bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations of Gab2 signalling complexes in imatinib and dasatinib treated chronic myeloid leukaemia cells
Authors: Halbach Sebastian , Rigbolt Kristoffer TG , Wöhrle Franziska U , Diedrich Britta , Gretzmeier Christine , Brummer Tilman , Dengjel Jörn
Published: April 2013

Background

The Gab2 docking protein acts as an important signal amplifier downstream of various growth factor receptors and Bcr-Abl, the driver of chronic myeloid leukaemia (CML). Despite the success of Bcr-Abl tyrosine kinase inhibitors (TKI) in the therapy of CML, TKI-resistance remains an unsolved problem in the clinic. We have recently shown that Gab2 signalling counteracts the efficacy of four distinct Bcr-Abl inhibitors. In the course of that project, we noticed that two clinically relevant drugs, imatinib and dasatinib, provoke distinct alterations in the electrophoretic mobility of Gab2, its signalling output and protein interactions. As the signalling potential of the docking protein is highly modulated by its phosphorylation status, we set out to obtain more insights into the impact of TKIs on Gab2 phosphorylation.

Findings

Using stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative mass spectrometry (MS), we show now that imatinib and dasatinib provoke distinct effects on the phosphorylation status and interactome of Gab2. This study identifies several new phosphorylation sites on Gab2 and confirms many sites previously known from other experimental systems. At equimolar concentrations, dasatinib is more effective in preventing Gab2 tyrosine and serine/threonine phosphorylation than imatinib. It also affects the phosphorylation status of more residues than imatinib. In addition, we also identify novel components of the Gab2 signalling complex, such as casein kinases, stathmins and PIP1 as well as known interaction partners whose association with Gab2 is disrupted by imatinib and/or dasatinib.

Conclusions

By using MS-based proteomics, we have identified new and confirmed known phosphorylation sites and interaction partners of Gab2, which may play an important role in the regulation of this docking protein. Given the growing importance of Gab2 in several tumour entities we expect that our results will help to understand the complex regulation of Gab2 and how this docking protein can contribute to malignancy.
Effects of age on noninvasive assessments of vascular function in nonhuman primates: implications for translational drug discovery
Authors: Knight Delvin R , Smith Andrew H , Schroeder Richard L , Huang Chunli , Beebe David A , Sokolowski Sharon A , Wang Miao
Published: April 2013

Background

Endothelium-dependent flow mediated dilation (FMD) and pulse-wave velocity (PWV), are used as measures of vascular health and predictors of cardiovascular risk in clinical studies, and both are age-dependent. Numbers of circulating endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) are also associated with cardiovascular risk, but independent of age in humans. The use of these measurements for pre-clinical assessment of drug cardiovascular safety and efficacy in non-human primates (NHPs) may promote the translation of drug-induced effects on vascular function to clinic outcomes. However, in NHPs, the age effects on the non-invasive measurements of FMD and PWV and the relationship of EMPs/EPCs with FMD are unknown.

Methods

A non-invasive, clinically-relevant approach to assess FMD and PWV was used to examine their relationship with age and with EMPs/EPCs in NHPs. The effects on FMD of nicotine and rosiglitazone were evaluated in senescent primates in an effort to validate our FMD method for pre-clinical assessment of vascular function.

Results

FMD and PWV methods were established in a colony (n = 25) of metabolically healthy, cynomolgus monkeys ranging in age from 6 to 26 years. FMD, defined as the percent change, at 1 min of cuff release, from baseline vascular diameter (0.15 ± 0.03 cm), had a strong, negative correlation with age (r = -0.892, p < 0.0001), ranging from 6% to 33%. PWV positively correlated with age (r = 0.622, p < 0.002) in the same healthy monkeys. Nicotine and rosiglitazone, were evaluated in subsets of senescent primates (mean age 16.3 ± 1.5[SEM] years). Rosiglitazone significantly improved FMD (21.0 ± 1.6% vs. vehicle 16.3 ± 1.6%, p < 0.01) without changing baseline diameters, and coincided with a significant increase in circulating numbers of endothelial progenitor cells (CD45-CD31 + CD34 + VEGFR2+ 7.1 ± 1.3 vs. 4.8 ± 1.1 counts/μl) and a decrease in endothelial microparticles (CD45-CD42a-CD54+ 26.7 ± 11.1 vs. 62.2 ± 9.8 counts/μl)(p < 0.05). Conversely, FMD was significantly reduced with nicotine (8.7 ± 1.4% vs. vehicle 20.1 ± 2.2%, p < 0.05).

