bluuebunny/crossref_metadata_2025 huggingface dataset:
Adsorption and diffusion of strontium in simulated rock fractures quantified via ion beam analysis
Authors: Ohe T. , Zou B. , Noshita K. , Gomez-Morilla I. , Jeynes C. , Morris P. M. , Wogelius R. A.
Published: January 2013

An experimental technique has been developed and applied to the problem of determining effective diffusion coefficients and partition coefficients of Sr in low permeability geological materials. This technique, the micro-reactor simulated channel method (MRSC), allows rapid determination of contaminant transport parameters with resulting values comparable to those determined by more traditional methods and also creates product surfaces that are amenable for direct chemical analysis. An attempt to further constrain mass flux was completed by detailed ion beam analysis of polished tuff surfaces (tuff is a polycrystalline polyminerallic aggregate dominated by silicate phases) that had been reacted with Sr solutions at concentrations of 10−5, 10−3 and 10−1 mol l−1. Ion beam analysis was carried out using beams of both protons (using particle induced X-ray emission and elastic backscattering spectrometry or EBS) and alpha-particles (using Rutherford backscattering spectrometry). The ion beam analyses showed that increased solution concentrations resulted in increased surface concentrations and that in the highest concentration experiment, Sr penetrated to at least 4 μm below the primary interface. The Sr surface concentrations determined by EBS were 0.06 (±0.05), 0.87 (±0.30) and 2.40 (±1.0) atomic weight % in the experiments with starting solution concentrations of 10−5, 10−3, and 10−1 mol l−1, respectively.
Biosphere studies supporting the disposal system safety case in the UK
Authors: Walke R. C. , Thorne M. C. , Norris S.
Published: January 2013

Higher activity radioactive wastes remain hazardous for extremely long timescales, of up to hundreds of thousands of years. Disposing of such wastes deep underground presents the internationally accepted best solution for isolating them from the surface environment on associated timescales. Geological disposal programmes need to assess potential releases from such facilities on long timescales to inform siting and design decisions and to help build confidence that they will provide an adequate degree of safety. Assessments of geological disposal include consideration of the wastes, the engineered facility, the host geology and the surface and near-surface environment including the biosphere. This paper presents an overview of recent post-closure biosphere assessment studies undertaken in support of the Nuclear Decommissioning Authority Radioactive Waste Management Directorate disposal system safety case for geological disposal of the United Kingdom's higher activity radioactive wastes. Recent biosphere studies have included: (1) ensuring that the United Kingdom's approach to consideration of the biosphere in safety case studies continues to be fit for purpose, irrespective of which site or sites are considered in the United Kingdom's geological disposal programme; (2) updating projections of global climate and sea level, together with consideration of the potential importance of transitions between climate states; (3) considering geosphere–biosphere interface issues and their representation, including redox modelling and catchment-scale hydrological modelling; and (4) identifying key radionuclides and developing a series of reports describing their behaviour in the biosphere together with an evaluation of associated implications for post-closure assessment calculations.
Evidence for gas-induced pathways in clay using a nanoparticle injection technique
Authors: Harrington J. F. , Milodowski A. E. , Graham C. C. , Rushton J. C. , Cuss R. J.
Published: January 2013

Corrosion, water radiolysis and microbial degradation will result in the generation of gas within repositories designed for the geological disposal of high-level radioactive waste. It is therefore crucial in the design of such facilities that the relevant mechanisms allowing gas migration through repository materials, both engineered barriers and clay-based candidate host rocks, are correctly identified. In Belgium, the Boom Clay represents a candidate host material for which the advective gas breakthrough characteristics and transport properties have been extensively tested and are well defined by numerous studies. The Boom Clay displays a significant capacity for self-sealing and both laboratory and field tests indicate that advective gas transport occurs not by visco-capillary flow, but instead through the formation of pressure-induced dilatant pathways. In this study, we present results from a gas injection test designed to demonstrate the presence of these features by injecting nanoparticulate tracers with helium gas into a sample of Boom Clay. The results provide conclusive evidence for the formation of transient, dilatant gas pathways within a candidate clay-based host rock. This technique provides a novel diagnostic tool for the identification of processes governing multi-phase flow, supporting robust long-term assessments of repository performance.
Multicomponent gas flow through compacted clay buffer in a higher activity radioactive waste geological disposal facility
Authors: Masum S. A. , Vardon P. J. , Thomas H. R. , Chen Q. , Nicholson D.
Published: January 2013

At the post-closure stage of a geological disposal facility for higher activity radioactive waste several species of gas are likely to be generated in the near-field environment. These could alter the sealing and chemical properties of the bentonite buffer and the local geochemical environment significantly. The authors' attempt to simulate multicomponent gas flow through variably saturated porous media is presented. Governing equations have been developed for a reactive gas-flow model to simulate the thermo-hydro-gas-chemical-mechanical behaviour, with specific reference to the performance of highly compacted bentonite buffer subjected to repository gas generation and migration. The developed equations have been included in the bespoke numerical model COMPASS and some generic simulations are also presented. The model presented extends current capability to assess buffer performance.
Towards an 'implementing geological disposal technology platform' in Europe
Authors: Palmu M. , Eng T. , Beattie T. M.
Published: January 2013

