bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of fetomaternal hemorrhage
Authors: Kim Yeowon A. , Makar Robert S.
Published: November 2011

The prevention of Rhesus D alloimmunization through Rh immune globulin (RhIg) administration is the major indication for the accurate detection and quantification of fetomaternal hemorrhage (FMH). In the setting of D incompatibility, D‐positive fetal cells can sensitize the D‐negative mother, resulting in maternal anti‐D alloantibody production. These anti‐D alloantibodies may lead to undesirable sequelae such as hemolytic disease of the newborn (HDN). Since the widespread adoption of FMH screening and RhIg immunoprophylaxis, the overall risk of Rh alloimmunization and infant mortality from HDN has substantially decreased. The rosette screen, the initial test of choice, is highly sensitive in qualitatively detecting 10 mL of fetal whole blood in the maternal circulation. As the screen is reliant on the presence of the D antigen to distinguish fetal from maternal cells, it cannot be used to detect FMH in D‐positive mothers or in D‐negative mothers carrying a D‐negative fetus. The Kleihauer‐Betke acid‐elution test, the most widely used confirmatory test for quantifying FMH, relies on the principle that fetal RBCs contain mostly fetal hemoglobin (HbF), which is resistant to acid‐elution whereas adult hemoglobin is acid‐sensitive. Although the Kleihauer‐Betke test is inexpensive and requires no special equipment, it lacks standardization and precision, and may not be accurate in conditions with elevated F‐cells. Anti‐HbF flow cytometry is a promising alternative, although its use is limited by equipment and staffing costs. Hematology analyzers with flow cytometry capabilities may be adapted for fetal cell detection, thus giving clinical laboratories a potentially attractive automated alternative for quantifying FMH. Am. J. Hematol., 2012. © 2011 Wiley Periodicals, Inc.
Otto Stern (1888–1969): The founding father of experimental atomic physics
Authors: Toennies J.P. , Schmidt‐Böcking H. , Friedrich B. , Lower J.C.A.
Published: November 2011

We review the work and life of Otto Stern who developed the molecular beam technique and with its aid laid the foundations of experimental atomic physics. Among the key results of his research are: the experimental test of the Maxwell‐Boltzmann distribution of molecular velocities (1920), experimental demonstration of space quantization of angular momentum (1922), diffraction of matter waves comprised of atoms and molecules by crystals (1931) and the determination of the magnetic dipole moments of the proton and deuteron (1933).
Bayesian hierarchical models to analyze customer satisfaction data for quality improvement: a case study
Authors: Gasparini Mauro , Pellerey Franco , Proietti Mauro
Published: November 2011

Customer satisfaction data collected by a large cellular phone service provider are to be used to evaluate and improve the quality of their service. For this purpose, we propose a Bayesian treatment of a joint‐response chain graph relating partial assessments of specific aspects of quality to an overall assessment of the service quality. The resulting Bayesian model can be used to render basic geographical and temporal differentiation, allowing the company to undertake direct corrective actions. Both normal and binary models are considered for our customer satisfaction data and are compared with other currently used methods in the study of customer satisfaction. Copyright © 2011 John Wiley & Sons, Ltd.
L1penalty and shrinkage estimation in partially linear models with random coefficient autoregressive errors
Authors: Fallahpour Saber , Ahmed S. Ejaz , Doksum Kjell A.
Published: November 2011

In partially linear models, we consider methodology for simultaneous model selection and parameter estimation with random coefficient autoregressive errors by using lasso and shrinkage strategies. We provide natural adaptive estimators that significantly improve upon the classical procedures in the situation where some of the predictors are nuisance variables that may or may not affect the association between the response and the main predictors. In the context of two competing partially linear regression models (full and submodels), we consider an adaptive shrinkage estimation strategy and propose the shrinkage estimator and the positive‐rule shrinkage estimator. We develop the properties of these estimators by using the notion of asymptotic distributional risk. The shrinkage estimators are shown to have a higher efficiency than the classical estimators for a wide class of models. For the lasso‐type estimation strategy, we devise efficient algorithms to obtain numerical results. We compare the relative performance of lasso with the shrinkage estimator and the other estimators. Monte Carlo simulation experiments are conducted for various combinations of the nuisance parameters and sample size, and the performance of each method is evaluated in terms of simulated mean squared error. The comparison reveals that lasso and shrinkage strategies outperform the classical procedure. The relative performance of lasso and shrinkage strategies is comparable. The shrinkage estimators perform better than the lasso strategy in the effective part of the parameter space when, and only when, there are many nuisance variables in the model. A data example is showcased to illustrate the usefulness of suggested methods. Copyright © 2011 John Wiley & Sons, Ltd.
Epoxyquinone Formation Catalyzed by a Two‐Component Flavin‐Dependent Monooxygenase Involved in Biosynthesis of the Antibiotic Actinorhodin
Authors: Taguchi Takaaki , Okamoto Susumu , Hasegawa Kimiko , Ichinose Koji
Published: November 2011

