Characterization of Mitochondrial Alterations in Aicardi–Goutières Patients Mutated in RNASEH2A and RNASEH2B Genes

Aicardi–Goutières syndrome (AGS) is a rare encephalopathy characterized by neurological and immunological features. Mitochondrial dysfunctions may lead to mitochondrial DNA (mtDNA) release and consequent immune system activation. We investigated the role of mitochondria and mtDNA in AGS pathogenesis by studying patients mutated in RNASEH2B and RNASEH2A genes. Lymphoblastoid cell lines (LCLs) from RNASEH2A- and RNASEH2B-mutated patients and healthy control were used. Transmission Electron Microscopy (TEM) and flow cytometry were used to assess morphological alterations, reactive oxygen species (ROS) production and mitochondrial membrane potential variations. Seahorse Analyzer was used to investigate metabolic alterations, and mtDNA oxidation and VDAC1 oligomerization were assessed by immunofluorescence. Western blot and RT-qPCR were used to quantify mtTFA protein and mtDNA release. Morphological alterations of mitochondria were observed in both mutated LCLs, and loss of physiological membrane potential was mainly identified in RNASEH2A LCLs. ROS production and 8-oxoGuanine levels were increased in RNASEH2B LCLs. Additionally, the VDAC1 signal was increased, suggesting a mitochondrial pore formation possibly determining mtDNA release. Indeed, higher cytoplasmic mtDNA levels were found in RNASEH2B LCLs. Metabolic alterations confirmed mitochondrial damage in both LCLs. Data highlighted mitochondrial alterations in AGS patients’ LCLs suggesting a pivotal role in AGS pathogenesis.     

Factorial Design of Phenylpropanolamine Prolonged Release Tablets Formulations Using Fluid Bed Dryer Granulator

A two level factorial design approach was applied to the formulation of prolonged release phenylpropanolamine tablets using three factors: Ethylacrylate-methyl meth-acrylate co-polymer (Eudragit NE-40D) concentration, Microcrystalline cellulose (Avicel PH102) addition to the tablets formula, and the milling of the granulations before compression. The release rate of the drug was the measured parameter. The rate of drug release was mainly affected by the level of the Eudragit. Avicel promotes the release of the drug, specially at low Eudragit level concentrations. Tablets prepared from unmilled lots showed slower drug release than the corresponding lots of milled granules.     

Data Fault Detection in Wireless Sensor Networks Using Machine Learning Techniques

Wireless Personal Communications - Wireless Sensor Network (WSN) is a wireless network that consists of spatially distributed autonomous devices with sophisticated subsystem called sensors to...     

PSEN1 Compound Heterozygous Mutations Associated with Cerebral Amyloid Angiopathy and Cognitive Decline Phenotype

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder caused by the deposition of amyloid beta-peptide (Aβ) aggregates. Aβ aggregates lead to vessel rupture and intracerebral hemorrhages, detected by magnetic resonance imaging (MRI). Presenile CAA is usually genetically determined by mutations in the amyloid precursor protein (APP) gene. However, mutations after codon 200 in the presenilin 1 (PSEN1) gene have been reported to facilitate CAA onset. Here, we analyzed the genetic bases in a patient of 55 years old affected by CAA and cognitive decline. DNA was isolated and genetic analysis was performed by Next-Generation Sequencing (NGS). RNA was extracted and retro-transcribed to perform segregation analysis by TOPO-TA cloning. WB analysis was carried out to check the impact of the mutations on protein. Two compound heterozygous mutations in PSEN1 exon 10, such as a novel stop-gain mutation (c.1070C > G) and a pathogenic splice variant (c.1129A > T), were found by NGS. Both mutations altered the presenilin 1 protein, truncating its C-terminal portion. This is the first case of CAA and cognitive decline caused by two compound mutations in PSEN1. With this report, we suggest extending the genetic analysis to PSEN1 when cerebral microbleeds are observed by MRI investigation in a patient affected by presenile cognitive decline.     

Argument and Decision Making in Computer-Mediated Groups

Following Gouran (1994), the authors proposed four hypotheses that predict the probability of computer-mediated groups (CMGs) endorsing proposals based on (a) the number of reasons offered for them, (b) the number of members advancing these reasons, (c) the net number of positive reactions to the reasons advanced, and (d) the development of support for the reasons. Results from 11 groups that had long collaborated exclusively through computer-mediated means indicated that members in support of a proposal relative to those in opposition as well as the development of their arguments were significant predictors of decision outcomes. Moreover, the number of responses for/against a proposal and the difference in the positive and negative reactions to decision proposals were good independent predictors of decision outcomes.     

Narrow-linewidth, singlemode erbium-doped fibre laser withintracavity wave mixing in saturable absorber

Narrow-linewidth, single longitudinal mode operation is demonstrated in an erbium-doped fibre laser with an intracavity nonlinear absorptive wave mixing of the counter propagating beams. An unpumped length of erbium-doped fibre serves as the saturable absorber. Linewidths of the order of a few kilohertz are obtained     

Continuous monitoring of EDTA extractable iron from mineral slurries using a microfluidic chip

In mineral processing, iron oxidation species formed on the mineral surface play a dominant role in depressing mineral flotation and must be monitored. Current analytical methods rely on off-line sample preparation followed by conventional analytical techniques, which are labour intensive and time delayed. This paper reports the successful application of an open microfluidic chip for real-time continuous monitoring of ethylenediaminetetraacetic acid (EDTA) extractable iron (derived from iron oxidation species) in mineral slurries. A detailed mineralogical study of the mineral ore before and after leaching by EDTA has been undertaken to understand the leaching behaviour of the EDTA-slurry extraction system, showing good agreement with solution analysis.     

New large-scale production method for C/C-SiC ceramics: Investigating the influence of chopped and nonwoven CF

Carbon fibre reinforced carbon and silicon carbide dual matrix composites are a commercially produced using the liquid silicon infiltration (LSI) process. In comparison to the state of the art LSI process, the first production step—the shaping of the carbon fibre reinforced plastic green body—is realised through thermoset injection moulding. Using this method, the complete process can be automated. Simultaneously, the injection moulding technology allows complex geometries with near net shape in short cycle times of about two to five minutes. Thereby, this large-scale process offers a wide range of shot weights from a few mg up to 100?kg, also in multi-component technology. Also, several manufacturing steps can be omitted. This improves the reproducibility, and working in closed environments improves the employees’ health protection. Further process steps, like pyrolysis and silicon infiltration follow the state of the art. Although, this promising approach significantly shortens the fibres, the defined plastic processing is highly reproducible and generates similar mechanical properties like manual processes, due to the better fibre/matrix interaction in the plastic composite. In addition, continuous fibre preforms can be inserted to fulfil higher requirements.