompanied by a change in cell spreading. Conversely, chronic treatment with 6‐hydroxy‐2,5,7,8‐tetramethylchroman‐2‐carboxylic acid (Trolox), a derivative of vitamin E, markedly decreased the oxidant level and cell spreading in both control and patient fibroblasts.

Conclusions:

We present a reliable method for simultaneous quantification of oxidant levels and cell spreading in living cells. © 2006 International Society for Analytical Cytology
Parameter identification of framed structures using an improved finite element model‐updating method—Part II: application to experimental data
Authors: Yu Eunjong , Wallace John W. , Taciroglu Ertugrul
Published: October 2006

In this study, we determine an updated finite element model of a reinforced concrete building—which was damaged from shaking during 1994 Northridge earthquake—using forced‐vibration test data and a novel model‐updating technique. Developed and verified in the companion paper (viz. BVLSrc, Earthquake Eng. Struct. Dyn. 2006; this issue), this iterative technique incorporates novel sensitivity‐based relative constraints to avoid ill conditioning that results from spatial incompleteness of measured data. We used frequency response functions and natural frequencies as input for the model‐updating problem. These data were extracted from measurements obtained during a white‐noise excitation applied at the roof of the building using a linear inertial shaker. Flexural stiffness values of properly grouped structural members, modal damping ratios, and translational and rotational mass values were chosen as the updating parameters, so that the converged results had direct physical interpretations, and thus, comparisons with common parameters used in seismic design and evaluation of buildings could be made. We investigated the veracity of the updated finite element model by comparing the predicted and measured dynamic responses under a second, and different type of forced (sine‐sweep) vibration, test. These results indicate that the updated model replicates the dynamic behaviour of the building reasonably well. Furthermore, the updated stiffness factors appear to be well correlated with the observed building damage patterns (i.e. their location and severity). Copyright © 2006 John Wiley & Sons, Ltd.
Modelling thermal degradation of composite materials
Authors: Trelles Javier , Lattimer Brian Y.
Published: October 2006

A one–dimensional, transient thermal degradation heat transfer model for the response of composite materials when exposed to fire is presented. The model can handle layers of different materials. Material properties are functions of temperature. The reaction can be specified using Arrhenius‐type parameters or by inputting a density–temperature relationship determined by any experimental technique such as thermogravimetric analysis. The model is validated against the experimental data presented in Boyer's 1984 dissertation. Overall, the model provides excellent agreement with the experimental data. It is shown that very little difference is found between results arrived at by Arrhenius kinetics and results obtained by specifying the easier to measure density–temperature relationship. From this it is concluded that this technique is a viable alternative to Arrhenius‐type models. Copyright © 2006 John Wiley & Sons, Ltd.
Numerical simulation of turbulent impinging jet on a rotating disk
Authors: Abdel‐Fattah A.
Published: October 2006

The calculations of quasi‐three‐dimensional momentum equations were carried out to study the influence of wall rotation on the characteristics of an impinging jet. The pressure coefficient, the mean velocity distributions and the components of Reynolds stress are calculated. The flow is assumed to be steady, incompressible and turbulent. The finite volume scheme is used to solve the continuity equation, momentum equations and k–ε model equations. The flow characteristics were studied by varying rotation speed ω for 0⩽ω⩽167.6 rad/s, the distance from nozzle to disk (H/d) was (3, 5, 8 and 10) and the Reynolds number Re base on VJ and d was 1.45 × 104. The results showed that, the radial velocity and turbulence intensity increase by increasing the rotation speed and decrease in the impingement zone as nozzle to disk spacing increases. When the centrifugal force increases, the radial normal stresses and shear stresses increase. The location of maximum radial velocity decreases as the local velocity ratio (α) increases. The pressure coefficient depends on the centrifugal force and it decreases as the distance from nozzle to plate increases. In impingement zone and radial wall jet, the spread of flow increases as the angular velocity decreases The numerical results give good agreement with the experiment data of Minagawa and Obi (Int. J. of Heat and Fluid Flow 2004; 25:759–766). Copyright © 2006 John Wiley & Sons, Ltd.
Synthesis of some novel imidazolidine derivatives and their metal complexes with biological and antitumor activity
Authors: Al‐Raqa Shaya Y. , ElSharief Ahmed M. Sh. , Khalil Saied M. E. , Al‐Amri Abdulkhaliq M.
Published: October 2006