Conclusions

Adult NHPs demonstrate the characteristic linear relationship between age and vascular function using the non-invasive clinically-related measurements of FMD and PWV. However, numbers of circulating EMPs and EPCs did not correlate with age. Endothelial function assessed with FMD, together with EMPs/EPCs assessment, may serve as a novel approach for translational research and therapeutic discovery. Age should be considered in the study design or data analyses when FMD or PWV is used in NHPs.
Study of nanostructure growth with nanoscale apex induced by femtosecond laser irradiation at megahertz repetition rate
Authors: Patel Nikunj B , Tan Bo , Venkatakrishnan Krishnan
Published: April 2013

Leaf-like nanostructures with nanoscale apex are induced on dielectric target surfaces by high-repetition-rate femtosecond laser irradiation in ambient conditions. We have recently developed this unique technique to grow leaf-like nanostructures with such interesting geometry without the use of any catalyst. It was found to be possible only in the presence of background nitrogen gas flow. In this synthesis method, the target serves as the source for building material as well as the substrate upon which these nanostructures can grow. In our investigation, it was found that there are three possible kinds of nanotips that can grow on target surfaces. In this report, we have presented the study of the growth mechanisms of such leaf-like nanostructures under various conditions such as different laser pulse widths, pulse repetition rates, dwell times, and laser polarizations. We observed a clear transformation in the kind of nanotips that grew for the given laser conditions.
Infant gut microbiota and the hygiene hypothesis of allergic disease: impact of household pets and siblings on microbiota composition and diversity
Authors: Azad Meghan B , Konya Theodore , Maughan Heather , Guttman David S , Field Catherine J , Sears Malcolm R , Becker Allan B , Scott James A , Kozyrskyj Anita L ,   CHILD Study Investigators
Published: April 2013

Background

Multiple studies have demonstrated that early-life exposure to pets or siblings affords protection against allergic disease; these associations are commonly attributed to the “hygiene hypothesis”. Recently, low diversity of the infant gut microbiota has also been linked to allergic disease. In this study, we characterize the infant gut microbiota in relation to pets and siblings.

Methods

The study population comprised a small sub-sample of 24 healthy, full term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mothers reported on household pets and siblings. Fecal samples were collected at 4 months of age, and microbiota composition was characterized by high-throughput signature gene sequencing.

Results

Microbiota richness and diversity tended to be increased in infants living with pets, whereas these measures were decreased in infants with older siblings. Infants living with pets exhibited under-representation of Bifidobacteriaceae and over-representation of Peptostreptococcaceae; infants with older siblings exhibited under-representation of Peptostreptococcaceae.

Conclusions

This study provides new evidence that exposure to pets and siblings may influence the early development of the gut microbiota, with potential implications for allergic disease. These two traditionally protective “hygiene hypothesis” factors appear to differentially impact gut microbiota composition and diversity, calling into question the clinical significance of these measures. Further research is required to confirm and expand these findings.
A juvenile case of conjunctival atypical nevus
Authors: Colarossi Cristina , Milazzo Mario , Paglierani Milena , Massi Daniela , Memeo Lorenzo , Canzonieri Vincenzo
Published: April 2013

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2973228795724608

Melanocytic nevi are the most common tumors of the conjunctiva, accounting for 28% of all neoplastic lesions. These tumors, despite their benign behavior, share some atypical histological features with nevi found in other anatomic sites like the genital and acral regions, globally designated as nevi with site-related atypia. Moreover, in children and adolescents, rapidly growing conjunctival nevi show sometimes worrisome histological patterns in association with a prominent inflammatory infiltrate that may lead to diagnostic problems. In this paper we describe a juvenile compound nevus characterized by marked melanocytic atypia and severe inflammation, which can be considered a rare case of juvenile conjunctival atypical nevus. The final diagnosis relied on morphological and immunohistochemical characterization of the large epithelioid melanocytic cells, and on the results of FISH analysis.
Clinical validation of the gastrointestinal NET grading system: Ki67 index criteria of the WHO 2010 classification is appropriate to predict metastasis or recurrence
Authors: Yamaguchi Takeshi , Fujimori Takahiro , Tomita Shigeki , Ichikawa Kazuhito , Mitomi Hiroyuki , Ohno Kazuya , Shida Yosuke , Kato Hiroyuki
Published: April 2013

Background

In the WHO 2010 classification, the neuroendocrine tumors (NETs) are subdivided by their mitotic index or Ki67 index into either G1 or G2 NETs. Tumors with a Ki67 index of <2% are classified as G1 and those with 3—20% are classified as G2. However, the assessment of tumors with Ki67 index of greater than 2% and less than or equal to 3% is still unclear. To resolve the problem, we validated the Ki67 index criteria of gastrointestinal NETs of the WHO 2010 classification.

Methods

The medical records of 45 patients who were pathologically diagnosed as having NET G1/G2 of the gastrointestinal tract were analyzed retrospectively. According to the WHO 2010 classification, Ki67 index were calculated. Computer-assisted cytometrical analysis of Ki67 immunoreactivity was performed using the WinRooF image processing software. Receiver operating characteristic (ROC) curves were generated to determine the best discriminating Ki67 index. To clarify the assessment of tumors with Ki67 index between 2—3%, the calculated cutoff of Ki67 index was evaluated using Fisher’s exact test.

Results

ROC curve analysis confirmed that 2.8% was the best Ki67 index cutoff value for predicting metastasis or recurrence. The sensitivity of the new Ki67 index cutoff was 42.9%, and the specificity was 86.8%.