The biosynthetic gene cluster of the aromatic polyketide antibiotic actinorhodin (ACT) in Streptomyces coelicolor A3(2) carries a pair of genes, actVA‐ORF5 and actVB, that encode a two‐component flavin‐dependent monooxygenase (FMO). Our previous studies have demonstrated that the ActVA‐ORF5/ActVB system functions as a quinone‐forming C‐6 oxygenase in ACT biosynthesis. Furthermore, we found that this enzyme system exhibits an additional oxygenation activity with dihydrokalafungin (DHK), a proposed intermediate in the ACT biosynthetic pathway, and generates two reaction products. These compounds were revealed to be monooxygenated derivatives of kalafungin, which is spontaneously formed through oxidative lactonization of DHK. Their absolute structures were elucidated from their NMR spectroscopic data and by computer modeling and X‐ray crystallography as (5S,14R)‐epoxykalafungin and (5R,14S)‐epoxykalafungin, demonstrating an additional epoxyquinone‐forming activity of the ActVA‐ORF5/ActVB system in vitro.
Cardiac decellularisation with long‐term storage and repopulation with canine peripheral blood progenitor cells
Authors: Crawford Bredon , Koshy Sandeep Tharian , Jhamb Geeta , Woodford Curtis , Thompson Chistine M. , Levy Andrew S. , Rush Jim W. E. , Guillemette J. Guy , Lillicrap David , Jervis Eric
Published: November 2011

Perfusion decellularisation is a promising technique in scaffold production for tissue engineering. The similarity of decellularised extracellular matrix to native matrix is attractive for the development of compatible and functional constructs for therapeutic applications. Here, whole organs were processed for tissue culture with an emphasis on production staging. Adult rat hearts were perfusion‐decellularised on a modified chromatography system that facilitated the study of flow properties and effluent material to better understand the transport processes of decellularisation. Tracer pulse experiments confirmed gross integrity of the ECM, and suggested the accumulation of debris in tissue lumen at late decellularisation. The rate of protein loss matched visual indications of decellularisation, slowing to zero as the tissue achieved a uniform appearance. Decellularised hearts were cryopreserved for up to 1 year before reconditioning including disinfection and soluble protein perfusion to remove adsorbed detergents. Canine blood outgrowth endothelial cells were seeded and cultured in a novel recellularisation apparatus with bubble‐free aeration. After 9 days of culture, cells seeded in the lumen remained viable and exhibited well‐attached morphology. This work presents approaches for the process analysis and non‐destructive evaluation of decellularising tissue and demonstrates that cells may be successfully cultured on whole decellularised organs following long‐term storage. © 2011 Canadian Society for Chemical Engineering
Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation
Authors: Perez Rodrigo Oliva , Habr‐Gama Angelita , Gama‐Rodrigues Joaquim , Proscurshim Igor , Julião Guilherme Pagin São , Lynn Patricio , Ono Carla Rachel , Campos Fabio Guilherme , Silva e Sousa Afonso Henrique , Imperiale Antonio Rocco , Nahas Sergio Carlos , Buchpiguel Carlos Alberto
Published: November 2011

BACKGROUND:

Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies.

METHODS:

Patients with clinical T2 (cT2) through cT4NxM0 rectal adenocarcinoma were included prospectively. Neoadjuvant therapy consisted of 54 grays of radiation and 5‐fluorouracil‐based chemotherapy. Baseline PET/CT studies were obtained before CRT followed by PET/CT studies at 6 weeks and 12 weeks after the completion of CRT. Clinical assessment was performed at 12 weeks after CRT completion. PET/CT results were compared with clinical and pathologic data.

RESULTS:

In total, 99 patients were included in the study. Twenty‐three patients were complete responders (16 had a complete clinical response, and 7 had a complete pathologic response). The PET/CT response evaluation at 12 weeks indicated that 18 patients had a complete response, and 81 patients had an incomplete response. There were 5 false‐negative and 10 false‐positive PET/CT results. PET/CT for the detection of residual cancer had 93% sensitivity, 53% specificity, a 73% negative predictive value, an 87% positive predictive value, and 85% accuracy. Clinical assessment alone resulted in an accuracy of 91%. PET/CT information may have detected misdiagnoses made by clinical assessment alone, improving overall accuracy to 96%.

CONCLUSIONS:

Assessment of tumor response at 12 weeks after CRT completion with PET/CT imaging may provide a useful additional tool with good overall accuracy for the selection of patients who may avoid unnecessary radical resection after achieving a complete clinical response. Cancer 2012;3501–3511. © 2011 American Cancer Society.
Durable remission with salvage second autotransplants in patients with multiple myeloma
Authors: Shah Nina , Ahmed Fraz , Bashir Qaiser , Qureshi Sofia , Dinh Yvonne , Rondon Gabriela , Wen Sijin , Thall Peter , Khan Hassan , Giralt Sergio , Champlin Richard , Qazilbash Muzaffar H.
Published: November 2011

BACKGROUND:

High‐dose chemotherapy with autologous hematopoietic cell transplant (auto‐HCT) has been shown to improve survival in patients with newly diagnosed multiple myeloma. However, the role of salvage auto‐HCT for relapsed patients, particularly in the era of novel therapeutics, is not well defined.

METHODS:

The authors performed a retrospective analysis of all 44 myeloma patients (24 men, 20 women) who received a second auto‐HCT as salvage between January 3, 1992 and November 4, 2008 at The University of Texas MD Anderson Cancer Center.