Halogenated imidazo(pyrazine,[1,4]diazocine and quinoxaline), 9,10‐anthraquinone‐ [6,7‐e], phenanthroline[5,6‐e] {imidazo[4,5‐b]pyrazine}, and naphtho[1,8‐ef]imidazo[4,5‐b][1,4] diazipen were obtained through interaction of imidazolidineiminothiones with the corresponding diamino compounds. Imidazo[4,5‐e] triazine and pyrrolo[2,3‐d]imidazole were prepared when the iminothiones were reacted with thiocarbohydrazide and with ethylphenyl acetate, separately. Some of the synthesized compounds exhibited better biological and antitumor activities. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:634–647, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20244
Radical 4‐exo Cyclizations onto O‐Alkyloxime Acceptors: Towards the Synthesis of Penicillin‐Containing Antibiotics
Authors: Scanlan Eoin M. , Walton John C.
Published: October 2006

The 4‐exo cyclizations of two types of carbamoyl radicals onto O‐alkyloxime acceptor groups were studied as potential routes to 3‐amino‐substituted azetidinones and hence to penicillins. A general synthetic route to ‘benzaldehyde oxime oxalate amides’ (= 2‐[(benzylideneamino)oxy]‐2‐oxoacetamides; see, e.g., 10c) of 2‐{[(benzyloxy)imino]methyl}‐substituted thiazolidine‐4‐carboxylic acid methyl esters 9 was developed (Scheme 3). It was shown by EPR spectroscopy that these compounds underwent sensitized photodissociation to the corresponding carbamoyl radicals but that these did not ring close. An analogous open‐chain precursor, benzaldehyde O‐(benzylaminoacetaldehyde‐O‐benzyloxalyl)oxime, 15, lacking the 5‐membered thiazolidine ring, was shown by EPR spectroscopy to release the corresponding carbamoyl radical (Scheme 4). The latter underwent 4‐exo cyclization onto its CNOBn bond in non‐H‐atom donor solvents. The rate constant for this cyclization was determined by the steady‐state EPR method. Spectroscopic evidence indicated that the reverse ring‐opening process was slower than cyclization.
Deriving evolutionary tree models of the oncogenesis of endometrial adenocarcinoma
Authors: Chen Lei , Nordlander Carola , Behboudi Afrouz , Olsson Björn , Levan Karin Klinga
Published: October 2006

Endometrial adenocarcinoma (EAC) is the fourth leading cause of cancer death in women worldwide, but not much is known about the underlying genetic factors involved in the development of this complex disease. In the present work, we used 3 different algorithms to derive tree models of EAC oncogenesis from data on the frequencies of genomic alterations in rat chromosome 10 (RNO10). The tumor material was derived from progenies of crosses between the EAC susceptible BDII inbred rat strain and two non susceptible inbred rat strains. Data from allelic imbalance scans of RNO10 with microsatellite markers on solid tumor material and corresponding tissue cultures were used. For the analysis, RNO10 was divided into 24 segments containing a total of 59 informative microsatellite markers. The derived tree models show that genomic alterations have occurred in 11 of the 24 segments. In addition, the models provide information about the likely order of the alterations as well as their relationship with each other. Interestingly, there was a high degree of consistency among the different tree models and with the results of previous studies, which supports the reliability of the tree models. Our results may be extended into a general approach for tree modeling of whole genome alterations during oncogenesis. © 2006 Wiley‐Liss, Inc.
Mammalian peroxidases activate anticancer drug ellipticine to intermediates forming deoxyguanosine adducts in DNA identical to those found in vivo and generated from 12‐hydroxyellipticine and 13‐hydroxyellipticine
Authors: Stiborová Marie , Poljaková Jitka , Ryšlavá Helena , Dračínský Martin , Eckschlager Tomáš , Frei Eva
Published: October 2006

Ellipticine is a potent antineoplastic agent, whose mode of action is considered to be based mainly on DNA intercalation, inhibition of topoisomerase II and cytochrome P450‐mediated formation of covalent DNA adducts. This is the first report on the molecular mechanism of ellipticine oxidation by peroxidases (human myeloperoxidase, human and ovine cyclooxygenases, bovine lactoperoxidase, horseradish peroxidase) to species forming ellipticine‐DNA adducts. Using NMR spectroscopy, the structures of 2 ellipticine metabolites were identified; the major product is the ellipticine dimer, in which the 2 ellipticine skeletons are connected via N6 of the pyrrole ring of one ellipticine molecule and C9 in the second one. The minor metabolite is ellipticine N2‐oxide. Using 32P‐postlabeling and [3H]‐labeled ellipticine, we showed that ellipticine binds covalently to DNA after its activation by peroxidases. The DNA adduct pattern induced by ellipticine consisted of a cluster of up to 4 adducts. The 2 adducts are indistinguishable from the 2 major adducts generated between deoxyguanosine in DNA and either 13‐hydroxy‐ or 12‐hydroxyellipticine or in rats treated with ellipticine, or if ellipticine was activated with human hepatic and renal microsomes. The results presented here are the first characterization of the peroxidase‐mediated oxidative metabolites of ellipticine and we have proposed species, 2 carbenium ions, ellipticine‐13‐ylium and ellipticine‐12‐ylium, as reactive species generating 2 major DNA adducts seen in vivo in rats treated with ellipticine. The study forms the basis to further predict the susceptibility of human cancers to ellipticine. © 2006 Wiley‐Liss, Inc.
Body size in relation to cancer of the uterine corpus in 1 million Norwegian women
Authors: Bjørge Tone , Engeland Anders , Tretli Steinar , Weiderpass Elisabete
Published: October 2006

