bluuebunny/crossref_metadata_2025 huggingface dataset:
Axin gene methylation status correlates with radiosensitivity of lung cancer cells
Authors: Yang Lian-He , Han Yang , Li Guang , Xu Hong-Tao , Jiang Gui-Yang , Miao Yuan , Zhang Xiu-Peng , Zhao Huan-Yu , Xu Zheng-Fan , Stoecker Maggie , Wang Endi , Xu Ke , Wang En-Hua
Published: August 2013

Background

We previously reported that Axin1 (Axin) is down-regulated in many cases of lung cancer, and X-ray irradiation increased Axin expression and inhibited lung cancer cells. The mechanisms, however, were not clear.

Methods

Four lung cancer cell lines were used to detect the methylation status of Axin with or without X-ray treatment. Real-time PCR was used to quantify the expression of Axin, and western blot analysis was applied to measure protein levels of Axin, β-catenin, Cyclin D1, MMP-7, DNMTS, MeCP2 and acetylated histones. Flow cytometric analysis, colony formation assay, transwell assay and xenograft growth experiment were used to study the biological behavior of the cells with hypermethylated or unmethylated Axin gene after X-ray treatment.

Results

Hypermethylated Axin gene was detected in 2 of 4 cell lines, and it correlated inversely with Axin expression. X-ray treatment significantly up-regulated Axin expression in H446 and H157 cells, which possess intrinsic hypermethylation of the Axin gene (P<0.01), but did not show up-regulation in LTE and H460 cells, which have unmethylated Axin gene. 2Gy X-ray significantly reduced colony formation (from 71% to 10.5%) in H157 cells, while the reduction was lower in LTE cells (from 71% to 20%). After X-ray irradiation, xenograft growth was significantly decreased in H157 cells (from 1.15 g to 0.28 g) in comparison with LTE cells (from 1.06 g to 0.65 g). Significantly decreased cell invasiveness and increased apoptosis were also observed in H157 cells treated with X-ray irradiation (P<0.01). Down-regulation of DNMTs and MeCP2 and up-regulation of acetylated histones could be detected in lung cancer cells.

Conclusions

X-ray-induced inhibition of lung cancer cells may be mediated by enhanced expression of Axin via genomic DNA demethylation and histone acetylation. Lung cancer cells with a different methylation status of the Axin gene showed different radiosensitivity, suggesting that the methylation status of the Axin gene may be one important factor to predict radiosensitivity of the tumor.
The effect of pelvic physiotherapy on reduction of functional constipation in children: design of a multicentre randomised controlled trial
Authors: van Engelenburg – van Lonkhuyzen Marieke L , Bols Esther MJ , Benninga Marc A , Verwijs Wim A , Bluijssen Netty MWL , de Bie Rob A
Published: August 2013

Background

Functional constipation is a common disorder worldwide and is found in all paediatric age groups. Functional constipation can be caused by delayed colonic transit or dysfunction of the pelvic floor muscles. Standard medical care in paediatric practice is often based on clinical experience and mainly consists of a behavioural approach and toilet training, along with the prescription of laxatives. Evidence to evaluate the effectiveness of pelvic physiotherapy for this complaint is lacking.

Methods/design

A two-armed multicentre randomised controlled trial has been designed. We hypothesise that the combination of pelvic physiotherapy and standard medical care will be more effective than standard medical care alone for constipated children, aged 5 to 17 years. Children with functional constipation according to the Rome III will be included. Web-based baseline and follow-up measurements, scheduled at 3 and 6 months after inclusion, consist of the numeric rating scale in relation to the perceived severity of the problem, the Strength and Difficulties Questionnaire and subjective improvement post-intervention (global perceived effect). Examination of the pelvic floor muscle functions, including digital testing and biofeedback, will take place during baseline and follow-up measurements at the physiotherapist. The control group will only receive standard medical care, involving at least three contacts during five months, whereas the experimental group will receive standard medical care plus pelvic physiotherapy, with a maximum of six contacts. The physiotherapy intervention will include standard medical care, pelvic floor muscle training, attention to breathing, relaxation and awareness of body and posture. The study duration will be six months from randomisation, with a three-year recruitment period. The primary outcome is the absence of functional constipation according to the Rome III criteria.

Discussion

This section discusses the relevance of publishing the study design and the development of the presented physiotherapy protocol. It also addresses difficulties when interpreting the literature with regard to the effectiveness of biofeedback, potential confounding, and future research indications. To our knowledge, this article is the first to describe the design of a randomised controlled trial among children with constipation to assess the effect of pelvic physiotherapy as an add-on to standard medical care.

Trial registration

Current Controlled TrialsNL30551.068.09
Combined DNA extraction and antibody elution from filter papers for the assessment of malaria transmission intensity in epidemiological studies
Authors: Baidjoe Amrish , Stone Will , Ploemen Ivo , Shagari Shehu , Grignard Lynn , Osoti Victor , Makori Euniah , Stevenson Jennifer , Kariuki Simon , Sutherland Colin , Sauerwein Robert , Cox Jonathan , Drakeley Chris , Bousema Teun
Published: August 2013

Background

Informing and evaluating malaria control efforts relies on knowledge of local transmission dynamics. Serological and molecular tools have demonstrated great sensitivity to quantify transmission intensity in low endemic settings where the sensitivity of traditional methods is limited. Filter paper blood spots are commonly used a source of both DNA and antibodies. To enhance the operational practicability of malaria surveys, a method is presented for combined DNA extraction and antibody elution.