RESULTS:

Median interval between the first and salvage auto‐HCT was 30 months (range, 2‐78 months). Median age at salvage HCT was 54 years (range, 38‐73 years), and median number of salvage treatment regimens was 2 (range, 0‐5). Eleven (25%) patients had high‐risk chromosomal abnormalities on conventional cytogenetic studies between diagnosis and salvage auto‐HCT. Ten patients (23%) experienced grade 3 or higher nonhematologic toxicity after the salvage auto‐HCT. One patient died within 100 days, for a treatment‐related mortality of 2%. Best responses after salvage chemotherapy + salvage auto‐HCT were as follows: complete response (CR) + near CR, 11%; partial response, 79%; overall response rate, 90%. Eighteen (41%) patients received post auto‐HCT maintenance therapy. Median follow‐up from salvage HCT was 41 months. Kaplan‐Meier estimates of median progression‐free survival (PFS) and overall survival (OS) from time of salvage auto‐HCT were 12.3 and 31.7 months, respectively. Median OS from the time of diagnosis was 75 months. In a fitted Bayesian multivariate model, shorter time to progression after first auto‐HCT, greater number of prior therapies, African American race, and immunoglobulin G subtype were significantly associated with worse OS.

CONCLUSIONS:

In selected myeloma patients, a second auto‐HCT for salvage therapy is well tolerated, with acceptable toxicity. The overall response rate and PFS are comparable to other salvage regimens. Cancer 2012;3549–3555. © 2011 American Cancer Society.
Comparative analyses of overall survival in patients with anaplastic lymphoma kinase‐positive and matched wild‐type advanced nonsmall cell lung cancer
Authors: Lee June Koo , Park Heae Surng , Kim Dong‐Wan , Kulig Kimary , Kim Tae Min , Lee Se‐Hoon , Jeon Yoon‐Kyung , Chung Doo Hyun , Heo Dae Seog , Kim Woo‐Ho , Bang Yung‐Jue
Published: November 2011

BACKGROUND:

The purpose of this study was to investigate the overall survival (OS) of patients with advanced ALK‐positive nonsmall cell lung cancer (NSCLC) who were managed in the pre‐ALK inhibitor era and to compare their survival with that of a matched case cohort of ALK wild‐type (WT) patients.

METHODS:

Data from 1166 patients who had stage IIIB/IV NSCLC with nonsquamous histology were collected from the NSCLC database of Seoul National University Hospital between 2003 and 2009. ALK fluorescence in situ hybridization (FISH) was used to analyze 262 patients who either had the WT epidermal growth factor receptor (EGFR) or were nonresponders to previous EGFR tyrosine kinase inhibitor (TKI) therapy. Overall survival (OS) was compared between 3 groups: 1) ALK‐positive patients, 2) EGFR mutation‐positive patients, and 3) ALK‐WT/EGFR‐WT patients. Progression‐free survival (PFS) after first‐line chemotherapy and EGFR TKIs also was analyzed.

RESULTS:

Twenty‐three patients were ALK‐positive according to FISH analysis and did not receive ALK inhibitors during follow‐up. The median OS for ALK‐positive patients, EGFR mutation‐positive patients, and WT/WT patients was 12.2 months, 29.6 months, and 19.3 months, respectively (vs EGFR mutation‐positive patients, P = .001; vs WT/WT, P = .127). The PFS after first‐line chemotherapy for the 3 groups was not different. However, the PFS for patients who received EGFR TKIs was shorter in ALK‐positive patients compared with the other 2 groups (vs EGFR mutation‐positive patients, P < .001; vs WT/WT, P < .021).

CONCLUSIONS:

In the pre‐ALK inhibitor era, ALK‐positive patients experienced the shortest survival, although it did not differ statistically from that of WT/WT patients. Although their responses to platinum‐based chemotherapy were not different from comparator groups, ALK‐positive patients were even more resistant to EGFR TKI treatment than WT/WT patients. Cancer 2012;3579–3586. © 2011 American Cancer Society.
Polarity proteins are required for left–right axis orientation and twin–twin instruction
Authors: Vandenberg Laura N. , Levin Michael
Published: November 2011

Two main classes of models address the earliest steps of left–right patterning: those postulating that asymmetry is initiated via cilia‐driven fluid flow in a multicellular tissue at gastrulation, and those postulating that asymmetry is amplified from intrinsic chirality of individual cells at very early embryonic stages. A recent study revealed that cultured human cells have consistent left–right (LR) biases that are dependent on apical‐basal polarity machinery. The ability of single cells to set up asymmetry suggests that cellular chirality could be converted to embryonic laterality by cilia‐independent polarity mechanisms in cell fields. To examine the link between cellular polarity and LR patterning in a vertebrate model organism, we probed the roles of apical‐basal and planar polarity proteins in the orientation of the LR axis in Xenopus. Molecular loss‐of‐function targeting these polarity pathways specifically randomizes organ situs independently of contribution to the ciliated organ. Alterations in cell polarity also disrupt tight junction integrity, localization of the LR signaling molecule serotonin, the normally left‐sided expression of Xnr‐1, and the LR instruction occurring between native and ectopic organizers. We propose that well‐conserved polarity complexes are required for LR asymmetry and that cell polarity signals establish the flow of laterality information across the early blastoderm independently of later ciliary functions. genesis 50:219–234, 2012. © 2011 Wiley Periodicals, Inc.
Lipids accumulation in Rhodotorula glutinis and Cryptococcus curvatus growing on distillery wastewater as culture medium
Authors: Gonzalez‐Garcia Yolanda , Hernandez Rafael , Zhang Gouchang , Escalante Froylan M.E. , Holmes William , French W. Todd
Published: November 2011