A positive association between overweight/obesity and endometrial cancer has been observed. It has been hypothesized that obesity is mostly associated with a subtype described as estrogen‐dependent (Type I tumors), constituting about 80% of the endometrial tumors. Few epidemiologic studies have, however, analyzed different histological subtypes separately. The present study aimed at exploring the relations between body size and histological subtypes of cancer of the uterine corpus. Height and weight were measured in over 1 million Norwegian women aged 20–74 during 1963–2001. During follow‐up, 9,227 cancers of the uterine corpus were diagnosed. The tumors were classified as Type I tumors (mostly endometrial adenocarcinomas with subgroups), Type II tumors (papillary, serous, and clear cell adenocarcinomas and some poorly differentiated carcinomas), sarcomas, and mixed tumors. Relative risks (RRs) of cancer of the uterine corpus were estimated using Cox proportional hazards regression. Compared with women with normal BMI, overweight and obese women had an overall RR of cancer of the uterine corpus of 1.36 (95% CI: 1.29–1.42) and 2.51 (95% CI: 2.83–2.66). The increase in risk was most pronounced for Type I tumors, but was also seen for Type II tumors, sarcomas and mixed tumors. The overall RR of corpus uteri cancer associated with a 10‐cm increase in height was 1.09 (95% CI: 1.05–1.13), and was mostly observed for Type I tumors. © 2006 Wiley‐Liss, Inc.
5α‐Reductase type 1 and aromatase in breast carcinoma as regulators of in situ androgen production
Authors: Suzuki Takashi , Miki Yasuhiro , Moriya Takuya , Akahira Jun‐ichi , Ishida Takanori , Hirakawa Hisashi , Yamaguchi Yuri , Hayashi Shin‐ichi , Sasano Hironobu
Published: October 2006

Previous in vitro studies demonstrated that bioactive androgen 5α‐dihydrotestosterone (DHT) exerted antiproliferative effects through an interaction with androgen receptor (AR) in breast carcinoma cells. However, AR status has not been examined in association with DHT concentration in breast carcinoma tissues, and significance of androgenic actions remains unclear in breast carcinomas. Therefore, in our study, we first examined intratumoral DHT concentrations in 38 breast carcinoma tissues using liquid chromatography/electrospray tandem mass spectrometry. Intratumoral DHT concentration was positively associated with 5α‐reductase type 1 (5αRed1), and negatively correlated with aromatase. We then examined clinical significance of AR and 5αRed1 status in 115 breast carcinoma tissues by immunohistochemistry. Breast carcinomas positive for both AR and 5αRed1 were inversely associated with tumor size or Ki‐67. These patients showed significant associations with a decreased risk of recurrence and improved prognosis for overall survival, and the AR / 5αRed1 status was demonstrated an independent prognostic factor. Moreover, we examined possible regulation of DHT production by aromatase in in vitro studies. DHT synthesis from androstenedione in MCF‐7 cells was significantly inhibited by coculture with aromatase‐positive stromal cells, which was significantly reversed by addition of aromatase inhibitor exemestane. These results suggest that intratumoral DHT concentration is mainly determined by 5αRed1 and aromatase in breast carcinoma tissues, and antiproliferative effect of DHT may primarily occur in the cases positive for both AR and 5αRed1. Aromatase inhibitors may be more effective in these patients, possibly due to increasing local DHT concentration with estrogen deprivation. © 2006 Wiley‐Liss, Inc.
Effect of fish oil supplementation for 2 generations on changes in macrophage function induced by Walker 256 cancer cachexia in rats
Authors: Folador Alessandra , Hirabara Sandro M. , Bonatto Sandro J.R. , Aikawa Júlia , Yamazaki Ricardo K. , Curi Rui , Fernandes Luiz C.
Published: October 2006

