bluuebunny/crossref_metadata_2025 huggingface dataset:
Intensively timed combination chemotherapy for the induction of adult patients with acute myeloid leukemia
Authors: Rytting Michael , Ravandi Farhad , Estey Elihu , Cortes Jorge , Faderl Stefan , Garcia‐Manero Guillermo , Jeha Sima , Ouzounian Souzanne , Pierce Sherry , Kantarjian Hagop
Published: July 2010

BACKGROUND:

Despite advances in therapy, the majority of adult patients diagnosed with acute myeloid leukemia (AML) develop disease recurrence and die of their disease. Early intensification of treatment for AML using timed sequential therapy (TST) has been proposed as a means of improving the survival outcome in children. The Children's Cancer Group demonstrated that children with AML who were randomized to receive 2 courses of daunorubicin, cytarabine, thioguanine, etoposide, and dexamethasone (the DCTER regimen) given 10 days apart had an improved event‐free survival (EFS) and disease‐free survival (DFS) (42% ± 7% and 55% ± 9%, respectively, at 2 years). Reports have suggested an improved outcome in adult patients with AML using TST (at the cost of increased toxicity). The current study was conducted to evaluate the feasibility and effectiveness of the intensively timed DCTER regimen for non‐core–binding factor AML in adult patients aged <50 years.

METHODS:

Between February 2004 and August 2005, 61 patients received this timed sequential induction regimen. Their outcomes were compared with matched historical patients treated with the combination of idarubicin and cytarabine (IA).

RESULTS:

The median follow‐up for surviving patients was 67 months (range, 35‐85 months). The timed sequential DCTER regimen had a lower complete remission (CR) rate when compared with the IA combination,, (71% vs 80%, respectively), but this appeared to be counterbalanced by a higher long‐term leukemia‐free survival rate using the intensified regimen (48% vs 30%, respectively) in patients who achieved a CR (P = .06).

CONCLUSIONS:

The intensively timed regimen of DCTER was found to induce durable remissions in adult patients with AML, including those patients with high‐risk disease. The identification of patients who would potentially benefit from such an intensive regimen may justify the higher early risk of early treatment failure that was found to accompany the intensified DCTER regimen in selected patients. Cancer 2010. © 2010 American Cancer Society.
TNM seventh edition: What's new, what's changed
Authors: Sobin Leslie H , Compton Carolyn C.
Published: July 2010

The seventh edition of the TNM Classification of Malignant Tumors contains several new and modified component classifications. The purpose of this communication was to briefly summarize these changes.
Evaluation of risk by patients' and with clinicians' ratings: A CORE‐OM and CORE‐A investigation
Authors: Bedford Alan , Lukic Goran , Tibbles Jennifer
Published: July 2010

While Whewell and Bonanno reported significant relationships between therapists' ratings of risk and patients' ratings of categorized Clinical Outcome in Routine Evaluation‐Outcome Measures (CORE‐OM) risk items, Rowsell and Stennett‐Cox found that only two non‐risk items of the total 34 CORE‐OM items correlated significantly with reported risk behaviours. The current study of 870 patients examined the intercorrelations of the CORE‐OM item matrix, including the 28 non‐risk items, and their correlations with the Risk domain items. Additionally, CORE‐Assessment clinicians' risk ratings were compared with the patients' risk self‐ratings. The results differed from the findings of Rowsell and Stennett‐Cox and provided validatory evidence supplementing that of Whewell and Bonanno. The Harm to Self items appeared to be of particular behavioural significance. Copyright © 2010 John Wiley & Sons, Ltd.

Key Practitioner Message:

• Clinicians' ratings of Suicide risk and Self‐harm were significantly related to patients' self‐ratings on the Harm to Self sub‐domain items.

• Clinicians' ratings of Risk to others were significantly related to patients' self‐ratings on the Harm to Others sub‐domain items.
Reactions of Amine– and Phosphane–Borane Adducts with Frustrated Lewis Pair Combinations of Group 14 Triflates and Sterically Hindered Nitrogen Bases
Authors: Whittell George R. , Balmond Edward I. , Robertson Alasdair P. M. , Patra Sanjib K. , Haddow Mairi F. , Manners Ian
Published: July 2010

The ability of trialkyl Group 14 triflates in combination with amine and pyridine bases to dehydrogenate amine– and phosphane–borane adducts has been investigated. By using multinuclear NMR spectroscopy, it has been shown that Me2NH·BH3 (11) is efficiently converted to [Me2N–BH2]2 (12) by the so‐called “frustrated Lewis pair” (FLP) of nBu3SnOTf (4, –OTf = –OSO2CF3) and 2,2,6,6‐tetramethylpiperidine (6). Within the scope of the study, exchange of the Lewis acid effects the rate of dehydrogenation in the order: 4 > Me3SiOTf (2) > Et3SiOTf (3). Exchange of the Lewis base for 2,6‐di‐tert‐butylpyridine (5) has also been shown to reduce the rate of reaction, whereas 1,3‐di‐tert‐butylimidazol‐2‐ylidene (7) reacted directly with 2 to afford 1,3‐bis‐tert‐butyl‐4‐(trimethylsilyl)imidazolium triflate (8[OTf]). For FLP combinations for which dehydrogenation reaction times are longer, detectable quantities of [H2B(μ‐H)(μ‐NMe2)BH2] (14) are observed. Both the dehydrogenation reaction and competitive formation of this product are proposed to proceed by initial hydride abstraction by the Lewis acid, followed by deprotonation by the Lewis base, or combination with further dimethylamine–borane and elimination of [Me2NH2]OTf (18[OTf]), respectively. In contrast to 11, MeNH2·BH3 (22) was not found to cleanly dehydrogenate to either [MeNH–BH2]3 or [MeN–BH]3 under the same conditions. An alternative reaction pathway was observed with either 2 or 4 and 6 with Ph2PH·BH3 (23), resulting in P‐silylation or P‐stannylation of the phosphane–borane, respectively.
Rapid identification of Candida albicans in blood by combined capillary electrophoresis and fluorescence in situ hybridization
Authors: Lantz Andrew W. , Bisha Bledar , Tong Man‐Yung , Nelson Ryan E. , Brehm‐Stecher Byron F. , Armstrong Daniel W.
Published: July 2010