Methods

Filter paper blood spots were collected as part of a large cross-sectional survey in the Kenyan highlands. DNA was extracted using a saponin/chelex method. The eluate of the first wash during the DNA extraction process was used for antibody detection and compared with previously validated antibody elution procedures. Antibody elution efficiency was assessed by total IgG ELISA for malaria antigens apical membrane antigen-1 (AMA-1) and merozoite-surface protein-1 (MSP-142). The sensitivity of nested 18S rRNA and cytochrome b PCR assays and the impact of doubling filter paper material for PCR sensitivity were determined. The distribution of cell material and antibodies throughout filter paper blood spots were examined using luminescent and fluorescent reporter assays.

Results

Antibody levels measured after the combined antibody/DNA extraction technique were strongly correlated to those measured after standard antibody elution (p < 0.0001). Antibody levels for both AMA-1 and MSP-142 were generally slightly lower (11.3-21.4%) but age-seroprevalence patterns were indistinguishable. The proportion of parasite positive samples ranged from 12.9% to 19.2% in the different PCR assays. Despite strong agreement between outcomes of different PCR assays, none of the assays detected all parasite-positive individuals. For all assays doubling filter paper material for DNA extraction increased sensitivity. The concentration of cell and antibody material was not homogenously distributed throughout blood spots.

Conclusion

Combined DNA extraction and antibody elution is an operationally attractive approach for high throughput assessment of cumulative malaria exposure and current infection prevalence in endemic settings. Estimates of antibody prevalence are unaffected by the combined extraction and elution procedure. The choice of target gene and the amount and source of filter paper material for DNA extraction can have a marked impact on PCR sensitivity.
Complete pathological regression of hepatocellular carcinoma with portal vein thrombosis treated with sorafenib
Authors: Kermiche-Rahali Sabrina , Di Fiore Aude , Drieux Fanny , Di Fiore Frédéric , François Arnaud , Scotté Michel
Published: August 2013

Sorafenib is a molecular-targeted therapy used in palliative treatment of advanced hepatocellular carcinoma (HCC) in Child-Pugh A patients. We describe the case of a patient who presented with a large HCC in the left liver associated with portal vein thrombosis (PVT). After 9 months of sorafenib treatment, reassessment showed that the tumors had decreased in size with recanalization of the portal vein. A lateral left hepatectomy was performed and pathology showed complete necrosis of the tumor. Sorafenib can downstage HCC in patients with cirrhosis allowing further surgical resection.
Analysis of oxidative stress during the menstrual cycle
Authors: Cornelli Umberto , Belcaro Gianni , Cesarone Maria Rosaria , Finco Annarosa
Published: August 2013

Background

Few data concerning the oxidative stress (OS) in plasma during the entire menstrual cycle of eumenorrheic women are available.

Methods

OS was assessed in 20 healthy volunteers during the phase of the menstrual cycle by determining the plasmatic hydroperoxides levels (d-ROMs test). The assessment was performed every three days, starting from the first day (t1) up the end of the menstrual phase (t27). Concomitantly, the estrogen (E2) and progestin (P4) levels were determined at the same time intervals.

Results

From a base value (t1) of 284 +/− 38.0 CARR.U., which is essentially within the normal range (<300 Carratelli units or CARR.U.), the OS levels progressively increased to 378 +/− 115 CARR.U. at t15, and then slightly decreased over the subsequent time but with average values >300 CARR.U. Analysis of the E2 levels showed that the maximum OS values were noticed near the estrogen peak, while remaining above the base levels, and then decreased during the progestin phase until returning to normal at the end of the menstrual cycle.

Conclusions

It may concludes that the healthy women go into OS for 2/3 of the menstrual cycle.
Organization and regulation of intracellular plasma membrane-connected HIV-1 assembly compartments in macrophages
Authors: Mlcochova Petra , Pelchen-Matthews Annegret , Marsh Mark
Published: August 2013

Background

In HIV-1-infected human monocyte-derived macrophages (MDMs), virus particles assemble primarily on intracellularly sequestered plasma membrane domains termed intracellular plasma membrane-connected compartments (IPMCs). Despite their clear role in virus formation, little is known of the organization, composition, dynamics or function of these compartments.

Results

We have used amphipathic membrane dyes to reveal the complex three-dimensional structure of IPMCs in whole MDMs and to visualize connections between IPMCs and the cell surface. The observation of similar IPMC structures in both infected and uninfected cells indicates that these compartments are not induced by virus infection, but are present constitutively in MDMs. By expressing a phospholipase Cδ pleckstrin homology domain linked to green fluorescent protein, we demonstrate that IPMCs contain phosphatidylinositol 4,5-bisphosphate. Live cell imaging of cells expressing this probe shows that IPMCs are dynamic, but relatively stable, sub-domains of the plasma membrane. As recent electron microscopy studies indicated that portions of IPMCs are coated with β2 integrin-containing focal adhesion-like complexes linked to actin, we investigated whether the actin cytoskeleton is required for the organization of IPMCs. In MDMs treated with the actin polymerization inhibitor latrunculin, the normally compact IPMCs dispersed into smaller structures that remained connected to the plasma membrane. Moreover, latrunculin enhanced the release of preformed, mature HIV-1 particles from infected MDMs.