Several European waste management organizations have started work on creating a technology platform to accelerate the implementation of deep geological disposal of radioactive waste in Europe. There is an increasing consensus in the international community about geological disposal as the preferred option for solving the long-term management of spent fuel, high-level waste and other longlived radioactive wastes. At the same time, European citizens have a widespread desire for a permanent solution for high-level radioactive waste disposal. A majority of European countries with nuclear power have active waste-management programmes, but the current status and the main challenges of those programmes vary. The most advanced waste management programmes in Europe (i.e. those in Sweden, Finland and France) are prepared to start the licensing process of deep geological disposal facilities within the next decade. Despite the differences between the timing and the challenges of the different programmes, there is a joint awareness that cooperation on the scientific, technical and social challenges related to geological disposal is needed, and that it is beneficial for the timely and safe implementation of the first geological disposal facilities. Such a demonstration of a viable solution for the management of high-level radioactive waste will enhance stakeholder confidence in Europe. It is envisaged that a technology platform would enhance European cooperation in this area. The platform will provide a tool for reducing overlapping work, to produce savings in total costs of research and implementation, and to make better use of existing competence and research infrastructures. From 2008, SKB (Sweden) and Posiva (Finland) led the preparation work to set up the implementing geological disposal of radioactive waste technology platform (IGD-TP). Since then other implementers from France, Germany, Switzerland, United Kingdom, Spain and Belgium have joined the project. To date a strategic research agenda for the platform has been prepared and consulted upon, which is now the basis for taking the platform into a deployment phase.
Geological disposal programme design and prioritization in the face of uncertainty: use of structured evidence support logic techniques
Authors: Paulley A. , Metcalfe R. , Egan M.
Published: January 2013

Programmes for the geological disposal of radioactive wastes are by nature extremely complex. A structured approach for making and documenting varied kinds of decisions is required to support programme design and implementation. At each programme stage, the decision-making process must be able to identify and justify key priorities for work, to reduce uncertainties.

To support structured decision-making evidence support logic (ESL) has been developed and applied to varied complex projects, nationally and internationally, in several industries. Evidence support logic involves breaking down a hypothesis that informs a decision into a hierarchical 'decision tree'. Examples of hypotheses are 'the geology associated with site x will provide sufficient disposal capacity', 'container x will contain waste form y for z years' and 'the engineered barrier system will provide the required safety functions'. Independent evaluations of confidence 'for' and 'against' bottom-level hypotheses allow the level of remaining uncertainty (or conflict) to be recognized explicitly, and the overall confidence (and uncertainty) relevant to the overall decision, and key sensitivities, to be represented clearly and succinctly.

Thus ESL can help (1) break down decisions into a manageable and logical structure, assisting clear presentation; (2) identify key uncertainties and sensitivities to inform prioritization; and (3) test whether the outcomes of specific studies have improved confidence.
Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A
Authors: Liang Der-Cherng , Liu Hsi-Che , Yang Chao-Ping , Jaing Tang-Her , Hung Iou-Jih , Yeh Ting-Chi , Chen Shih-Hsiang , Hou Jen-Yin , Huang Ying-Jung , Shih Yu-Shu , Huang Yu-Hui , Lin Tung-Huei , Shih Lee-Yung
Published: January 2013

Key Points

A comprehensive study of 19 gene mutations and their cooperation, including the first report of ASXL1 and TET2 mutations in pediatric AML. The development of pediatric AML requires fewer gene mutations than adult AML.
Differential control of Helios+/− Treg development by monocyte subsets through disparate inflammatory cytokines
Authors: Zhong Hui , Yazdanbakhsh Karina
Published: January 2013

Key Points

Control of Helios+/− Treg subset development is mediated through distinct cytokines and monocyte subpopulations. CD16+ monocytes inhibit Helios+ Treg proliferation through IL-12, whereas CD16− monocytes suppress Helios− Treg development through TNF-α.
Robo4 is an effective tumor endothelial marker for antibody-drug conjugates based on the rapid isolation of the anti-Robo4 cell-internalizing antibody
Authors: Yoshikawa Mai , Mukai Yohei , Okada Yoshiaki , Tsumori Yuki , Tsunoda Shin-ichi , Tsutsumi Yasuo , Aird William C. , Yoshioka Yasuo , Okada Naoki , Doi Takefumi , Nakagawa Shinsaku
Published: January 2013

Key Points

First therapeutic application that targets Robo4 on the tumor blood vasculature High-throughput screening system to isolate cell-internalizing monoclonal antibodies useful to develop effective antibody-drug conjugates
Genome-wide identification, characterization, and expression analysis of lineage-specific genes within zebrafish
Authors: Yang Liandong , Zou Ming , Fu Beide , He Shunping
Published: January 2013

Background

The genomic basis of teleost phenotypic complexity remains obscure, despite increasing availability of genome and transcriptome sequence data. Fish-specific genome duplication cannot provide sufficient explanation for the morphological complexity of teleosts, considering the relatively large number of extinct basal ray-finned fishes.

