Precision medicine relies on validated biomarkers with which to better classify patients by their probable disease risk, prognosis and/or response to treatment. Although affordable 'omics'-based ...technology has enabled faster identification of putative biomarkers, the validation of biomarkers is still stymied by low statistical power and poor reproducibility of results. This Review summarizes the successes and challenges of using different types of molecule as biomarkers, using lung cancer as a key illustrative example. Efforts at the national level of several countries to tie molecular measurement of samples to patient data via electronic medical records are the future of precision medicine research.
Utilisation of supplementary cementitious materials (SCM) has been found as a suitable alternative to reduce CO2 emissions from cement production. Fly ash (FA) is the most well-known of these ...materials and has been used for decades in cement applications. Amongst these applications, the most significant is the replacement of clinker in cement blends, which reduces the consumption of resources and energy and at the same time, avoids the environmental burden associated with clinker production. Despite the existence of these opportunities, a large fraction of the FA produced worldwide is still unused and disposed as waste or stored in landfills. This occurs mostly because FA is unable to meet the quality requirements for replacing clinker in cement blends. Upgrading of FA to a suitable material that can effectively replace clinker is possible via upgrading processes (UP). These processes carry their own environmental impacts because in most of the cases, thermal and electric energy are used in them. Due to this fact, the use and implementation of upgraded fly ash involves additional environmental impacts to the life-cycle of the product. The most relevant of these impacts during the upgrading stage, is the generation of additional direct and indirect CO2 emissions from energy consumption. From a life-cycle perspective, the generation of these additional CO2 emissions decreases the net abatement achieved by using fly ash as a SCM. Therefore, it is necessary to account these emissions and calculate the net abatement achieved by replacing clinker and fossil fuel consumption.
A system dynamics model is presented by simulating five different cement life-cycle scenarios in order to quantify the net CO2 reductions when using upgrading processes of fly ash. Ultra-fine grinding for the mechanical activation of FA is the UP modelled using published and direct data from the equipment manufacturer. A material flow analysis (MFA) was carried out to describe the scenarios and to simplify the life-cycle approach. It was found that the upgrading process modelled can have maximum value of 3.98 GJ/tonne of fly ash and still be able to produce net reductions. The same model also estimated that an 80% of the total reductions are avoided when ultra-fine grinding consumes 0.75 GJ/tonneFA of energy, compared to emissions from the baseline cement. The model is also complemented by reviewing the current use of FA as a SCM in the cement industry and by presenting a holistic systems thinking analysis. The model can also be further expanded to simulate other life-cycle scenarios which can include multiple upgrading processes and other materials.
•We developed a computer model to calculate CO2 emissions from an ultra-fine grinding process to upgrade fly ash.•Current upgrading of fly ash with ultra-fine grinding processes produces net CO2 emission reductions when fly ash is used.•Upgrading processes with specific energy consumption under 3.98 GJ/tonne of fly ash can produce CO2 reductions.•Emission reduction benefits increase when upgrading technologies become more efficient.
Genetic and pathological studies link α-synuclein to the etiology of Parkinson's disease (PD), but the normal function of this presynaptic protein remains unknown. α-Synuclein, an acidic lipid ...binding protein, shares high sequence identity with β- and γ-synuclein. Previous studies have implicated synucleins in synaptic vesicle (SV) trafficking, although the precise site of synuclein action continues to be unclear. Here we show, using optical imaging, electron microscopy, and slice electrophysiology, that synucleins are required for the fast kinetics of SV endocytosis. Slowed endocytosis observed in synuclein null cultures can be rescued by individually expressing mouse α-, β-, or γ-synuclein, indicating they are functionally redundant. Through comparisons to dynamin knock-out synapses and biochemical experiments, we suggest that synucleins act at early steps of SV endocytosis. Our results categorize α-synuclein with other familial PD genes known to regulate SV endocytosis, implicating this pathway in PD.
Aim
A current biogeographic paradigm states that climate regulates species distributions at continental scales and that biotic interactions are undetectable at coarse‐grain extents. However, advances ...in spatial modelling show that incorporating food resource distributions are important for improving model predictions at large distribution scales. This is particularly relevant to understand the factors limiting the distribution of widespread apex predators whose diets are likely to vary across their range.
Location
Neotropical Central and South America.
Methods
The harpy eagle (Harpia harpyja) is a large raptor, whose diet is largely comprised of arboreal mammals, all with broad distributions across Neotropical lowland forest. Here, we used a hierarchical modelling approach to determine the relative importance of abiotic factors and prey resource distribution on harpy eagle range limits. Our hierarchical approach consisted of the following modelling sequence of explanatory variables: (a) abiotic covariates, (b) prey resource distributions predicted by an equivalent modelling for each prey, (c) the combination of (a) and (b), and (d) as in (c) but with prey resources considered as a single prediction equivalent to prey species richness.
Results
Incorporating prey distributions improved model predictions but using solely biotic covariates still resulted in a high‐performing model. In the Abiotic model, Climatic Moisture Index (CMI) was the most important predictor, contributing 76% to model prediction. Three‐toed sloth (Bradypus spp.) was the most important prey resource, contributing 64% in a combined Abiotic‐Biotic model, followed by CMI contributing 30%. Harpy eagle distribution had high environmental overlap across all individual prey distributions, with highest coincidence through Central America, eastern Colombia, and across the Guiana Shield into northern Amazonia.
Main Conclusions
With strong reliance on prey distributions across its range, harpy eagle conservation programmes must therefore consider its most important food resources as a key element in the protection of this threatened raptor.
In the past few years, 3D electron microscopy (3DEM) has undergone a revolution in instrumentation and methodology. One of the central players in this wide-reaching change is the continuous ...development of image processing software. Here we present Scipion, a software framework for integrating several 3DEM software packages through a workflow-based approach. Scipion allows the execution of reusable, standardized, traceable and reproducible image-processing protocols. These protocols incorporate tools from different programs while providing full interoperability among them. Scipion is an open-source project that can be downloaded from http://scipion.cnb.csic.es.
The number and types of venom components that affect ion-channel function are reviewed. These are the most important venom components responsible for human intoxication, deserving medical attention, ...often requiring the use of specific anti-venoms. Special emphasis is given to peptides that recognize Na+-, K+- and Ca++-channels of excitable cells. Knowledge generated by direct isolation of peptides from venom and components deduced from cloned genes, whose amino acid sequences are deposited into databanks are nowadays in the order of 1.5 thousands, out of an estimate biodiversity closed to 300,000. Here the diversity of components is briefly reviewed with mention to specific references. Structural characteristic are discussed with examples taken from published work. The principal mechanisms of action of the three different types of peptides are also reviewed. Na+-channel specific venom components usually are modifier of the open and closing kinetic mechanisms of the ion-channels, whereas peptides affecting K+-channels are normally pore blocking agents. The Ryanodine Ca++-channel specific peptides are known for causing sub-conducting stages of the channels conductance and some were shown to be able to internalize penetrating inside the muscle cells.
•An updated review on what is known about scorpion venom components is compiled.•The biodiversity of venom components identified from venom or based on cDNA cloning is revised.•Special emphasis is given to toxins affecting: Na+-, K+-, and Ryanodine sensitive Ca2+-channels.•Aspects related to the 3D-structure of important toxins are also included.•Medical aspects of scorpion intoxication by these peptides are mentioned.
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