A model for reactive porous transport during re-wetting of hardened concrete

A mathematical model is developed that captures the transport of liquid water in hardened concrete, as well as the chemical reactions that occur between the imbibed water and the residual calcium silicate compounds residing in the porous concrete matrix. The main hypothesis in this model is that the reaction product -- calcium silicate hydrate gel -- clogs the pores within the concrete thereby hindering water transport. Numerical simulations are employed to determine the sensitivity of the model solution to changes in various physical parameters, and compare to experimental results available in the literature.Comment: 30 page

Comparative Study of Superabsorbent Polymers and Pre‐soaked Pumice as Internal Curing Agents in Rice Husk Ash Based High‐Performance Concrete

Utilisation of superabsorbent polymers (SAP) and pre‐soaked lightweight aggregates (LWA) as internal curing (IC) agents for the mitigation of autogenous shrinkage and micro‐cracking of high strength/highperformance concrete (HSC/HPC) have been well researched and documented in literature. Rice husk ash (RHA) on the other hand has been adjudged to be of good pozzolanic activity and a possible alternative to silica fume (SF) in low water/binder (W/B) concrete production. An experimental comparative study was conducted in the current work to assess the effectiveness of the two known ICagents on rice husk ash (RHA) based HPC. HPC mixtures of fc,cube28=60 MPa minimum target strength produced and internally cured with 0.3% content of SAP by weight of binder (bwob) and varied content of pre‐soaked pumice (5 to 10% in steps of 2.5%) by weight of coarse aggregate (bwocg) were cast using 100 mm cubes samples. Thereafter, the samples were cured for 7, 14, 28 and 56 days by water immersion before subjecting them to compressive strength test. The results showed 0.2% bwob SAP HPC (SHPC1) to be the best performed internally cured HPC at the early ages with similar long‐term strength values as 5 and 7.5% bwocg saturated pumiced HPC (PHPC1&2). The study thereby recommends SAP content of 0.2% bwob and saturated pumice content up to 7.5% bwocg for use as ICagent in HPC

Two highly divergent alcohol dehydrogenases of melon exhibit fruit ripening-specific expression and distinct biochemical characteristics

Alcohol dehydrogenases (ADH) participate in the biosynthetic pathway of aroma volatiles in fruit by interconverting aldehydes to alcohols and providing substrates for the formation of esters. Two highly divergent ADH genes (15% identity at the amino acid level) of Cantaloupe Charentais melon (Cucumis melo var. Cantalupensis) have been isolated. Cm-ADH1 belongs to the medium-chain zinc-binding type of ADHs and is highly similar to all ADH genes expressed in fruit isolated so far. Cm-ADH2 belongs to the short-chain type of ADHs. The two encoded proteins are enzymatically active upon expression in yeast. Cm-ADH1 has strong preference for NAPDH as a co-factor, whereas Cm-ADH2 preferentially uses NADH. Both Cm-ADH proteins are much more active as reductases with Kms 10–20 times lower for the conversion of aldehydes to alcohols than for the dehydrogenation of alcohols to aldehydes. They both show strong preference for aliphatic aldehydes but Cm-ADH1 is capable of reducing branched aldehydes such as 3-methylbutyraldehyde, whereas Cm-ADH2 cannot. Both Cm-ADH genes are expressed specifically in fruit and up-regulated during ripening. Gene expression as well as total ADH activity are strongly inhibited in antisense ACC oxidase melons and in melon fruit treated with the ethylene antagonist 1-methylcyclopropene (1-MCP), indicating a positive regulation by ethylene. These data suggest that each of the Cm-ADH protein plays a specific role in the regulation of aroma biosynthesis in melon fruit

CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response

Here, we report that genome editing by CRISPR-Cas9 induces a p53-mediated DNA damage response and cell cycle arrest in immortalized human retinal pigment epithelial cells, leading to a selection against cells with a functional p53 pathway. Inhibition of p53 prevents the damage response and increases the rate of homologous recombination from a donor template. These results suggest that p53 inhibition may improve the efficiency of genome editing of untransformed cells and that p53 function should be monitored when developing cell-based therapies utilizing CRISPR-Cas9.Peer reviewe

Distance decay in delivery care utilisation associated with neonatal mortality. A case referent study in northern Vietnam

BACKGROUND: Efforts to reduce neonatal mortality are essential if the Millennium Development Goal (MDG) 4 is to be met. The impact of spatial dimensions of neonatal survival has not been thoroughly investigated even though access to good quality delivery care is considered to be one of the main priorities when trying to reduce neonatal mortality. This study examined the association between distance from the mother's home to the closest health facility and neonatal mortality, and investigated the influence of distance on patterns of perinatal health care utilisation. METHODS: A surveillance system of live births and neonatal deaths was set up in eight districts of Quang Ninh province, Vietnam, from July 2008 to December 2009. Case referent design including all neonatal deaths and randomly selected newborn referents from the same population. Interviews were performed with mothers of all subjects and GIS coordinates for mothers' homes and all health facilities in the study area were obtained. Straight-line distances were calculated using ArcGIS software. RESULTS: A total of 197 neonatal deaths and 11 708 births were registered and 686 referents selected. Health care utilisation prior to and at delivery varied with distance to the health facility. Mothers living farthest away (4th and 5th quintile, ≥1257 meters) from a health facility had an increased risk of neonatal mortality (OR 1.96, 95% CI 1.40 - 2.75, adjusted for maternal age at delivery and marital status). When stratified for socio-economic factors there was an increased risk for neonatal mortality for mothers with low education and from poor households who lived farther away from a health facility. Mothers who delivered at home had more than twice as long to a health facility compared to mothers who delivered at a health care facility. There was no difference in age at death when comparing neonates born at home or health facility deliveries (p = 0.56). CONCLUSION: Distance to the closest health facility was negatively associated with neonatal mortality risk. Health care utilisation in the prenatal period could partly explain this risk elevation since there was a distance decay in health system usage prior to and at delivery. The geographical dimension must be taken into consideration when planning interventions for improved neonatal survival, especially when targeting socio-economically disadvantaged groups

Non-Metabolic Membrane Tubulation and Permeability Induced by Bioactive Peptides

BACKGROUND: Basic cell-penetrating peptides are potential vectors for therapeutic molecules and display antimicrobial activity. The peptide-membrane contact is the first step of the sequential processes leading to peptide internalization and cell activity. However, the molecular mechanisms involved in peptide-membrane interaction are not well understood and are frequently controversial. Herein, we compared the membrane activities of six basic peptides with different size, charge density and amphipaticity: Two cell-penetrating peptides (penetratin and R9), three amphipathic peptides and the neuromodulator substance P. METHODOLOGY/PRINCIPAL FINDINGS: Experiments of X ray diffraction, video-microscopy of giant vesicles, fluorescence spectroscopy, turbidimetry and calcein leakage from large vesicles are reported. Permeability and toxicity experiments were performed on cultured cells. The peptides showed differences in bilayer thickness perturbations, vesicles aggregation and local bending properties which form lipidic tubular structures. These structures invade the vesicle lumen in the absence of exogenous energy. CONCLUSIONS/SIGNIFICANCE: We showed that the degree of membrane permeabilization with amphipathic peptides is dependent on both peptide size and hydrophobic nature of the residues. We propose a model for peptide-induced membrane perturbations that explains the differences in peptide membrane activities and suggests the existence of a facilitated “physical endocytosis,” which represents a new pathway for peptide cellular internalization

Insights in 17β-HSD1 Enzyme Kinetics and Ligand Binding by Dynamic Motion Investigation

