bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Restraint Stress on Lead‐Induced Male Reproductive Toxicity in Rats
Authors: HARI PRIYA P. , REDDY P. SREENIVASULA
Published: June 2012

This study was undertaken to investigate whether chronic immobilization stress interferes with lead‐induced reproductive toxicity in rats. Early pubertal male Wistar rats were subjected to either restraint stress (5 hr/day) or maintained on lead (0.15%) containing water or both for 60 days. Restraint stress or lead treatment significantly decreased the weight of the testes and epididymis. The daily sperm production, epididymal sperm count, sperm motility, and sperm viability were also decreased after exposure to lead or subjected to restraint stress. The levels of serum testosterone and also activity levels of testicular hydroxysteroid dehydrogenases were significantly decreased with a significant increase in the serum follicle stimulating and luteinizing hormone levels in rats exposed to lead or restraint stress indicating decreased steroidogenesis. A significant increase in lipid peroxidation levels and decrease in catalase and superoxide dismutase activity levels were observed in the testes of rats subjected to restraint stress or exposed to lead indicating increased oxidative stress. Extensive histopathological malformations were observed in the testis of the treated rats. From the findings, the study suggests that restraint stress or exposure to lead affects male reproduction in rats by inducing oxidative stress followed by decreasing steroidogenesis and spermatogenesis. A significant decrease in spermatogenesis and steroidogenesis was also observed in rats subjected to both restraint stress and lead treatment as compared to lead alone treated rats indicating immobilization stress augments lead‐induced testicular and epididymal toxicity in rats. J. Exp. Zool. 000A:1‐11, 2012. © 2012 Wiley Periodicals, Inc.
Fighting Fish (Betta splendens) Bubble Nests Do Not Inhibit Microbial Growth
Authors: BROWN ALEXANDRIA C. , CLOTFELTER ETHAN D.
Published: June 2012

Some organisms produce antimicrobial substances in nesting foam to favorably manipulate the environment to which their developing offspring are exposed. We tested if fighting fishBetta splendensfoamy nest material, which is comprised of bubbles produced in the oral cavity of nesting males, has antimicrobial properties against a pathogenic bacteria (Edwardsiella tarda), a nonpathogenic bacteria (Escherichia coli), or a pathogenic oomycete (Saprolegnia parasitica). We also tested if exposure to nest material increases larval survival by performing in vitro fertilizations and individually incubating eggs in bubble nest extract or tank water (control). Our results show no evidence of antimicrobial properties of bubble nests. On the contrary, bubble nests provided favorable microenvironments for the growth ofSaprolegnia parasitica. Our results confirm earlier work citing the importance of male nest attendance, and suggest that the mechanism responsible for decreased survival in the absence of attending males is pathogenic microbes. J. Exp. Zool. 317A:481‐487, 2012. © 2012 Wiley Periodicals, Inc.
An improved synthesis of [2‐14C]2, 5‐dichloropyrimidine
Authors: Cao Kai , Tran Scott B. , Maxwell Brad D. , Bonacorsi Samuel J.
Published: June 2012

A previously described, five‐step synthesis of [2‐14C]2, 5‐dichloropyrimidine was based on condensation of [14C]urea with an acetal, followed by bromination, chlorination, boronic acid formation, and finally chlorination. This improved synthesis also started from readily available [14C]urea, which was condensed with 2‐chloromalonaldehyde, followed by chlorination with POCl3 yielding [2‐14C]2, 5‐dichloropyrimidine with a radiochemical purity of 99% in an overall radiochemical yield of 72%. Copyright © 2012 John Wiley & Sons, Ltd.
Preparation and in vivo biological investigation of 99mTc‐HEIDP as a novel radioligand for bone scanning
Authors: Qiu Ling , Xue Li , Chen Yongshi , Lin Jianguo , Nan Beibei , Cheng Wen , Luo Shineng
Published: June 2012

A novel diphosphonic acid, 1‐hydroxy‐2‐(1‐ethyl‐imidazol‐2‐yl) ethane‐1,1‐diphosphonic acid (HEIDP), was prepared and labeled with 99mTc in a high labeling yield under optimized labeling conditions. The biodistribution in mice shows that 99mTc‐HEIDP has high specificity and efficacy in bone and joint uptake with 5.73 and 9.93%ID/g at 5 min, which increases continuously to a maximum of 7.62 and 18.0%ID/g at 30 min, respectively. Kinetics of blood clearance showed that distribution half‐life (T1/2α) and elimination half‐life (T1/2β) of 99mTc‐HEIDP were 9.91 and 81.1 min, respectively. The total clearance rate was 1.94%ID/g•min‐1. A plain and clear bone image was obtained at 1 h by using single photon emission computed tomography. All results indicate that 99mTc‐HEIDP holds potential as a superior tracer agent for bone scanning. Copyright © 2012 John Wiley & Sons, Ltd.
Time‐resolved dual‐station calf–foot three‐dimensional bolus chase MR angiography with fluoroscopic tracking
Authors: Johnson Casey P. , Borisch Eric A. , Glockner James F. , Young Phillip M. , Riederer Stephen J.
Published: June 2012

Purpose:

To refine, adapt, and evaluate the technical aspects of fluoroscopic tracking for generating dual‐station high‐spatial‐resolution MR angiograms of the calves and feet using a single injection of contrast material.