Conclusions

Division of NETs into G1/G2 based on Ki67 index of 3% was appropriate to predict metastases or recurrences. The WHO grading system may be the most useful classification to predict metastases or recurrences.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1553036118943799
Shear- vs. nanotopography-guided control of growth of endothelial cells on RGD-nanoparticle-nanowell arrays
Authors: McCracken Katherine E , Tran Phat L , You David J , Slepian Marvin J , Yoon Jeong-Yeol
Published: April 2013

Endothelialization of therapeutic cardiovascular implants is essential for their intravascular hemocompatibility. We previously described a novel nanowell-RGD-nanoparticle ensemble, which when applied to surfaces led to enhanced endothelialization and retention under static conditions and low flow rates. In the present study we extend our work to determine the interrelated effects of flow rate and the orientation of ensemble-decorated surface arrays on the growth, adhesion and morphology of endothelial cells. Human umbilical vascular endothelial cells (HUVECs) were grown on array surfaces with either 1 μm × 5 μm spacing (“parallel to flow”) and 5 μm × 1 μm spacing (“perpendicular to flow”) and were exposed to a range of shear stress of (0 to 4.7 ± 0.2 dyn·cm-2 ), utilizing a pulsatile flow chamber. Under physiological flow (4.7 ± 0.2 dyn·cm-2), RGD-nanoparticle-nanowell array patterning significantly enhanced cell adhesion and spreading compared with control surfaces and with static conditions. Furthermore, improved adhesion coincided with higher alignment to surface patterning, intimating the importance of interaction and response to the array surface as a means of resisting flow detachment. Under sub-physiological condition (1.7 ± 0.3 dyn·cm-2; corresponding to early angiogenesis), nanowell-nanoparticle patterning did not provide enhanced cell growth and adhesion compared with control surfaces. However, it revealed increased alignment along the direction of flow, rather than the direction of the pattern, thus potentially indicating a threshold for cell guidance and related retention. These results could provide a cue for controlling cell growth and alignment under varying physiological conditions.
Phylogeny and chronology of the major lineages of New World hystricognath rodents: insights on the biogeography of the Eocene/Oligocene arrival of mammals in South America
Authors: Voloch Carolina M , Vilela Julio F , Loss-Oliveira Leticia , Schrago Carlos G
Published: April 2013

Background

The hystricognath rodents of the New World, the Caviomorpha, are a diverse lineage with a long evolutionary history, and their representation in South American fossil record begins with their occurrence in Eocene deposits from Peru. Debates regarding the origin and diversification of this group represent longstanding issues in mammalian evolution because early hystricognaths, as well as Platyrrhini primates, appeared when South American was an isolated landmass, which raised the possibility of a synchronous arrival of these mammalian groups. Thus, an immediate biogeographic problem is posed by the study of caviomorph origins. This problem has motivated the analysis of hystricognath evolution with molecular dating techniques that relied essentially on nuclear data. However, questions remain about the phylogeny and chronology of the major caviomorph lineages. To enhance the understanding of the evolution of the Hystricognathi in the New World, we sequenced new mitochondrial genomes of caviomorphs and performed a combined analysis with nuclear genes.

Results

Our analysis supports the existence of two major caviomorph lineages: the (Chinchilloidea + Octodontoidea) and the (Cavioidea + Erethizontoidea), which diverged in the late Eocene. The Caviomorpha/phiomorph divergence also occurred at approximately 43 Ma. We inferred that all family-level divergences of New World hystricognaths occurred in the early Miocene.

Conclusion

The molecular estimates presented in this study, inferred from the combined analysis of mitochondrial genomes and nuclear data, are in complete agreement with the recently proposed paleontological scenario of Caviomorpha evolution. A comparison with recent studies on New World primate diversification indicate that although the hypothesis that both lineages arrived synchronously in the Neotropics cannot be discarded, the times elapsed since the most recent common ancestor of the extant representatives of both groups are different.
Genetic differentiation between sandfly populations of Phlebotomus chinensis and Phlebotomus sichuanensis (Diptera: Psychodidae) in China inferred by microsatellites
Authors: Zhang Li , Ma Yajun , Xu Jiannong
Published: April 2013

Background

Phlebotomus chinensis is a primary vector of visceral leishmaniasis; it occurs in various biotopes with a large geographical distribution, ranging from Yangtze River to northeast China. Phlebotomus sichuanensis, a species closely related to P. chinensis in high altitude regions, has a long term disputation on its taxonomic status. Both species occur in the current epidemic regions and are responsible for the transmission of leishmaniasis. Population genetic analysis will help to understand the population structure and infer the relationship for morphologically indistinguishable cryptic species. In this study, microsatellite markers were used for studying the genetic differentiation between P. chinensis and P. sichuanensis.

Methods

Sandflies were collected in 6 representative localities in China in 2005-2009. Ten microsatellite loci were used to estimate population genetic diversity. The intra-population genetic diversity, genetic differentiation and effective population size were estimated.

Results

All 10 microsatellite loci were highly polymorphic across populations, with high allelic richness and heterozygosity. Hardy-Weinberg disequilibrium was found in 23 out of 60 (38.33%) comparisons associated with heterozygote deficits, which was likely caused by the presence of null allele and the Wahlund effect. Bayesian clustering analysis revealed three clusters. The cluster I included almost all specimens in the sample SCD collected at high altitude habitats in Sichuan. The other two clusters were shared by the remaining 5 populations, SCJ in Sichuan, GSZ in Gansu, SXL and SXX in Shaanxi and HNS in Henan. The diversity among these 5 populations was low (F
ST = -0.003-0.090) and no isolation by distance was detected. AMOVA analysis suggested that the variations were largely derived from individuals within populations and among individuals. Consistently, the analysis of ribosomal DNA second internal transcribed spacer (ITS2) sequence uncovered three types of variants, which corresponded with the three gene pools revealed by microsatellites.