Oleaginous yeasts R. glutinis and C. curvatus were grown in batch culture on high strength distillery wastewaters from the Tequila production process (Tequila's vinasses). Both strains were able to grow either on decolorized charcoal or on naturally colored regular vinasses, with no extra nutrients addition. After 144 h of culture, lipids were accumulated up to 25.2 ± 1.98 and 27.02 ± 2.36% of cell dry weight, in C. curvatus and R. glutinis, respectively. At the same time, the chemical oxygen demand of vinasses (23,125 ± 5,557) was removed by C. curvatus and R. glutinis up to 78.98 ± 1.38 and 84.44 ± 3.52%, respectively. The fatty acid profile of the lipids accumulated by both strains was composed by myristic, palmitic, stearic, oleic, and linoleic. Linolenic acid was also found but only in the intracellular lipids of R. glutinis. This is the first report of the utilization of Tequila's vinasses for the production of microbial oil by oleaginous yeast. This process could become a strategy to transform this highly contaminant wastewater into value added lipids. © 2011 American Institute of Chemical Engineers Environ Prog, 32: 69–74, 2013.
Digital automatic voltage regulator for synchronous generator considering sensor failure
Authors: Li Weilin , Li Huimin , Ni Fei , Zhang Xiaobin , Monti Antonello
Published: November 2011

In this paper, digital signal processor (DSP) based automatic voltage regulator (AVR) for synchronous generator is proposed. The control performance of AVR is guaranteed to be more reliable by the application of measurement validation method based on Polynomial Chaos Theory. Analysis and development of the proposed regulator is done by both computer simulations and DSP implementation. A hardware platform of the AVR, which consists of two DSPs as the microprocessor is set up, one DSP is used for calculation of the sampled data and sensor validation, the other is used for control algorithm application. Several other methods have also been adopted in the configuration of the hardware for a better dynamic performance. Steady state and dynamic control performance of the regulator are investigated on different working conditions (such as voltage establishment, load connection, and sensor failure). Experimental results show good consistency to the theoretical analysis. Copyright © 2011 John Wiley & Sons, Ltd.
Patellar tilt correlates with vastus lateralis: Vastus medialis activation ratio in maltracking patellofemoral pain patients
Authors: Pal Saikat , Besier Thor F. , Draper Christine E. , Fredericson Michael , Gold Garry E. , Beaupre Gary S. , Delp Scott L.
Published: November 2011

Patellofemoral (PF) pain is a common ailment of the lower extremity. A theorized cause for pain is patellar maltracking due to vasti muscle activation imbalance, represented as large vastus lateralis:vastus medialis (VL:VM) activation ratios. However, evidence relating vasti muscle activation imbalance to patellar maltracking is limited. The purpose of this study was to investigate the relationship between VL:VM activation ratio and patellar tracking measures, patellar tilt and bisect offset, in PF pain subjects and pain‐free controls. We evaluated VL:VM activation ratio and VM activation delay relative to VL activation in 39 PF pain subjects and 15 pain‐free controls during walking. We classified the PF pain subjects into normal tracking and maltracking groups based on patellar tilt and bisect offset measured from weight‐bearing magnetic resonance imaging. Patellar tilt correlated with VL:VM activation ratio only in PF pain subjects classified as maltrackers. This suggests that a clinical intervention targeting vasti muscle activation imbalance may be effective only in PF pain subjects classified as maltrackers. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:927–933, 2012
The first spectroscopic analysis of Ethiopian prehistoric rock painting
Authors: Lofrumento Cristiana , Ricci Marilena , Bachechi Luca , De Feo Denise , Castellucci Emilio Mario
Published: November 2011

An extensive micro‐Raman spectroscopic study of prehistoric rock paintings found in Hararghe region, Ethiopia, was carried out, with the aim to evaluate the production skill of the local artist and the period of production of the discovered paintings. Attenuated Total Reflection Fourier Transform Infrared (ATR‐FTIR) Spectroscopy and Laser Induced Breakdown Spectroscopy (LIBS) were used as auxiliary techniques. Micro sampling were carried out on parts of red, white, black painting figures representing domestic and wild animals. The pigments used by artists were hematite for red color, calcite or gypsum for white color, and carbonaceous material for black coloration. A green pigment was also investigated; it resulted made of green earth. A consistent amount of Ca‐oxalate was found particularly on red samples as well as on the white ones. Former studies attributed oxalates origin to a biological substrate attack, whereas in the present case Ca‐oxalate is ascribed to the use of an organic stuff to spread properly the pigments on the substrate.Principal Component Analysis was performed on the hematite spectra; it evinced that the spectral features could be indicative of different sites and of the relative age.1These novel evaluations put into new perspective the knowledge about rock art pictorial technology of the Horn of Africa. Copyright © 2011 John Wiley & Sons, Ltd.
Two‐dimensional LC‐MS fractioning and cross‐matching of mass spectrometric data for rational identification of bioactive compounds in crude extracts
Authors: Klinkenberg Geir , Sletta Håvard , Fjærvik Espen , Zahlsen Kolbjørn , Bruheim Per
Published: November 2011