Materials and Methods:

Nine subjects (seven healthy volunteers followed by two patients) were imaged using a two‐station calf–foot three‐dimensional time‐resolved bolus chase MR angiography protocol which provided <1.0 mm3 spatial resolution throughout and 2.5‐ and 6.6‐s frame times at the calf and foot stations, respectively. Real‐time reconstruction of calf station time frames allowed visually guided triggering of table advance to the foot station. The studies were independently read and scored by two radiologists in six image quality categories.

Results:

On average, overall diagnostic quality at the calf and foot stations was good‐to‐excellent, the calf arteries and all but the smallest foot arteries had good‐to‐excellent signal and sharpness, artifact and venous contamination were minor, and signal continuity across the inter‐station interface was good.

Conclusion:

The feasibility of fluoroscopic tracking has been demonstrated as an efficient approach for high spatiotemporal imaging of the arteries of the calves and feet with good‐to‐excellent diagnostic quality and low degrading venous contamination. J. Magn. Reson. Imaging 2012;36:1168–1178. © 2012 Wiley Periodicals, Inc.
Influence of sulfur deficiency on chlorophyll‐meter readings of corn leaves
Authors: Pagani Agustín , Echeverría Hernán E.
Published: June 2012

Sulfur (S)‐diagnostic tools are essential for rational use of S fertilizers. There is little information about the suitability of leaf greenness intensity to detect S deficiency in corn (Zea mays L.). This work evaluates, under controlled S‐stressed conditions, (1) the performance of leaf greenness intensity as an indicator of the degree of S deficiency in corn, and (2) the advantage of the upper leaves in relation to the middle leaves for S‐deficiency determination. A pot experiment using sand as growth medium was conducted in greenhouse with corn at S rates of 0, 5, 10, 20, and 40 mg kg–1 and sufficiency of other nutrients. Measurements of aboveground biomass (AB), total nitrogen (N), and S concentrations, and chlorophyll‐meter readings (CMR) in upper and middle leaves, were performed at the growth stages of 6–7, 11–12, and 14–15 fully expanded leaves (V6‐V7, V11‐V12, and V14‐V15, respectively). Sulfur application significantly increased AB, leaf S concentration, and CMR. Significantly positive relationships were obtained between leaf S concentration and CMR. A sulfur‐sufficiency index (SSI) based on CMR measured in upper and middle leaves was significantly associated with AB (R2 = 0.58 and 0.62 for the middle and upper leaves, respectively). It is concluded that under sufficiency of other nutrients and high‐S‐stressed conditions, leaf greenness intensity could be a good indicator of corn S status, although little or no advantage was found for taking CMR from the upper leaves.
Self‐assembled CdSe/CdS nanorod micro‐lasers fabricated from solution by capillary jet deposition
Authors: Zavelani‐Rossi M. , Krahne R. , Della Valle G. , Longhi S. , Franchini I.R. , Girardo S. , Scotognella F. , Pisignano D. , Manna L. , Lanzani G. , Tassone F.
Published: June 2012

Here we show an innovative, simple and reliable method to fabricate micro‐lasers by self‐assembly of rod‐shaped nanocrystals. We use dot/rod core/shell CdSe/CdS nanorods to form optical micro‐resonators by exploiting their self‐organization into well‐defined coffee stain rings. The fabrication process merely consists of capillary jet deposition of a nanorod solution onto a glass substrate, and is scalable, economic, and highly reproducible. Upon optical pumping of the micro‐resonators we obtain laser emission in the red or in the blue‐green spectral region, demonstrating lasing both from core and shell transitions, with low pumping thresholds. Modeling by full‐wave numerical simulations according to generalized (i. e. scattering) formulation of laser theory demonstrates lasing from complex modes of the self‐assembled cavity.
Overexpression of crkl correlates with poor prognosis and cell proliferation in non‐small cell lung cancer
Authors: Wang Yan , Dong Qian‐ze , Fu Ling , Stoecker Maggie , Wang Endi , Wang En‐Hua
Published: June 2012

Crk‐Like (CRKL) is an adapter protein that has crucial roles in multiple biological processes, including cell proliferation, adhesion, and migration. Amplification of CRKL gene was found in non‐small cell lung cancer (NSCLC). However, the expression pattern of CRKL protein and its clinical significance in human NSCLC have not been well characterized to date. In this study, expression of CRKL was evaluated in 131 NSCLC tissues by immumohistochemistry. CRKL protein was up‐regulated in the lung carcinomas compared with adjacent normal lung tissue. Overexpression of CRKL was found in 58 of 131 (44.3%) NSCLC samples and correlated with poor tumor differentiation (P = 0.0042), histological type (adenocarcinoma; P = 0.001), advanced p‐TNM stage (P = 0.0004), nodal metastasis (P = 0.0273), high proliferation index (P = 0.0062) and poor overall survival (P = 0.0084). Further univariate and multivariate analysis showed a significant association of CRKL overexpression and worse overall survival in lung cancer patients. In addition, overexpression of CRKL in HBE and H1299 cell lines promoted cell proliferation by facilitating cell cycle progression. Further analysis of cell cycle related molecules showed that CRKL induced cyclin D1, cyclin B1 expression, and increased Rb phosphorylation. In conclusion, this study demonstrated overexpression of CRKL correlated with poor prognosis and lung cancer proliferation by cell cycle regulation. © 2012 Wiley Periodicals, Inc.
31P and1H MRS of DB‐1 melanoma xenografts: lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan
Authors: Nath Kavindra , Nelson David S. , Ho Andrew M. , Lee Seung‐Cheol , Darpolor Moses M. , Pickup Stephen , Zhou Rong , Heitjan Daniel F. , Leeper Dennis B. , Glickson Jerry D.
Published: June 2012