Conclusions

The data suggested that the SCD population carried a distinct gene pool, which was differentiated from the other populations. The high altitude ecological habitats, distinctive ITS2 and herein divergence inferred by microsatellite loci support the species status of P. sichuanensis. The P. chinensis populations did not have a significant divergence from each another.
Use of Bacillus thuringiensis var israelensis as a viable option in an Integrated Malaria Vector Control Programme in the Kumasi Metropolis, Ghana
Authors: Nartey Rita , Owusu-Dabo Ellis , Kruppa Thomas , Baffour-Awuah Sandra , Annan Augustina , Oppong Samuel , Becker Norbert , Obiri-Danso Kwasi
Published: April 2013

Background

Integrated Vector Control (IVC) remains the approach for managing the malaria-causing vector. The study investigated the contribution of Bacillus thuringiensis israelensis (Bti) in the control of malaria by targeting the larvae and also mapped and documented major breeding sites in the Kumasi metropolis, Ghana.

Methods

Using a hand held GPS receiver unit, major breeding sites within the metropolis were mapped out during the larval survey. Mosquito larvae were then collected from the breeding sites and reared in an insectary to obtain an F1 generation for laboratory bioassays. The minimum effective dosage of Bti Water Dispersible Granular (WDG) formulation was determined by a series of bioassays. Based on the results obtained in the laboratory, the optimum effective dosage of Bti formulations against naturally occurring larvae of the indigenous mosquito species was determined through open field trials.

Results

A total of 33 breeding sites were identified and geo-referenced during the larval surveys with the majority of the breeding sites located in the Asokwa sub-metropolis, Kumasi, Ghana. A Bti (3,000 International Toxic Unit (ITU)/mg) concentration of 0.026 mg/l resulted in 50% mortality whilst a concentration of 0.136 mg/l resulted in 95% mortality. Results from the open field trials with Bti showed that a dosage of 0.2 kg/ha is as effective as 0.4 kg/ha in suppressing late instars and resulting pupae.

Conclusion

This study reveals that Bti at a very low dosage of 0.2 kg/ha is highly effective against Anopheles larvae and therefore offers viable options for the management of vector mosquitoes. Further research is needed to extend this to the field in order to determine its ability to reduce malaria incidence.
Vancomycin-resistant Gram-positive bacterial endophthalmitis: epidemiology, treatment options, and outcomes
Authors: Khera Manav , Pathengay Avinash , Jindal Animesh , Jalali Subhadra , Mathai Annie , Pappuru Rajeev Reddy , Relhan Nidhi , Das Taraprasad , Sharma Savitri , Flynn Harry W
Published: April 2013

Background

The purpose of this study is to evaluate the microbiological profile and treatment outcomes of vancomycin-resistant Gram-positive bacterial endophthalmitis. Medical records of all patients with Gram-positive bacterial endophthalmitis resistant to vancomycin presenting between 1 January 2005 and 31 December 2010 were reviewed in this noncomparative, consecutive, retrospective case series. Favorable outcome was defined as a best-corrected visual acuity of ≥20/200.

Results

Out of 682 culture-positive endophthalmitis isolates, 448/682 (65.6%) were associated with Gram-positive bacteria. In vitro resistance to vancomycin was noted in 7/448 (1.56%). Three cases were posttraumatic, three were postoperative, and one was endogenous in origin. Four Bacillus isolates, two Staphylococcus isolates, and an Enterococcus isolate were resistant. Isolates resistant to vancomycin were sensitive in vitro to ciprofloxacin in 6/7 (86%) patients. Presenting visual acuity was light perception in all seven cases. Favorable outcome was achieved in only 1/7 (14.3%) cases.

Conclusions

Vancomycin-resistant endophthalmitis is uncommon and usually associated with poor visual outcome. Bacillus sp. is the most frequent Gram-positive bacteria resistant to vancomycin. Fluoroquinolones like ciprofloxacin may be considered as a useful alternative in vancomycin-resistant endophthalmitis.
Primary surgery versus chemoradiotherapy for advanced oropharyngeal cancers: A longitudinal population study
Authors: O'Connell Daniel , Seikaly Hadi , Murphy Russell , Fung Charles , Cooper Tim , Knox Aaron , Scrimger Rufus , Harris Jeffrey R
Published: April 2013

Background

Treatment for advanced stage oropharyngeal squamous cell carcinoma (OPSCC) includes combined chemoradiation therapy or surgery followed by radiation therapy alone or in combination with chemotherapy. The goal of this study was to utilize available evidence to examine survival outcome differences in patients with advanced stage OPSCC treated with these different modalities.

Methods

Patients with advanced stage OPSCC were identified. Primary outcome measurements were disease specific and overall survival rates with differences examined via Kaplan-Meier and logistic regression analysis.

