204 research outputs found
Shrinkage and mitigation strategies to improve the dimensional stability of CaO-FeOx-Al2O3-SiO2 inorganic polymers
Volumetric stability is an important aspect of the performance of building materials, and the shrinkage of CaO-FeOx-Al2O3-SiO2-rich inorganic polymers (IPs) has not been thoroughly investigated yet. Hence, this paper describes the outcome of a study conducted to investigate ways to minimize their shrinkage using different curing regimes. Two different slags were used as case studies to assess the robustness of the developed mitigation strategies. IP pastes and mortars were cured at (i) room condition, (ii) in slightly elevated temperature (60 \ub0C for 2 d) and (iii) in a water-saturated environment. The reaction kinetics and formed products were examined on IP pastes, while mortars were made to characterize the 28 d pore structure, autogenous shrinkage, drying shrinkage, and strength development. The results showed that the precursors\u2019 reactivity and curing conditions severely affect shrinkage mechanisms and magnitude. Volumetric changes in the plastic stage can be related to the precursors\u2019 reactivity but drying shrinkage was the driving mechanism affecting the volumetric stability of all IP mortars. Understanding the effect of a precursor\u2019s composition and curing conditions on shrinkage is fundamental to develop proper mitigation strategies and to overcome one of IPs\u2019 main technical drawbacks
Identification of plant-derived alkaloids with therapeutic potential for myotonic dystrophy type I
Myotonic dystrophy type I (DM1) is a disabling neuromuscular disease with no causal treatment available. This disease is caused by expanded CTG trinucleotide repeats in the 3 UTR of the dystrophia myotonica protein kinase gene. On the RNA level, expanded (CUG)n repeats form hairpin structures that sequester splicing factors such as muscleblind-like 1 (MBNL1). Lack of availableMBNL1leads to misregulated alternative splicing of many target pre-mRNAs, leading to the multisystemic symptoms in DM1. Many studies aiming to identify small molecules that target the (CUG)n-MBNL1 complex focused on synthetic molecules. In an effort to identify new small molecules that liberate sequesteredMBNL1from (CUG)n RNA, we focused specifically on small molecules of natural origin. Natural products remain an important source for drugs and play a significant role in providing novel leads and pharmacophores for medicinal chemistry. In a new DM1 mechanism-based biochemical assay, we screened a collection of isolated natural compounds and a library of over 2100 extracts from plants and fungal strains. HPLC-based activity profiling in combination with spectroscopic methods were used to identify the active principles in the extracts. The bioactivity of the identified compounds was investigated in a human cell model and in a mouse model of DM1.We identified several alkaloids, including the -carboline harmine and the isoquinoline berberine, that ameliorated certain aspects of theDM1pathology in these models. Alkaloids as a compound class may have potential for drug discovery in other RNA-mediated diseases
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Prenatal maternal antidepressants, anxiety, and depression and offspring DNA methylation: epigenome-wide associations at birth and persistence into early childhood
Background
Maternal mood disorders and their treatment during pregnancy may have effects on the offspring epigenome. We aim to evaluate associations of maternal prenatal antidepressant use, anxiety, and depression with cord blood DNA methylation across the genome at birth and test for persistence of associations in early and mid-childhood blood DNA.
Methods
A discovery phase was conducted in Project Viva, a prospective pre-birth cohort study with external replication in an independent cohort, the Generation R Study. In Project Viva, pregnant women were recruited between 1999 and 2002 in Eastern Massachusetts, USA. In the Generation R Study, pregnant women were recruited between 2002 and 2006 in Rotterdam, the Netherlands. In Project Viva, 479 infants had data on maternal antidepressant use, anxiety, depression, and cord blood DNA methylation, 120 children had DNA methylation measured in early childhood (~ 3 years), and 460 in mid-childhood (~ 7 years). In the Generation R Study, 999 infants had data on maternal antidepressants and cord blood DNA methylation. The prenatal antidepressant prescription was obtained from medical records. At-mid pregnancy, symptoms of anxiety and depression were assessed with the Pregnancy-Related Anxiety Scale and the Edinburgh Postnatal Depression Scale in Project Viva and with the Brief Symptom Inventory in the Generation R Study. Genome-wide DNA methylation was measured using the Infinium HumanMethylation450 BeadChip in both cohorts.
Results
In Project Viva, 2.9% (14/479) pregnant women were prescribed antidepressants, 9.0% (40/445) experienced high pregnancy-related anxiety, and 8.2% (33/402) reported symptoms consistent with depression. Newborns exposed to antidepressants in pregnancy had 7.2% lower DNA methylation (95% CI, − 10.4, − 4.1; P = 1.03 × 10−8) at cg22159528 located in the gene body of ZNF575, and this association replicated in the Generation R Study (β = − 2.5%; 95% CI − 4.2, − 0.7; P = 0.006). In Project Viva, the association persisted in early (β = − 6.2%; 95% CI − 10.7, − 1.6) but not mid-childhood. We observed cohort-specific associations for maternal anxiety and depression in Project Viva that did not replicate.