In vivo31P MRS demonstrates that human melanoma xenografts in immunosuppressed mice treated with lonidamine (LND, 100 mg/kg intraperitoneally) exhibit a decrease in intracellular pH (pHi) from 6.90 ± 0.05 to 6.33 ± 0.10 (p < 0.001), a slight decrease in extracellular pH (pHe) from 7.00 ± 0.04 to 6.80 ± 0.07 (p > 0.05) and a monotonic decline in bioenergetics (nucleoside triphosphate/inorganic phosphate) of 66.8 ± 5.7% (p < 0.001) relative to the baseline level. Both bioenergetics and pHidecreases were sustained for at least 3 h following LND treatment. Liver exhibited a transient intracellular acidification by 0.2 ± 0.1 pH units (p > 0.05) at 20 min post‐LND, with no significant change in pHeand a small transient decrease in bioenergetics (32.9 ± 10.6%,p > 0.05) at 40 min post‐LND. No changes in pHior adenosine triphosphate/inorganic phosphate were detected in the brain (pHi, bioenergetics;p > 0.1) or skeletal muscle (pHi, pHe, bioenergetics;p > 0.1) for at least 120 min post‐LND. Steady‐state tumor lactate monitored by1H MRS with a selective multiquantum pulse sequence with Hadamard localization increased approximately three‐fold (p = 0.009). Treatment with LND increased the systemic melanoma response to melphalan (LPAM; 7.5 mg/kg intravenously), producing a growth delay of 19.9 ± 2.0 days (tumor doubling time, 6.15 ± 0.31 days; log10cell kill, 0.975 ± 0.110; cell kill, 89.4 ± 2.2%) compared with LND alone of 1.1 ± 0.1 days and LPAM alone of 4.0 ± 0.0 days. The study demonstrates that the effects of LND on tumor pHiand bioenergetics may sensitize melanoma to pH‐dependent therapeutics, such as chemotherapy with alkylating agents or hyperthermia. Copyright © 2012 John Wiley & Sons, Ltd.
Ultra‐performance Liquid Chromatography–High‐definition Mass Spectrometry Analysis of Constituents in the Root of Radix Stemonae and those Absorbed in Blood after Oral Administration of the Extract of the Crude Drug
Authors: Dong Wei , Wang Ping , Meng Xiangcai , Sun Hui , Zhang Aihua , Wang Weiming , Dong Hui , Wang Xijun
Published: June 2012

Introduction

Radix Stemonae, first recorded in the herbal ‘Additional Records of Famous Physicians’ (Mingyi Bielu), has been widely used as an oral anti‐tussive agent in traditional Chinese medicine (TCM) for thousands of years in China. Current analysis methods are usually time‐consuming and inaccurate.

Objective

The aim of this study was to develop a more rapid and sensitive method to detect the active compounds in Radix Stemonae.

Methodology

A rapid, sensitive and selective ultra‐performance liquid chromatography–high‐resolution mass spectrometric (UPLC–HDMS) method with automated data analysis software MetaboLynxTM was developed for analysis and identification of the bioactive components and their metabolites in rat plasma following oral administration of Radix Stemonae extract.

Results

Twenty‐nine compounds in the Radix Stemonae extract and 47 compounds in the rat plasma samples were detected in the MSE mode in a single injection within 21 min. Among the compounds detected, 23 were identified in vitro and 42 were identified in rat plasma, either by comparing the retention time and mass spectrometry data with those of reference compounds or by mass spectrometry analysis and retrieving the reference literature.

Conclusion

It is concluded that the screening capability of MetaboLynxTM, together with the utilisation of MSE in structural elucidation, can facilitate a rapid and comprehensive detection and effective structural characterisation of Stemona alkaloids in Radix Stemonae extract, which could be applied to other Chinese medicine. The results provide helpful chemical information of Radix Stemonae extract for further pharmacology and active mechanism research. Copyright © 2012 John Wiley & Sons, Ltd.
Pharmacovigilance teaching in UK undergraduate pharmacy programmes
Authors: Smith Melvyn P. , Webley Sherael D.
Published: June 2012

Purpose

Pharmacists in the UK are able to report spontaneous adverse drug reactions (ADRs) to the Medicines and Healthcare Products Regulatory Authority. The level of reporting by UK pharmacists remains low. This could be explained by poor knowledge of ADR reporting. The primary objective of this study was to investigate the level of pharmacovigilance education provided to pharmacy students on undergraduate pharmacy programmes in the UK.

Methods

A cross‐sectional survey was used to obtain data relating to the teaching of pharmacovigilance within schools of pharmacy. The survey was designed to reveal whether core elements pertinent to pharmacovigilance and specifically to spontaneous reporting were taught and to what extent.

Results

All of the respondents taught pharmacovigilance within an assessed compulsory module. A small number (23%) did not include pharmacovigilance law within their syllabus. In 54%, the amount of time devoted to teaching pharmacy students about their role in pharmacovigilance was less than 4 h in the 4‐year course; only one respondent spent approximately 20 h, the remaining respondents (38%) spent between 4 and 8 h.