Results

344 patients were enrolled. 94 patients underwent triple modality therapy inclusive of surgery followed by adjuvant combined chemotherapy and radiation therapy (S-CRT). 131 had surgery and radiation therapy (S-RT), while 56 had chemoradiation (CRT) therapy as their primary treatment. A total of 63 patients had single modality radiation therapy and were excluded from analysis due to the large number of palliative patients. Kaplan-Meier overall survival analysis showed that therapy with S-CRT had the highest disease specific survival at five years (71.1%). This is contrasted against S-RT and CRT, with five year survival rates at 53.9%, and 48.6%, respectively. Cox regression showed that the comparison of S-CRT vs. S-RT, and CRT is associated with statistically significant increased hazard ratios of 1.974, and 2.785, indicating that both S-RT and CRT are associated with a reduced likelihood of survival at 5 years when compared to S-CRT.

Conclusions

In this population based cohort study S-CRT is associated with a 17–22% 5 year disease specific survival benefit compared to CRT or S-RT.
Inhibition of Flavobacterium psychrophilum biofilm formation using a biofilm of the antagonist Pseudomonas fluorescen s FF48
Authors: De la Fuente Mery , Vidal José M , Miranda Claudio D , González Gerardo , Urrutia Homero
Published: April 2013

The most important bacterial pathology currently occurring in Chilean freshwater salmon farming is the cold-water disease produced by the psychrotrophic bacteria Flavobacterium psychrophilum. The main aim of this study was to characterize the inhibitory activity of an antagonist strain on the formation of biofilms of a F. psychrophilum strain. The antagonistic strain Pseudomonas fluorescens FF48 was isolated from the sediment beneath the salmon cages of a freshwater Chilean salmon farm and was identified by using the 16S rRNA gene sequence analysis. The production of siderophores, mainly during the stationary phase of growth of the antagonist strain was demonstrated using the Chrome Azurol S method and through F. psychrophilum inhibition under iron saturation conditions. Subsequently, the effect of the antagonist supernatant on the formation of F. psychrophilum biofilm was tested using the crystal violet staining method observing an inhibition of the growth of F. psychrophilum, but no effect was observed when iron saturation concentrations were used. Furthermore, when the antagonist strain was previously deposited on the support, it completely inhibited the formation of F. psychrophilum biofilms, but when both bacteria were inoculated simultaneously no inhibitory effect was detected. In conclusion, it was demonstrated that FF48 strain is able to inhibit the formation of F. psychrophilum biofilms in vitro probably mediated by the siderophore production, suggesting its potential use as a biocontrol biofilm in freshwater fish rearing systems to prevent the persistence of biofilms of the fish pathogenic species F. psychrophilum.
Phytosynthesis of silver nanoparticles by Cissus quadrangularis: influence of physicochemical factors
Authors: Vanaja Mahendran , Gnanajobitha Gnanadhas , Paulkumar Kanniah , Rajeshkumar Shanmugam , Malarkodi Chelladurai , Annadurai Gurusamy
Published: April 2013

Phytosynthesis process of silver nanoparticles using plant extract is simple, cost-effective, and ecofriendly. In this present investigation, we report the green nanoparticles prepared by using stem extract of Cissus quadrangularis and assess the physical and chemical factors such as time duration, metal ion concentration, pH, and temperature that play vital role in the nanoparticles synthesis. The maximum synthesis of silver nanoparticles was attained within 1 h, at pH 8 and 1 mM AgNO3 concentration, and 70°C. The nanoparticles obtained are characterized by UV–vis spectroscopy. Silver nanoparticles that were synthesized under these conditions show crystalline nature confirmed by X-ray diffraction and show mostly spherical and some rod and triangle shapes with sizes ranging from 37 to 44 nm, which were characterized by scanning electron microscopy. Fourier transform infrared spectroscopy shows that the functional groups are carboxyl, amine, and phenolic compounds of stem extract which are involved in the reduction of silver ions. Thus, synthesized silver nanoparticles show more antibacterial activity against Klebsiella planticola and Bacillus subtilis, which was analyzed by disc diffusion method.
Relationship of serum estrogens and estrogen metabolites to postmenopausal breast cancer risk: a nested case-control study
Authors: Falk Roni T , Brinton Louise A , Dorgan Joanne F , Fuhrman Barbara J , Veenstra Timothy D , Xu Xia , Gierach Gretchen L
Published: April 2013

Introduction

Elevated levels of circulating estrogens are linked to breast cancer risk among postmenopausal women but little is known about the importance of estrogen metabolism. A recently developed liquid chromatography tandem mass spectrometry-based method (LC-MS/MS) measuring a panel of 15 estrogen metabolites (EM) has been evaluated in one study, linking high levels of 2-pathway metabolites relative to the parent estrogens to reduced breast cancer risk. We analyzed this panel of EM in a nested case-control study of postmenopausal breast cancer.