A CE method based on whole‐cell molecular labeling via fluorescence in situ hybridization was developed for the detection of Candida albicans in whole blood. Removal of potentially interfering red blood cells (RBC) with a simple hypotonic/detergent lysis step enabled us to detect and quantitate contaminating C. albicans cells at concentrations that were orders of magnitude lower than background RBC counts (∼7.0×109 RBC/mL). In the presence of the lysed blood matrix, yeast cells aggregated without the use of a blocking plug to stack the cells. Short (15 min) hybridizations yielded bright Candida‐specific fluorescence in situ hybridization signals, enabling us to detect as few as a single injected cell. The peak area response of the stacked Candida cells showed a strong linear correlation with cell concentrations determined by plate counts, up to ∼107 CFU/mL (or ∼1×104 injected cells). This rapid and quantitative method for detecting Candida in blood may have advantageous applications in both human and veterinary diagnostics.
Evaluation and optimization of removal of an acid‐insoluble surfactant for shotgun analysis of membrane proteome
Authors: Lin Yong , Liu Yi , Li Jianjun , Zhao Yan , He Quanze , Han Wenjun , Chen Ping , Wang Xianchun , Liang Songping
Published: July 2010

Due to its compatibility with protease activity at high concentration, sodium deoxycholate (SDC) can be used to effectively improve the solubilization and enzymolysis of membrane proteins and has received increasing attention in the field of membrane proteome analysis in recent years. SDC can be removed from digests by means of acidification followed by centrifugation (i.e. acid precipitation, AP) or extraction with ethyl acetate (i.e. phase transfer, PT) so as not to interfere with the downstream analyses like LC‐MS/MS. In this study, the two strategies were systematically evaluated, compared and optimized. The results of the study demonstrated that both of the AP and PT strategies led to a certain amount of tryptic peptides being lost, and in PT strategy even more peptides were lost during SDC removal process. However, the lost peptides could be mostly recovered by washing the pellet and solid content produced during AP and PT, respectively. By recovering the lost peptides, the identification efficiency of proteins, especially transmembrane and low abundance ones, was significantly improved. Comparatively, after optimization by recovering the lost peptides, AP strategy was superior to PT strategy because the former not only could achieve the comparable identification efficiency with the latter but also was more economical, safer and easier to operate than the latter.
Determination of 4‐hydroxyproline‐2‐epimerase activity by capillary electrophoresis: A stereoselective platform for inhibitor screening of amino acid isomerases
Authors: Gavina Jennilee M. A. , White Catharine E. , Finan Turlough M. , Britz‐McKibbin Philip
Published: July 2010

Isomerases involved in the metabolism of D/L‐amino acids represent promising therapeutic targets for treatment of disease. Herein, we report a tunable platform for the assessment of enzymatic kinetics involving amino acid isomerization by CE that offers improved selectivity and sensitivity over traditional methods. Enzyme activity and competition assays were evaluated for various hydroxyproline diastereoisomers, proline enantiomers and their structural analogs using 4‐hydroxyproline‐2‐epimerase as a model system. In this work, pyrrole 2‐carboxylic acid was found to be a selective inhibitor of 4‐hydroxyproline‐2‐epimerase with a half‐maximal inhibition concentration of (2.3±0.1) mM. Reliable methods for unambiguous characterization of amino acid isomerases are required for the screening of novel inhibitors with epimerase and/or racemase activity.
Portable capillary electrophoresis system for identification of cattle breeds based on DNA mobility
Authors: Lee Miji , Cho Keunchang , Yoon Duhak , Yoo Dong Jin , Kang Seong Ho
Published: July 2010

A portable CE system was developed for the identification of cattle breeds. The system had a width of 44 cm, depth of 27 cm, height of 13 cm, and a weight of only ∼8 kg and included an LIF detector, with everything integrated into a small box. The specific sizes of genes were quickly separated and detected with a high sensitivity based on the difference in the DNA mobility using a diode‐pumped solid‐state LIF detector. Using this system, the 100‐bp DNA ladder was analyzed under a 1.0% PVP (Mr=300 000) sieving gel matrix in a fused silica capillary with LODs of 4.4–13.0 pg/μL (S/N=3) for 100–3000 bp DNAs, which indicates ten times improved value than other commercialized portable CE system. The migration times and the peak areas showed good reproducibilities with relative standard deviations that were less than 0.49 and 1.3% (n=5), respectively. Based on the difference in the DNA mobility of the microsatellite and SNP markers, Korean cattle and Holstein were exactly identified as the model cattle breeds within 32 and 3.5 min, respectively.
A microfluidic magnetic bead impact generator for physical stimulation of osteoblast cell
Authors: Song Suk‐Heung , Choi Jeongheon , Jung Hyo‐Il
Published: July 2010