BACKGROUND: Bisubstrate enzymes, such as 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), exist in solution as an ensemble of conformations. 17beta-HSD1 catalyzes the last step of the biosynthesis of estradiol and, thus, it is a potentially attractive target for breast cancer treatment. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the conformational transitions of its catalytic cycle, a structural analysis of all available crystal structures was performed and representative conformations were assigned to each step of the putative kinetic mechanism. To cover most of the conformational space, all-atom molecular dynamic simulations were performed using the four crystallographic structures best describing apoform, opened, occluded and closed state of 17beta-HSD1 as starting structures. With three of them, binary and ternary complexes were built with NADPH and NADPH-estrone, respectively, while two were investigated as apoform. Free energy calculations were performed in order to judge more accurately which of the MD complexes describes a specific kinetic step. CONCLUSIONS/SIGNIFICANCE: Remarkably, the analysis of the eight long range trajectories resulting from this multi-trajectory/-complex approach revealed an essential role played by the backbone and side chain motions, especially of the betaF alphaG'-loop, in cofactor and substrate binding. Thus, a selected-fit mechanism is suggested for 17beta-HSD1, where ligand-binding induced concerted motions of the FG-segment and the C-terminal part guide the enzyme along its preferred catalytic pathway. Overall, we could assign different enzyme conformations to the five steps of the random bi-bi kinetic cycle of 17beta-HSD1 and we could postulate a preferred pathway for it. This study lays the basis for more-targeted biochemical studies on 17beta-HSD1, as well as for the design of specific inhibitors of this enzyme. Moreover, it provides a useful guideline for other enzymes, also characterized by a rigid core and a flexible region directing their catalysis

Early Colonization with a Group of Lactobacilli Decreases the Risk for Allergy at Five Years of Age Despite Allergic Heredity

Background: Microbial deprivation early in life can potentially influence immune mediated disease development such as allergy. The aims of this study were to investigate the influence of parental allergy on the infant gut colonization and associations between infant gut microbiota and allergic disease at five years of age. Methods and Findings: Fecal samples were collected from 58 infants, with allergic or non-allergic parents respectively, at one and two weeks as well as at one, two and twelve months of life. DNA was extracted from the fecal samples and Real time PCR, using species-specific primers, was used for detection of Bifidobacterium (B.) adolescentis, B. breve, B. bifidum, Clostridium (C.) difficile, a group of Lactobacilli (Lactobacillus (L.) casei, L. paracasei and L. rhamnosus) as well as Staphylococcus (S.) aureus. Infants with non-allergic parents were more frequently colonized by Lactobacilli compared to infants with allergic parents (p = 0.014). However, non-allergic five-year olds acquired Lactobacilli more frequently during their first weeks of life, than their allergic counterparts, irrespectively of parental allergy (p = 0.009, p = 0.028). Further the non-allergic children were colonized with Lactobacilli on more occasions during the first two months of life (p = 0.038). Also, significantly more non-allergic children were colonized with B. bifidum at one week of age than the children allergic at five years (p = 0.048). Conclusion: In this study we show that heredity for allergy has an impact on the gut microbiota in infants but also that earl

Global lake thermal regions shift under climate change

Water temperature is critical for the ecology of lakes. However, the ability to predict its spatial and seasonal variation is constrained by the lack of a thermal classification system. Here we define lake thermal regions using objective analysis of seasonal surface temperature dynamics from satellite observations. Nine lake thermal regions are identified that mapped largely contiguously globally, and robustly even for small lakes. The regions differed from other global patterns, and so provide unique information. Using a lake model forced by 21st century climate projections we found that 12, 27 and 66% of lakes will change to a lower latitude thermal region by 2080-2099 for low, medium and high greenhouse gas concentration trajectories (Representative Concentration Pathways 2.6, 6.0 and 8.5) respectively. Under the worst-case scenario, a 79% reduction in the number of lakes in the northernmost thermal region is projected. This thermal region framework will facilitate the global scaling of lake-research