Conclusions

The amount of time dedicated to the teaching of pharmacovigilance on pharmacy undergraduate degree programmes is low. Considering the importance of spontaneous reporting in drug safety and the shift in the role of the pharmacists, more time may need to be devoted to pharmacovigilance on pharmacy undergraduate courses. By doing so, new pharmacists would be more informed of the important role they play in drug safety and thereby potentially help enhance the level of ADR reporting. Copyright © 2012 John Wiley & Sons, Ltd.
Quantitative proteomic analysis and functional studies reveal that nucleophosmin is involved in cell death in glioblastoma cell line transfected with siRNA
Authors: Gimenez Marcela , Marie Suely K.N. , Oba‐Shinjo Sueli M. , Uno Miyuki , da Silva Roseli , Laure Helen Julie , Izumi Clarice , Otake Andreia , Chammas Roger , Rosa Jose Cesar
Published: June 2012

Previously, we reported that nucleophosmin (NPM) was increased in glioblastoma multiforme (GBM). NPM is a phosphoprotein related to apoptosis, ribosome biogenesis, mitosis, and DNA repair, but details about its function remain unclear. We treated U87MG and A172 cells with small interference RNA (siRNA) and obtained a reduction of 80% in NPM1 expression. Knockdown at the protein level was evident after the 4th day and was maintained until the 7th day of transfection that was investigated by quantitative proteomic analysis using isobaric tags. The comparison of proteomic analysis of NPM1‐siRNA against controls allowed the identification of 14 proteins, two proteins showed increase and 12 presented a reduction of expression levels. Gene ontology assigned most of the hypoexpressed proteins to apoptosis regulation, including GRP78. NPM1 silencing did not impair cell proliferation until the 7th day after transfection, but sensitized U87MG cells to temozolomide (TMZ), culminating with an increase in cell death and provoking at a later period a reduction of colony formation. In a large data set of GBM patients, both GRP78 and NPM1 genes were upregulated and presented a tendency to shorter overall survival time. In conclusion, NPM proved to participate in the apoptotic process, sensitizing TMZ‐treated U87MG and A172 cells to cell death, and in association with upregulation of GRP78 may be helpful as a predictive factor of poor prognosis in GBM patients.
Tools and challenges for diversity‐driven proteomics in Brazil
Authors: Junqueira Magno , Carvalho Paulo Costa
Published: June 2012

Our current knowledge in biology has been mostly derived from studying model organisms and cell lines in which only a small fraction of all described species have been extensively studied. Although these model organisms are amenable to genetic manipulations, this blinds researchers to the true variability of life. Groundbreaking discoveries are often achieved by analyzing “noncanonical” species; for example, the characterization of Taq polymerase from Thermus aquaticus ultimately led to a revolution in the field of molecular biology. Brazil possesses a rich biodiversity and a considerable fraction of Brazilian groups use current proteomic techniques to explore this natural treasure‐trove. However, in our opinion, much more than the widely adopted peptide spectrum match approach is required to explore this rich “proteomosphere.” Here, we provide a critical overview of the available strategies for the analysis of proteomic data from “noncanonical” biological samples (e.g. proteins from unsequenced genomes or genomes with high levels of polymorphisms), and demonstrate some limitations of existing approaches for large‐scale protein identification and quantitation. An understanding of the premises behind these computational tools is necessary to properly deal with their limitations and draw accurate conclusions.
Using mass spectrometry to explore the neglected glycan moieties of the antiophidic proteins DM43 and DM64
Authors: León Ileana Rodriguez , da Costa Neves‐Ferreira Ana Gisele , da Rocha Surza Lucia Gonçalves , de Oliveira Trugilho Monique Ramos , Perales Jonas , Valente Richard Hemmi
Published: June 2012

The resistance of the opossum Didelphis aurita to Bothrops snake venoms is attributed to the opossum's antihemorrhagic (DM43) and antimyotoxic (DM64) acidic serum glycoproteins. The aim of this study was to characterize the N‐glycosylation sites of these antiophidic proteins and to determine whether their glycans influence the biological activity measured by in vitro assays. Our experimental pipeline included the sequential enzymatic digestion of the inhibitors with two different proteinases (trypsin and endoproteinase Asp‐N) and eventually with trypsin, peptide‐N‐glycosidase F (PNGase F) and endoproteinase Asp‐N, used in that order. All of the peptide and protein samples were analyzed by MALDI‐TOF/TOF MS. The results experimentally confirmed the putative N‐glycosylation sites of DM43 (Asn23, Asn156, Asn160, and Asn175) and DM64 (Asn46, Asn179, Asn183, and Asn379). Following treatments with specific glycosidases, complex‐type oligosaccharides containing galactose and sialic acid could be assigned to both proteins. The removal of these monosaccharide units by exoglycosidase digestion did not measurably affect the inhibitory activity. In contrast, partially deglycosylated DM43 treated with PNGase F under nondenaturing conditions was half as effective as native DM43. In conclusion, we have demonstrated that the contribution of the carbohydrate portion of these potentially therapeutic molecules, for their mechanism of action, should not be overlooked.
Secretome analysis of the fungus Trichoderma harzianum grown on cellulose
Authors: Do Vale Luis H. F. , Gómez‐Mendoza Diana P. , Kim Min‐Sik , Pandey Akhilesh , Ricart Carlos A. O. , Edivaldo Ximenes F. Filho , Sousa Marcelo V.
Published: June 2012