We developed a novel microfluidic cell culture device in which magnetic beads repetitively collide with osteoblast cells, MC3T3‐E1, owing to attractive forces generated by pulsed electromagnetic fields and consequently the cells were physically stimulated by bead impacts. Our device consists of an on‐chip microelectromagnet and a microfluidic channel which were fabricated by a microelectromechanical system technique. The impact forces and stresses acting on a cell were numerically analyzed and experimentally generated with different sizes of bead (4.5, 7.6 and 8.4 μm) and at various pulse frequencies (60 Hz, 1 kHz and 1 MHz). Cells were synchronized at each specific phase of the cell cycle before stimulation in order to determine the most susceptible phase against bead impacts. The cells were stimulated with different sizes of bead at various pulse frequencies for 1 min at G1, S and G2 phases, respectively, and then counted immediately after one doubling time. The growth rate of cells was highly accelerated when they were stimulated with 4.5 μm beads at G1 phase and a pulse frequency of 1 MHz. Almost all of the cells were viable after stimulation, indicating that our cell stimulator did not cause any cellular damage and is suitable for use in new physical stimulus modalities.
Simultaneous determination of aripiprazole and its active metabolite, dehydroaripiprazole, in plasma by capillary electrophoresis combining on‐column field‐amplified sample injection and application in schizophrenia
Authors: Hwang Pei‐Lin , Wei Shao‐Yun , Yeh Hsin‐Hua , Ko Ju‐Yun , Chang Cheng‐Chen , Chen Su‐Hwei
Published: July 2010

A sensitive high‐performance CZE combining on‐column field‐amplified sample injection (FASI) has been developed for simultaneous determination of aripiprazole and its active metabolite, dehydroaripiprazole, in human plasma. A sample pretreatment by means of liquid–liquid extraction (LLE) (diethyl ether) with subsequent quantitation by FASI‐CZE was used. The separation of aripiprazole and dehydroaripiprazole was performed using a BGE containing 150 mM phosphate buffer (pH 3.5) with 40% methanol and 0.02% PVA as a dynamic coating to reduce interaction of analytes with the capillary wall. Before sample loading, a methanol plug (0.3 psi, 6 s) was injected to permit FASI for stacking. The samples were injected electrokinetically (10 kV, 30 s) to introduce sample cations and the applied voltage was 20 kV with on‐column detection at 214 nm. Several parameters affecting the separation and sensitivity of the drug and its active metabolite were studied, including reconstitution solvent, organic modifier, pH and concentration of phosphate buffer. The linear ranges of the method for test drug and its active metabolite, in plasma using amlodipine as an internal standard, were over the range 5.0–100.0 ng/mL. One female volunteer (25 years old) was orally administered a single dose of 10 mg aripiprazole (Abilify®, Otsuka) and blood samples were drawn over a 60 h period for pharmacokinetic study. The method was also applied to monitor the concentration of aripiprazole and dehydroaripiprazole in plasma collected after oral administration of 20 or 30 mg aripiprazole (Abilify®, Otsuka) daily at steady state in one schizophrenic patient.
A study on using wide‐flange section web under out‐of‐plane flexure for passive energy dissipation
Authors: Benavent‐Climent Amadeo , Morillas Leandro , Vico Juan M.
Published: July 2010

It is not common to purposely subject the web of wide‐flange or I‐sections to out‐of‐plane bending. However, yielding the web under this loading condition can be a stable source of energy dissipation as the transition at the corner from the web to the flanges is smooth and weld‐free; this prevents stress concentrations causing premature failure and eliminates uncertainties and imperfections associated with welding. Further, short segments of wide‐flange or I‐sections constitute a simple and inexpensive energy dissipating device as minimum manufacturing is required and leftovers not useful for other structural purposes can be re‐utilized. This paper proposes a new type of seismic damper in the form of braces based on yielding the web of short length segments of wide‐flange or I‐shaped steel sections under out‐of‐plane bending. The hysteretic behavior and ultimate energy dissipation capacity is investigated via component tests under cyclic loads. The experimental results indicate that the damping device has stable restoring force characteristics and a high energy dissipation capacity. Based on these results, a simple hysteretic model for predicting the load–displacement curve of the seismic damper is proposed, along with a procedure for predicting its ultimate energy dissipation capacity and anticipating its failure under arbitrarily applied cyclic loads. The procedure considers the influence of the loading path on the ultimate energy dissipation capacity. Finally, shaking table tests on half‐scale structures are conducted to further verify the feasibility and effectiveness of the new damper, and to assess the accuracy of the hysteretic model and the procedure for predicting its failure. Copyright © 2010 John Wiley & Sons, Ltd.
Spatial characterization of salt accumulation in early stage limestone weathering using probe permeametry
Authors: Buj O. , Gisbert J. , McKinley J. M. , Smith B.
Published: July 2010