Conclusions

IPMCs are constitutive features of MDMs that are continuous with the plasma membrane and are used as unique sites for the assembly of new virions following infection by HIV-1. A functionally intact actin cytoskeleton is required to maintain the organization of the IPMCs and, in HIV-1-infected cells, perturbation of the actin cytoskeleton influences both the organization of the compartment and the release of sequestered virus.
Prehypertension and incidence of cardiovascular disease: a meta-analysis
Authors: Huang Yuli , Wang Sheng , Cai Xiaoyan , Mai Weiyi , Hu Yunzhao , Tang Hongfeng , Xu Dingli
Published: August 2013

Background

Prospective cohort studies of prehypertension and the incidence of cardiovascular disease (CVD) are controversial after adjusting for other cardiovascular risk factors. This meta-analysis evaluated the association between prehypertension and CVD morbidity.

Methods

Databases (PubMed, EMBASE and the Cochrane Library) and conference proceedings were searched for prospective cohort studies with data on prehypertension and cardiovascular morbidity. Two independent reviewers assessed the reports and extracted data. The relative risks (RRs) of CVD, coronary heart disease (CHD) and stroke morbidity were calculated and reported with 95% confidence intervals (95% CIs). Subgroup analyses were conducted on blood pressure, age, gender, ethnicity, follow-up duration, number of participants and study quality.

Results

Pooled data included the results from 468,561 participants from 18 prospective cohort studies. Prehypertension elevated the risks of CVD (RR = 1.55; 95% CI = 1.41 to 1.71); CHD (RR = 1.50; 95% CI = 1.30 to 1.74); and stroke (RR = 1.71; 95% CI = 1.55 to 1.89). In the subgroup analyses, even for low-range prehypertension, the risk of CVD was significantly higher than for optimal BP (RR = 1.46, 95% CI = 1.32 to 1.62), and further increased with high-range prehypertension (RR = 1.80, 95% CI = 1.41 to 2.31). The relative risk was significantly higher in the high-range prehypertensive populations than in the low-range populations (χ2
= 5.69, P = 0.02). There were no significant differences among the other subgroup analyses (P>0.05).

Conclusions

Prehypertension, even in the low range, elevates the risk of CVD after adjusting for multiple cardiovascular risk factors.
Galactosialidosis: review and analysis of CTSA gene mutations
Authors: Caciotti Anna , Catarzi Serena , Tonin Rodolfo , Lugli Licia , Perez Carmen Rodriguez , Michelakakis Helen , Mavridou Irene , Donati Maria Alice , Guerrini Renzo , d’Azzo Alessandra , Morrone Amelia
Published: August 2013

Background

Mutations in the CTSA gene, that encodes the protective protein/cathepsin A or PPCA, lead to the secondary deficiency of β-galactosidase (GLB1) and neuraminidase 1 (NEU1), causing the lysosomal storage disorder galactosialidosis (GS). Few clinical cases of GS have been reported in the literature, the majority of them belonging to the juvenile/adult group of patients.

Methods

The correct nomenclature of mutations for this gene is discussed through the analysis of the three PPCA/CTSA isoforms available in the GenBank database. Phenotype-genotype correlation has been assessed by computational analysis and review of previously reported single amino acid substitutions.

Results

We report the clinical and mutational analyses of four cases with the rare infantile form of GS. We identified three novel nucleotide changes, two of them resulting in the missense mutations, c.347A>G (p.His116Arg), c.775T>C (p.Cys259Arg), and the third, c.1216C>T, resulting in the p.Gln406* stop codon, a type of mutation identified for the first time in GS. An Italian founder effect of the c.114delG mutation can be suggested according to the origin of the only three patients carrying this mutation reported here and in the literature.

Conclusions

In early reports mutations nomenclature was selected according to all CTSA isoforms (three different isoforms), thus generating a lot of confusion. In order to assist physicians in the interpretation of detected mutations, we mark the correct nomenclature for CTSA mutations. The complexity of pathology caused by the multifunctions of CTSA, and the very low numbers of mutations (only 23 overall) in relation to the length of the CTSA gene are discussed.

In addition, the in silico functional predictions of all reported missense mutations allowed us to closely predict the early infantile, late infantile and juvenile phenotypes, also disclosing different degrees of severity in the juvenile phenotype.
Analysis of nine compounds from Alpinia oxyphyllafruit at different harvest time using UFLC-MS/MS and an extraction method optimized by orthogonal design
Authors: Li Yong-Hui , Chen Feng , Wang Jun-fang , Wang Yong , Zhang Jun-Qing , Guo Tao
Published: August 2013

Background

The dried fruits of Alpinia oxyphylla Miq have been widely used as an herbal medicine for the treatment of diarrhea and enuresis in China. Medicinal chemistry studies revealed that the tepenes, diphenylheptanes and flavones were the main components. Therefore, these three kinds of components should be chosen as the bioactive marker compounds for the quality control of A. oxyphylla fruits. Moreover, multiple active components has been widely recognized to be a more feasible method for the quality control of herbal medicines. This study firstly provided a better method for comprehensive component analysis of A. oxyphylla fruits. Meanwhile, the different harvest time was also evaluated.