The effect of coconut fat (rich in medium saturated fatty acids) or fish oil (rich in ω‐3 polyunsaturated fatty acids) supplementation for 2 generations on tumor growth, cancer cachexia, animal survival and macrophage function was investigated in Walker 256 tumor‐bearing rats. Female Wistar rats were supplemented with coconut fat or fish oil prior to mating and then throughout pregnancy and gestation. Both supplementations were daily and orally given at 1 g per kg body weight as a single bolus. Same treatment was performed by the 2 following generations. At 90 days of age, male offspring (50%) from F2 generation were subcutaneously inoculated with 2 × 107 Walker 256 tumor cells. At 14 days after tumor implantation, rats not supplemented displayed cancer cachexia characterized by loss of body weight, hypoglycemia, hyperlacticidemia, hypertriglyceridemia, decreased food intake and depletion of glycogen stores in the liver and skeletal muscles. Supplementation with coconut fat did not affect these parameters. However, supplementation with fish oil decreased tumor growth (59%), prevented body weight loss and food intake reduction and attenuated cancer cachexia. In addition, fish oil increased animal survival up to 20 days (from 25% in rats not supplemented to 67% in rats supplemented with fish oil) and improved macrophage function characterized by increased phagocytosis capacity and production of hydrogen peroxide and nitric oxide. These results suggest that fish oil supplementation for 2 generations improves macrophage function in association to reduced tumor growth and attenuated cancer cachexia, maintaining food intake and increasing animal survival. © 2006 Wiley‐Liss, Inc.
Human climates of Egypt
Authors: Robaa S. M. , Hasanean H. M.
Published: October 2006

The clo index values for different wear have been estimated for daytime and nighttime for different months of the year in order to investigate human climates in Egypt. The clo values may also be used as a good guide to gauge the thermal human comfort under different atmospheric conditions and also express the resistance to heat transfer by clothing, and are expressed relative to the units of thermal insulation. A complete set of measurements for air temperature and cloud amount in addition to wind speed for the daytime (1200 GMT) and nighttime (0000 GMT) hours for the period 1991–2002 at 40 meteorological stations in Egypt have been used. The percentage area (%) requiring different weather wear during daytime and nighttime for all the months of the year have been determined. The study revealed that the whole country is characterized by the requirement of very cold weather wear during winter nighttime while 72% of the area of the country requires tropical weather wear during summer daytime. Only 71% of the area of the country requires comfortable weather wear during summer nighttime while there is no area requiring comfortable weather wear during winter nighttime. Latitudinal gradient of clo values was observed during all months of the year. Maximum latitudinal gradients of clo values during the daytime were found for the months of April and May. The clo classification in relation to climate has been done for Egypt. Copyright © 2006 Royal Meteorological Society
Survivin mRNA in peripheral blood is frequently detected and significantly decreased following resection of gastrointestinal cancers
Authors: Hoffmann A.‐C. , Warnecke‐Eberz U. , Luebke T. , Prenzel K. , Metzger R. , Heitmann M. , Neiss S. , Vallbohmer D. , Hoelscher A.H. , Schneider P.M.
Published: October 2006

Background and Objectives

We evaluated if mRNA expression of survivin, an inhibitor of apoptosis, can be used to detect circulating tumor cells in peripheral blood of patients with various gastrointestinal cancers and if they decrease following complete surgical resection.

Methods

Blood samples from 40 gastrointestinal cancer patients were analyzed prior and following surgical resection by direct quantitative real‐time reverse transcriptase‐PCR (RT‐PCR) assays.

Results

Survivin mRNA expression was pre‐operatively detected in 35 of 40 cancer patients (88%). Post‐operative survivin levels were significantly lower than pre‐operative levels in 59% of resected patients and were non‐detectable in 38% (Wilcoxon rank test: P < 0.04).

Conclusions

This is the first report showing that direct quantitative real‐time RT‐PCR analysis of survivin mRNA expression in peripheral blood of patients with gastrointestinal cancers is technically feasible. Survivin mRNA levels fall significantly following complete resection and might become a molecular marker for the completeness of surgical resection. J. Surg. Oncol. 2007; 95:51–54. © 2006 Wiley‐Liss, Inc.
Liquid chromatography–mass spectrometric analysis of puerarin and its metabolite in human urine
Authors: Tian Hongzhe , Yang Bingcheng , Xu Jing , Wang Hua , Guan Yafeng
Published: October 2006

A specific LC‐MS method was developed that allowed simultaneous determination of puerarin (PU) and its major metabolite, daidzein (DA), in human urine samples. PU and DA were separated on a packed capillary ODS column with on column concentration. Identification and quantification of the analytes were performed with ESI‐Q‐TOF mass spectroscopy in negative ionization mode. The method was validated, yielding calibration curves with correlation coefficients greater than 0.998. The LOQ for PU and DA from human urine samples was 0.1 and 0.05 nmol/mL, respectively. Assay accuracy and precision of quality control samples were within ±15%. Recoveries of PU and DA in spiked samples were in the range of 79.6–90.4 and 82.3–92.4%, respectively.
Analysis of nuclear proteome in C57 mouse liver tissue by a nano‐flow 2‐D‐LC–ESI‐MS/MS approach
Authors: Zhang Jie , Xu Xiuqing , Shen Huali , Zhang Xiangmin
Published: October 2006