This research characterizes the weathering of natural building stone using an unsteady‐state portable probe permeameter. Variations between the permeability properties of fresh rock and the same rocks after the early stages of a salt weathering simulation are used to examine the effects of salt accumulation on spatial variations in surface rock permeability properties in two limestones from Spain. The Fraga and Tudela limestones are from the Ebro basin and are of Miocene age. Both stone types figure largely in the architectural heritage of Spain and, in common with many other building limestones, they are prone to physical damage from salt crystallization in pore spaces. To examine feedbacks associated with salt accumulation during the early stages of this weathering process, samples of the two stone types were subjected to simulated salt weathering under laboratory conditions using magnesium sulphate and sodium chloride at concentrations of 5% and 15%. Permeability mapping and statistical analysis (aspatial statistics and spatial prediction) before and after salt accumulation are used to assess changes in the spatial variability of permeability and to correlate these changes with salt movement, porosity change, potential rock deterioration and textural characteristics. Statistical analyses of small‐scale permeability measurements are used to evaluate the drivers for decay and hence aid the prediction of the weathering behaviour of the two limestones. Copyright © 2010 John Wiley & Sons, Ltd.
Optimization of operating conditions of Tunisian myrtle (Myrtus communis L.) essential oil extraction by a hydrodistillation process using a 24 complete factorial design
Authors: Ammar Ahlem Haj , Zagrouba Fethi , Romdhane Mehrez
Published: July 2010

A 24 complete factorial design has been used to study the technological parameters that are responsible for the hydrodistillation process. After an appropriate choice of four critical variables, 16 experiments led to a mathematical model as a first degree polynomial presenting the response function (yield) in relation to the operating parameters. From the retained model, we were able to calculate the average response, the different effects and their interactions. The results showed that processing time, condensation flow and mass ratio plant material:water had significant effects (in absolute values) on myrtle essential oil yield (0.0350, −0.0421 and −0.0416, respectively), whereas granulometry presented a negligible effect (about −0.0084). The average essential oil yield extracted from 100 g myrtle leaves is 0.635%. Our study proved that experimental design methodology could efficiently be applied to characterize the analytical parameters affecting the hydrodistillation process and that it is an economical way of obtaining the maximum amount of information in a short period of time and with the smallest number of experiments. Copyright © 2010 John Wiley & Sons, Ltd.
An efficient implicit mesh‐less method for compressible flow calculations
Authors: Hashemi M. Y. , Jahangirian A.
Published: July 2010

A dual‐time implicit mesh‐less scheme is presented for calculation of compressible inviscid flow equations. The Taylor series least‐square method is used for approximation of spatial derivatives at each node which leads to a central difference discretization. Several convergence acceleration techniques such as local time stepping, enthalpy damping and residual smoothing are adopted in this approach. The capabilities of the method are demonstrated by flow computations around single and multi‐element airfoils at subsonic, transonic and supersonic flow conditions. Results are presented which indicate good agreements with other reliable finite‐volume results. The computational time is considerably reduced when using the proposed mesh‐less method compared with the explicit mesh‐less and finite‐volume schemes using the same point distributions. Copyright © 2010 John Wiley & Sons, Ltd.
A home‐delivered intervention for depressed, cognitively impaired, disabled elders
Authors: Kiosses Dimitris N. , Teri Linda , Velligan Dawn I. , Alexopoulos George S.
Published: July 2010

Objective

Problem Adaptation Therapy (PATH) is a new home‐delivered intervention designed to reduce depression and disability in depressed, cognitively impaired, disabled elders. A new intervention is needed in this population as antidepressant treatment is effective in only a minority of these patients.

Methods

PATH focuses on the patient's ecosystem, which includes the patient, the caregiver, and the home environment, to address the needs of depressed, cognitively impaired, disabled elders. It builds on the therapeutic framework of Problem Solving Therapy (PST), which has been efficacious in decreasing depression and disability in cognitively intact depressed elders. To address the needs of depressed elders with advanced cognitive impairment, PATH incorporates environmental adaptations and invites caregiver participation.

Results

To illustrate the administration of PATH, two case studies with varying degrees of cognitive impairment and caregiver participation are presented. Both patients were administered 12 weeks of PATH at their home. At the end of treatment their depression and disability was significantly reduced.

Conclusions

PATH is a new home‐delivered intervention for depressed elders with cognitive impairment and disability focusing on reducing depression and disability by employing environmental adaptations and inviting caregiver participation. This intervention may provide a treatment alternative for a population with limited success of antidepressant treatment. Copyright © 2010 John Wiley & Sons, Ltd.
Neurogenic marker abnormalities in the hippocampus in dementia with Lewy bodies
Authors: Johnson Mary , Ekonomou Antigoni , Hobbs Carl , Ballard Clive G. , Perry Robert H. , Perry Elaine K.
Published: July 2010

Dementia with Lewy bodies (DLB) is associated with alpha synuclein pathology and slowly progressive dementia. Progenitor abnormalities have previously been reported in the subventricular zone (SVZ) adjacent to the lateral ventricle. To evaluate changes in neural stem cells and progenitors in the hippocampal neurogenic niche, immunohistochemistry (IHC) using the neural stem cell markers Musashi 1, nestin, proliferating cell nuclear antigen (PCNA), doublecortin, and glial fibrillary acidic protein (GFAP) were examined in age‐matched control and DLB groups. Staining was quantified in the hippocampal SVZ, subgranular layer (SGL) and ependymal cell layer (EPL). There was a significant loss in DLB of Musashi 1 (P < 0.01) in all areas, an increase in PCNA in hippocampal SVZ (P = 0.01) and SGL (P = 0.05), and an increase in doublecortin in the hippocampal SVZ (P = 0.04) and EPL (P = 0.02). This is the first report of the changes in neurogenic markers in the hippocampal SVZ and EPL in DLB and may offer the potential for understanding disease pathology and in the devising of treatment. ©2010 Wiley‐Liss, Inc.
Chronic restraint stress in adolescence differentially influences hypothalamic‐pituitary‐adrenal axis function and adult hippocampal neurogenesis in male and female rats
Authors: Barha Cindy K. , Brummelte Susanne , Lieblich Stephanie E. , Galea Liisa A.M.
Published: July 2010

