The Protective Effects of the Autophagic and Lysosomal Machinery in Vascular and Valvular Calcification: A Systematic Review

Background: Autophagy is a highly conserved catabolic homeostatic process, crucial for cell survival. It has been shown that autophagy can modulate different cardiovascular pathologies, including vascular calcification (VCN). Objective: To assess how modulation of autophagy, either through induction or inhibition, affects vascular and valvular calcification and to determine the therapeutic applicability of inducing autophagy. Data sources: A systematic review of English language articles using MEDLINE/PubMed, Web of Science (WoS) and the Cochrane library. The search terms included autophagy, autolysosome, mitophagy, endoplasmic reticulum (ER)-phagy, lysosomal, calcification and calcinosis. Study characteristics: Thirty-seven articles were selected based on pre-defined eligibility criteria. Thirty-three studies (89%) studied vascular smooth muscle cell (VSMC) calcification of which 27 (82%) studies investigated autophagy and six (18%) studies lysosomal function in VCN. Four studies (11%) studied aortic valve calcification (AVCN). Thirty-four studies were published in the time period 2015–2020 (92%). Conclusion: There is compelling evidence that both autophagy and lysosomal function are critical regulators of VCN, which opens new perspectives for treatment strategies. However, there are still challenges to overcome, such as the development of more selective pharmacological agents and standardization of methods to measure autophagic flux.     

Formalizing a hierarchical file system

An abstract file system is defined here as a partial function from (absolute) paths to data. Such a file system determines the set of valid paths. It allows the file system to be read and written at a valid path, and it allows the system to be modified by the Unix operations for creation, removal, and moving of files and directories. We present abstract definitions (axioms) for these operations. This specification is refined towards a pointer implementation. The challenge is to have a natural abstraction function from the implementation to the specification, to define operations on the concrete store that behave exactly in the same way as the corresponding functions on the abstract store, and to prove these facts. To mitigate the problems attached to partial functions, we do this in two steps: first a refinement towards a pointer implementation with total functions, followed by one that allows partial functions. These two refinements are proved correct by means of a number of invariants. Indeed, the insights gained consist, on the one hand, of the invariants of the pointer implementation that are needed for the refinement functions, and on the other hand of the precise enabling conditions of the operations on the different levels of abstraction. Each of the three specification levels is enriched with a permission system for reading, writing, or executing, and the refinement relations between these permission systems are explored. Files and directories are distinguished from the outset, but this rarely affects our part of the specifications. All results have been verified with the proof assistant PVS, in particular, that the invariants are preserved by the operations, and that, where the invariants hold, the operations commute with the refinement functions.     

Experiencing standardized media fragment annotations within HTML5

W3C’s Video in the Web activity aims at a better integration of media within the Web. In this paper, we show how two specifications currently under development within this activity, i.e., Media Fragment URIs and Media Annotations, can be combined within media-enabled HTML5 Web applications. In particular, we introduce a number of extensions for the Media Annotations ontology in order to close the gap with Media Fragment URIs. Additionally, we show how rich media fragment annotations can be converted into a WebVTT file. The latter can be used by HTML5-enabled players to show the annotations in a synchronized way. Further, a fully integrated Web application has been developed that shows how both specifications can work together within an HTML5 environment. This application relies on NinSuna, our media delivery platform targeted at multichannel publication that provides server-side support for both Media Fragment URIs and Media Annotations.     

High-speed single cable synchronization system for data-converters

A clock-cycle accurate synchronization technique for fully integrated data-converters is presented. Only a single cable is needed to distribute both the required synchronization signal and the converter clock. Different possible implementations, both to generate and decompose the distributed signal, are presented. A discrete component generator circuit is discussed. To avoid setup and hold time violations, on-chip signal reconstruction is unavoidable. A 40 nm CMOS recovery circuit was developed. Simulation results, including layout parasitics, show the wide frequency operating range of the proposed technique.     