Results

The solvent-to-sample ratio was the most important factor comparing with solvent, extraction time and temperature. The highest yield of nine compounds was achieved with 70% ethanol-water and a solvent-to-sample ratio of 20:1 at 60°C for 30 min. The optimized analytical method for ultra fast high performance liquid chromatography (UFLC) was a gradient elution using water containing 0.04‰ formic acid (A) and methanol containing 0.04‰ formic acid (B), at a flow rate of 0.3 mL/min. Using this optimized method, nine compounds were simultaneously separated and quantified by UFLC coupled with tandem electro-spray ionized mass spectrometry (MS/MS).

Conclusions

The contents of the six bioactive compounds were reported in A. oxyphylla for the first time. The contents of nine compounds of different harvest time fruits of A. oxyphylla were assessed under the optimized extraction and UFLC-MS/MS analytical conditions, and the 45-day culture fruit had the highest content levels.
Hydrogen atoms in protein structures: high-resolution X-ray diffraction structure of the DFPase
Authors: Elias Mikael , Liebschner Dorothee , Koepke Jurgen , Lecomte Claude , Guillot Benoit , Jelsch Christian , Chabriere Eric
Published: August 2013

Background

Hydrogen atoms represent about half of the total number of atoms in proteins and are often involved in substrate recognition and catalysis. Unfortunately, X-ray protein crystallography at usual resolution fails to access directly their positioning, mainly because light atoms display weak contributions to diffraction. However, sub-Ångstrom diffraction data, careful modeling and a proper refinement strategy can allow the positioning of a significant part of hydrogen atoms.

Results

A comprehensive study on the X-ray structure of the diisopropyl-fluorophosphatase (DFPase) was performed, and the hydrogen atoms were modeled, including those of solvent molecules. This model was compared to the available neutron structure of DFPase, and differences in the protein and the active site solvation were noticed.

Conclusions

A further examination of the DFPase X-ray structure provides substantial evidence about the presence of an activated water molecule that may constitute an interesting piece of information as regard to the enzymatic hydrolysis mechanism.
Immunomodulation therapy with lenalidomide in follicular, transformed and diffuse large B cell lymphoma: current data on safety and efficacy
Authors: Desai Madhav , Newberry Kate J , Romaguera Jorge , Zhang Liang , Ou Zhishuo , Wang Michael
Published: August 2013

Lenalidomide is an immunomodulatory agent which has been approved for multiple myeloma. Lenalidomide is also effective in and tolerated well by patients with follicular lymphoma, diffuse large B-cell lymphoma, and transformed large cell lymphoma. This review summarizes the results of current preclinical and clinical studies of lenalidomide, alone or in combination with the monoclonal antibody rituximab, as a therapeutic option for these three lymphoma types. This review will serve as a tool guiding future clinical investigations to improve survival rates for these three lymphomas.
DNA methylation and differentiation: HOX genes in muscle cells
Authors: Tsumagari Koji , Baribault Carl , Terragni Jolyon , Chandra Sruti , Renshaw Chloe , Sun Zhiyi , Song Lingyun , Crawford Gregory E , Pradhan Sriharsa , Lacey Michelle , Ehrlich Melanie
Published: August 2013

Background

Tight regulation of homeobox genes is essential for vertebrate development. In a study of genome-wide differential methylation, we recently found that homeobox genes, including those in the HOX gene clusters, were highly overrepresented among the genes with hypermethylation in the skeletal muscle lineage. Methylation was analyzed by reduced representation bisulfite sequencing (RRBS) of postnatal myoblasts, myotubes and adult skeletal muscle tissue and 30 types of non-muscle-cell cultures or tissues.

Results

In this study, we found that myogenic hypermethylation was present in specific subregions of all four HOX gene clusters and was associated with various chromatin epigenetic features. Although the 3′ half of the HOXD cluster was silenced and enriched in polycomb repression-associated H3 lysine 27 trimethylation in most examined cell types, including myoblasts and myotubes, myogenic samples were unusual in also displaying much DNA methylation in this region. In contrast, both HOXA and HOXC clusters displayed myogenic hypermethylation bordering a central region containing many genes preferentially expressed in myogenic progenitor cells and consisting largely of chromatin with modifications typical of promoters and enhancers in these cells. A particularly interesting example of myogenic hypermethylation was HOTAIR, a HOXC noncoding RNA gene, which can silence HOXD genes in trans via recruitment of polycomb proteins. In myogenic progenitor cells, the preferential expression of HOTAIR was associated with hypermethylation immediately downstream of the gene. Other HOX gene regions also displayed myogenic DNA hypermethylation despite being moderately expressed in myogenic cells. Analysis of representative myogenic hypermethylated sites for 5-hydroxymethylcytosine revealed little or none of this base, except for an intragenic site in HOXB5 which was specifically enriched in this base in skeletal muscle tissue, whereas myoblasts had predominantly 5-methylcytosine at the same CpG site.

Conclusions

Our results suggest that myogenic hypermethylation of HOX genes helps fine-tune HOX sense and antisense gene expression through effects on 5′ promoters, intragenic and intergenic enhancers and internal promoters. Myogenic hypermethylation might also affect the relative abundance of different RNA isoforms, facilitate transcription termination, help stop the spread of activation-associated chromatin domains and stabilize repressive chromatin structures.
Reduced expression of brain cannabinoid receptor 1 (Cnr1) is coupled with an increased complementary micro-RNA (miR-26b) in a mouse model of fetal alcohol spectrum disorders
Authors: Stringer Randa L , Laufer Benjamin I , Kleiber Morgan L , Singh Shiva M
Published: August 2013

Background

Prenatal alcohol exposure is known to result in fetal alcohol spectrum disorders, a continuum of physiological, behavioural, and cognitive phenotypes that include increased risk for anxiety and learning-associated disorders. Prenatal alcohol exposure results in life-long disorders that may manifest in part through the induction of long-term gene expression changes, potentially maintained through epigenetic mechanisms.