Trichoderma harzianum is a mycoparasitic filamentous fungus that produces and secretes a wide range of extracellular hydrolytic enzymes used in cell wall degradation. Due to its potential in biomass conversion, T. harzianum draws great attention from biofuel and biocontrol industries and research. Here, we report an extensive secretome analysis of T. harzianum. The fungus was grown on cellulose medium, and its secretome was analyzed by a combination of enzymology, 2DE, MALDI‐MS and ‐MS/MS (Autoflex II), and LC‐MS/MS (LTQ‐Orbitrap XL). A total of 56 proteins were identified using high‐resolution MS. Interestingly, although cellulases were found, the major hydrolytic enzymes secreted in the cellulose medium were chitinases and endochitinases, which may reflect the biocontrol feature of T. harzianum. The glycoside hydrolase family, including chitinases (EC 3.2.1.14), endo‐N‐acetylglucosaminidases (EC 3.2.1.96), hexosaminidases (EC 3.2.1.52), galactosidases (EC 3.2.1.23), xylanases (EC 3.2.1.8), exo‐1,3‐glucanases (EC 3.2.1.58), endoglucanases (EC 3.2.1.4), xylosidases (EC 3.2.1.37), α‐L‐arabinofuranosidase (EC 3.2.1.55), N‐acetylhexosaminidases (EC 3.2.1.52), and other enzymes represented 51.36% of the total secretome. Few representatives were classified in the protease family (8.90%). Others (17.60%) are mostly intracellular proteins. A considerable part of the secretome was composed of hypothetical proteins (22.14%), probably because of the absence of an annotated T. harzianum genome. The T. harzianum secretome composition highlights the importance of this fungus as a rich source of hydrolytic enzymes for bioconversion and biocontrol applications.
Dopaminergic modulation of the hippocampal neuropil proteome identified by bioorthogonal noncanonical amino acid tagging (BONCAT)
Authors: Hodas Jennifer J. L. , Nehring Anne , Höche Nicole , Sweredoski Michael J. , Pielot Rainer , Hess Sonja , Tirrell David A. , Dieterich Daniela C. , Schuman Erin M.
Published: June 2012

Local protein synthesis and its activity‐dependent modulation via dopamine receptor stimulation play an important role in synaptic plasticity – allowing synapses to respond dynamically to changes in their activity patterns. We describe here the metabolic labeling, enrichment, and MS‐based identification of candidate proteins specifically translated in intact hippocampal neuropil sections upon treatment with the selective D1/D5 receptor agonist SKF81297. Using the noncanonical amino acid azidohomoalanine and click chemistry, we identified over 300 newly synthesized proteins specific to dendrites and axons. Candidates specific for the SKF81297‐treated samples were predominantly involved in protein synthesis and synapse‐specific functions. Furthermore, we demonstrate a dendrite‐specific increase in proteins synthesis upon application of SKF81297. This study provides the first snapshot in the dynamics of the dopaminergic hippocampal neuropil proteome.
Correlations of Bond and Breakage Parameters of Some Ores with the Corresponding Point Load Index
Authors: Aras Ali , Ozkan Alper , Aydogan Salih
Published: June 2012

This paper presents significant correlations of the Bond parameter (work index, Wi and grindability, G) and the breakage parameters (specific rate of breakage, Si and the fineness value, γ) with the point load index (Is(50)). The experimental results obtained from calcite, barite, colemanite and bauxite samples have demonstrated that the Bond and breakage parameters were closely correlated with the point load index. That is, the values of G, Si and aT parameters decreased with the increase in the values of the point load index; however, the γ parameter of Bi,j increased with increasing Is(50) values.
Design of recombinant antibody microarrays for urinary proteomics
Authors: Kristensson Malin , Olsson Karolina , Carlson Joyce , Wullt Björn , Sturfelt Gunnar , Borrebaeck Carl A.K. , Wingren Christer
Published: June 2012

Purpose

Urinary proteomics has become a key discipline within clinical proteomics for noninvasive diagnosis and monitoring of disease, and biomarker discovery. In order to decipher complex proteomes, high demands will, however, be placed upon the methodology applied. The purpose of this study was to develop a recombinant antibody microarray platform for urinary proteomics.

Experimental design

We adopted our previously in‐house developed recombinant antibody microarray set‐up and redesigned the platform for urinary proteomics. In this process, the key antibody array assay parameters, such as sample handling, sample labeling protocol, and assay conditions, etc, reflecting the unique properties of urine as sample format, were addressed and reoptimized in a step‐by‐step procedure.

Results

In this proof‐of‐concept study, we have designed the first generation of a recombinant antibody microarray technology platform for urinary proteomics. The results showed that multiplexed, sensitive (pg/mL range), and reproducible urine protein expression profiling could be performed targeting directly labeled, nonfractionated urine.

Conclusion and clinical relevance

We have demonstrated that crude, directly labeled urine samples could be profiled in a rapid, reproducible, sensitive, and multiplexed manner after minimal sample prehandling. These findings could potentially pave the way for enhanced urinary proteomics and understanding of renal physiology with implications in both health and disease.
Interaction of acetic acid and phenylacetaldehyde as attractants for trapping pest species of moths (Lepidoptera: Noctuidae)
Authors: Landolt Peter J , Tóth Miklós , Meagher Robert L , Szarukán István
Published: June 2012

BACKGROUND: Phenylacetaldehyde is a flower volatile and attractant for many nectar‐seeking moths. Acetic acid is a microbial fermentation product that is present in insect sweet baits. It is weakly attractive to some moths and other insects, but can be additive or synergistic with other compounds to make more powerful insect lures.