Previous studies have shown a relationship between adversity in adolescence and health outcomes in adulthood in a sex‐specific manner. Adolescence is characterized by major changes in stress‐responsive regions of the brain, including the hippocampus, the site of ongoing neurogenesis throughout the lifespan. Prepubertal male and female rats exhibit different acute reactions to chronic stress compared to adults, but less is known about whether these stress‐induced changes persist into adulthood. Therefore, in this study, we investigated the effects of chronic, intermittent stress during adolescence on basal corticosterone levels, dentate gyrus (DG) volume, and neurogenesis in the hippocampus of adult male and female Sprague‐Dawley rats. Adolescent male and female rats were either restrained for 1 h every other day for 3 weeks from postnatal days (PDs) 30–52 at unpredictable times or left undisturbed. All rats received a single injection of bromodeoxyuridine (BrdU; 200 mg/kg) in adulthood on PD70 and were perfused 3 weeks later. Brains were processed for Ki67 (endogenous marker of cell proliferation) and BrdU (to estimate effects on cell survival). In addition, blood samples were taken during the restraint stress period and in adulthood. Results show that males and females exhibit different corticosterone responses to chronic stress during adolescence and that only adult female rats exposed to stress during adolescence show higher basal corticosterone levels compared to nonstressed controls. Furthermore, stressed females showed a reduced number of proliferating and surviving cells in the DG in adulthood compared to nonstressed same‐sex controls. The majority of BrdU‐labeled cells were co‐labeled with NeuN, an endogenous marker of mature neurons, indicating that neurogenesis was decreased in the DG of adult female rats that had undergone chronic restraint stress in adolescence. Although male rats were more responsive to the chronic stress as adolescents showing higher corticosterone levels and reduced body weight, as adults they showed a slight increase in cellsurvival and no effect of adolescent stress on basal corticosterone levels. These results suggest that stress during adolescence can have effects on hypothalamic‐pituitary‐adrenal axis function and hippocampus plasticity in adulthood, particularly in female rats. ©2010 Wiley‐Liss,Inc.
Increase in polysialyltransferase gene expression following LTP in adult rat dentate gyrus
Authors: Guiraudie‐Capraz G. , Chaillan F.A. , Truchet B. , Franc J.L. , Mourre C. , Roman F.S.
Published: July 2010

Neural cell adhesion molecule (NCAM) is frequently associated with polysialic acid (PSA), and its function is highly dependent on this polysialylation. PSA‐NCAM plays an important role in synaptic plasticity in the hippocampus. STX and PST are the enzymes responsible for NCAM polysialylation. We investigated whether unilateral long‐term potentiation (LTP) induction in vivo, in adult rat dentate gyrus (DG), triggered NCAM polysialylation by STX and PST produced in the hippocampus. We found that levels of STX and PST mRNA increased strongly since the early stage of hippocampal LTP and remained high during the maintenance of DG‐LTP for 4 h. This rapid increase in polysialyltransferase gene expression occurred in both the hippocampi, probably resulting from bilateral LTP induction by strong unilateral HFS. Thus, LTP triggers interhemispheric molecular changes in the hippocampal network. This study is the first to describe the effects of LTP induction and maintenance on polysialyltransferases in vivo. Our findings suggest that hippocampal synaptic remodeling requires NCAM polysialylation. ©2010 Wiley Periodicals, Inc.
Modelling heterogeneity and dynamics in the volatility of individual wages
Authors: Hospido L.
Published: July 2010

This paper presents a model for the heterogeneity and dynamics of the conditional mean and conditional variance of individual wages. A bias‐corrected likelihood approach, which reduces the estimation bias to a term of order 1/T2, is used for estimation and inference. The small‐sample performance of the proposed estimator is investigated in a Monte Carlo study. The simulation results show that the bias of the maximum likelihood estimator is substantially corrected for designs calibrated to the data used in the empirical analysis, drawn from the PSID. The empirical results show that it is important to account for individual unobserved heterogeneity and dynamics in the variance, and that the latter is driven by job mobility. The model also explains the non‐normality observed in log‐wage data. Copyright © 2010 John Wiley & Sons, Ltd.
Hydrogen peroxide regulates glucose‐regulated protein 78 expression via a cyclooxygenase‐2 dependent mechanism
Authors: Chen Ying‐ying , Zheng Ming‐zhi , Lv Ping‐ping , Hu Lin , Wang Lin‐lin , Shen Yue‐Liang
Published: July 2010

This study was designed to investigate the effect of hydrogen peroxide on the expression of endoplasmic reticulum stress marker glucose‐regulated protein 78 (GRP78) in endothelial cells and reveals the possible role of cyclooxygenase in this effect. The porcine endothelial cell line was cultured in 1640 medium. Western blot and immunocytochemistry were used to detect the expression of GRP78. The caspase‐12 activity was analyzed with the immune fluorescence method. The results showed that after the endothelial cells were incubated with 250 μM of hydrogen peroxide for 12 h, apoptosis increased, which was antagonized by the cyclooxygenase‐2 inhibitor nimesulide or the nonselective cyclooxygenase inhibitor aspirin, but not by the cyclooxygenase‐1 inhibitor piroxicam. The expression of GRP78 was induced in endothelial cells after exposure to hydrogen peroxide for 12 h. The overexpression of GRP78 was inhibited by nimesulide and aspirin, but not by piroxicam. There are no significant differences in caspase‐12 activity among all groups. The present study provides evidence that hydrogen peroxide induced GRP78 overexpression in endothelial cells by a mechanism involving cyclooxygenase‐2‐dependent pathway. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:279–285, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20336
Modification of the detrimental effect of TNF‐α on human endothelial progenitor cells by fasudil and Y27632
Authors: Balestrieri Maria Luisa , Giovane Alfonso , Milone Lara , Felice Francesca , Fiorito Carmela , Crudele Valeria , Esposito Annaclaudia , Rossiello Raffaele , Minucci Pellegrino Biagio , Farzati Bartolomeo , Servillo Luigi , Napoli Claudio
Published: July 2010

