Plastic shrinkage cracking of concrete - Roles of osmotic suction

Plastic shrinkage cracking of concrete occurs when the stresses arising in the concrete, due to a combination of suction and restraints of deformation such as reinforcement or formwork, equal its strength. However, three different types of suctions should be distinguished, namely total, matric and osmotic suctions. Although the total suction comprises matric and osmotic suctions, it is often used interchangeably with matric suction, with the underlying unconfirmed assumption that either the osmotic suction or its effect is negligible. In this paper, after a discussion of the pore moisture suctions and strength of unsaturated early-age concrete, experimental investigations of the suctions arising in, and the tensile strength and shear strength of, fly ash mixed with solutions of different osmotic suctions are described. It was found that osmotic suction has negligible effect on the shear and tensile strength, and hence, by inference, the inter-particle stresses in the fly ash mixture and early-age concrete. This strongly suggests that the role played by osmotic suction in the plastic shrinkage cracking of concrete is minimal and, accordingly, justifies the focus of earlier researchers on matric suction only

Sampling and Kriging Spatial Means: Efficiency and Conditions

Sampling and estimation of geographical attributes that vary across space (e.g., area temperature, urban pollution level, provincial cultivated land, regional population mortality and state agricultural production) are common yet important constituents of many real-world applications. Spatial attribute estimation and the associated accuracy depend on the available sampling design and statistical inference modelling. In the present work, our concern is areal attribute estimation, in which the spatial sampling and Kriging means are compared in terms of mean values, variances of mean values, comparative efficiencies and underlying conditions. Both the theoretical analysis and the empirical study show that the mean Kriging technique outperforms other commonly-used techniques. Estimation techniques that account for spatial correlation (dependence) are more efficient than those that do not, whereas the comparative efficiencies of the various methods change with surface features. The mean Kriging technique can be applied to other spatially distributed attributes, as well

Is decreased bone mineral density associated with development of scoliosis? A bipedal osteopenic rat model

<p>Abstract</p> <p>Background</p> <p>An association between adolescent idiopathic scoliosis and osteopenia has been proposed to exist. It is still not clear whether there is such an association and if so, whether osteopenia is a causative factor or a consequence. Our previous pilot studies have suggested the presence of osteopenia in scoliotic animals. The aim of this study was to investigate the development of scoliosis in an unpinealectomized bipedal osteopenic rat model, implementing osteoporosis as a causative factor.</p> <p>Methods</p> <p>Fifty Sprague-Dawley rats were rendered bipedal at the 3^rdpostnatal week and separated into control (25 rats) and heparin (25 rats receiving 1 IU/gr body weight/day) groups. DEXA scans after 4 weeks of heparin administration showed low bone mass in the heparin group. Anteroposterior and lateral x-rays of the surviving 42 animals (19 in heparin and 23 in control groups) were taken under anesthesia at the 40^thweek to evaluate for spinal deformity. Additional histomorphometric analysis was done on spine specimens to confirm the low bone mass in heparin receiving animals. Results of the DEXA scans, histomorphometric analysis and radiological data were compared between the groups.</p> <p>Results</p> <p>Bone mineral densities of rats in the heparin group were significantly lower than the control group as evidenced by both the DEXA scans and histomorphometric analyses. However, the incidence of scoliosis (82% in heparin and 65% in control; p > 0.05) as well as the curve magnitudes (12.1 ± 3.8 in heparin versus 10.1 ± 4.3 degrees in control; p > 0.05) were not significantly different. Osteopenic rats were significantly less kyphotic compared to control specimens (p = 0.001).</p> <p>Conclusions</p> <p>This study has revealed two important findings. One is that bipedality (in the absence of pinealectomy) by itself may be a cause of scoliosis in this animal model. Further studies on animal models need to consider bipedality as an independent factor. Secondly, relative hypokyphosis in osteopenic animals may have important implications. The absence of sagittal plane analyses in previous studies makes comparison impossible, but nonetheless these findings suggest that osteopenia may be important in the development of 3D deformity in adolescent idiopathic scoliosis.</p

Ocean currents shape the microbiome of Arctic marine sediments

Prokaryote communities were investigated on the seasonally stratified Alaska Beaufort Shelf (ABS). Water and sediment directly underlying water with origin in the Arctic, Pacific or Atlantic oceans were analyzed by pyrosequencing and length heterogeneity-PCR in conjunction with physicochemical and geographic distance data to determine what features structure ABS microbiomes. Distinct bacterial communities were evident in all water masses. Alphaproteobacteria explained similarity in Arctic surface water and Pacific derived water. Deltaproteobacteria were abundant in Atlantic origin water and drove similarity among samples. Most archaeal sequences in water were related to unclassified marine Euryarchaeota. Sediment communities influenced by Pacific and Atlantic water were distinct from each other and pelagic communities. Firmicutes and Chloroflexi were abundant in sediment, although their distribution varied in Atlantic and Pacific influenced sites. Thermoprotei dominated archaea in Pacific influenced sediments and Methanomicrobia dominated in methane-containing Atlantic influenced sediments. Length heterogeneity-PCR data from this study were analyzed with data from methane-containing sediments in other regions. Pacific influenced ABS sediments clustered with Pacific sites from New Zealand and Chilean coastal margins. Atlantic influenced ABS sediments formed another distinct cluster. Density and salinity were significant structuring features on pelagic communities. Porosity co-varied with benthic community structure across sites and methane did not. This study indicates that the origin of water overlying sediments shapes benthic communities locally and globally and that hydrography exerts greater influence on microbial community structure than the availability of methane