Results

In this study, we performed comparative genomic analysis to discover the Conserved Teleost-Specific Genes (CTSGs) and orphan genes within zebrafish and found that these two sets of lineage-specific genes may have played important roles during zebrafish embryogenesis. Lineage-specific genes within zebrafish share many of the characteristics of their counterparts in other species: shorter length, fewer exon numbers, higher GC content, and fewer of them have transcript support. Chromosomal location analysis indicated that neither the CTSGs nor the orphan genes were distributed evenly in the chromosomes of zebrafish. The significant enrichment of immunity proteins in CTSGs annotated by gene ontology (GO) or predicted ab initio may imply that defense against pathogens may be an important reason for the diversification of teleosts. The evolutionary origin of the lineage-specific genes was determined and a very high percentage of lineage-specific genes were generated via gene duplications. The temporal and spatial expression profile of lineage-specific genes obtained by expressed sequence tags (EST) and RNA-seq data revealed two novel properties: in addition to being highly tissue-preferred expression, lineage-specific genes are also highly temporally restricted, namely they are expressed in narrower time windows than evolutionarily conserved genes and are specifically enriched in later-stage embryos and early larval stages.

Conclusions

Our study provides the first systematic identification of two different sets of lineage-specific genes within zebrafish and provides valuable information leading towards a better understanding of the molecular mechanisms of the genomic basis of teleost phenotypic complexity for future studies.
Transgenerational programming of maternal behaviour by prenatal stress
Authors: Ward Isaac D , Zucchi Fabíola CR , Robbins Jerrah C , Falkenberg Erin A , Olson David M , Benzies Karen , Metz Gerlinde A
Published: January 2013

Peripartum events hold the potential to have dramatic effects in the programming of physiology and behaviour of offspring and possibly subsequent generations. Here we have characterized transgenerational changes in rat maternal behaviour as a function of gestational and prenatal stress. Pregnant dams of the parental generation were exposed to stress from days 12-18 (F0-S). Their daughters and grand-daughters were either stressed (F1-SS, F2-SSS) or non-stressed (F1-SN, F2-SNN). Maternal antepartum behaviours were analyzed at a time when pregnant dams usually show a high frequency of tail chasing behaviours. F1-SS, F2-SNN and F2-SSS groups showed a significant reduction in tail chasing behaviours when compared with controls. The effects of multigenerational stress (SSS) slightly exceeded those of transgenerational stress (SNN) and resulted in absence of tail chasing behaviour. These findings suggest that antepartum maternal behaviour in rats is programmed by transgenerational inheritance of stress responses. Thus, altered antepartum maternal behaviour may serve as an indicator of an activated stress response during gestation.
Harnessing the power of the grassroots to conduct public health research in sub-Saharan Africa: a case study from western Kenya in the adaptation of community-based participatory research (CBPR) approaches
Authors: Kamanda Allan , Embleton Lonnie , Ayuku David , Atwoli Lukoye , Gisore Peter , Ayaya Samuel , Vreeman Rachel , Braitstein Paula
Published: January 2013

Background

Community-based participatory research (CBPR) is a collaborative approach to research that involves the equitable participation of those affected by an issue. As the field of global public health grows, the potential of CBPR to build capacity and to engage communities in identification of problems and development and implementation of solutions in sub-Saharan Africa has yet to be fully tapped. The Orphaned and Separated Children’s Assessments Related to their Health and Well-Being (OSCAR) project is a longitudinal cohort of orphaned and non-orphaned children in Kenya. This paper will describe how CBPR approaches and principles can be incorporated and adapted into the study design and methods of a longitudinal epidemiological study in sub-Saharan Africa using this project as an example.

Methods

The CBPR framework we used involves problem identification, feasibility and planning; implementation; and evaluation and dissemination. This case study will describe how we have engaged the community and adapted CBPR methods to OSCAR’s Health and Well-being Project’s corresponding to this framework in four phases: 1) community engagement, 2) sampling and recruitment, 3) retention, validation, and follow-up, and 4) analysis, interpretation and dissemination.

Results

To date the study has enrolled 3130 orphaned and separated children, including children living in institutional environments, those living in extended family or other households in the community, and street-involved children and youth. Community engagement and participation was integral in refining the study design and identifying research questions that were impacting the community. Through the participation of village Chiefs and elders we were able to successfully identify eligible households and randomize the selection of participants. The on-going contribution of the community in the research process has been vital to participant retention and data validation while ensuring cultural and community relevance and equity in the research agenda.

Conclusion

CBPR methods have the ability to enable and strengthen epidemiological and public health research in sub-Saharan Africa within the social, political, economic and cultural contexts of the diverse communities on the continent. This project demonstrates that adaptation of these methods is crucial to the successful implementation of a community-based project involving a highly vulnerable population.
Lower circulating preptin levels in male patients with osteoporosis are correlated with bone mineral density and bone formation
Authors: Li Ning , Zheng Yi-Bo , Han Jie , Liang Wei , Wang Jia-Yi , Zhou Jie-Ru , Shen Yi , Zhang Jie
Published: January 2013

Background

Serum preptin levels among subjects with different bone mineral densities (BMD) were measured and investigated to determine the correlation between BMD and bone-metabolic markers.