Ilmenite with addition of NiO as oxygen carrier for chemical-looping combustion

The naturally occurring mineral ilmenite, FeTiO₃, has been examined as oxygen carrier for chemical-looping combustion. NiO-based particles have been used as an additive, in order to examine if it is possible to utilize the catalytic properties of metallic Ni to facilitate decomposition of hydrocarbons into more reactive combustion intermediates such as CO and H₂. Firstly, ilmenite was examined by oxidation and reduction experiments in a batch fluidized-bed reactor. These experiments indicated moderate reactivity between ilmenite and CH₄, which was used as reducing gas. However, adding 5 wt.% of NiO-based particles to the ilmenite improved the conversion of CH₄ greatly, resulting in an increase in combustion efficiency with a factor of 3. Secondly, 83 h of chemical-looping combustion experiments were conducted in a small circulating fluidized-bed reactor, using ilmenite as oxygen carrier and natural gas as fuel. A wide range of process parameters and different levels of NiO addition were examined. Occasionally, there were problems with the circulation of solids between the air reactor and fuel reactor, but most of the time the experiments worked well. The products were mostly CO₂, H₂O and unconverted CH₄. Adding small amounts of NiO-based particles to the reactor increased the conversion of the fuel considerably. For the base case conducted at 900°, the combustion efficiency was 76% for pure ilmenite and 90% for the corresponding experiments with 1 wt.% NiO-based particles added to the reactor. The properties of ilmenite were found to change considerably during operation. Used particles had lower density, were more reactive and more porous than fresh particles. These changes appear to have been physical, and no unexpected chemical phases could be identified.     

Kinetic modeling of Fe‐BEA as NH3‐SCR catalyst—effect of phosphorous

The focus of this work is to investigate whether a previously developed microkinetic deactivation model for hydrothermally treated Fe‐BEA as NH₃‐SCR catalyst can be applied to describe chemical deactivation of Fe‐BEA due to phosphorous exposure. The model describes the experiments well for Fe‐BEA before and after phosphorous exposure by decreasing the site density, representing deactivation of sites due to formation of metaphosphates blocking the active iron sites, while the kinetic parameters are kept constant. Furthermore, the results show that the activity for low‐temperature selective catalytic reduction (SCR) is very sensitive to loss of active monomeric iron species due to phosphorous poisoning compared to high‐temperature SCR. Finally, the ammonia inhibition simulations show that exposure to phosphorous may affect the internal transport of ammonia between ammonia storage sites buffering the active iron sites, which results in a lower SCR performance during transient conditions. © 2014 American Institute of Chemical Engineers AIChE J, 61: 215–223, 2015     

Associations between driving under the influence of alcohol or drugs,speeding and seatbelt use among fatally injured car drivers in Norway

Since 2005, all fatal road traffic crashes in Norway have been analyzed in-depth by multidisciplinary investigation teams organized by the Norwegian Public Roads Administration (NPRA). During the period 2005–2010, 608 drivers of cars or vans were killed in road traffic crashes. Blood samples were collected from 372 (61%) of the drivers and analyzed for alcohol and a large number of psychoactive drugs at the Norwegian Institute of Public Health (NIPH). After coupling the analytical results with the NPRA crash database, 369 drivers with a fatal outcome were identified and included. Alcohol or drug concentrations in blood above the legal limits were found in 39.8% of the drivers who were investigated for alcohol or drug impairment; 33.9% had blood alcohol concentrations above 0.5 g/L or concentrations of drugs above the equivalent Norwegian legal impairment limits or concentrations of amphetamines above 200 μg/L. Among drivers with a fatal outcome who had been impaired by alcohol or drugs, 64.6% were unbelted and 71.7% were speeding when the crash occurred; whereas 24.2% and 33.2% of the sober drivers were unbelted or speeding, respectively. Statistically significant associations were found between impairment by alcohol or amphetamines and driving unbelted or speeding. Excessive speeding is one of the main reasons for road traffic crashes and together with being unbelted the main reasons for a fatal outcome. This behavior might in many cases be due to increased risk-taking or negligence of safety measures as a result of alcohol or drug use.     

Multi-laboratory evaluations of the performance of Catellicoccus marimammalium PCR assays developed to target gull fecal sources

Here we report results from a multi-laboratory (n = 11) evaluation of four different PCR methods targeting the 16S rRNA gene of Catellicoccus marimammalium originally developed to detect gull fecal contamination in coastal environments. The methods included a conventional end-point PCR method, a SYBR^® Green qPCR method, and two TaqMan^® qPCR methods. Different techniques for data normalization and analysis were tested. Data analysis methods had a pronounced impact on assay sensitivity and specificity calculations. Across-laboratory standardization of metrics including the lower limit of quantification (LLOQ), target detected but not quantifiable (DNQ), and target not detected (ND) significantly improved results compared to results submitted by individual laboratories prior to definition standardization. The unit of measure used for data normalization also had a pronounced effect on measured assay performance. Data normalization to DNA mass improved quantitative method performance as compared to enterococcus normalization. The MST methods tested here were originally designed for gulls but were found in this study to also detect feces from other birds, particularly feces composited from pigeons. Sequencing efforts showed that some pigeon feces from California contained sequences similar to C. marimammalium found in gull feces. These data suggest that the prevalence, geographic scope, and ecology of C. marimammalium in host birds other than gulls require further investigation. This study represents an important first step in the multi-laboratory assessment of these methods and highlights the need to broaden and standardize additional evaluations, including environmentally relevant target concentrations in ambient waters from diverse geographic regions.