Methods

Between 1977 and 1987, 6,915 women provided blood samples to the Columbia Missouri Serum Bank and were followed for incident breast cancer through December 2002. We studied 215 postmenopausal breast cancer cases and 215 matched controls who were postmenopausal and not using exogenous hormones at the time of blood draw. EM were examined individually, grouped by pathway (hydroxylation at the C-2, C-4 or C-16 positions of the steroid ring) and by ratios of the groupings. Logistic regression models controlling for matching and breast cancer risk factors were used to calculate quartile-specific odds ratios (ORs) and 95% CIs.

Results

Significant elevated risks were not observed for individual EM, except for quartiles of 16-epiestriol (P trend = 0.07). The OR for total EM, the parent estrogens estrone and estradiol, and 2-pathway catechol EM (2-hydroxyestrone and 2-hydroxyestradiol) were elevated but the trends were not statistically significant. Among 2-pathway metabolites, risks for the highest levels of 2-hydroxyestrone-3-methyl ether and 2-methoxyestradiol were reduced; ORs for women in the highest versus lowest quartiles were 0.57 (95% CI = 0.33 to 0.99) and 0.53 (95% CI = 0.30 to 0.96), respectively. Overall, women with higher levels of 2-pathway EM had a reduced risk of breast cancer, which remained after accounting for levels of parent EM, 4-pathway EM and 16-pathway EM (all trends, P <0.11).

Conclusions

Women with more extensive hydroxylation along the 2-pathway may have a reduced risk of postmenopausal breast cancer. Further studies are needed to clarify the risks for specific EM and complex patterns of estrogen metabolism. This will require aggregation of EM results from several studies.
Classification of corporate development projects
Authors: ������  , Pertsev Dmitriy , �������  , Pertseva Elena
Published: April 2013

Increasing organization efficiency with project approach techniques is one of the topic problems in project management. Nowadays, foreign literature parallels the introduction of changes in the organization (including those aimed at improving the effectiveness of companies� activities) and project management, but in Russian business practice and between academics there is no common approach to this problem. This article examines the role of the projects which are not pointed ongetting of additional cash flow and aimed at improving the efficiency of the organization; also the authors offer options their typology.
Biodiagnostics of Activated Sludge as a Method for Rapid Control of Wastewater Biological Treatment
Authors: Гайнетдинова  , Gaynetdinova R. , Закиров  , Zakirov R. , Балымова  , Balymova E. , Ахмадуллина  , Akhmadullina F.
Published: April 2013

In article are studied the main regularities of the industrial waste priority pollutants impact on bioagents reduction potential based on the quantitative estimation of activated sludge and wastewater from organic synthesis plants, including biological and chemical monitoring. Obtained regression equation adequately describes the state of the of activated sludge in biological treatment of a complex and variable composition wastewater.
Optimization of Oil and Gas Complex Facililities Placement in a Variety of Geoecological Conditions
Authors: Клейменова  , Kleymenova I.
Published: April 2013

Article represents examples of regional zoning of the territory on the basis of the analysis of multi-disciplinary information on the example of the promising oil and gas sites located in different atural-climatic and environmental conditions.
Forecasting and Prevention of Aircraft Accidents as a Method of Reducing the Air Transport Environmental Risk
Authors: Макаров  , Makarov V. , Николайкин  , Nikolaykin N.
Published: April 2013

This article describes a method of forecasting and prevention of aircraft accidents, allowing to reduce the air transport environmental hazard.
Toxicological Characteristics of Physiologically Active Substances
Authors: Резничек  , Reznichek V. , Карнюшкин  , Karnyushkin A. , Кармишин  , Karmishin A. , Киреев  , Kireev V.
Published: April 2013

The article deals with the basic laws of toxicity and toxicological characteristics of physiologically active substances that have a damaging effect on the human body.
Russia's intellectual potential managment within main general education system modernization
Authors: Мяснянкина
Published: April 2013

Process of education modernization in Russia from 2005 to 2012 in context of the problem of formation, development and management of younger generation’s intellectual potential is analyzed. The author focuses attention on disclosure of the content of education modernization’s basic principles and key elements of FSESs (federal state educational standards of second generation). The discrepancy of perception by professional community of education’s current state in the country and its impacts on development of younger generation’s intellectual potential is shown on the basis of sociological polls.
Motivational potential development of industrial enterprices' employees
Authors: Мюллер  , Myullyer YElyena , Катаева
Published: April 2013

The need of conscious application of various scientifi c approaches to development of motivational potential of industrial enterprises’ employees for their eff ective activity increasing is considered in this article. Authors reveal the motivational profi le content, show the social and economic importance of motivation in industrial enterprises activity in the whole and reveal motivating factors for employees of surveyed enterprises in Orenburg region.

Analyzing the concept of characteristics of J. Hekman and G. Oldham’ works, authors come to conclusion that by means of works’ motivational potential indicator introduced by Hekman and G. Oldham it becomes possible to predict the labor behavior of workers with a certain degree of accuracy.