Findings

Here we report a decrease in the expression of Canabinoid receptor 1 (Cnr1) and an increase in the expression of the regulatory microRNA miR-26b in the brains of adult mice exposed to ethanol during neurodevelopment. Furthermore, we show that miR-26b has significant complementarity to the 3’-UTR of the Cnr1 transcript, giving it the potential to bind and reduce the level of Cnr1 expression.

Conclusions

These findings elucidate a mechanism through which some genes show long-term altered expression following prenatal alcohol exposure, leading to persistent alterations to cognitive function and behavioural phenotypes observed in fetal alcohol spectrum disorders.
Single-feature polymorphism mapping of isogenic rice lines identifies the influence of terpene synthase on brown planthopper feeding preferences
Authors: Kamolsukyunyong Wintai , Sukhaket Wissarut , Ruanjaichon Vinitchan , Toojinda Theerayut , Vanavichit Apichart
Published: August 2013

Background

Bph3, a major brown planthopper (BPH) resistance locus derived from the rice cultivar Rathu Heenati (RH), has been used as a stable donor of traits that improve highly susceptible aromatic rice varieties in Thailand. Map-based cloning was initiated using a set of isogenic lines (ILs) harboring the major Bph3 locus on chromosome 6. IL genomes were scanned with a 57 K Affymetrix Rice GeneChip to identify the gene responsible for Bph3.

Findings

Single-feature polymorphism (SFP) mapping was used to localize 84 candidate genes. An expression analysis of 15 selected candidate genes in the aromatic rice cultivar KDML105 (KD) and the ILs under normal conditions revealed two differentially expressed sequences. Following hopper feeding, only one candidate gene, Os04g27430, was differentially expressed. Os04g27430 encodes a putative sesquiterpene synthase (STPS) gene that was induced by BPH feeding in ILs. An antixenosis test in three selected ILs revealed a major role for STPS in insect preference during the first 120 hours of the rice-insect interaction. Functional SNPs in exon 5 that resulted in the deletion of seven amino acids in the susceptible rice line were identified. Moreover, three additional SNPs associated with three transcription binding sites were also identified, which might explain the differential response of Os04g27430 during the anti-feeding test.

Conclusion

Os04g27430 is the second known rice STPS induced by BPH. The gene may involve an antixenosis BPH resistance mechanism. The combination of the STPS and the Bph3 locus was more effective than Bph3 alone in the tested ILs.
Organizational performance, Marketing strategy, and Financial strategic alignment: an empirical study on Iranian pharmaceutical firms
Authors: Mohammadzadeh Mehdi , Aarabi Sied Mohammad , Salamzadeh Jamshid
Published: August 2013

Background

Strategic Functional-level planning should be aligned with business level and other functional strategies of a company. It is presumed that assimilating the strategies could have positive contribution to business performance, in this regard alignment between marketing strategy and financial strategy seems to be the most important strategies being studied. An empirical work in generic pharmaceutical manufacturing companies for evaluating effect of alignment between these two functions on organizational performance was developed in this paper.

Methods

All Iranian pharmaceutical generic manufactures listed in Tehran stock market have been tested for period of five years between 2006–2010 and their marketing strategies were determined by using Slater and Olson taxonomy and their financial strategies have been developed by calculating total risk and total return of sample companies for five years based on rate of risk and return in the frame of a 2 × 2 matrix. For the business performance three profitability indices including Q-Tubin (Rate of market value to net asset value), ROA (Return on Asset), ROE (Return on Equity) have been tested. For analysis, a series of one-way ANOVAs as a collection of statistical models within marketing strategies considering financial strategy as independent variable and the three performance measures as dependent variables was used.

Results

Results show strategic alignment between financial and marketing has significant impact on profitability of company resulting in arise of all three profitability indices. Q tubing’s rate were 2.33,2.09,2.29,2.58 and rate of ROA were 0.21,0.194,0.25,0.22 and rate of ROE were 0.44,0.46,0.45,0.42 for matched strategy types, respectively the rates shown here are more than average meaning that specific type of marketing strategy is fitted with specific type of financial strategy.

Conclusion

Managers should not consider decisions regarding marketing strategy independently of their financial strategy.
18F-MK-9470 PET imaging of the type 1 cannabinoid receptor in prostate carcinoma: a pilot study
Authors: Emonds Kimy M , Koole Michel , Casteels Cindy , Van den Bergh Laura , Bormans Guy M , Claus Filip , De Wever Liesbeth , Lerut Evelyne , Van Poppel Hendrik , Joniau Steven , Dumez Herlinde , Haustermans Karin , Mortelmans Luc , Goffin Karolien , Van Laere Koen , Deroose Christophe M , Mottaghy Felix M
Published: August 2013

Background

Preclinical and histological data show overexpression of the type 1 cannabinoid receptor (CB1R) in prostate carcinoma (PCa). In a prospective study, the feasibility of 18F-MK-9470 positron emission tomography (PET) imaging in patients with primary and metastatic PCa was evaluated.