The analysis of whole cell or tissue extracts is too complex for current protein identification technology and not suitable for the study of proteins with low copy levels. To concentrate and enrich low abundance proteins, organelle proteomics is a promising strategy. This approach can not only reduce the protein sample complexity but also provide information about protein location in cells, organs, or tissues under analysis. Nano‐flow two‐dimensional strong‐cation exchange chromatography (SCX)–RPLC–ESI‐MS/MS is an ideal platform for analyzing organelle extracts because of its advantages of sample non‐bias, low amounts of sample required, powerful separation capability, and high detection sensitivity. In this study, we apply nano‐scale multidimensional protein identification technology to the analysis of C57 mouse liver nuclear proteins. Organelle isolation has been optimized to obtain highly pure nuclei. Evaluation of nucleus integrity and purity has been performed to demonstrate the effectiveness of the optimized isolation procedure. The extracted nuclear proteins were identified by five independent nano‐flow on‐line SCX–RPLC–ESI‐MS/MS analyses to improve the proteome coverage. Finally, a total of 462 proteins were identified. Corresponding analyses of protein molecular mass and pI distribution and biological function categorization have been undertaken to further validate our identification strategy.
Quality evaluation of Ganoderma through simultaneous determination of nine triterpenes and sterols using pressurized liquid extraction and high performance liquid chromatography
Authors: Zhao Jing , Zhang Xiao‐Qi , Li Shao‐Ping , Yang Feng‐Qing , Wang Yi‐Tao , Ye Wen‐Cai
Published: October 2006

A method combining HPLC and pressurized liquid extraction was developed for simultaneous quantification of nine components, including eight triterpenes (ganoderic acid A, ganoderic acid Y, ganoderic acid DM, ganoderol A, ganoderol B, ganoderal A, methyl ganoderate D and ganoderate G) and a sterol (ergosterol), in Ganoderma. The determination was achieved by using a Zorbax ODS C18 analytical column (4.6×250 mm id, 5 μm) and gradient elution with diode‐array detection. All calibration curves showed good linearity (r2 >0.9997) within the test ranges. The developed method showed good repeatability for the quantification of the nine investigated components in Ganoderma with intra‐ and inter‐day variations of less than 2.4% and 4.1%, respectively. The validated method was successfully applied to quantify the nine components in two species of Ganoderma, i. e. G. lucidum and G. sinense, used as Lingzhi in China. Furthermore, hierarchical clustering analysis based on the nine components in HPLC profiles from the tested 11 samples showed that chemical characteristics were significantly different between G. lucidum and G. sinense, which suggested that clinical investigation should be performed so as to ensure the safety and efficacy of medication.
Front Cover: Macromol. Mater. Eng. 10/2006
Authors: Li Yongjin , Oono Yuko , Nakayama Kazuo , Shimizu Hiroshi
Published: October 2006

Front Cover: The picture on the cover shows TEM images of PVDF micro‐crystals dispersed in ACM matrix. It also shows the strain‐stress curves and strain recovery curves for the PVDF tiny crystal crosslinked acrylic rubber. Further details can be found in the article by Y. Li,* Y. Oono, K. Nakayama, and H. Shimizu on page 1201.
2D partially parallel imaging with k‐space surrounding neighbors‐based data reconstruction
Authors: Wang Ze , Fernández‐Seara María A.
Published: October 2006

Partially parallel imaging (PPI) achieves imaging acceleration by replacing partial phase encoding (PE) with the spatially localized sensitivity encoding of a receiver surface coil array. Further accelerations can be achieved through 2D PPI along two PE directions in 3D MRI. This paper is to explore the k‐space‐based PPI acquisition and reconstruction strategies for 3D MRI. A surrounding neighbors‐based autocalibrating PPI (SNAPPI) was first presented by generalizing the 2D multicolumn multiline interpolation method. Several 2D PPI reconstruction methods were then provided by applying SNAPPI to recover the partially skipped k‐space data along two PE directions separately or nonseparately, in k‐space or in the hybrid k and image space. An optimal 2D PPI sampling‐based reconstruction approach was also presented for applying PPI along certain spatial direction along which the array coil has not sufficient sensitivity variation for a valid PPI reconstruction. Both simulated and in vivo 2D PPI data were used to evaluate the proposed methods. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Synthesis and characterization of polyurethane microspheres and their application for immobilization of maltogenase
Authors: Budriene Saulute , Romaskevic Tatjana , Pielichowski Krzysztof , Pielichowski Jan
Published: October 2006