Exposure of human endothelial progenitor cells (EPCs) to tumor necrosis factor‐α (TNF‐α) reduced their number and biological activity. Yet, signal transduction events linked to TNF‐α action are still poorly understood. To address this issue, we examined the possible effect of fasudil and Y27632, two inhibitors of Rho kinase pathway, which is involved in endothelial dysfunction, atherosclerosis, and in‐ flammation. Results demonstrated that incubation with fasudil starting from 50 μM but not Y27632 determined a dose‐dependent improvement of EPC number during exposure to TNF‐α (P < 0.05 vs. TNF‐α alone). Analysis of the signal transduction pathway activated by TNF‐α revealed that the increased expression of p‐p38 was not significantly altered by fasudil. Instead, fasudil blocked the TNF‐α induced phosphorylation of Erk1/2 (P < 0.05 vs. TNF‐α) as well as the inhibitor of Erk1/2‐specific phosphorylated form, i.e., PD98059 (P < 0.05 vs. TNF‐α). These results were confirmed by analysis of these kinases by confocal microscopy. Finally, 2D‐DIGE and MALDI‐TOF/TOF analysis of EPCs treated with fasudil revealed increased expression levels of an actin‐related protein and an adenylyl cyclase associated protein and decreased expression levels of proteins related to radical scavenger and nucleotide metabolism. These findings suggest that fasudil positively affects EPC number and that other major signals might take part to this complex pathway. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:351–360, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20345
Proteomic analysis of urine in rats chronically exposed to fluoride
Authors: Kobayashi Claudia Ayumi Nakai , Leite Aline de Lima , Silva Thelma Lopes da , Santos Lucilene Delazari dos , Nogueira Fábio César Sousa , Santos Keity Souza , Oliveira Rodrigo Cardoso de , Palma Mario Sérgio , Domont Gilberto Barbosa , Buzalaf Marília Afonso Rabelo
Published: July 2010

Urine is an ideal source of materials to search for potential disease‐related biomarkers as it is produced by the affected tissues and can be easily obtained by noninvasive methods. 2‐DE‐based proteomic approach was used to better understand the molecular mechanisms of injury induced by fluoride (F−) and define potential biomarkers of dental fluorosis. Three groups of weanling male Wistar rats were treated with drinking water containing 0 (control), 5, or 50 ppm F− for 60 days (n = 15/group). During the experimental period, the animals were kept individually in metabolic cages, to analyze the water and food consumption, as well as fecal and urinary F− excretion. Urinary proteome profiles were examined using 2‐DE and Colloidal Coomassie Brilliant Blue staining. A dose‐response regarding F− intake and excretion was detected. Quantitative intensity analysis revealed 8, 11, and 8 significantly altered proteins between control vs. 5 ppm F−, control vs. 50 ppm F− and 5 ppm F− vs. 50 ppm F− groups, respectively. Two proteins regulated by androgens (androgen‐regulated 20‐KDa protein and α‐2μ‐globulin) and one related to detoxification (aflatoxin‐B1‐aldehyde‐reductase) were identified by MALDI‐TOF‐TOF MS/MS. Thus, proteomic analysis can help to better understand the mechanisms underlying F− toxicity, even in low doses. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:8–14 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20353
The odontogenic ameloblast‐associated protein (ODAM) cooperates with RUNX2 and modulates enamel mineralization via regulation of MMP‐20
Authors: Lee Hye‐Kyung , Lee Dong‐Seol , Ryoo Hyun‐Mo , Park Jong‐Tae , Park Su‐Jin , Bae Hyun‐Sook , Cho Moon‐Il , Park Joo‐Cheol
Published: July 2010

We have previously reported that the odontogenic ameloblast‐associated protein (ODAM) plays important roles in enamel mineralization through the regulation of matrix metalloproteinase‐20 (MMP‐20). However, the precise function of ODAM in MMP‐20 regulation remains largely unknown. The aim of the present study was to uncover the molecular mechanisms responsible for MMP‐20 regulation. The subcellular localization of ODAM varies in a stage‐specific fashion during ameloblast differentiation. During the secretory stage of amelogenesis ODAM was localized to both the nucleus and cytoplasm of ameloblasts. However, during the maturation stage of amelogenesis, ODAM was observed in the cytoplasm and at the interface between ameloblasts and the enamel layer, but not in the nucleus. Secreted ODAM was detected in the conditioned medium of ameloblast‐lineage cell line (ALC) from days 14 to 21, which coincided with the maturation stage of amelogenesis. Interestingly, the expression of Runx2 and nuclear ODAM correlated with MMP‐20 expression in ALC. We therefore examined whether ODAM cooperates with Runx2 to regulate MMP‐20 and modulate enamel mineralization. Increased expression of ODAM and Runx2 augmented MMP‐20 expression, and Runx2 expression enhanced expression of ODAM, although overexpression of ODAM did not influence Runx2 expression. Conversely, loss of Runx2 in ALC decreased ODAM expression, resulting in down‐regulation of MMP‐20 expression. Increased MMP‐20 expression accelerated amelogenin processing during enamel mineralization. Our data suggest that Runx2 regulates the expression of ODAM and that nuclear ODAM serves an important regulatory function in the mineralization of enamel through the regulation of MMP‐20 apart from a different, currently unidentified, function of extracellular ODAM. J. Cell. Biochem. 111: 755–767, 2010. © 2010 Wiley‐Liss, Inc.
Depolarization of the membrane potential by hyaluronan
Authors: Hagenfeld Daniel , Schulz Tobias , Ehling Petra , Budde Thomas , Schumacher Udo , Prehm Peter
Published: July 2010