Methods

Eight patients were included and underwent 18F-MK-9470 PET/CT imaging. For five patients with primary PCa, dynamic PET/CT imaging was performed over three acquisition intervals (0 to 30, 60 to 90 and 120 to 150 min post-injection). In malignant and benign prostate tissue regions, time activity curves of the mean standardized uptake value (SUVmean) were determined as well as the corresponding area under the curve to compare 18F-MK-9470 uptake over time. Muscle uptake of 18F-MK-9470 was used as reference for non-specific binding. Magnetic resonance imaging (MRI) was used as anatomical reference and for delineating intraprostatic tumours. Histological and immunohistochemical (IHC) examination was performed on the whole-mount histopathology sections of four patients who underwent radical prostatectomy to assess the MRI-based tumour versus benign tissue classification. For three patients with proven advanced metastatic disease, two static PET/CTs were performed 1 and 3 h post-injection. 18F-MK-9470 uptake was evaluated in bone lesions of metastatic PCa by comparing SUVmean values of metastases with these of the contralateral bone tissue.

Results

18F-MK-9470 uptake was significantly higher in benign and malignant prostate tissue compared to muscle, but it did not differ between both prostate tissue compartments. IHC findings of corresponding prostatic histopathological sections indicated weak CB1R expression in locally confined PCa, which was not visualized with 18F-MK-9470 PET. Metastases in the axial skeleton could not be detected while some metastases in the appendicular skeleton showed higher 18F-MK-9470 uptake as compared to the uptake in contralateral normal bone.

Conclusions

18F-MK-9470 PET could not detect local PCa or bone metastases in the axial skeleton but was able to visualize metastases in the appendicular skeleton. Based on these pilot observations, it seems unlikely that CB1R PET will play a significant role in the evaluation of PCa.
Effect of mercaptoethanol and Na2S dropwise addition rate on zinc sulfide semiconductor nanocrystals: synthesis and characterization
Authors: Rahdar Abbas
Published: August 2013

Zinc sulfide (ZnS) semiconductor nanocrystals with mercaptoethanol (ME) as a stabilizer (capping agent) were synthesized by coprecipitation method in room temperature using the solution of zinc chloride (ZnCl2) and sodium sulfide (Na2S) as starting material. The effect of ME and Na2S dropwise addition rate on the preparation of these samples was measured using UV–vis absorption and X-ray diffraction (XRD). The ultraviolet–visible (UV–vis) absorption and XRD of the prepared ZnS nanoparticles show increase of band gap and decrease of particle size with decrease in ME and Na2S dropwise addition rate to the reaction medium. This behavior is related to the size quantization effect due to the small size of the particles. The photoluminescence emission peak positions exhibit obvious blue shift from 510 to 455 nm. The particle sizes were obtained from transmission electron microscopy images.
Trace detection of thiols with Fourier transforms cyclic voltammetry technique in flowing solutions
Authors: Barshan-Tashnizi Mohammad , Ebrahimi-Hoseinzadeh Bahman , Daneshgar Parandis , Norouzi Parviz
Published: August 2013

Electrochemical experiments have an increasing demand for determining the concentration of biological and environmental samples as simple, inexpensive, and rapid analytical methods. Most developments in electroanalytical chemistry in recent years have originated from advances in sensor design, chemical modification, and functionalization of electrodes for enhanced sensitivity and selectivity of electroanalysis. In this work, a novel method for the fast monitoring of a thiol compound in flow injection systems has been developed. The fast Fourier transform continuous cyclic voltammetry at carbon paste electrode in flowing solution system was used for the determination of a thiol compound. The suggested technique demonstrated some advantages over other reported methods. Picomolar detection limit that is fast enough for the determination of any thiol compound was achieved. The linearization equation was current = 24.601x + 3.7068, with the correlation coefficients of 0.9812. The obtained detection limit was calculated to be 14.80 × 10−14 mol thiocholine (thiol compound sample). This system offers the necessary accuracy, sensitivity, and selectivity to assay a thiol compound in various sensors.
Fruit-mediated synthesis of silver nanoparticles using Vitis vinifera and evaluation of their antimicrobial efficacy
Authors: Gnanajobitha Gnanadhas , Paulkumar Kanniah , Vanaja Mahendran , Rajeshkumar Shanmugam , Malarkodi Chelladurai , Annadurai Gurusamy , Kannan Cellapandian
Published: August 2013

Nanobiotechnology is a rapidly growing scientific field of producing and constructing devices utilizing nanosized particles of about nanometer scale level (1 to 100 nm). Nowadays, nanoparticles have potential effects in life sciences and human health care applications. Among the nanoparticles, silver nanoparticles are playing a major role in the field of biomedical nanotechnology and nanomedicine. Silver is a naturally occurring precious metal, most often as a mineral ore in association with other elements. Silver nanoparticle has a natural antimicrobial effect against many pathogens such as bacteria, fungus, viruses, and yeast. In this present study, the silver nanoparticle is produced using Vitis vinifera fruit extract, and the purified nanoparticles will be used as an antibacterial agent against Bacillus subtilis and Klebsiella planticola. This green chemistry for the biosynthesis of silver nanoparticles has several advantages such as cost-effectiveness and compatibility for biomedical and pharmaceutical applications as well as for large-scale commercial production. Apart from this, it is an eco-friendly process, and compared with microorganisms, plant extract biorecovery unit has an added benefit of ease handling.
Human TLR8 is activated upon recognition ofBorrelia burgdorferiRNA in the phagosome of human monocytes
Authors: Cervantes Jorge L , La Vake Carson J , Weinerman Bennett , Luu Stephanie , O'Connell Caitlin , Verardi Paulo H , Salazar Juan C
Published: August 2013