A series of polyurethane (PU) microspheres, based on 4,4′‐diphenylmethane diisocyanate and 1,4‐butanediol or a mixture of 1,4‐butanediol and polyether glycol (M = 1400) were synthesized by a one‐step method. The obtained PU microspheres were characterized by infrared spectroscopy, polarizing optical microscopy and dynamic thermogravimetry. Morphology studies of PU microspheres revealed that the material consists of spherical particles with relatively narrow particle size distribution in the range 1–100 µm and preferably between 10 to 50 µm; the obtained polymers were thermally stable up to 533–573 K. Maltogenase from Bacillus stearothermophilus was immobilized onto PU microspheres, synthesized using different ratios of components. High yield (about 100%) and efficiency (over 100%) of immobilization were obtained. Copyright © 2006 John Wiley & Sons, Ltd.
Neuroblastoma presenting with dilated cardiomyopathy
Authors: Kato M. , Hirata S. , Kikuchi A. , Ogawa K. , Kishimoto H. , Hanada R.
Published: October 2006

We report an infant with neuroblastoma who presented with dilated cardiomyopathy. A 3‐month‐old girl presented with dilated cardiomyopathy diagnosed as stage III neuroblastoma. Since total resection was impossible, chemotherapy was started. Cardiomyopathy was normalized by improvement of neuroblastoma. The prompt improvement of cardiac function following treatment of neuroblastoma suggested that cardiomyopathy in this patient was caused by the increase in catecholamines secreted by neuroblastoma and that reduction in catecholamines by treatment of neuroblastoma led to improvement in the cardiomyopathy. Pediatr Blood Cancer 2008;50:391–392. © 2006 Wiley‐Liss, Inc.
Simultaneous determination of benzophenones and gentisein in hypericum annulatum moris by high‐performance liquid chromatography
Authors: Zheleva‐Dimitrova D. , Gevrenova R. , Nedialkov P. , Kitanov G.
Published: October 2006

The content of the benzophenones, hypericophenonoside, neoannulatophenonoside, annulatophenonoside, annulat‐ophenone, acetylannulatophenonoside and the xanthone derivative gentisein have been determined in aerial parts, leaves, flowers and stems of Hypericum annulatum Moris. Extraction of samples with methanol by magnetic stirring at room temperature allowed a good recovery of analytes (from 90.70% for gentisein to 103.81% for annulatophenonoside) and the precision of the entire procedure was <6.05%. The subsequent HPLC separation and quantification was achieved using a Hypersil ODS C18 column and UV detection at 290 nm. The mobile phase comprised methanol and 20 mm potassium dihydrogen phosphate (adjusted to a pH of 3.19 with o‐phosphoric acid), and gradient elution mode was applied. The detection limits were 0.03, 0.02 and 0.001 µg/mL for hypericophenonoside, acetylannulatophenonoside and gentisein, respectively. The total amounts of the phenolic compounds assayed ranged from 10.92 mg/g in stems to 82.86 mg/g in leaves. Hypericophenonoside was the dominant benzophenone present in the majority of the plant samples, being present in amounts between 7.54 ± 0.25 mg/g in stems and 64.22 ± 2.44 mg/g in leaves. Hypericophenonoside accounted for up to 77.50% of the components found in the leaves, whereas annulatophenonoside (6.29 ± 0.15 mg/g) and acetylannulatophenonoside (8.95 ± 0.09 mg/g) were detected in much lower quantities. In contrast to leaves, flowers showed a tendency towards higher contents of gentisein (9.35 ± 0.07 mg/g) and neoannulatophenonoside (4.72 ± 0.04 mg/g) than the other parts assayed. Copyright © 2006 John Wiley & Sons, Ltd.
Influence of age on the prescription of vitamin K antagonists in outpatients with permanent atrial fibrillation in France
Authors:   The FALSTAF Study Group
Published: October 2006

Purpose

The aim of the study was to describe the current rate and determinants of the prescription of antithrombotics in outpatients with permanent atrial fibrillation, with a pre‐specified emphasis on the influence of age on the prescription of vitamin K antagonists.

Methods

This was a prospective observational survey in France among 5893 consecutive outpatients with documented permanent atrial fibrillation being seen by 770 physicians from August to December 2002. We recruited physicians from two random lists of general practitioners and cardiologists, respectively, stratified according to their administrative region, from the list of all French private general practitioners and cardiologists.

Results

The mean age of patients was 75.8 years. Mean duration since diagnosis of atrial fibrillation was 5.0 years; 31.7% of patients had valvular heart disease and 60.3% hypertension. An antithrombotic was prescribed to 95.5% of patients at the time of consultation. The percentage of patients treated with vitamin K antagonists was 76.4%; it decreased from 86.0% in patients aged 60–70 years to 63.5% in patients aged 80 years or above. On multivariate analysis, high age was a significant predictor (p = 0.001) for the non‐prescription of vitamin K antagonists. In patients above 70 years currently receiving an antithrombotic, the probability of prescription of vitamin K antagonists decreased on average by 9.6% per year.