RESULTS: Acetic acid and phenylacetaldehyde presented together in traps made a stronger lure than either chemical alone for moths of the alfalfa looper Autographa californica (Speyer) and the armyworm Spodoptera albula (Walker). However, this combination of chemicals reduced captures of the cabbage looper moth Trichoplusia ni (Hübner), the silver Y moth Autographa gamma (L.), MacDunnoughia confusa (Stephens) and the soybean looper moth Chrysodeixis includens (Walker) by comparison with phenylacetaldehyde alone.

CONCLUSION: These results indicate both positive and negative interactions of acetic acid, a sugar fermentation odor cue, and phenylacetaldehyde, a floral scent cue, in eliciting orientation responses of moths. This research provides a new two‐component lure for the alfalfa looper A. californica and for the armyworm S. albula for potential use in pest management. Copyright © 2012 Society of Chemical Industry
Intrinsic spin Hall effect in silicene: transition from spin Hall to normal insulator
Authors: Dyrdał A. , Barnaś J.
Published: June 2012

An intrinsic contribution to the spin Hall effect in two‐dimensional silicene is considered theoretically within the linear response theory and Green's function formalism. When an external voltage normal to the silicene plane is applied, the spin Hall conductivity is shown to reveal a transition from the spin Hall insulator phase at low bias to the conventional insulator phase at higher voltages. This transition resembles the recently reported phase transition in bilayer graphene. The spin–orbit interaction responsible for this transition in silicene is much stronger than in graphene, which should make the transition observable experimentally. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dihydroxy‐Isosteviol Methyl Ester from Pulsatilla nigricans Induces Apoptosis in HeLa Cells: Its Cytoxicity and Interaction with Calf Thymus DNA
Authors: Das Sreemanti , Das Jayeeta , Samadder Asmita , Khuda‐Bukhsh Anisur Rahman
Published: June 2012

Dihydroxy‐isosteviol methyl ester (DIME), the principal biological compound isolated from the medicinal plant Pulsatilla nigricans (Fam: Ranunculaceae) having the molecular formula of C21H34O3 (molecular weight 334.25), was administered to cervical cancer cells (HeLa) in vitro to evaluate its possible apoptotic (anti‐cancer) potentials. We analyzed the expression of p53, Bax, Bcl2, Apaf and caspase 3 signal proteins and analyzed the early apoptotic events in HeLa cells induced by DIME using protocols like Annexin V‐FITC and PI staining. DIME caused a significant decrease in cell viability, induced nuclear condensation and inter‐nucleosomal DNA fragmentation. We further studied the interaction of DIME with calf thymus DNA as target through circular‐dichroism spectra. Results showed that DIME interacted with DNA, bringing indiscernible changes in structure and conformation. Thus, DIME showed its capability to induce apoptosis in cancer cells, signifying its utility in drug design as a possible candidate for chemoprevention. Copyright © 2012 John Wiley & Sons, Ltd.
Creating Transport Vibration Simulation Profiles from Vehicle and Road Characteristics
Authors: Rouillard Vincent , Sek Michael
Published: June 2012

It is today generally accepted that to carry‐out realistic transport simulation trials, field data must be acquired from vehicles travelling on the actual route(s) to be used for a particular distribution environment. This approach requires time, effort, access to data recording equipment as well as the necessary expertise to analyse the collected data. Often, this is out of reach of smaller operators who want a reasonable approximation without the time and expense. Currently, the only available option is the adoption of generic test spectra and levels that have been shown to be approximate representations of distribution environments. This paper discusses an alternative and practical method that uses some knowledge of the dynamic characteristics of various vehicle types along with an assessment of the types of roads (road roughness) to be encountered along a particular route. The method exploits the fact that the spectral characteristics (power spectral density) of road profiles are well known. The paper shows how this road surface elevation spectral function is combined with a numerical model of a particular vehicle type and speed to produce a target vibration power spectral density suitable for vibration test systems. One added benefit is that the method is capable of calculating the variations in root mean square levels of the response vibrations. This is presented as the root mean square distribution which, when coupled with the target power spectral density, can be used to synthesize realistic random vibrations that bear statistical similitude with real, field vibrations. Copyright © 2012 John Wiley & Sons, Ltd.
Stabilization of a spatially non‐causal reaction–diffusion equation by boundary control
Authors: Guo C. , Xie C. , Zhou C.
Published: June 2012

Stabilization of a reaction–diffusion equation, in which the heat source depends on the temperature of the whole space, is considered by using boundary control. A new backstepping transformation is introduced, in which there are two kernels. Through a series of mathematical tricks, the exact solutions of kernels are obtained, and a control law is obtained specifically. The inverse transformation is derived, and stability of the closed loop system established. Simulation results show that the closed loop system is stable. Copyright © 2012 John Wiley & Sons, Ltd.
Nanoscale Line Segment Fabrication Using Super‐Resolution Near‐Field Photolithography
Authors: Yang Ching‐Been
Published: June 2012