The membrane potential is mainly maintained by the K+ concentration gradient across the cell membrane between the cytosol and the extracellular matrix. Here, we show that extracellular addition of high‐molecular weight hyaluronan depolarized the membrane potential of human fibroblasts, human embryonic kidney cells (HEK), and central nervous system neurons in a concentration‐dependent manner, whereas digestion of cell surface hyaluronan by hyaluronidase caused hyperpolarization. This effect could not be achieved by other glycosaminoglycans or hyaluronan oligosaccharides, chondroitin sulfate, and heparin which did not affect the membrane potential. Mixtures of high‐molecular weight hyaluronan and bovine serum albumin had a larger depolarization effect than expected as the sum of both individual components. The different behavior of high‐molecular weight hyaluronan versus hyaluronan oligosaccharides and other glycosaminoglycans can be explained by a Donnan effect combined with a steric exclusion of other molecules from the water solvated chains of high‐molecular weight hyaluronan. Depolarization of the plasma membrane by hyaluronan represents an additional pathway of signal transduction to the classical CD44 signal transduction pathway, which links the extracellular matrix to intracellular metabolism. J. Cell. Biochem. 111: 858–864, 2010. © 2010 Wiley‐Liss, Inc.
Effects of platelets on the protein expression in aortic segments: A proteomic approach
Authors: Modrego Javier , Moñux Guillermo , Mateos‐Cáceres Petra J. , Martínez‐López Isaac , Segura Antonio , Zamorano‐León José J. , Rodríguez‐Sierra Pablo , Serrano Javier , Macaya Carlos , López‐Farré Antonio J.
Published: July 2010

It is well known the effects of the vascular wall on platelet activity but little is known about the effects of platelets on the proteins expression in the vascular wall. We analyzed whether platelets may modify the protein expression in the vascular wall. We used an in vitro model coincubating human platelet rich plasma (PRP) with control and 10 ng/ml tumor necrosis factor‐α (TNF‐α)‐preincubated bovine aortic segments. 2DE, mass spectrometry and Western blot analysis were used to determine changes in the expression of proteins associated with the cytoskeleton and energetic metabolism in the aortic segments. In control healthy vascular wall, only the cytoskeleton‐related proteins expression was modified by PRP. However, when PRP was coincubated with TNF‐α pre‐stimulated aortic segments lesser number of cytoskeleton‐related proteins were modified. With respect to energetic metabolism, in control segments, PRP failed to modify any of the analyzed energetic‐related proteins. However, in TNF‐α‐preincubated segments the presence of PRP upexpressed glyceraldehyde‐3‐phosphate dehydrogenase. Moreover, by western blot experiments it was observed that in TNF‐α‐preincubated segments the expression of fructose 1,6‐bisphosphate aldolase was downregulated by platelets. However, no differences were found in the expression of triosephosphate isomerase and ATP synthase α‐chain. In addition, the activity of fructose 1,6‐bisphosphate aldolase and piruvate content was significantly reduced without modification on triosephosphate isomerase activity. In conclusion, the crosstalk between platelets and vascular wall is bidirectional and platelets regulated in the vascular wall the expression of proteins associated with the cytoskeleton and energetic metabolism, particularly in the healthy vascular wall. J. Cell. Biochem. 111: 889–898, 2010. © 2010 Wiley‐Liss, Inc.
Novel batch reactor design for the adsorption of arsenate on chitosan
Authors: Kwok Katrina C.M. , McKay Gordon
Published: July 2010

BACKGROUND: The sorption of arsenate, a poison of acute toxicity found in natural waters, onto chitosan, a biosorbent derived from waste seafood shells has been studied. A batch adsorber design model was developed to determine how much chitosan adsorbent is required to reduce the arsenate concentration in solutions to the WHO standard of 10 µg L−1.

RESULTS: A series of batch kinetic experiments has been carried out at different initial pH values. The initial arsenate sorption appears to be completed after 30 min, however, a steady reversible reaction takes place resulting in the desorption of arsenate over 48 h. These phenomena in the batch kinetic data have been correlated simultaneously using the newly developed pseudo‐first order reversible model. Two batch reactor design models have been developed and compared. The first model is a conventional approach based on the equilibrium isotherm capacity equation. A second batch adsorption reactor design is based on the principle of contacting time required, tmax, for the chitosan to achieve its maximum adsorption capacity, qmax. The practical outcome from the second batch adsorber model results in a saving in adsorbent mass per batch of approximately 39.4%, 96.2% and 92.3% chitosan adsorbent at pH conditions of 3.5, 4.0 and 5.0, respectively.