Cost-utility analysis of genetic screening in families of patients with germline MUTYH mutations

<p>Abstract</p> <p>Background</p> <p>MUTYH associated polyposis (MAP) is an autosomal recessive inherited disorder. Carriers of bi-allelic <it>MUTYH </it>germline mutations have a risk of approximately 60% to develop colorectal carcinoma (CRC). In the general population about 1.5% is a heterozygous <it>MUTYH </it>mutation carrier. Children of MAP patients have an increased risk of inheriting two <it>MUTYH </it>mutations compared to the general population, implicating an increased risk for developing CRC.</p> <p>Methods</p> <p>Using data from the literature and Dutch MAP patients (n = 40), we constructed a Markov model to perform a societal cost-utility analysis of genetic screening in MAP families. Genetic screening was done by testing the spouse first and, in case of a heterozygous spouse, also testing of the children.</p> <p>Results</p> <p>The cost of genetic screening of families of MAP patients, when compared to no genetic screening, was estimated at €25,000 per quality-adjusted life year (QALY). The presence of Fecal Occult Blood testing (FOBT) population screening only slightly increased this cost-utility ratio to €25,500 per QALY. For a MUTYH heterozygote index-patient, the ratio was €51,500 per QALY. The results of our analysis were sensitive to several of the parameters in the model, including the cost assumed for molecular genetic testing.</p> <p>Conclusion</p> <p>The costs per QALY of genetic screening in families of MAP patients are acceptable according to international standards. Therefore, genetic testing of spouses and/or children should be discussed with and offered to counselees.</p

Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy

How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C&gt;A and TT&gt;CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful

Rad51 and DNA-PKcs are involved in the generation of specific telomere aberrations induced by the quadruplex ligand 360A that impair mitotic cell progression and lead to cell death

Functional telomeres are protected from non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways. Replication is a critical period for telomeres because of the requirement for reconstitution of functional protected telomere conformations, a process that involves DNA repair proteins. Using knockdown of DNA-PKcs and Rad51 expression in three different cell lines, we demonstrate the respective involvement of NHEJ and HR in the formation of telomere aberrations induced by the G-quadruplex ligand 360A during or after replication. HR contributed to specific chromatid-type aberrations (telomere losses and doublets) affecting the lagging strand telomeres, whereas DNA-PKcs-dependent NHEJ was responsible for sister telomere fusions as a direct consequence of G-quadruplex formation and/or stabilization induced by 360A on parental telomere G strands. NHEJ and HR activation at telomeres altered mitotic progression in treated cells. In particular, NHEJ-mediated sister telomere fusions were associated with altered metaphase-anaphase transition and anaphase bridges and resulted in cell death during mitosis or early G1. Collectively, these data elucidate specific molecular and cellular mechanisms triggered by telomere targeting by the G-quadruplex ligand 360A, leading to cancer cell death

High and low levels of an NTRK2-driven genetic profile affect motor- and cognition-associated frontal gray matter in prodromal Huntington’s disease

This study assessed how BDNF (brain-derived neurotrophic factor) and other genes involved in its signaling influence brain structure and clinical functioning in pre-diagnosis Huntington’s disease (HD). Parallel independent component analysis (pICA), a multivariate method for identifying correlated patterns in multimodal datasets, was applied to gray matter concentration (GMC) and genomic data from a sizeable PREDICT-HD prodromal cohort (N = 715). pICA identified a genetic component highlighting NTRK2, which encodes BDNF’s TrkB receptor, that correlated with a GMC component including supplementary motor, precentral/premotor cortex, and other frontal areas (p < 0.001); this association appeared to be driven by participants with high or low levels of the genetic profile. The frontal GMC profile correlated with cognitive and motor variables (Trail Making Test A (p = 0.03); Stroop Color (p = 0.017); Stroop Interference (p = 0.04); Symbol Digit Modalities Test (p = 0.031); Total Motor Score (p = 0.01)). A top-weighted NTRK2 variant (rs2277193) was protectively associated with Trail Making Test B (p = 0.007); greater minor allele numbers were linked to a better performance. These results support the idea of a protective role of NTRK2 in prodromal HD, particularly in individuals with certain genotypes, and suggest that this gene may influence the preservation of frontal gray matter that is important for clinical functioning.This project was supported by 1U01NS082074 (V.C. and J.T., co-principal investigators) from the National Institutes of Health, National Institute of Neurological Disorders and Stroke. The PREDICT-HD study was supported by NIH/NINDS grant 5R01NS040068 awarded to J.P.; CHDI Foundation, Inc., A3917 and 6266 awarded to J.P.; Cognitive and Functional Brain Changes in Preclinical Huntington’s Disease (HD) 5R01NS054893 awarded to J.P.; 4D Shape Analysis for Modeling Spatiotemporal Change Trajectories in Huntington’s 1U01NS082086; Functional Connectivity in Premanifest Huntington’s Disease 1U01NS082083; and Basal Ganglia Shape Analysis and Circuitry in Huntington’s Disease 1U01NS082085 awarded to Christopher A. Ross