This study proposed a method to combine near‐field photolithography (NFP) with thermally induced super‐resolution, and conducted simulation and analysis on nanoscale line segment fabrication. A theoretical model of optical metal film was used to calculate the transmittance of indium film during line segment fabrication. A theoretical heat transfer model was employed to analyze the exposure power density on the surface of the photoresist after laser beams penetrated the indium film. This study divided the photoresist into finite nodes. Through a simulation combining an exposure energy density formula, an exposure model, and a developmental model, we derived the theoretical width and profile of the line segment fabricated using super‐resolution NFP. The widths of the derived line segments were 88 nm for photoresist with indium coating and 130 nm without. The indium film accounted for a reduction in width of 32%. SCANNING 34: 284–294, 2012. © 2012 Wiley Periodicals, Inc.
Regression calibration with more surrogates than mismeasured variables
Authors: Kipnis Victor , Midthune Douglas , Freedman Laurence S. , Carroll Raymond J.
Published: June 2012

In a recent paper (Weller EA, Milton DK, Eisen EA, Spiegelman D. Regression calibration for logistic regression with multiple surrogates for one exposure. Journal of Statistical Planning and Inference 2007; 137: 449‐461), the authors discussed fitting logistic regression models when a scalar main explanatory variable is measured with error by several surrogates, that is, a situation with more surrogates than variables measured with error. They compared two methods of adjusting for measurement error using a regression calibration approximate model as if it were exact. One is the standard regression calibration approach consisting of substituting an estimated conditional expectation of the true covariate given observed data in the logistic regression. The other is a novel two‐stage approach when the logistic regression is fitted to multiple surrogates, and then a linear combination of estimated slopes is formed as the estimate of interest. Applying estimated asymptotic variances for both methods in a single data set with some sensitivity analysis, the authors asserted superiority of their two‐stage approach. We investigate this claim in some detail. A troubling aspect of the proposed two‐stage method is that, unlike standard regression calibration and a natural form of maximum likelihood, the resulting estimates are not invariant to reparameterization of nuisance parameters in the model. We show, however, that, under the regression calibration approximation, the two‐stage method is asymptotically equivalent to a maximum likelihood formulation, and is therefore in theory superior to standard regression calibration. However, our extensive finite‐sample simulations in the practically important parameter space where the regression calibration model provides a good approximation failed to uncover such superiority of the two‐stage method. We also discuss extensions to different data structures. Copyright © 2012 John Wiley & Sons, Ltd.
Frailty modeling of age–incidence curves of osteosarcoma and Ewing sarcoma among individuals younger than 40 years
Authors: Valberg Morten , Grotmol Tom , Tretli Steinar , Veierød Marit B. , Devesa Susan S. , Aalen Odd O.
Published: June 2012

The Armitage–Doll model with random frailty can fail to describe incidence rates of rare cancers influenced by an accelerated biological mechanism at some, possibly short, period of life. We propose a new model to account for this influence. Osteosarcoma and Ewing sarcoma are primary bone cancers with characteristic age–incidence patterns that peak in adolescence. We analyze Surveillance, Epidemiology and End Result program incidence data for whites younger than 40 years diagnosed during the period 1975–2005, with an Armitage–Doll model with compound Poisson frailty. A new model treating the adolescent growth spurt as the accelerated mechanism affecting cancer development is a significant improvement over that model. We also model the incidence rate conditioning on the event of having developed the cancers before the age of 40 years and compare the results with those predicted by the Armitage–Doll model. Our results support existing evidence of an underlying susceptibility for the two cancers among a very small proportion of the population. In addition, the modeling results suggest that susceptible individuals with a rapid growth spurt acquire the cancers sooner than they otherwise would have if their growth had been slower. The new model is suitable for modeling incidence rates of rare diseases influenced by an accelerated biological mechanism. Copyright © 2012 John Wiley & Sons, Ltd.
Key properties of D‐optimal designs for event‐related functional MRI experiments with application to nonlinear models
Authors: Delzell Darcie A. P. , Gunst Richard F. , Schucany William R. , Carmack Patrick S. , Lin Qihua , Spence Jeffrey S. , Haley Robert W.
Published: June 2012

To properly formulate functional magnetic resonance imaging (fMRI) experiments with complex mental activity, it is advantageous to permit great flexibility in the statistical components of the design of these studies. The length of an experiment, the placement of various stimuli and the modeling approach used all affect the ability to detect mental activity. Major advances in understanding the implications of various designs of fMRI experiments have taken place over the last decade. Nevertheless, new and increasingly difficult issues relating to the modeling of hemodynamic responses and the detection of activated brain regions continue to arise because of the increasing complexity of the experiments. In this article, the D‐optimality criterion is used in conjunction with a genetic algorithm to create probability‐based design generators for the selection of designs in event‐related fMRI experiments where the hemodynamic response function is modeled with a function that is nonlinear in the parameters. The designs produced by these generators are shown to perform well compared with locally D‐optimal designs and provide insight into optimal design characteristics that investigators can utilize in the selection of interstimulus intervals. Designs with these characteristics are shown to be applicable to fMRI studies involving one or two stimulus types. The designs are also shown to be robust with respect to misspecification of an AR(1) error autocorrelation and compare favorably with a maximin procedure. Copyright © 2012 John Wiley & Sons, Ltd.
Extension of three‐arm non‐inferiority studies to trials with multiple new treatments
Authors: Kwong Koon Shing , Cheung Siu Hung , Hayter Anthony J. , Wen Miin‐Jye
Published: June 2012