Conclusions

Vitamin K antagonists are administered to most outpatients with permanent atrial fibrillation at high thromboembolic risk seen by French physicians in private practice. However, their use decreases with age. Copyright © 2006 John Wiley & Sons, Ltd.
Structural analysis and prediction of protein mutant stability using distance and torsion potentials: Role of secondary structure and solvent accessibility
Authors: Parthiban Vijaya , Gromiha M. Michael , Hoppe Christian , Schomburg Dietmar
Published: October 2006

Analyzing the factors behind protein stability is a key research topic in molecular biology, and has direct implications on protein structure prediction and protein–protein interactions. We have analyzed protein stability upon point mutations using a distance‐dependant pair potential representing mainly through‐space interactions, and torsion angle potential representing mainly neighboring effects as a basic statistical mechanical setup for the analysis. The synergetic effect of accessible surface area and secondary structure preferences was used as a classifier for the potentials. In addition, short‐, medium‐, and long‐range interactions of the protein environment were also analyzed. Two datasets of point mutations were taken for the comparison of theoretically predicted stabilizing energy values with experimental ΔΔG and ΔΔGH2O from thermal and chemical denaturation experiments. These include 1538 and 1603 mutations, respectively, and contain 101 proteins that share a wide range of sequence identity. The resulting force fields were carefully evaluated with different statistical tests. Results show a maximum correlation of 0.87 with a standard error of 0.71 kcal/mol between predicted and measured ΔΔG values and a prediction accuracy of 85.3% (stabilizing or destabilizing) for all mutations together. A correlation of 0.77 (more than 80% prediction accuracy with a standard error of 0.95 kcal/mol) each for the test dataset of split‐sample validation and fivefold crossvalidation was obtained and a correlation of 0.70 (77.4% prediction accuracy with a standard error of 1.17 kcal/mol) was shown by the jackknife test. The same model was implemented, and the results were analyzed for mutations with ΔΔGH2O. A correlation of 0.78 (standard error 0.96 kcal/mol) was observed with a prediction efficiency of 84.65%. This model can be used for the future prediction of protein structural stability together with various experimental techniques. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Accurate Prediction of the Folding Rate for Two‐State Proteins Based on Amino Acid Sequences
Authors: Zhao Chunyan , Zhu Yu , Zhang Haixia , Liu Mancang , Fan Botao
Published: October 2006

One of the most important challenges in biology is to understand and simulate the folding behavior of some simple two‐state proteins. In this work, a large pool for descriptors of proteins was developed including amino acid descriptors, topological descriptors and charged partial surface area descriptors. A heuristic method was employed to select significant features. As a result, three descriptors, total contact distance, unfolding entropy change and total charge weighted partial negative surface area were chosen. Total contact distance was proved to be the most relevant factor controlling the folding behavior. Based on these descriptors, a support vector machine method was applied to build a predictive model. Comparing the statistical results of other works and methods, support vector machine method exhibited the best whole performance. Our results demonstrate that the native‐state topology is the major determinant for the folding rates of two‐state proteins and that the support vector machine method is a powerful tool to build a predictive model. In turn, the method and the knowledge can be used to develop in‐silico predictive models to simulate the folding process of proteins.
The molecular scanner in microscope mode
Authors: Luxembourg Stefan L. , Vaezaddeh Ali R. , Amstalden Erika R. , Zimmermann‐Ivol Catherine G. , Hochstrasser Denis F. , Heeren Ron M.A.
Published: October 2006

The combination of microscope mode matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) with protein identification methodology: the molecular scanner, was explored. The molecular scanner approach provides improvement of sensitivity of detection and identification of high‐mass proteins in microscope mode IMS. The methodology was tested on protein distributions obtained after separation by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS‐PAGE). High‐quality, high‐spatial‐resolution ion images were recorded on a TRIFT‐II ion microscope after gold coating of the MALDI sample preparation on the poly(vinylidenedifluoride) capture membranes. The sensitivity of the combined method is estimated to be 5 pmol. The minimum amount of sample consumed, needed for identification, was estimated to be better than 100 fmol. Software tools were developed to analyze the spectral data and to generate broad mass range and single molecular component microscope mode ion images and single mass‐to‐charge ratio microprobe mode images. Copyright © 2006 John Wiley & Sons, Ltd.
Biased odds ratios from dichotomization of age
Authors: Chen Henian , Cohen Patricia , Chen Sophie
Published: October 2006