Conclusions
The ZNF575 gene is involved in transcriptional regulation but specific functions are largely unknown. Given the widespread use of antidepressants in pregnancy, as well as the effects of exposure to anxiety and depression, implications of potential fetal epigenetic programming by these risk factors and their impacts on development merit further investigation
A new confinement model for FRCM confined concrete
Confined concrete by means of FRCM (Fabric Reinforced Cementitious Matrix), also known as TRM (Textile Reinforced Mortar), may exhibit alternative stress–strain behaviors, depending on different variables including the unconfined concrete strength, concrete cross-section, fibers type and number of layers. Specifically, increasing the confinement level, the experimental observed response changes from a softening to a hardening one, after an initial peak that coincides roughly to that of the unconfined strength. To consider the peculiar behavior of FRCM-confined concrete, a new analytical model is proposed in this work. The formulation allows to calculate both the first and ultimate peak strength values, being more adherent to the real observed experimental behavior of FRCM-confined concrete members. The model is calibrated on a set of experimental data obtained by the same authors, and then its accuracy is validated on a different, larger dataset. Model performance indicators are compared to those calculated for other existing formulations, demonstrating the goodness of the new proposal
Effect of axial cyclic loading on frcm confined concrete
This study presents the results of an experimental campaign aimed at testing the behavior of fiber-reinforced cementitious matrix (FRCM) confined concrete subjected to axial cyclic and monotonic loading. Several parameters were investigated in the campaign, including fiber material (glass and carbon), number of layers applied (1-4 layers) and loading protocol. The results of 22 cylindrical specimens, between control and confined ones, were tested while carefully monitoring axial stress and strain developments. Lateral strain development was also monitored, through electrical strain gauges (eSGs), directly on the fibers of each confinement layer applied to better understand fiber exploitation during cyclic loading. Test results show that even though concrete strength was enhanced in all confined specimens, ductility is the one that is most improved. Both strength and ductility enhancements strongly depend on fiber properties and have a linear proportional enhancement with an increase in the FRCM layers applied. Additionally, no significant difference was observed between the envelope stress-strain curve from cyclic tests with respect to the monotonic ones
FRCM-Confined Concrete: Influence of Cross-Section Geometry on Cyclic Stress–Strain Behavior
This work presents the results of an experimental campaign aimed at assessing the influence of cross-section geometry on the confinement of concrete samples. Four geometries were investigated: circular, square and two rectangular ones, characterized by different aspect ratios. Carbon fibers were used in the Fiber Reinforced Cementitious Matrix (FRCM) employed to realize the confining jackets. Samples were tested under uniaxial compressive stress, both adopting a cyclic and monotonic loading, to evaluate compressive strength, ductility and fibers strain exploitation ratio. Results indicate that the best performance is achieved by circular specimens, displaying the highest lateral pressure
Environmental Performance Indicators for Roadway and Highway Infrastructures Management
This work reviews the main performance indicators (PIs) currently used in literature to assess the environmental-related impacts for the phases of construction and quality control and management of infrastructures, with special attention to those applied on roadways and highways. Particularly, the adoption of such non-technical PIs may have a significant impact on decision-making processes to define both constructive choices, and also managing and maintanance protocols. Among the analysed PIs, on one hand, simplified indicators, such as those based on simplified mass balance functions, are suitable to quickly highlight if recycling/reuse strategies are adopted. On the other hand, those derived through a Life Cycle Assessment (LCA) are worth to be mentioned, due to their ability of capturing the whole impacts within defined system boundaries during the life-cycle of the infrastructure. Such impacts can also be translated into costs, indicating the economic value loss caused by the degradation of the environmental indicators
Environmental impacts of recycled aggregate concrete
Concrete is the most diffused building material worldwide; its large availability is however responsible for great environmental emissions, causing the production of up to 5% of worldwide man-made emissions of carbon dioxide. In this contribution, the effects of using recycled concrete aggregate (RCA) to produce recycled aggregate concrete (RAC) are analyzed, both in terms of mechanical and environmental performances. Four concrete mixtures have been designed: a control, made with only natural aggregates, and three containing RCA. Fresh and hardened concrete properties have been analyzed, and then savings in environmental emissions due to the use of RCA have been quantified. Environmental analysis has been conducted through Life Cycle Assessment (LCA). Results show that the quality of the adhered mortar in RCA is a key parameter to allow recycled concrete to be designed with satisfying mechanical properties, and about 50% of carbon can be saved using RCA instead than NA
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