Methods

Approximately 52 elderly male patients with osteoporosis, 50 elderly men with osteopaenia, and 31 age-matched normal bone mass controls participated in the study. The serum preptin levels and bone metabolic markers were measured by enzyme-linked immunosorbent assay. The relationships between preptin levels, BMD, and metabolic parameters were also assessed.

Results

The serum preptin level was the lowest in the osteoporosis group and positively correlated with BMD. All the bone formation markers in the osteoporosis and osteopaenia groups were significantly reduced compared with those in the normal group. Serum preptin level was positively correlated with all the bone formation markers, whereas no correlation was observed with the bone resorption marker TRACP-5b.

Conclusions

Serum preptin levels are decreased in osteoporosis and osteopaenia patients and positively correlated with BMD. Therefore, preptin is involved in the pathogenesis of osteoporosis, probably through bone formation rather than bone resorption.
Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats
Authors: Nyadjeu Paulin , Nguelefack-Mbuyo Elvine Pami , Atsamo Albert Donatien , Nguelefack Telesphore Benoît , Dongmo Alain Bertrand , Kamanyi Albert
Published: January 2013

Background

Previous study showed that the aqueous extract of the stem bark of Cinnamomum zeylanicum possesses antihypertensive and vasodilatory properties. The present work investigates the acute and chronic antihypertensive effects of the methanol extract of Cinnamomum zeylanicum stem bark (MECZ) in L-NAME-induced hypertensive rats.

Methods

The acute antihypertensive effects of MECZ (5, 10 and 20 mg/kg) administered intravenously were evaluated in rats in which acute arterial hypertension has been induced by intravenous administration of L-NAME (20 mg/kg). For chronic antihypertensive effects, animals were treated with L-NAME (40 mg/kg/day) plus the vehicle or L-NAME (40 mg/kg/day) in combination with captopril (20 mg/kg/day) or MECZ (300 mg/kg/day) and compared with control group receiving only distilled water. All drugs were administered per os and at the end of the experiment that lasted for four consecutive weeks, blood pressure was measured by invasive method and blood samples were collected for the determination of the lipid profile. The heart and aorta were collected, weighed and used for both histological analysis and determination of NO tissue content.

Results

Acute intravenous administration of C. zeylanicum extract (5, 10 and 20 mg/kg) to L-NAME-induced hypertensive rats provoked a long-lasting decrease in blood pressure. Mean arterial blood pressure decreased by 12.5%, 26.6% and 30.6% at the doses of 5, 10 and 20 mg/kg, respectively. In chronic administration, MECZ and captopril significantly prevented the increase in blood pressure and organs’ weights, as well as tissue histological damages and were able to reverse the depletion in NO tissue’s concentration. The MECZ also significantly lower the plasma level of triglycerides (38.1%), total cholesterol (32.1%) and LDL-cholesterol (75.3%) while increasing that of HDL-cholesterol (58.4%) with a significant low atherogenic index (1.4 versus 5.3 for L-NAME group).

Conclusion

MECZ possesses antihypertensive and organ protective effects that may result from its ability to increase the production of the endogenous NO and/or to regulate dyslipidemia.
Health-related quality of life and economic impact of urinary incontinence due to detrusor overactivity associated with a neurologic condition: a systematic review
Authors: Tapia Crisanta I , Khalaf Kristin , Berenson Karina , Globe Denise , Chancellor Michael , Carr Lesley K
Published: January 2013

Background

Patients with neurologic diseases often have neurogenic detrusor overactivity (NDO), which can result in a loss of voluntary bladder control and uncontrollable urinary incontinence (UI).The impact of UI due to NDO on patients’ lives has not been well studied. The objective of this review was to assess the health-related quality of life (HRQoL) and economic burden in patients with urgency UI due to NDO in select countries in North America, the European Union, Asia, and Australia.

Methods

Systematic literature searches and reviews of articles published in English (January 2000 to February 2011) were conducted using MEDLINE®, EMBASE®, and the Cochrane Library. Studies assessing the impact of UI on HRQoL of patients with an underlying neurologic condition of interest (i.e., multiple sclerosis, spinal cord injury, Parkinson’s disease, stroke, or spina bifida) were included. Economic studies in urgency UI also were included.

Results

Of 876 citations generated in the initial search, a total of 27 articles were deemed relevant: 16 articles presented HRQoL data and 11 articles presented information on the economic burden of UI. Humanistic studies used a range of HRQoL instruments to measure HRQoL burden, and the economic studies included different cost components to quantify the economic burden, making meaningful comparisons challenging. Despite this heterogeneity, the literature suggests that HRQoL in patients with UI due to NDO is worse than patients with UI in general or those with the same underlying neurologic condition without UI. In addition, urgency UI also results in substantial economic costs.