Phagocytosed Borrelia burgdorferi (Bb), the Lyme disease spirochete, induces a robust and complex innate immune response in human monocytes, in which TLR8 cooperates with TLR2 in the induction of NF-κB-mediated cytokine production, whereas TLR8 is solely responsible for transcription of IFN-β through IRF7. We now establish the role of Bb RNA in TLR8-mediated induction of IFN-β. First, using TLR2-transfected HEK.293 cells, which were unable to phagocytose intact Bb, we observed TLR2 activation by lipoprotein-rich borrelial lysates and TLR2 synthetic ligands but not in response to live spirochetes. Purified Bb RNA, but not borrelial DNA, triggered TLR8 activation. Neither of these 2 ligands induced activation of TLR7. Using purified human monocytes we then show that phagocytosed live Bb, as well as equivalent amounts of borrelial RNA delivered into the phagosome by polyethylenimine (PEI), induces transcription of IFN-β and secretion of TNF-α. The cytokine response to purified Bb RNA was markedly impaired in human monocytes naturally deficient in IRAK-4 and in cells with knockdown TLR8 expression by small interfering RNA. Using confocal microscopy we provide evidence that TLR8 colocalizes with internalized Bb RNA in both early (EEA1) and late endosomes (LAMP1). Live bacterial RNA staining indicates that spirochetal RNA does not transfer from the phagosome into the cytosol. Using fluorescent dextran particles we show that phagosomal integrity in Bb-infected monocytes is not affected. We demonstrate, for the first time, that Bb RNA is a TLR8 ligand in human monocytes and that transcription of IFN-β in response to the spirochete is induced from within the phagosomal vacuole through the TLR8-MyD88 pathway.
Proton Conductivity of Graphene Oxide Hybrids with Covalently Functionalized Alkylamines
Authors: Ikeda Yukino , Karim Mohammad Razaul , Takehira Hiroshi , Matsui Takeshi , Taniguchi Takaaki , Koinuma Michio , Matsumoto Yasumichi , Hayami Shinya
Published: August 2013

Graphene oxide–alkylamine (GO–Cnamine; n = 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, and 18) hybrids were synthesized and found to be stable through bonding between the N-terminals of the amine precursors and the epoxy sites of graphene. The hybrids were characterized by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and powder X-ray diffraction (PXRD) analysis. The hybrids with short alkyl chains were found to exhibit high proton conductivity. The hybrids indicate the possibility of designing new materials through chemical bonding between long alkyl chains and graphene materials.
What Does Health Reform Mean for the Health Care Industry? Evidence from the Massachusetts Special Senate Election
Authors: Al-Ississ Mohamad M , Miller Nolan H
Published: August 2013

We exploit the surprise election of Republican Scott Brown to the US Senate to evaluate the market's assessment of the impact of the recent US health reform legislation on the health care industry. We find that Brown's election was associated with abnormal returns of 2.1 percent and 6 percent for investments in the health care sector overall and managed care firms, respectively. Investments in the pharmaceutical sector experienced abnormal returns of 2.8 percent, while health care facilities (e.g., hospitals) experienced abnormal losses of 3.5 percent. Firms involved with Medicare Advantage benefitted more, while those involved with Medicaid Managed Care benefitted less from the election. (JEL D72, H51, I11, I18)
Local Responses to Federal Grants: Evidence from the Introduction of Title I in the South
Authors: Cascio Elizabeth U , Gordon Nora , Reber Sarah
Published: August 2013

We analyze the effects of the introduction of Title I of the 1965 Elementary and Secondary Education Act, a large federal grants program designed to increase poor students' educational services and achievement. We focus on the South, the poorest region of the country. Title I increased school spending by $0.50 on the dollar in the average southern school district and by more in districts with less ability to offset grants through local tax reductions. Title I-induced increases in school budgets appear to have reduced high school dropout rates of whites, but not blacks. (JEL H52, H75, I21, I28, J15)
The Effect of a Universal Child Benefit on Conceptions, Abortions, and Early Maternal Labor Supply
Authors: González Libertad
Published: August 2013

I study the impact of a universal child benefit on fertility and maternal labor supply. I exploit the unanticipated introduction of a sizable child benefit in Spain in 2007. Following a regression discontinuity-type design, I find that the benefit significantly increased fertility, in part through a reduction in abortions. Families who received the benefit did not increase consumption. Instead, eligible mothers stayed out of the labor force longer after childbirth, which led to their children spending less time in formal child care. (JEL I38, J13, J16, J22)
Substitution and Stigma: Evidence on Religious Markets from the Catholic Sex Abuse Scandal
Authors: Hungerman Daniel M
Published: August 2013