Bioprospecting aims at the identification of biological compounds with novel properties. Identification of such compounds in crude complex biological extracts is a comprehensive challenge. As a large number of extracts must be screened for successful identification of one potential promising lead, rational screening strategies must be developed. Here we report on a novel two stage rational LC‐MS strategy of extracts already pre‐screened and proven to contain bioactive compound(s). All extracts are initially fractionated using one and the same LC condition with parallel mass spectrometric detection. Fractions containing bioactive compound(s) are then subjected to a second fractional stage using two different chromatographic conditions. Mass detection is also included at this stage, and a cross‐matching algorithm for comparison of processed mass chromatograms from the two dimensions was developed. The algorithm reports only masses present in bioactive fractions in both dimensions and enable therefore an efficient identification of potential masses that causes the bioactivity. This mass list can be used to search in natural compound database(s) for a rapid evaluation if the mass belongs to an already identified compound or if it is a potentially new one. This strategy enables thorough screening of several hundred crude extracts in one week on one single instrument.
Benefit Segmentation of Seaside Destination in the Phase of Market Repositioning: the Case of Portorož
Authors: Rudež Helena Nemec , Sedmak Gorazd , Bojnec Štefan
Published: November 2011

The purpose of the paper is to present benefit segmentation of visitors to Portorož, a mature seaside Mediterranean destination, during a phase of repositioning, to understand whether it attracts visitors who seek benefits other than just passive leisure, which characterized Portorož in the past. Four distinct segments of visitors and their characteristics were identified. The largest segment, ‘well‐being visitors’, is looking for physical activity and convenience. The results give us better insight into the demand side; on the other hand, they have practical implications for tourism suppliers, who try to adapt their product to new conditions. Copyright © 2011 John Wiley & Sons, Ltd.
Role of retreatment in minimal‐power argon laser therapy for port wine stains
Authors: Cosman Bard
Published: November 2011

Retreatment of previously lased areas of port wine stains can offer significant additional improvement over initial results. From 1977 to 1981 123 patients were subjected to 191 treatments employing the argon laser using an individually varied minimal power dose. Thirty‐three areas have been treated a second time a year after the first therapy and six doubly treated areas have also been studied. The additional improvement achieved by retreatment together with the minimal additional chance of complication adds to the safety and practicality of minimal dosage technique. The theoretical considerations allowing successful retreatment are presented and the results of this approach are demonstrated. The timing of retreatment and its limitations are also considered.
Comparative experimental study on the use of the carbon dioxide laser beam in partial nephrectomy
Authors: Barzilay Benjamin , Lijovetzky Graciela , Perlberg Saul , Caine Marco
Published: November 2011

A report is given on an experimental study in 20 dogs designed to compare the use of the CO2 laser beam as a cutting instrument in resection of the kidney parenchyma, with the simple scalpel and the cutting diathermy current. It was found that the laser can be used with impunity. It shortens the time of operation by facilitating hemostasis, diminishes blood loss, and does not interfere with the final kidney function. The damage to the kidney parenchyma compares favorably with that produced by the other instruments.
Dysfunctional telomeres promote genomic instability and metastasis in the absence of telomerase activity in oncogene induced mammary cancer
Authors: Bojovic Bojana , Crowe David L.
Published: November 2011

Telomerase is a ribonucleoprotein that maintains the ends of chromosomes (telomeres). In normal cells lacking telomerase activity, telomeres shorten with each cell division because of the inability to completely synthesize the lagging strand. Critically shortened telomeres elicit DNA damage responses and limit cellular division and lifespan, providing an important tumor suppressor function. Most human cancer cells express telomerase which contributes significantly to the tumor phenotype. In human breast cancer, telomerase expression is predictive of clinical outcomes such as lymph node metastasis and survival. In mouse models of mammary cancer, telomerase expression is also upregulated. Telomerase overexpression resulted in spontaneous mammary tumor development in aged female mice. Increased mammary cancer also was observed when telomerase deficient mice were crossed with p53 null mutant animals. However, the effects of telomerase and telomere length on oncogene driven mammary cancer have not been completely characterized. To address these issues we characterized neu proto‐oncogene driven mammary tumor formation in G1 Terc−/− (telomerase deficient with long telomeres), G3 Terc−/− (telomerase deficient with short telomeres), and Terc+/+ mice. Telomerase deficiency reduced the number of mammary tumors and increased tumor latency regardless of telomere length. Decreased tumor formation correlated with increased apoptosis in Terc deficient tumors. Short telomeres dramatically increased lung metastasis which correlated with increased genomic instability, and specific alterations in DNA copy number and gene expression. We concluded that short telomeres promote metastasis in the absence of telomerase activity in neu oncogene driven mammary tumors. © 2011 Wiley Periodicals, Inc.
Bortezomib‐induced sensitization of malignant human glioma cells to vorinostat‐induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl‐1 cleavage, and DNA damage
Authors: Premkumar Daniel R. , Jane Esther P. , Agostino Naomi R. , DiDomenico Joseph D. , Pollack Ian F.
Published: November 2011