Conclusions

Incontinent patients with underlying neurologic conditions have impaired HRQoL as well as substantial economic burden attributable to UI due to NDO. There is a need for urgency UI treatments that improve HRQoL of these patients and alleviate the economic burden of this condition.
Correlations between cytoplasmic CSE1L in neoplastic colorectal glands and depth of tumor penetration and cancer stage
Authors: Tai Cheng-Jeng , Su Tzu-Cheng , Jiang Ming-Chung , Chen Hung-Chang , Shen Shing-Chuan , Lee Woan-Ruoh , Liao Ching-Fong , Chen Ying-Chun , Lin Shu-Hui , Li Li-Tzu , Shen Ko-Hung , Yeh Chung-Min , Yeh Kun-Tu , Lee Ching-Hsiao , Shih Hsin-Yi , Chang Chun-Chao
Published: January 2013

Background

Colorectal carcinomas spread easily to nearby tissues around the colon or rectum, and display strong potential for invasion and metastasis. CSE1L, the chromosome segregation 1-like protein, is implicated in cancer progression and is located in both the cytoplasm and nuclei of tumor cells. We investigated the prognostic significance of cytoplasmic vs. nuclear CSE1L expression in colorectal cancer.

Methods

The invasion- and metastasis-stimulating activities of CSE1L were studied by in vitro invasion and animal experiments. CSE1L expression in colorectal cancer was assayed by immunohistochemistry, with tissue microarray consisting of 128 surgically resected specimens; and scored using a semiquantitative method. The correlations between CSE1L expression and clinicopathological parameters were analyzed.

Results

CSE1L overexpression was associated with increased invasiveness and metastasis of cancer cells. Non-neoplastic colorectal glands showed minimal CSE1L staining, whereas most colorectal carcinomas (99.2%, 127/128) were significantly positive for CSE1L staining. Cytoplasmic CSE1L was associated with cancer stage (P=0.003) and depth of tumor penetration (P=0.007). Cytoplasmic CSE1L expression also correlated with lymph node metastasis of the disease in Cox regression analysis

Conclusions

CSE1L regulates the invasiveness and metastasis of cancer cells, and immunohistochemical analysis of cytoplasmic CSE1L in colorectal tumors may provide a useful aid to prognosis.
A new extragradient-like method for solving variational inequality problems
Authors: Huang Na , Ma Changfeng , Liu Zhenggang
Published: January 2013

In this paper, we present a new extragradient-like method for the classical variational inequality problem based on our constructed novel descent direction. Furthermore, we show the global convergence and R-linear convergence rate of the new method under certain conditions. Numerical results also confirm the good theoretical properties of our approach.

MSC:90C33, 65K10.
Dynamics of symbiont-mediated antibiotic production reveal efficient long-term protection for beewolf offspring
Authors: Koehler Sabrina , Doubský Jan , Kaltenpoth Martin
Published: January 2013

Background

Insects have evolved a wide range of mechanisms to defend themselves and their offspring against antagonists. One of these strategies involves the utilization of antimicrobial compounds provided by symbiotic bacteria to protect the host or its nutritional resources from pathogens and parasites. In the symbiosis of the solitary digger wasp,Philanthus triangulum(Hymenoptera, Crabronidae), the bacterial symbiont ‘CandidatusStreptomyces philanthi’ defends the developing larvae against pathogens by producing a mixture of at least nine antimicrobial substances on the cocoon surface.This antibiotic cocktail inhibits the growth of a broad range of detrimental fungi and bacteria, thereby significantly enhancing the offspring’s survival probability.

Results

Here we show that the production of antimicrobial compounds by the beewolf symbionts is confined to the first two weeks after cocoon spinning, leading to a high concentration of piericidins and streptochlorin on the cocoon surface. Expression profiling of housekeeping, sporulation, and antibiotic biosynthesis genes indicates that antibiotic production coincides with morphological differentiation that enables the symbionts to survive the nutrient-limited conditions on the beewolf cocoon. The antibiotic substances remain stable on the cocoon surface for the entire duration of the beewolf’s hibernation period, demonstrating that the compounds are resistant against environmental influences.

Conclusions

The antibiotic production by the beewolf symbionts serves as a reliable protection for the wasp offspring against pathogenic microorganisms during the long and unpredictable developmental phase in the subterranean brood cells. Thus, the beewolf-Streptomycessymbiosis provides one of the rare examples of antibiotics serving as an efficient defense in the natural environment and may aid in devising new strategies for the utilization of antibiotic combination therapies in human medicine against increasingly resistant bacterial and fungal pathogens.
A novel DNA vaccine expressing the Ag85A-HA2 fusion protein provides protection against influenza A virus and Staphylococcus aureus
Authors: Dai Jun , Pei Decui , Wang Baoning , Kuang Yu , Ren Laifeng , Cao Kang , Zuo Bin , Shao Jingjing , Li Sha , Jiang Zhonghua , Li Hong , Li Mingyuan
Published: January 2013

