ROS regulation of axonal mitochondrial transport

Mitochondria perform critical functions including aerobic ATP production and calcium (Ca2+) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two. Using primaryDrosophila neuronal cell culture and the third instar larval nervous system as in vitro and in vivo models, respectively, we studied mitochondrial transport under oxidative stress conditions. In vitro, hydrogen peroxide (H2O2) diminished the percentage of moving mitochondria, the mitochondrial length and inner membrane potential. In vivo, ROS inhibited specifically mitochondrial axonal transport, primarily due to reduced flux and velocity, but did not affect transport of other organelles. In addition to excess ROS, down-regulation of Nox or Duox expression, which reduces endogenous ROS levels, mitochondrial transport was impaired. To understand the mechanisms underlying these effects, we examined Ca2+ levels and the JNK (c-Jun N-terminal Kinase) pathway, which have been shown to regulate mitochondrial transport and general fast axonal transport, respectively. We found that elevated ROS increased Ca 2+levels, and that the Ca2+ chelator EGTA rescued ROS-induced defects in mitochondrial transport. In addition, activation of the JNK pathway reduced mitochondrial flux and velocities, while JNK knockdown partially rescued ROS-induced defects in the anterograde direction. We conclude that ROS have the capacity to regulate mitochondrial traffic, and that Ca 2+ and JNK signaling play roles in mediating these effects

Brain informed transfer learning for categorizing construction hazards

A transfer learning paradigm is proposed for "knowledge" transfer between the human brain and convolutional neural network (CNN) for a construction hazard categorization task. Participants' brain activities are recorded using electroencephalogram (EEG) measurements when viewing the same images (target dataset) as the CNN. The CNN is pretrained on the EEG data and then fine-tuned on the construction scene images. The results reveal that the EEG-pretrained CNN achieves a 9 % higher accuracy compared with a network with same architecture but randomly initialized parameters on a three-class classification task. Brain activity from the left frontal cortex exhibits the highest performance gains, thus indicating high-level cognitive processing during hazard recognition. This work is a step toward improving machine learning algorithms by learning from human-brain signals recorded via a commercially available brain-computer interface. More generalized visual recognition systems can be effectively developed based on this approach of "keep human in the loop"

A privacy-preserving data storage and service framework based on deep learning and blockchain for construction workers' wearable IoT sensors

Classifying brain signals collected by wearable Internet of Things (IoT) sensors, especially brain-computer interfaces (BCIs), is one of the fastest-growing areas of research. However, research has mostly ignored the secure storage and privacy protection issues of collected personal neurophysiological data. Therefore, in this article, we try to bridge this gap and propose a secure privacy-preserving protocol for implementing BCI applications. We first transformed brain signals into images and used generative adversarial network to generate synthetic signals to protect data privacy. Subsequently, we applied the paradigm of transfer learning for signal classification. The proposed method was evaluated by a case study and results indicate that real electroencephalogram data augmented with artificially generated samples provide superior classification performance. In addition, we proposed a blockchain-based scheme and developed a prototype on Ethereum, which aims to make storing, querying and sharing personal neurophysiological data and analysis reports secure and privacy-aware. The rights of three main transaction bodies - construction workers, BCI service providers and project managers - are described and the advantages of the proposed system are discussed. We believe this paper provides a well-rounded solution to safeguard private data against cyber-attacks, level the playing field for BCI application developers, and to the end improve professional well-being in the industry

Mitochondrial targeting of human NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUFV2) and its association with early-onset hypertrophic cardiomyopathy and encephalopathy