Glioblastomas are invasive tumors with poor prognosis despite current therapies. Histone deacetylase inhibitors (HDACIs) represent a class of agents that can modulate gene expression to reduce tumor growth, and we and others have noted some antiglioma activity from HDACIs, such as vorinostat, although insufficient to warrant use as monotherapy. We have recently demonstrated that proteasome inhibitors, such as bortezomib, dramatically sensitized highly resistant glioma cells to apoptosis induction, suggesting that proteasomal inhibition may be a promising combination strategy for glioma therapeutics. In this study, we examined whether bortezomib could enhance response to HDAC inhibition in glioma cells. Although primary cells from glioblastoma multiforme (GBM) patients and established glioma cell lines did not show significant induction of apoptosis with vorinostat treatment alone, the combination of vorinostat plus bortezomib significantly enhanced apoptosis. The enhanced efficacy was due to proapoptotic mitochondrial injury and increased generation of reactive oxygen species. Our results also revealed that combination of bortezomib with vorinostat enhanced apoptosis by increasing Mcl‐1 cleavage, Noxa upregulation, Bak and Bax activation, and cytochrome c release. Further downregulation of Mcl‐1 using shRNA enhanced cell killing by the bortezomib/vorinostat combination. Vorinostat induced a rapid and sustained phosphorylation of histone H2AX in primary GBM and T98G cells, and this effect was significantly enhanced by co‐administration of bortezomib. Vorinostat/bortezomib combination also induced Rad51 downregulation, which plays an important role in the synergistic enhancement of DNA damage and apoptosis. The significantly enhanced antitumor activity that results from the combination of bortezomib and HDACIs offers promise as a novel treatment for glioma patients. © 2011 Wiley Periodicals, Inc.
Pemetrexed induces both intrinsic and extrinsic apoptosis through ataxia telangiectasia mutated/p53‐dependent and ‐independent signaling pathways
Authors: Yang Tsung‐Ying , Chang Gee‐Chen , Chen Kun‐Chieh , Hung Hsiao‐Wen , Hsu Kuo‐Hsuan , Wu Chi‐Hao , Sheu Gwo‐Tarng , Hsu Shih‐Lan
Published: November 2011

Pemetrexed, a new‐generation antifolate, has demonstrated promising single‐agent activity in front‐ and second‐line treatments of non‐small cell lung cancer. However, the molecular mechanism of pemetrexed‐mediated antitumor activity remains unclear. The current study shows that pemetrexed induced DNA damage and caspase‐2, ‐3, ‐8, and ‐9 activation in A549 cells and that treatment with caspase inhibitors significantly abolished cell death, suggesting a caspase‐dependent apoptotic mechanism. The molecular events of pemetrexed‐mediated apoptosis was associated with the activation of ataxia telangiectasia mutated (ATM)/p53‐dependent and ‐independent signaling pathways, which promoted intrinsic and extrinsic apoptosis by upregulating Bax, PUMA, Fas, DR4, and DR5 and activating the caspase signaling cascade. Supplementation with dTTP allowed normal S‐phase progression and rescued apoptotic death in response to pemetrexed. Overall, our findings reveal that the decrease of thymidylate synthase and the increase of Bax, PUMA, Fas, DR4, and DR5 genes may serve as biomarkers for predicting responsiveness to pemetrexed. © 2011 Wiley Periodicals, Inc.
Description of deformation process in inherently anisotropic granular materials
Authors: Pietruszczak S. , Guo P.
Published: November 2011

The main focus in this work is on modeling of mechanical response of granular materials that display inherent anisotropy. Both the experimental and numerical investigations are described. First, the results of direct shear as well as drained/undrained triaxial tests that involve crushed limestone with elongated angular‐shaped particles are reviewed. Afterward, a mathematical framework is presented for modeling of elastic/ inelastic deformation that incorporates the multi‐laminate approach. The deformation is monitored on a set of randomly oriented planes, and the formulation incorporates the thickness of the shear band that is associated with sliding/separation process. A systematic procedure for identification of material functions/ parameters is outlined that is based on the results of direct shear tests, and the framework is later applied to simulate the behavior under triaxial conditions. The results of numerical simulations are compared with the experimental data. Copyright © 2011 John Wiley & Sons, Ltd.
Annealing‐induced structural rearrangement and its toughening effect in injection‐molded isotactic polypropylene
Authors: Na Bing , Li Zhujun , Lv Ruihua , Zou Shufen
Published: November 2011

To improve the toughness of isotactic polypropylene (iPP), by blending modification or special processing techniques, is an ongoing pursuit in the polymer community. In this study, the toughness of injection‐molded iPP bars has been enhanced by about four times upon annealing at 140°C, in parallel with slight increasing of stiffness. Through various structural characterizations it has been confirmed that the remarkable toughening effect in the annealed iPP bars mostly results from the enhanced molecular mobility in the amorphous phase due to lamellar perfection, rather than from the change of molecular orientation, crystal modification, crystallinity, and so on. Moreover, it is deduced that the gain of mobile amorphous fraction in the hierarchical iPP bars upon annealing follows the order of skin > intermediate > core, same to that contributing to the toughness enhancement. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Synergistic effect of polyaniline and multiwalled carbon nanotube on the microstructure and the electric property in PP/PANI/MWNT composites
Authors: Yang Lin , Chen Jinyao , Li Huilin , Zhang Zhiye , Wang Xinlong
Published: November 2011