Secondary pneumonia due to Staphylococcus aureus (S. aureus) causes significant morbidity and mortality. The aim of the research was designed a novel DNA vaccine encoding the Mycobacterium tuberculosis secreted antigen Ag85A fused with the influenza A virus (IAV) HA2 protein to provide protection against both influenza and secondary infection with S. aureus. The DNA vaccine vector efficiently expressed the encoded antigen in mammalian cells, as determined by RT-PCR, Western blotting and immunofluorescence analysis. Mice were immunized with the vaccine by intramuscular injection before challenge with IAV and S. aureus. The pulmonary and the splenocyte culture IFN-γ levels were significant higher in immunized mice than their respective controls. Although the antibody titer in the HI test was low, the sera of mice immunized with the novel vaccine vector were effective in neutralisation assay in vitro. The vaccine could reduce the loss of body weight in mice during IAV challenge. Both Western blotting and RT-PCR showed that the vaccine markedly enhanced toll like receptor 2 (TLR2) expression in splenocytes after the secondary infection with S. aureus. The survival rate of mice with high TLR2 expression (pEGFP/Ag85A-HA2 or iPR) was significantly increased compared with mice immunized with pEGFP/HA2 after challenge with S. aureus. However, the pulmonary IL-10 concentration and S. aureus titer were significantly decreased in immunized mice, and expression of TLR2 was increased after challenge with S. aureus. These results demonstrated that Ag85A could strengthen the immune response to IAV and S. aureus, and TLR2 was involved in the host response to S. aureus.
The Melbourne Diabetes Prevention Study (MDPS): study protocol for a randomized controlled trial
Authors: Davis-Lameloise Nathalie , Hernan Andrea , Janus Edward D , Stewart Elizabeth , Carter Rob , Bennett Catherine M , O’Reilly Sharleen , Philpot Benjamin , Vartiainen Erkki , Dunbar James A
Published: January 2013

Background

Worldwide, type 2 diabetes (T2DM) prevalence has more than doubled over two decades. In Australia, diabetes is the second highest contributor to the burden of disease. Lifestyle modification programs comprising diet changes, weight loss and moderate physical activity, have been proven to reduce the incidence of T2DM in high risk individuals.

As part of the Council of Australia Governments, the State of Victoria committed to develop and support the diabetes prevention program ‘Life! Taking action on diabetes’ (Life!) which has direct lineage from effective clinical and implementation trials from Finland and Australia. The Melbourne Diabetes Prevention Study (MDPS) has been set up to evaluate the effectiveness and cost-effectiveness of a specific version of the Life! program.

Methods/design

We intend to recruit 796 participants for this open randomized clinical trial; 398 will be allocated to the intervention arm and 398 to the usual care arm. Several methods of recruitment will be used in order to maximize the number of participants. Individuals aged 50 to 75 years will be screened with a risk tool (AUSDRISK) to detect those at high risk of developing T2DM. Those with existing diabetes will be excluded. Intervention participants will undergo anthropometric and laboratory tests, and comprehensive surveys at baseline, following the fourth group session (approximately three months after the commencement of the intervention) and 12 months after commencement of the intervention, while control participants will undergo testing at baseline and 12 months only.

The intervention consists of an initial individual session followed by a series of five structured-group sessions. The first four group sessions will be carried out at two week intervals and the fifth session will occur eight months after the first group session. The intervention is based on the Health Action Process Approach (HAPA) model and sessions will empower and enable the participants to follow the five goals of the Life! program.

Discussion

This study will determine whether the effect of this intervention is larger than the effect of usual care in reducing central obesity and cardiovascular risk factors and thus the risk of developing diabetes and cardiovascular disease. Also it will evaluate how these two options compare economically.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12609000507280
Multi-institutional comparison of volumetric modulated arc therapy vs. intensity-modulated radiation therapy for head-and-neck cancer: a planning study
Authors: Holt Andrea , Van Gestel Dirk , Arends Mark P , Korevaar Erik W , Schuring Danny , Kunze-Busch Martina C , Louwe Rob JW , van Vliet-Vroegindeweij Corine
Published: January 2013

Background

Compared to static beam Intensity-Modulated Radiation Therapy (IMRT), the main advantage of Volumetric Modulated Arc Therapy (VMAT) is a shortened delivery time, which leads to improved patient comfort and possibly smaller intra-fraction movements. This study aims at a treatment planner-independent comparison of radiotherapy treatment planning of IMRT and VMAT for head-and-neck cancer performed by several institutes and based on the same CT- and contouring data.

Methods

Five institutes generated IMRT and VMAT plans for five oropharyngeal cancer patients using either Pinnacle3 or Oncentra Masterplan to be delivered on Elekta linear accelerators.

Results

Comparison of VMAT and IMRT plans within the same patient and institute showed significantly better sparing for almost all OARs with VMAT. The average mean dose to the parotid glands and oral cavity was reduced from 27.2 Gy and 39.4 Gy for IMRT to 25.0 Gy and 36.7 Gy for VMAT, respectively. The dose conformity at 95% of the prescribed dose for PTVboost and PTVtotal was 1.45 and 1.62 for IMRT and 1.37 and 1.50 for VMAT, respectively. The average effective delivery time was reduced from 13:15 min for IMRT to 5:54 min for VMAT.

Conclusions

Independently of institution-specific optimization strategies, the quality of the VMAT plans including double arcs was superior to step-and-shoot IMRT plans including 5–9 beam ports, while the effective treatment delivery time was shortened by ~50% with VMAT.
Efficacy of low-dose radiotherapy in painful gonarthritis: experiences from a retrospective East German bicenter study
Authors: Keller Stephanie , Müller Klaus , Kortmann Rolf-Dieter , Wolf Ulrich , Hildebrandt Guido , Liebmann André , Micke Oliver , Flemming Gert , Baaske Dieter
Published: January 2013

Purpose

To evaluate the efficacy of low-dose radiotherapy in painful gonarthritis.

Methods

We assessed the medical records of 1037 patients with painful gonarthritis who had undergone low-dose radiotherapy between 1981 and 2008. The subjective patient perception of the response to irradiation as graded immediately or up to two months after the completion of a radiotherapy series was evaluated and correlated with age, gender, radiological grading and the duration of symptoms before radiotherapy. Moreover, we performed a mail survey to obtain additional long-term follow-up information and received one hundred and six evaluable questionnaires.

Results

We assessed 1659 series of radiotherapy in 1037 patients. In 79.3% of the cases the patients experienced a slight, marked or complete pain relief immediately or up to two months after the completion of radiotherapy. Gender, age and the duration of pain before radiotherapy did not have a significant influence on the response to irradiation. In contrast, severe signs of osteoarthritis were associated with more effective pain relief. In more than 50% of the patients who reported a positive response to irradiation a sustained period of symptomatic improvement was observed.

Conclusions

Our results confirm that low-dose radiotherapy is an effective treatment for painful osteoarthritis of the knee. In contrast to an earlier retrospective study, severe signs of osteoarthritis constituted a positive prognostic factor for the response to irradiation. A randomized trial is urgently required to compare radiotherapy with other treatment modalities.
Age-related NADH oxidase (arNOX) activity is significantly reduced in coelomic fluid of long-lived sea urchins
Authors: Talbert Eric , Bodnar Andrea , Morré Dorothy M , Morré D James
Published: January 2013

Age-related NADH oxidase (arNOX) is a cell surface protein shed into the circulation and other body fluids, which generates superoxide. The activity increases with age in human tissues and body fluids (serum, saliva, and perspiration) and is a potential source of age-related oxidative damage. We measured arNOX activity in the coelomic fluid of sea urchin species with different life spans. Coelomic fluid of long-lived sea urchin species Strongylocentrotus purpuratus and Strongylocentrotus franciscanus exhibited low levels of arNOX compared to the short-lived urchin species Lytechinus variegatus. arNOX activity was positively correlated with animal size in L. variegatus, whereas with S. purpuratus and S. franciscanus, arNOX activity and animal size were inversely correlated. The inverse correlation of arNOX activity with life span and decreased levels of arNOX with age in the long-lived species is consistent with a contribution of reduced arNOX activity to slower aging.
Constructing narratives of heroism and villainy: case study of Myriad's BRACAnalysis® compared to Genentech's Herceptin®
Authors: Baldwin A Lane , Cook-Deegan Robert
Published: January 2013

Background

The development of Herceptin® is welcomed as a major advance in breast cancer treatment, while Myriad's development of BRACAnalysis® is a widely used diagnostic. However useful and successful this product is, its presence in the public eye is tainted by predominantly negative press about gene patenting and business practices.

Discussion

While retrospection invites a sharp contrast between Genentech's triumphal narrative of scientific achievement and Myriad's public image as a controversial monopolist, a comparative history of these companies' products reveals two striking consistencies: patents and public discontent. Despite these similarities, time has reduced the narrative to that of hero versus villain: Genentech is lauded - at least for the final outcome of the Herceptin® story - as a corporate good citizen, Myriad as a ruthless mercenary. Since patents undergird both products yet the narratives are so different, the stories raise the question: why have patents taken the fall as the scapegoat in current biotechnology policy debate?

A widely publicized lawsuit and accompanying bad press have cast Myriad as a villain in the evolving narrative of biotechnology. While the lawsuit suggests that this villainy is attributable to Myriad's intellectual property, we suggest through a comparative case study that, at least in the Myriad case, it is not simply about the patents but also other business strategies the company chose to pursue. Patents were a necessary but not sufficient cause of controversy.
Out of Tlatelolco’s Ruins: Patronage, Devotion, and Natural Disaster at the Shrine of Our Lady of the Angels, 1745–1781
Authors: Ramírez Paul , Taylor William B.
Published: January 2013

Colonial inhabitants of Mexico City were accustomed to coping with natural disasters, including disease epidemics, droughts, floods, and earthquakes, which menaced rich and poor alike and stirred fervent devotion to miraculous images and their shrines. This article revisits the late colonial history of the shrine of Our Lady of the Angels, an image preserved miraculously on an adobe wall in the Indian quarter of Santiago Tlatelolco. The assumption has been that archiepiscopal authorities aiming to deflect public worship toward a more austere, interior spirituality suppressed activities there after 1745 because they saw the devotion as excessively Indian and Baroque. The shrine has served as a barometer of eighteenth-century Bourbon reforms even though its story has not been fully told. This article explores the politics of patronage in the years after the shrine’s closure and in the decades prior to the arrival on the scene of a new Spanish patron in 1776, revealing that Indian caretakers kept the faith well beyond the official intervention, with some help from well-placed Spanish devotees and officials. The efforts of the new patron, a Spanish tailor from the city center, to renovate the building and image and secure the necessary permissions and privileges helped transform the site into one of the most famous in the capital. Attention to earlier patterns of patronage and to the social response to a series of tremors that coincided with his promotional efforts helps to explain why a devotion so carefully managed for enlightened audiences was nevertheless cut from old cloth.
Kit signaling is involved in melanocyte stem cell fate decisions in zebrafish embryos
Authors: O’Reilly-Pol Thomas , Johnson Stephen L.
Published: January 2013

