Evaluation of Local & Global Ductility Relationships for Low-Rise Masonry-Infilled Reinforced Concrete Frame Structures

The paper presents the findings on a parametric study of the period lengthening effects of low-rise masonryinfilled reinforced concrete frame buildings using an incremental dynamic analysis (IDA). Simplified 2D building models utilizing Bouc-Wen model for describing strength, stiffness degradation and pinching effect were subjected to some selected ground motion records ranging from far to near field earthquakes in low to high seismicity regions. Simple equations correlating local to global ductilities derived from pushover (PO) analysis for buildings under soft storey failure mechanism are proposed. The equations take into account the governing factors like critical interstorey drift and number of storeys. The applicability of the equations was verified up to 7-storey buildings from the results of IDA. Such simple ductility relationships are likely to facilitate mostly the coefficient-based method, in which the typical PO analysis may be bypassed and allows making intuitive insight into the seismic performance of buildings.published_or_final_versio

Typical collapse modes of confined masonry buildings under strong earthquake loads

Confined masonry structures are a widely applied structural system in many developing countries. During the past Wenchuan Earthquake in 2008, numerous confined masonry buildings collapsed, while many others suffered damage. This study reviews the construction practices of confined masonry buildings in China. Simple models and hand calculation methods are proposed for quantifying the tearing failure of diaphragms, the tensile failure of tie-columns and the sway-mode strength of masonry buildings. The results indicate very good agreement with field observations. The seismic measures that are stipulated in the seismic design codes are very effective for increasing the strength and integrity, but not the ductility of masonry buildings. For those buildings that survived the earthquake, strength rather than ductility protected the confined masonry from collapse or serious damage. Design recommendations are suggested for preventing various types of premature failures and enhancing the lateral strength of masonry buildings. © Su et al.published_or_final_versio

Secondary structure in the core of amyloid fibrils formed from human βm and its truncated variant Δn6

Amyloid fibrils formed from initially soluble proteins with diverse sequences are associated with an array of human diseases. In the human disorder, dialysis-related amyloidosis (DRA), fibrils contain two major constituents, full-length human β-microglobulin (hβm) and a truncation variant, ΔN6 which lacks the N-terminal six amino acids. These fibrils are assembled from initially natively folded proteins with an all antiparallel β-stranded structure. Here, backbone conformations of wild-type hβm and ΔN6 in their amyloid forms have been determined using a combination of dilute isotopic labeling strategies and multidimensional magic angle spinning (MAS) NMR techniques at high magnetic fields, providing valuable structural information at the atomic-level about the fibril architecture. The secondary structures of both fibril types, determined by the assignment of ∼80% of the backbone resonances of these 100- and 94-residue proteins, respectively, reveal substantial backbone rearrangement compared with the location of β-strands in their native immunoglobulin folds. The identification of seven β-strands in hβm fibrils indicates that approximately 70 residues are in a β-strand conformation in the fibril core. By contrast, nine β-strands comprise the fibrils formed from ΔN6, indicating a more extensive core. The precise location and length of β-strands in the two fibril forms also differ. The results indicate fibrils of ΔN6 and hβm have an extensive core architecture involving the majority of residues in the polypeptide sequence. The common elements of the backbone structure of the two proteins likely facilitates their ability to copolymerize during amyloid fibril assembly

Erosion characteristics and floc strenght of Athabasca river cohesive sediments: towards managing sediment-related issues

Purpose: Most of Canada’s tar sands exploitations are located in the Athabasca river basin. Deposited cohesive sediments in Athabasca river and tributaries are a potential source of PAHs in the basin. Erosional behavior of cohesive sediments depends not only of fluid turbulence but on sediments structure and particularly the influence of organic content. This research tries to describe this behavior in Athabasca river sediments. Methods: An experimental study of cohesive sediments dynamics in one of the tributaries, the Muskeg river, was developed in a rotating annular flume. Variation of the shear stress allowed the determination of erosional strength for beds with different consolidation periods. Particle size measurements were made with a laser diffraction device operated in a continuous flow through mode. Optical analyses of flocs (ESEM and TEM) were performed with samples taken at the end of the experiments. Results: An inverse relationship between suspended sediment concentration (SS) and the consolidation period was found. The differences are related in this research to the increasing organic content of the sediments with consolidation period. The particle size measurements during the experiments showed differences on floc strength that are also related to changing organic content during different consolidation periods. ESEM and TEM observations confirm the structural differences for beds with different consolidation periods. The effects of SFGL on floc structure and in biostabilization of the bed are discussed. Conclusions: It is recommended in this paper that consolidation period should be taken into account for the modeling of erosion of cohesive sediments in the Athabasca river. Relating to transport models of pollutants (PAHs) it is highly recommended to consider flocs organic content, particularly algae, in the resuspension module.Environment Canada, CONACY

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD

Breast cancer risk reduction:is it feasible to initiate a randomised controlled trial of a lifestyle intervention programme (ActWell) within a national breast screening programme?

BackgroundBreast cancer is the most commonly diagnosed cancer and the second cause of cancer deaths amongst women in the UK. The incidence of the disease is increasing and is highest in women from least deprived areas. It is estimated that around 42% of the disease in post-menopausal women could be prevented by increased physical activity and reductions in alcohol intake and body fatness. Breast cancer control endeavours focus on national screening programmes but these do not include communications or interventions for risk reductionThis study aimed to assess the feasibility of delivery, indicative effects and acceptability of a lifestyle intervention programme initiated within the NHS Scottish Breast Screening Programme (NHSSBSP).MethodsA 1:1 randomised controlled trial (RCT) of the 3 month ActWell programme (focussing on body weight, physical activity and alcohol) versus usual care conducted in two NHSSBSP sites between June 2013 and January 2014. Feasibility assessments included recruitment, retention, and fidelity to protocol. Indicative outcomes were measured at baseline and 3 month follow-up (body weight, waist circumference, eating and alcohol habits and physical activity. At study end, a questionnaire assessed participant satisfaction and qualitative interviews elicited women¿s, coaches and radiographers¿ experiences. Statistical analysis used Chi squared tests for comparisons in proportions and paired t tests for comparisons of means. Linear regression analyses were performed, adjusted for baseline values, with group allocation as a fixed effectResultsA pre-set recruitment target of 80 women was achieved within 12 weeks and 65 (81%) participants (29 intervention, 36 control) completed 3 month assessments. Mean age was 58¿±¿5.6 years, mean BMI was 29.2¿±¿7.0 kg/m2 and many (44%) reported a family history of breast cancer.The primary analysis (baseline body weight adjusted) showed a significant between group difference favouring the intervention group of 2.04 kg (95%CI ¿3.24 kg to ¿0.85 kg). Significant, favourable between group differences were also detected for BMI, waist circumference, physical activity and sitting time. Women rated the programme highly and 70% said they would recommend it to others.ConclusionsRecruitment, retention, indicative results and participant acceptability support the development of a definitive RCT to measure long term effects.Trial registrationThe trial was registered with Current Controlled Trials (ISRCTN56223933)