In this article, the volume conductivity of polypropylene (PP)/polyaniline (PANI)/multiwalled carbon nanotube (MWNT) composites was detected. When the ratio of PANI protonated with dodecylbenzene sulphonic acid (PANI‐DBSA) to MWNT is 2 to 3 and 3 to 17, the volume conductivity of the two composites is much higher than that of composites filled with solely PANI‐DBSA or MWNT. The synergistic effects of PANI‐DBSA and MWNT on the microstructure and the electric property of PP/PANI/MWNT composites were carefully analyzed by scanning electron microscope (SEM) and transmission electron microscopy. The SEM results illuminate that the dispersion and the continuity of the composites filled with PANI‐DBSA and MWNT are far better than that filled with only PANI‐DBSA or MWNT. Especially, the dispersion and continuity of PP/PANI/MWNT 5, in which the ratio of PANI‐DBSA to MWNT is 3 to 17, are the best among all the composites. When PANI‐DBSA is introduced in PP/PANI/MWNT composites, the size of agglomerated particles decreases, and the dispersion of conductive particles is improved evidently. Therefore, there is a synergistic action of PANI‐DBSA and MWNT, which is used to improve the dispersion of conductive particles and the volume conductivity of the PP/PANI/MWNT composites. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers
Polysiloxanes polymers with hyperbranched structure and multivinyl functionality
Authors: Zheng Yu , Thurecht Kristofer J. , Wang Wenxin
Published: November 2011

Hyperbranched polysiloxane polymers with multivinyl functionality were designed and synthesized through a “one‐step and one‐pot” deactivation enhanced atom transfer polymerization (DE‐ATRP) approach from the copolymerization of polydimethylsiloxane (PDMS) macromonomers and divinylbenzene (DVB). Various feed ratios of siloxane‐based monomer and divinyl monomers were investigated. We showed that even at DVB concentrations as high as 80 mol % in the feed, 65% yield of hyperbranched polymer could be obtained without gelation because the DE‐ATRP suppressed the rapid formation of macronetwork structures. The molecular weight, polydispersity, macromolecular structure of hyperbranched poly(DVB‐co‐PDMS) as well as its viscosity in silicone oil were characterized by GPC‐MALLS, 1H NMR and rheometer. By tracking the relationship between the radius of gyration, elution volume and molecular weight from MALLS analysis, solid evidences of the highly branched and condensed structure of the polymers were obtained. Furthermore, the oil thickening experiments demonstrate that this hyperbranched polymer can act as a well‐controlled viscosity‐modifier for Silicone oils, which potentially will have important application in coating, cosmetic and pharmaceutical products. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Electron and hole scattering dynamics in InN films investigated by infrared measurements
Authors: Ishitani Yoshihiro , Fujiwara Masayuki , Imai Daichi , Kusakabe Kazuhide , Yoshikawa Akihiko
Published: November 2011

InN layers have electron accumulation structure around the surfaces and interfaces with the substrates. Infrared (IR) spectroscopy enables the analysis of the inside bulk region in spite of the high sheet electron density of the order of 1013 cm−2 in the accumulation layers using the dispersion of the penetration depth. The polarization spectroscopy shows the anisotropic electron and hole scattering rates. The higher scattering rates of electron and hole plasmons vibrating along the c axis are attributed to edge‐type dislocations, while the scattering by Mg or related complex dominates the damping processes of hole plasmons vibrating vertical to the c axis in highly Mg‐doped p‐InN. The smaller photoluminescence (PL) intensity of p‐InN is attributed to the smaller activation energy of carriers to be captured by deep levels than that from the captured carriers to the ground state.
Evaluation of direct analysis in real time mass spectrometry for onsite monitoring of batch slurry reactions
Authors: Cho David S. , Gibson Stephen C. , Bhandari Deepak , McNally Mary Ellen , Hoffman Ron M. , Cook Kelsey D. , Song Liguo
Published: November 2011

Batch slurry reactions are widely used in the industrial manufacturing of chemicals, pharmaceuticals, petrochemicals and polymers. However, onsite monitoring of batch slurry reactions is still not feasible in production plants due to the challenge in analyzing heterogeneous samples without complicated sample preparation procedures. In this study, direct analysis in real time mass spectrometry (DART‐MS) has been evaluated for the onsite monitoring of a model batch slurry reaction. The results suggested that automation of the sampling process of DART‐MS is important to achieve quantitative results. With a sampling technique of manual sample deposition on melting point capillaries followed by automatic sample introduction across the helium beam, relative standard deviation (RSD) of the protonated molecule signals from the reaction product of the model batch slurry reaction ranged from 6 to 30%. This RSD range is improved greatly over a sampling technique of manual sample deposition followed by manual sample introduction where the RSDs are up to 110%. Furthermore, with the semi‐automated sampling approach, semi‐quantitative analysis of slurry samples has been achieved. Better quantification is expected with a fully automated sampling approach. Copyright © 2011 John Wiley & Sons, Ltd.
Biodegradability screening of soil amendments through coupling of wavelength‐scanned cavity ring‐down spectroscopy to multiple dynamic chambers
Authors: Bai Mo , Köstler Martin , Kunstmann Jürgen , Wilske Burkhard , Gattinger Andreas , Frede Hans‐Georg , Breuer Lutz
Published: November 2011

A system was developed for the automatic measurements of 13CO2 efflux to determine biodegradation of extra carbon amendments to soils. The system combines wavelength‐scanned cavity ring down laser spectroscopy (WS‐CRDS) with the open‐dynamic chamber (ODC) method. The WS‐CRDS instrument and a batch of 24 ODC are coupled via microprocessor‐controlled valves. Determination of the biodegradation requires a known δ13C value and the applied mass of the carbon compounds, and the biodegradation is calculated based on the 13CO2 mixing ratio (ppm) sampled from the headspace of the chambers. The WS‐CRDS system provided accurate detection based on parallel samples of three standard gases (13CO2 of 2, 11 and 22 ppm) that were measured simultaneously by isotope ratio mass spectrometry (linear regression R2 = 0.99). Repeated checking with the same standards showed that the WS‐CRDS system showed no drift over seven months.