Thus, development of motivational potential of enterprises’ employees gives the chance of additional result receiving from production ctivity as the eff ect source.
Factors which define the human capital use
Authors: Абакумова  , Abakumova Nadezhda , Булдашев
Published: April 2013

Article is devoted to identifi cation of investment effi ciency factors in the human capital. Nonlinear nature of dependence between investment in the human capital and growth of economic indicators is shown. Analyzing a number of indicators refl ecting investment effi ciency in the human capital, authors draw a conclusion that it is defi ned by the set which is assembled of factors of human capital formation and use – in particular, by duration of use of accumulated human capital. The presented analysis of infl uence of human capital use duration factor on example of three enterprises in Novosibirsk confi rms the conclusion given above.
Professional qualities of consultants for communicative processes in organization
Authors: Киреева
Published: April 2013

Personnel’s basic characteristics needed for work as consultants on organization of communicative processes are considered in this article.
Some features of cosulting as professional activity
Authors: Базлов
Published: April 2013

Article is devoted to the questions of administrative consultation and assessment features of resources of consultant or consulting fi rm.
Organizations' social responsibility role in labour potential development
Authors: Хадасевич  , Khadasevich Nailya
Published: April 2013

Organization’s social responsibility as a factor of labor potential development is considered in this article. In such a case the formation and realization of organization’s social and responsible activity shall have complex character. The subject of social responsibility of Russian business is analyzed in a context and taking into account the developed world practice. The author assigns a key role in increasing of organizations’ social responsibility to formation and development of labor potential and its separate elements.
Sociological analysis of current state of public governing bodies´ staff potential and problems of public civilian employees' professional and official development
Authors: Магомедов  , Magomedov Kerem
Published: April 2013

Analysis of results related to complex sociological research of social and professional problems of public civilian service in the Russian Federation, concerning the questions of assessment of public authorities’ staff potential capacity, of management quality and existing problems of public civilian employees’ professional and offi cial development is provided in this article. The author draws a conclusion according to which the current state of staff potential from the point of view related to even the current task decision is far from been perfect.
Crowdsourcing as technology of citizens´ intellectual potential use in public and municipal managment
Authors: Тарасова
Published: April 2013

Crowdsourcing technology use possibilities as one of communicative practice versions, gaining a wide circulation today, for increase of activity effi ciency of public authorities and local government in context of Open Government system creation problems are considered in this article. The author, on the basis of done analysis, comes to conclusion that crowdsourcing potential is far from been settled, and its directions (versions) can be successfully used for solution of a number of actual problems related to public and municipal administration.
MULTIPURPOSE HUMAN MEASUREMENTS
Authors: Леонтьев  , Leontev Boris
Published: April 2013

Open, massive, widespread and mandatory human measurements characterize the civilization level of relations in any modern society. In any state the most critical human missions should be implemented as a

result of personalities pre-selection. Any target selections and evaluations

of personalities don’t belong to the sphere of some particular science, for example, psychology, sociology, economics or law. The evaluation should be complex.
PROJECT DEVELOPMENT OF PROFESSIONAL STANDARD “EDUCATIONAL ORGANIZATION MANAGEMENT”
Authors: Шкляева  , Shklyaeva Nadezhda
Published: April 2013

The bibliographical analysis of research, dedicated to definition of professional standard intension as well as overview of the sources related to this theme is given in this article. The author directs the group of regional professional standard development. The research results on

specifi cation of educational institution director job functions are presented in this article too. The author proposes to discuss the project of regional professional standard “Educational Organization Management”.
USE OF LABOR POTENTIAL OF AGRICULTURAL ENTERPRISES
Authors: Михалкина  , Mikhalkina Elena , Коршунова
Published: April 2013

The work-force as labor potential implementation form is categorically identifi ed. The labor potential formation conditions in the agricultural sector are identifi ed. The rationing system infl uence on agricultural sector labor potential implementation is analyzed. A tool of labor potential use related to full-time and temporary workers of agricultural enterprises is proposed.
LECTURES ON DISCIPLINE “MOTIVATION AND STIMULATION OF LABOUR ACTIVITY” (part 5)
Authors: Кибанов  , Kibanov Ardalon
Published: April 2013

This article continues the abstract of lectures on discipline “Motivation and Stimulation of Labor Activity” at the bachelors’ training program degree “Human Resource Management”.
PROFESSIONAL CHOICE: WITH WHAT TO BEGIN
Authors: Лукьянова  , Lukyanova Tatyana
Published: April 2013

Professional choice process includes understanding of individual’s tendencies and abilities and awareness on channels and means of acquisition of knowledge and skills for learning of concrete trade. The essential role at this is belonged to true-life plans, system of values and specifi c social conditions.
Appraisal as semantic keynote of person representation in graffiti discourse
Authors: Ларионова  , Larionova Alla
Published: April 2013

The article is devoted to socium specific communication in the area of student graffiti discourse creation. The points at issue are means and methods of expression of valuating semantics, represented in graffiti by means of different person nominations which are included into key paradigm of the discourse being studied.
Russian language in modern communication: grammatical material and stylistic structure
Authors: Шапошников  , Shaposhnikov Vladimir
Published: April 2013

The communication and development of the language problem are considering. The language existence and communication realization are analyzing. The language change and its nature problem are describing. The language development criterions are noting. The language changes have been fixing and its typology making. The language changes have been with basic factors of language process correlating. The language signs semantics, lexical-grammatical transforms and its state in language system and role in communication have been studying.
Essence of information and communicative pedagogic interaction in the Internet environment
Authors: Раицкая  , Raitskaya Lilia
Published: April 2013