Dichotomizing a continuous variable is known to result in the loss of information, lower statistical power, and lower reliability. In many epidemiological studies, age is a scaled (continuous) variable prior to statistical analyses; however, despite pleas from methodologists, researchers frequently dichotomize age in their data analysis without an appropriate rationale. Using simulated case–control data, we show that dichotomizing age generally will lead to a biased odds ratio (OR). When age was a confounder (potentially representing common causes of risks and outcomes), including age as a scaled variable (whether the age effect was linear or non‐linear in the logit), provided satisfactory control, whereas when age was categorized, the estimated risk factor effect was biased. We also demonstrate that the further the cutpoint is from the median age, the greater the increase in the OR; thus, in cases where age dichotomization is warranted, researchers are cautioned not to allow the size of the empirical OR to influence their choice of cutpoint. Recommendations are made for analysing age in epidemiological data and interpretation of empirical findings. Copyright © 2006 John Wiley & Sons, Ltd.
[11C]LBT‐999: A suitable radioligand for investigation of extra‐striatal dopamine transporter with PET
Authors: Saba Wadad , Valette Héric , Schöllhorn‐Peyronneau Marie‐Anne , Coulon Christine , Ottaviani Michele , Chalon Sylvie , Dolle Frédéric , Emond Patrick , Halldin Christer , Helfenbein Julie , Madelmont Jean‐Claude , Deloye Jean‐Bernard , Guilloteau Denis , Bottlaender Michel
Published: October 2006

A new tropane derivative, (E)‐N‐(4‐fluorobut‐2‐enyl)‐2β‐carbomethoxy‐3β‐(4′‐tolyl)nortropane (LBT‐999), was evaluated in baboons as a carbon‐11 radioligand for studies of the dopamine transporter (DAT) using positron emission tomography (PET). Brain uptake was high in the striatum (17 and 13% ID/100 mL tissue in the putamen and the caudate, respectively), moderate in the midbrain and thalamus (5 and 3% ID/100 mL tissue, respectively), and low in the cortex and cerebellum (2% ID/100 mL tissue) at 30 min post injection. The striatum‐to‐cerebellum ratio was high (30 at 110 min post injection). Specific binding was completely blocked following pretreatment with the DAT antagonists GBR12909 (5 mg/kg i.v.) or PE2I (1 mg/kg i.v.). The [11C]LBT‐999 uptake was decreased by these antagonists in the putamen (−79 and −92%, respectively), caudate (−80 and −91%, respectively), midbrain (−73 and −78%, respectively), and thalamus (−34 and −46%, respectively). The serotonin transporter (SERT) antagonist citalopram (5 mg/kg i.v.) or the norepinephrine transporter antagonist maprotiline (5 mg/kg i.v.) had no effect on LBT specific binding. Pharmacological challenge with PE2I (1 mg/kg i.v.) induced a rapid and almost complete decrease of the specific binding in the putamen (−97%), caudate (−96%), midbrain (−96%), and thalamus (−81%), confirming the reversibility of [11C]LBT‐999 binding. The high brain uptake of [11C]LBT‐999 together with its low nonspecific binding (reflected by the very high brain structure‐to‐cerebellum ratio) indicate that this radiotracer is an excellent candidate for in vivo quantification of the DAT, especially in extrastriatal structures, such as the midbrain. Synapse 61:17–23, 2007. © 2006 Wiley‐Liss, Inc.
Programming effects of antenatal dexamethasone in the developing mesolimbic pathways
Authors: Leão P. , Sousa J.C. , Oliveira M. , Silva R. , Almeida O.F.X. , Sousa N.
Published: October 2006

Elevated glucocorticoids, during pregnancy, alter emotionality and increase propensity to drug abuse later in life, albeit through substrates and mechanisms are largely unknown. In this study, we examined whether antenatal glucocorticoid exposure induces enduring structural changes in the nucleus accumbens (NAcc), an important relay point in the reward limbic circuitry. To this end, rat dams were exposed to the synthetic glucocorticoid dexamethasone (DEX) on days 18 and 19 of gestation, and stereological tools were used to assess the total volume of, and neuronal numbers in, the NAcc, as well as the density of mesencephalic dopaminergic inputs from the ventral tegmental area (VTA) to the NAcc in their adult offspring. Further, we used measures of bromodeoxyuridine incorporation into NAcc cells to examine whether DEX‐induced effects on cell proliferation represent another mechanism through which glucocorticoids alter the structure of mesolimbic pathways and might influence addictive behavior. Our studies show that exposure to DEX during late gestation results in significantly reduced volumes and cell numbers in the NAcc. The latter measure correlated strongly with a reduced rate of cell proliferation in DEX‐exposed animals. Moreover, the treatment resulted in a decreased number of cells expressing tyrosine hydroxylase in the VTA and an impoverished dopaminergic innervation of the NAcc. These observations, which identify glucocorticoid‐sensitive structures and neurochemical targets within the developing “reward pathway,” pave way for future studies designed to understand how early life events can predispose individuals for developing drug dependence in adolescent and adult life. Synapse 61:40–49, 2007. © 2006 Wiley‐Liss, Inc.