The applicability of the ODC was checked against the closed static chamber (CSC) method using the rapid biodegradation of cane sugar – δ13C‐labeled through C4 photosynthesis. There was no significant difference between the results from 7‐min ODC and 120‐min CSC measurements. Further, a test using samples of either cane sugar (C4) or beetroot sugar (C3) mixed into standard soil proved the target functionality of the system, which is to identify the biodegradation of carbon sources with significantly different isotopic signatures. Copyright © 2011 John Wiley & Sons, Ltd.
Molecular histology analysis by matrix‐assisted laser desorption/ionization imaging mass spectrometry using gold nanoparticles as matrix
Authors: Tang Ho‐Wai , Wong Melody Yee‐Man , Lam Wing , Cheng Yung‐Chi , Che Chi‐Ming , Ng Kwan‐Ming
Published: November 2011

Gold nanoparticles (AuNPs) were applied and optimized as matrix for matrix‐assisted laser desorption/ionization mass spectrometry analysis of animal tissues, and enabled histological analysis of animal tissues at molecular level by imaging mass spectrometry (IMS). AuNPs were coated on animal tissue in a solvent‐free manner via argon ion sputtering. Metabolites, including neurotransmitters, fatty acids and nucleobases, were directly detected from mouse brain tissue. Based on region‐specific chemical profiles, fine histological features of mouse brain tissue and heterogeneous regions of tumor tissue were both revealed. Copyright © 2011 John Wiley & Sons, Ltd.
A new classification approach for comparing two active treatments when there is no prior projection on which one is better
Authors: Qu Yongming , Liu Rong , Dmitrienko Alexei , Offen Walter
Published: November 2011

We developed a new classification approach in this paper to compare two active treatments. This approach is especially useful when there is no prior judgment on which treatment is better and the traditional hypothesis testing approach is thus not applicable. Our method classifies all the possible outcomes into categories and draws conclusions on the difference in the outcome measurement between two treatment arms according to the location of the confidence interval for the treatment difference in the response variable. This method controls the misclassification rate regardless of the true difference in the response between the two treatment arms. The method was applied to a diabetes clinical trial. Copyright © 2011 John Wiley & Sons, Ltd.
Nanoscale DNA Tetrahedra Improve Biomolecular Recognition on Patterned Surfaces
Authors: Schlapak Robert , Danzberger Jürgen , Armitage David , Morgan David , Ebner Andreas , Hinterdorfer Peter , Pollheimer Philipp , Gruber Hermann J. , Schäffler Friedrich , Howorka Stefan
Published: November 2011

The bottom‐up approach of DNA nano‐biotechnology can create biomaterials with defined properties relevant for a wide range of applications. This report describes nanoscale DNA tetrahedra that are beneficial to the field of biosensing and the targeted immobilization of biochemical receptors on substrate surfaces. The DNA nanostructures act as immobilization agents that are able to present individual molecules at a defined nanoscale distance to the solvent thereby improving biomolecular recognition of analytes. The tetrahedral display devices are self‐assembled from four oligonucleotides. Three of the four tetrahedron vertices are equipped with disulfide groups to enable oriented binding to gold surfaces. The fourth vertex at the top of the bound tetrahedron presents the biomolecular receptor to the solvent. In assays testing the molecular accessibility via DNA hybridization and protein capturing, tetrahedron‐tethered receptors outperformed conventional immobilization approaches with regard to specificity and amount of captured polypeptide by a factor of up to seven. The bottom‐up strategy of creating DNA tetrahedrons is also compatible with the top‐down route of nanopatterning of inorganic substrates, as demonstrated by the specific coating of micro‐ to nanoscale gold squares amid surrounding blank or poly(ethylene glycol)‐passivated glass surfaces. DNA tetrahedra can create biofunctionalized surfaces of rationally designed properties that are of relevance in analytical chemistry, cell biology, and single‐molecule biophysics.
Requirements management within a full model‐based engineering approach
Authors: Bernard Yves
Published: November 2011

In this paper we show how the Property‐Based Requirements (PBR) theory can be used to fully integrate Requirements Engineering (RE) into a Model‐Based Systems Engineering (MBSE) method using OMG UML and its SysML profile. The objective is to avoid “in‐parallel” management of two distinct expressions of the same specification (or design): once in a set of textual requirements and once in a model, which must be maintained to be consistent. This is achieved by the identification, in common modeling concepts, of Requirement Tracker Artifacts (RTA) that match the pattern defined by the Property‐Based Requirement theory. An illustration is provided with both the UML and SysML modeling language. We also outline how relationships defined “by construction” in the model can be exploited to carry out requirements management activities without addition of dedicated and redundant data. © 2011 Wiley Periodicals, Inc.