The article considers the essence of the notion "information and communicative pedagogic interaction in the Internet environment" which stands for transformed computer-mediated pedagogic interaction in electronic environment including the Internet. The author compares the key approaches to the notion prevailing in modern Russian pedagogy.
Strenghts and weaknesses of the advertisement discourse
Authors: Лейчик  , Leychik Vladimir
Published: April 2013

As the positive attributes of the advertisement discourse — aggregated activity were examined the varied in form expressing lexical items, the explicit reference to the addressee, terse and interlocutory texts, slogans available. On the minus side there are hyperbolized advertising objects, failed poetry and slogans.
The functions of the advanced education
Authors: Рабаданова  , Rabadanova Raziyat
Published: April 2013

Analyzing the scientific literature, the author defines the main functions of the advanced education in relation to the higher instruction.
Realization of diagnosis models and quality rating of education
Authors: Афанасьев  , Afanasev Vladimir
Published: April 2013

There is presented a technology of the activity arrangement of teaching subjects on realization of diagnosis models and quality rating of education at school and university, which allows to understand possibilities of various means and methods of task solution of diagnosis and quality rating, their pros and cons; to operate them for the purpose of achieving a creative integration of existing knowledge and subjects’ experience in integral educational process of schools and universities.
Genealogical culture and its role in the identification of young people in Russia
Authors: Извеков  , Izvekov Igor
Published: April 2013

Identification of a person with the family and family branch origin is one of the topical tasks in consideration of evolution and future of Russia. It requires unification of efforts of the family, educational institutions, social organizations etc.
The role of tolerance in humanitarian psychology
Authors: Кондратьева  , Kondrateva Olga
Published: April 2013

The tolerance is considered from a position of humanist and humanitarian psychology. The tolerance is compared with tolerability, in connection with it psychological and dispositional aspects are being analyzed.
About solution to the problem of social activity
Authors: Юлина  , Yulina Galina
Published: April 2013

This article focuses on the strategic orientation of higher school, the principal objective of education which serves as a cohesive identity.
From the experience of organizing activities for high school students
Authors: Кальней  , Kalney Vladimir
Published: April 2013

The article is considering the building principles of the project activities of pupils on the example of creation, work and promotion of the project «Analysis of the social orphanhood problems in the Old Kryukovo Moscow». Attention is given to motivation of the choice of topics of the project, the formation of the creative team, the plan of project, competitive promote of the project and continuity in the creative team as the innovative components of the project activity.
Construction of a teacher training system based on a modular approach
Authors: Чернобай  , Chernobay Elena , Баграмян
Published: April 2013

A modular teacher training system is featuring in the article, the structure of a module, as part of a training unit, is shown, the effectiveness of a modular approach in terms of additional professional education is defined.
Negotiating the Spectre and Spectatorship of Trauma in Rithy Panh’s S-21: The Khmer Rouge Killing Machine (2003)
Authors: Aquino Rowena
Published: April 2013

Cambodian filmmaker and genocide survivor Rithy Panh discusses the necessity of leaving a record as part of a particular process of forgetting (and in effect, remembering) in the context of the traumatic events and memories of the Khmer Rouge regime headed by Pol Pot. The Khmer Rouge
established the state of Democratic Kampuchea (DK) on April 17, 1975 – overcoming the U.S.-backed government administration headed by General Lon Nol in the process – and existed until the Vietnamese invasion of Cambodia that dissolved DK on Jan. 7, 1979. During the Khmer Rouge
regime, around two million Cambodians (a quarter of the country’s population at the time) died as a result of starvation, exhaustion in labor camps, tortures/interrogations and mass executions in the name of creating a classless, agrarian society of a “pure” Khmer race. Panh’s
family members were among the two million Cambodians who died during the regime.
Holding the lotus to the rock: Creating dance community in Red-State America
Authors: Smith Christopher J.
Published: April 2013

In describing the dedication necessary to transplant Buddhism to North America, the Japanese Zen master Sokei-an Sasaki (1882–1945) famously said ‘it will be like holding a lotus to a rock, expecting it to take root’. Since 2001, the Texas Tech University Vernacular
Music Center (VMC) (whose mission statement includes ‘teaching, research, and advocacy in the world’s vernacular traditions’) has grown a community of collegiate dancers and musicians in the American Southwest, one that cuts across boundaries of class, age and ethnicity.
Paradoxically, in this socially and culturally conservative part of the world, while receptivity to music and dance is very high – Texas is the only state in the Union that still maintains required music and art in the public schools – awareness of the art forms’ available
stylistic and cultural diversity is very low. Here, vernacular music communities are separated, insulated and cut-off from one another: alienated both geographically, stylistically and sociologically. At the same time, university music programmes, while recognizing the benefits to all of inclusive
and diverse excellence, struggle to actualize this recognition: lacking resources, personnel, materials and/or community engagement. Drawing on musicology, ethnography, arts advocacy and mass communications theory, this article investigates the history, goals, means and methods by which the
VMC has developed a series of student-centered, boundary-crossing participatory arts communities in the American Southwest, and provides both a practical toolbox, a political vocabulary and a philosophical framework for building like bridges elsewhere