Adult stem cells are crucial for growth, homeostasis and repair of adult animals. The melanocyte stem cell (MSC) and melanocyte regeneration is an attractive model for studying regulation of adult stem cells. The process of melanocyte regeneration can be divided into establishment of the MSC, recruitment of the MSC to produce committed daughter cells, and the proliferation, differentiation and survival of these daughter cells. Reduction of Kit signaling results in dose-dependent reduction of melanocytes during larval regeneration. Here, we use clonal analysis techniques to develop assays to distinguish roles for these processes during zebrafish larval melanocyte regeneration. We use these clonal assays to investigate which processes are affected by the reduction in Kit signaling. We show that the regeneration defect in kita mutants is not due to defects in MSC recruitment or in the proliferation, differentiation or survival of the daughter cells, but is instead due to a defect in stem cell establishment. Our analysis suggests that the kit MSC establishment defect results from inappropriate differentiation of the MSC lineage.
Histone demethylase dUTX antagonizes JAK-STAT signaling to maintain proper gene expression and architecture of the Drosophila testis niche
Authors: Tarayrah Lama , Herz Hans-Martin , Shilatifard Ali , Chen Xin
Published: January 2013

Adult stem cells reside in microenvironments called niches, where they are regulated by both extrinsic cues, such as signaling from neighboring cells, and intrinsic factors, such as chromatin structure. Here we report that in the Drosophila testis niche an H3K27me3-specific histone demethylase encoded by Ubiquitously transcribed tetratricopeptide repeat gene on the X chromosome (dUTX) maintains active transcription of the Suppressor of cytokine signaling at 36E (Socs36E) gene by removing the repressive H3K27me3 modification near its transcription start site. Socs36E encodes an inhibitor of the Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway. Whereas much is known about niche-to-stem cell signaling, such as the JAK-STAT signaling that is crucial for stem cell identity and activity, comparatively little is known about signaling from stem cells to the niche. Our results reveal that stem cells send feedback to niche cells to maintain the proper gene expression and architecture of the niche. We found that dUTX acts in cyst stem cells to maintain gene expression in hub cells through activating Socs36E transcription and preventing hyperactivation of JAK-STAT signaling. dUTX also acts in germline stem cells to maintain hub structure through regulating DE-Cadherin levels. Therefore, our findings provide new insights into how an epigenetic factor regulates crosstalk among different cell types within an endogenous stem cell niche, and shed light on the biological functions of a histone demethylase in vivo.
The transcription factor Otx2 regulates choroid plexus development and function
Authors: Johansson Pia A. , Irmler Martin , Acampora Dario , Beckers Johannes , Simeone Antonio , Götz Magdalena
Published: January 2013

The choroid plexuses (ChPs) are the main regulators of cerebrospinal fluid (CSF) composition and thereby also control the composition of a principal source of signaling molecules that is in direct contact with neural stem cells in the developing brain. The regulators of ChP development mediating the acquisition of a fate that differs from the neighboring neuroepithelial cells are poorly understood. Here, we demonstrate in mice a crucial role for the transcription factor Otx2 in the development and maintenance of ChP cells. Deletion of Otx2 by the Otx2-CreERT2 driver line at E9 resulted in a lack of all ChPs, whereas deletion by the Gdf7-Cre driver line affected predominately the hindbrain ChP, which was reduced in size, primarily owing to an increase in apoptosis upon Otx2 deletion. Strikingly, Otx2 was still required for the maintenance of hindbrain ChP cells at later stages when Otx2 deletion was induced at E15, demonstrating a central role of Otx2 in ChP development and maintenance. Moreover, the predominant defects in the hindbrain ChP mediated by Gdf7-Cre deletion of Otx2 revealed its key role in regulating early CSF composition, which was altered in protein content, including the levels of Wnt4 and the Wnt modulator Tgm2. Accordingly, proliferation and Wnt signaling levels were increased in the distant cerebral cortex, suggesting a role of the hindbrain ChP in regulating CSF composition, including key signaling molecules. Thus, Otx2 acts as a master regulator of ChP development, thereby influencing one of the principal sources of signaling in the developing brain, the CSF.
A closer look at the structure of Hong Sangsoo’s Hahaha
Authors: Deutelbaum Marshall
Published: January 2013

Hahaha by Hong Sangsoo (2010) alternates between a conversation taking place in the present between narrators photographed in black-and-white still images who take turns describing the experiences each had in a small South Korean seaside town and images in colour and motion that present
those past experiences. Viewers quickly realize that the men were in the town at the same time, though the pair never understands this because they frequently crossed paths without encountering one another. The narrational shifts between past and present obscure how in Hahaha, Hong reworks
the potential for cross-cutting that existed, purposely unrealized, in a portion of Gang-wondo-ui him/The Power of Kangwon Province by Hong (1998), the director’s second film, into a single, linear but somewhat discontinuous chronology without the simultaneous action usually indicated
by alternating.