CONCLUSION: The adsorbent cost and handling costs are reduced in the second batch adsorber model. There is also a significant savings in the batch turnaround time required in the batch adsorber design when the design is based on the maximum adsorption capacity rather than the equilibrium adsorption capacity. Copyright © 2010 Society of Chemical Industry
Development of ambient sampling chemi/chemical ion source with dielectric barrier discharge
Authors: Chen Lee Chuin , Yu Zhan , Furuya Hiroko , Hashimoto Yutaka , Takekawa Kenichi , Suzuki Hiroaki , Ariyada Osamu , Hiraoka Kenzo
Published: July 2010

The development of a new configuration of chemical ionization (CI)‐based ion source is presented. The ambient air containing the gaseous sample is sniffed into an enclosed ionization chamber which is of sub‐ambient pressure, and is subsequently mixed with metastable species in front of the ion inlet of the mass spectrometer. Metastable helium atoms (He*) are used in this study as the primary ionizing agents and are generated from a dielectric barrier discharge (DBD) source. The DBD is powered by an AC high‐voltage supply and the configuration of the electrodes is in such a way that the generated plasma is confined within the discharge tube and is not extended into the ionization chamber. The construction of the ion source is simple, and volatile compounds released from the bulky sample can also be analyzed directly by approaching the sample to the sampling nozzle. When combined with heated nitrogen or other desorption methods, its application can also be extended to non‐volatile compounds, and the consumption for helium can be kept minimum solely for maintaining the stable discharge and gas phase ionization. Applications to non‐proximate sample analysis, direct determination of active ingredients in drug tablets and the detection of trace explosive such as hexamethylene triperoxide diamine are demonstrated. Copyright © 2010 John Wiley & Sons, Ltd.
Some critical aspects in the determination of binding constants by electrospray ionisation mass spectrometry at the example of arsenic bindings to sulphur‐containing biomolecules
Authors: Schmidt Anne‐Christine , Steier Sandra
Published: July 2010

The influences of reactant concentrations, solvent type, acid strength, pH conditions and ionic strength on the determination of apparent gas‐phase equilibrium constants K using electrospray ionisation mass spectrometry (ESI‐MS) were elucidated. As example serves the interaction of the tripeptide glutathione (GSH) with phenylarsine oxide (PAO). It was shown that rising initial concentrations of both reactants were not adequately compensated by increasing signal intensities of the reaction products in the mass spectra. The equilibrium constant for the formation of the phenylarsenic‐substituted peptide species decreased from 1.42 × 105 ± 1.81 × 104 l µmol−1 to 1.54 × 104 ± 1.5 × 103 l µmol−1 with rising initial GSH concentrations from 1 to 10 µM at fixed PAO molarity of 50 µM. K values resulting from a series with a fixed GSH molarity of 5 µM and a PAO molarity varied from 10 to 100 µM remained in a narrower range between 4.59 × 104 ± 2.15 × 104 l µmol−1 and 1.07 × 104 ± 4.0 × 103 l µmol−1. In contrast, consumption numbers calculated from the ion intensity ratios of reaction products to the unreacted peptide were not influenced by the initial reactant concentrations. In a water–acetonitrile–acetic acid mixture (48:50:2, v:v), the consumption of 5 µ M GSH increased from 8.3 ± 1.4% to 39.6 ± 1.6% with increased molar excess of PAO from 2 to 20, respectively. The GSH consumption was considerably enhanced in a changed solvent system consisting of 25% acetonitrile and 75% 10 mM ammonium formate, pH 5.0 (v:v) up to 80% of the original peptide amount at an only threefold molar arsenic excess. Copyright © 2010 John Wiley & Sons, Ltd.
Deimination stabilizes histone H2A/H2B dimers as revealed by electrospray ionization mass spectrometry
Authors: Shimoyama Shingo , Nagadoi Aritaka , Tachiwana Hiroaki , Yamada Michiyuki , Sato Mamoru , Kurumizaka Hitoshi , Nishimura Yoshifumi , Akashi Satoko
Published: July 2010

Post‐translational modifications of histones for reversibly changing chromosomal structures in promoter regions of genes are a prerequisite for transcriptional activation and repression of genes. Peptidylarginine deiminase 4 (PAD4), which mediates histone deimination by converting arginine residues into citrulline residues, is involved in the repression of gene transcription. However, the mechanism is still unclear. We studied the effects of deimination on the reconstituted histone H2A/H2B dimer structure by electrospray ionization mass spectrometry. Deimination of the H2A/H2B dimer by PAD4 indicated that the mass of H2A increased 2.7 Da, suggesting that two or three Arg residues of H2A were deiminated. Deimination of H2A monomer alone showed a 6.6‐Da increase in mass. This indicates that about four more Arg residues of H2A are modified in the monomer state than in the H2A/H2B dimer state. Taking account of the finding that the unstructured portions in proteins are susceptible to deimination by PAD4, it is likely that H2A in the monomer state has a more flexible structure than that in the dimer state. Furthermore, analysis of the association of the H2A/H2B dimer in 2 or 4 M ammonium acetate with nano‐electrospray ionization mass spectrometry showed that a modified H2A/H2B dimer was less dissociated into H2A and H2B monomers than an unmodified dimer when high voltages were applied to the sample cone. This study provides convincing evidence that PAD4 deimination stabilizes the histone H2A/H2B dimer. Copyright © 2010 John Wiley & Sons, Ltd.