This paper considers substitution between charitable activities in the context of religious practice by examining the Catholic Church sex abuse scandal's impact on both Catholic and non-Catholic religiosity. I find a fall in the Catholic population compensated by increases in non-Catholic participation and nonaffiliation. Back-of-the-envelope calculations suggest the scandal generated about $3 billion dollars in donations to non-Catholic faiths. Those leaving Catholicism frequently chose dissimilar alternatives: Baptist churches gained significantly while the Episcopal Church did not. These results challenge several theories of religiosity and suggest that policies or shocks specific to one religious group could have effects on other groups. (JEL D64, Z12)
The Sky Is Not Flat: How Discriminatory Is the Access to International Air Services?
Authors: Piermartini Roberta , Rousová Linda
Published: August 2013

Using information on 2,300 Air Services Agreements covering 184 countries, we investigate the impact of air services liberalization on passenger flows. We find that a certain level of liberalization is required to have a positive effect on passenger traffic. In particular, we estimate that the multilateralization of multiple designation provisions, Open Skies Agreements and European Economic Area-type agreements would increase passenger traffic worldwide by 0.5, 5, and 10 percent, respectively. The potential endogeneity problem is carefully dealt with using instrumental variables and propensity score matching. (JEL F13, L51, L93, L98, R41)
Beyond Work Ethic: Religion, Individual, and Political Preferences
Authors: Basten Christoph , Betz Frank
Published: August 2013

We investigate the effect of Reformed Protestantism, relative to Catholicism, on preferences for leisure, and for redistribution and intervention in the economy. We use a Fuzzy Spatial Regression Discontinuity Design to exploit a historical quasi-experiment in Western Switzerland, where in the sixteenth century a hitherto homogeneous region was split and one part assigned to adopt Protestantism. We find that Reformed Protestantism reduces referenda voting for more leisure by 14, redistribution by 5, and government intervention by 7 percentage points. These preferences translate into higher per capita income as well as greater income inequality. (JEL D12, D31, D72, H23, N33, Z12)
2-Matchings, the Traveling Salesman Problem, and the Subtour LP: A Proof of the Boyd-Carr Conjecture
Authors: Schalekamp Frans , Williamson David P. , van Zuylen Anke
Published: August 2013

Determining the precise integrality gap for the subtour linear programming (LP) relaxation of the traveling salesman problem is a significant open question, with little progress made in thirty years in the general case of symmetric costs that obey triangle inequality. Boyd and Carr [Boyd S, Carr R (2011) Finding low cost TSP and 2-matching solutions using certain half-integer subtour vertices. Discrete Optim. 8:525–539. Prior version accessed June 27, 2011, http://www.site.uottawa.ca/~sylvia/recentpapers/halftri.pdf .] observe that we do not even know the worst-case upper bound on the ratio of the optimal 2-matching to the subtour LP; they conjecture the ratio is at most 10/9.

In this paper, we prove the Boyd-Carr conjecture. In the case that the support of a fractional 2-matching has no cut edge, we can further prove that an optimal 2-matching has cost at most 10/9 times the cost of the fractional 2-matching.
On Optimal Policies for Production-Inventory Systems with Compound Poisson Demand and Setup Costs
Authors: Van Foreest Nicky D. , Wijngaard Jacob
Published: August 2013

In this paper, we consider a single-item, one-machine production-inventory system with compound Poisson demand. The production facility may be on or off. While on, the production rate is constant, and, while off, the production rate is zero. System costs consist of switching costs and inventory and backlogging costs. We provide conditions when (s, S)-policies are optimal under the long-run average expected cost criterion. These conditions are met in particular, but not necessarily, when the inventory costs are convex. The developed method in the proof is easy to apply to more general cases. Moreover, the method allows us to compute optimal policies very efficiently.
Knowledge and Perceptions About Fragile X Syndrome: Implications for Diagnosis, Intervention, and Research
Authors: Finucane Brenda , Haas-Givler Barbara , Simon Elliott W.
Published: August 2013

We surveyed 439 professionals in the field of autism to assess their knowledge and perceptions about fragile X syndrome (FXS) and related issues. Almost half had worked with at least one child diagnosed with FXS, yet most lacked basic knowledge about the condition, underestimated its significance in the etiology of autism spectrum disorders, and rarely accessed fragile X–specific resources. A majority perceived etiology to be an important variable in therapeutic response while three quarters felt that professionals in the field of autism should play an active role in referring children for etiological evaluation. Despite these opinions, most respondents either rarely or never inquired about etiology when working with a new client. The survey results underscore the need for training and education so that autism professionals can become effective partners in diagnostic genetic referral and in research and implementation of syndrome-specific interventions.
Reflective Impressions of a Precepted Clinical Experience Caring for People With Disabilities
Authors: Karl Renee , McGuigan Denise , Withiam-Leitch Matthew L. , Akl Elie A. , Symons Andrew B.
Published: August 2013

There is evidence that early and frequent encounters with people with disabilities can improve medical students' knowledge, skills, and attitudes about disability. As part of a 4-year integrated curriculum in caring for patients with disabilities, third-year medical students (n  =  144) in a Family Medicine clerkship participated in a day-long precepted clinical experience at a medical facility serving people with disabilities, predominantly developmental disabilities, where they met patients and worked with clinicians. At the conclusion of the program, students completed a reflective survey about their experience. These data were analyzed qualitatively using a constructivist grounded-theory approach. Students' responses indicated that the experience improved their comfort levels in working with people with disabilities and increased their awareness of attitudinal factors that influence patient care. Responses also demonstrated that students achieved an awareness of technical accommodations and organizational adaptations that improve patient care.