Non‐inferiority (NI) trials are becoming increasingly popular. The main purpose of NI trials is to assert the efficacy of a new treatment compared with an active control by demonstrating that the new treatment maintains a substantial fraction of the treatment effect of the control. Most of the statistical testing procedures in this area have been developed for three‐arm NI trials in which a new treatment is compared with an active control in the presence of a placebo. However, NI trials frequently involve comparisons of several new treatments with a control, such as in studies involving different doses of a new drug or different combinations of several new drugs. In seeking an adequate testing procedure for such cases, we use a new approach that modifies existing testing procedures to cover circumstances in which several new treatments are present. We also give methods and algorithms to produce the optimal sample size configuration. In addition, we also discuss the advantages of using different margins for the assay sensitivity test between the active control and the placebo and the NI test between the new treatments and the active control. We illustrate the new approach by using data from a clinical trial. Copyright © 2012 John Wiley & Sons, Ltd.
Gadolinium‐Doped Silica Nanoparticles Encapsulating Indocyanine Green for Near Infrared and Magnetic Resonance Imaging
Authors: Sharma Parvesh , Bengtsson Niclas E. , Walter Glenn A. , Sohn Han‐Byul , Zhou Guangyin , Iwakuma Nobutaka , Zeng Huadong , Grobmyer Stephen R. , Scott Edward W. , Moudgil Brij M.
Published: June 2012

Clinical applications of the indocyanine green (ICG) dye, the only near infrared (NIR) imaging dye approved by the Food and Drug Administration (FDA) in the USA, are limited due to rapid protein binding, fast clearance, and instability in physiologically relevant conditions. Encapsulating ICG in silica particles can enhance its photostability, minimize photobleaching, increase the signal‐to‐noise (S/N) ratio and enable in vivo studies. Furthermore, a combined magnetic resonance (MR) and NIR imaging particulate can integrate the advantage of high‐resolution 3D anatomical imaging with high‐sensitivity deep‐tissue in‐vivo fluorescent imaging. In this report, a novel synthesis technique that can achieve these goals is presented. A reverse‐microemulsion‐based synthesis protocol is employed to produce 25 nm ICG‐doped silica nanoparticles (NPs). The encapsulation of ICG is achieved by manipulating coulombic attractions with bivalent ions and aminated silanes and carrying out silica synthesis in salt‐catalyzed, mildly basic pH conditions using dioctyl sulfosuccinate (AOT)/heptane/water microemulsion system. Furthermore, paramagnetic properties are imparted by chelating paramagnetic Gd to the ICG‐doped silica NPs. Aqueous ICG‐dye‐doped silica NPs show increased photostability (over a week) and minimal photobleaching as compared to the dye alone. The MR and optical imaging capabilities of these particles are demonstrated through phantom, in vitro and in vivo experiments. The described particles have the potential to act as theranostic agents by combining photodynamic therapy through the absorption of NIR irradiated light.
Regression test suite selection using dependence analysis
Authors: Ural Hasan , Yenigün Hüsnü
Published: June 2012

Dependence analysis on an Extended Finite State Machine representation of the requirements of a system under test identifies various types of control and data dependencies between transitions caused by a set of modifications on the requirements. These particular types of dependencies capture the effects of the modifications, that is, their direct effects on the changed parts of the system and their side effects on the unchanged parts of the system. Recent work on model‐based regression testing shows that dependencies capturing direct effects and side effects of the changes made on the requirements can be used for regression test suite (RTS) reduction (reducing the size of a given test suite by eliminating redundancies), for RTS prioritization (ordering test cases in a given test suite for early fault detection), or for RTS generation (designing a test suite covering the identified dependencies). This paper proposes an additional use of such dependencies, namely, RTS selection, which is the process of selecting a subset of a given test suite to form an RTS by considering the coverage of dependencies related to the effects of the modifications. The dependencies marked during this process as uncovered provide a basis for augmenting an (incomplete) RTS with test cases covering uncovered dependencies. Copyright © 2012 John Wiley & Sons, Ltd.
Increasing Doublecortin Expression Promotes Migration of Human Embryonic Stem Cell-Derived Neurons
Authors: Filipovic Radmila , Santhosh Kumar Saranya , Fiondella Chris , Loturco Joseph
Published: June 2012

Human embryonic stem cell-derived neuronal progenitors (hNPs) provide a potential source for cellular replacement following neurodegenerative diseases. One of the greatest challenges for future neuron replacement therapies will be to control extensive cell proliferation and stimulate cell migration of transplanted cells. The doublecortin (DCX) gene encodes the protein DCX, a microtubule-associated protein essential for the migration of neurons in the human brain. In this study, we tested whether increasing the expression of DCX in hNPs would favorably alter their proliferation and migration. Migration and proliferation of hNPs was compared between hNPs expressing a bicistronic DCX/IRES-GFP transgene and those expressing a green fluorescent protein (GFP) transgene introduced by piggyBac-mediated transposition. The DCX-transfected hNPs showed a significant decrease in their proliferation and migrated significantly further on two different substrates, Matrigel and brain slices. Additionally, a dense network of nestin-positive (+) and vimentin+ fibers were found to extend from neurospheres transplanted onto brain slices, and this fiber growth was increased from neurospheres containing DCX-transfected hNPs. In summary, our results show that increased DCX expression inhibits proliferation and promotes migration of hNPs.