<p>Abstract</p> <p>Background</p> <p>NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUFV2), containing one iron sulfur cluster ([2Fe-2S] binuclear cluster N1a), is one of the core nuclear-encoded subunits existing in human mitochondrial complex I. Defects in this subunit have been associated with Parkinson's disease, Alzheimer's disease, Bipolar disorder, and Schizophrenia. The aim of this study is to examine the mitochondrial targeting of NDUFV2 and dissect the pathogenetic mechanism of one human deletion mutation present in patients with early-onset hypertrophic cardiomyopathy and encephalopathy.</p> <p>Methods</p> <p>A series of deletion and point-mutated constructs with the <it>c-myc </it>epitope tag were generated to identify the location and sequence features of mitochondrial targeting sequence for NDUFV2 in human cells using the confocal microscopy. In addition, various lengths of the NDUFV2 N-terminal and C-terminal fragments were fused with enhanced green fluorescent protein to investigate the minimal region required for correct mitochondrial import. Finally, a deletion construct that mimicked the IVS2+5_+8delGTAA mutation in <it>NDUFV2 </it>gene and would eventually produce a shortened NDUFV2 lacking 19-40 residues was generated to explore the connection between human gene mutation and disease.</p> <p>Results</p> <p>We identified that the cleavage site of NDUFV2 was located around amino acid 32 of the precursor protein, and the first 22 residues of NDUFV2 were enough to function as an efficient mitochondrial targeting sequence to carry the passenger protein into mitochondria. A site-directed mutagenesis study showed that none of the single-point mutations derived from basic, hydroxylated and hydrophobic residues in the NDUFV2 presequence had a significant effect on mitochondrial targeting, while increasing number of mutations in basic and hydrophobic residues gradually decreased the mitochondrial import efficacy of the protein. The deletion mutant mimicking the human early-onset hypertrophic cardiomyopathy and encephalopathy lacked 19-40 residues in NDUFV2 and exhibited a significant reduction in its mitochondrial targeting ability.</p> <p>Conclusions</p> <p>The mitochondrial targeting sequence of NDUFV2 is located at the N-terminus of the precursor protein. Maintaining a net positive charge and an amphiphilic structure with the overall balance and distribution of basic and hydrophobic amino acids in the N-terminus of NDUFV2 is important for mitochondrial targeting. The results of human disease cell model established that the impairment of mitochondrial localization of NDUFV2 as a mechanistic basis for early-onset hypertrophic cardiomyopathy and encephalopathy.</p

Measuring information dependency for construction engineering projects

Information dependency may be the most important key for managing information exchange to reduce project risks. Studies to date have not successfully discovered objective and quantitative surrogate to measure information dependency. This paper suggests an approach to measure information dependency with the productivity relationships among various disciplines for heavy industrial engineering projects. As part of a Construction Industry Institute (CII) study, the authors identified the information exchange pattern of engineering disciplines. Based on the patterns, the authors discovered the information dependency that various engineering disciplines had with their productivity relationships and conducted a survey afterwards for validation. Both results show significant and consistent evidence suggesting that: 1) information of equipment and piping disciplines is statistically dependent rather than the other paired disciplines; and 2) productivity relationship can be a legitimate surrogate to measure information dependency between equipment and piping disciplines. As such, this study enlightens a research trajectory for improvement of engineering productivity

Reduced expression of alpha-1,2-mannosidase I extends lifespan in Drosophila melanogaster and Caenorhabditis elegans

Exposure to sub-lethal levels of stress, or hormesis, was a means to induce longevity. By screening for mutations that enhance resistance to multiple stresses, we identified multiple alleles of alpha-1,2-mannosidase I (mas1) which, in addition to promoting stress resistance, also extended longevity. Longevity enhancement is also observed when mas1 expression is reduced via RNA interference in both Drosophila melanogaster and Caenorhabditis elegans. The screen also identified Edem1 (Edm1), a gene downstream of mas1, as a modulator of lifespan. As double mutants for both mas1 and Edm1 showed no additional longevity enhancement, it appeared that both mutations function within a common pathway to extend lifespan. Molecular analysis of these mutants revealed that the expression of BiP, a putative biomarker of dietary restriction (DR), is down-regulated in response to reductions in mas1 expression. These findings suggested that mutations in mas1 may extend longevity by modulating DR

Time for Singapore to Relook Abortion Law

Figure S1. Effect of anti-ITGA2 antibody on cell morphology. The AGS cells were treated with a 3 Οg of the anti-ITGA2 antibodies or isotype control antibodies (negative control) for 48 h, and cell morphology was observed at 200X magnification. Data are representative of three independent experiments. (PPTX 1463 kb

Latent provisions for building information modeling (BIM) contracts: a social network analysis approach

The effective adoption and use of Building Information Modeling (BIM) require appropriate contract design to fairly allocate the contracting parties’ rights and responsibilities. Several standards for BIM protocols and contracts have been developed for the industry. However, the awareness and the use of these are rather limited, leading to unclear provisions in BIM contracts. Therefore, the research aims to identify the influential legal aspects that serve as the latent contract provisions in BIM contracts. A questionnaire survey was conducted to survey experts and active BIM users in construction projects. The data were analyzed using social network analysis (SNA) by assuming interdependent relationships among various the legal aspects in BIM contacts. The key legal aspects associated with BIM contracts pertain to the roles and responsibilities of the project participants. The results also reveal that data security is the center of all latent legal aspects in the contracts. The study provides significant new insights into clarifying the required contract provisions in BIM contracts

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO