Metabolic impact of adenovirus-mediated overexpression of the glucose-6-phosphatase catalytic subunit in hepatocytes

Glucose-6-phosphatase (G6Pase) catalyzes the hydrolysis of glucose 6-phosphate (Glu-6-P) to free glucose and, as the last step in gluconeogenesis and glycogenolysis in liver, is thought to play an important role in glucose homeostasis. G6Pase activity appears to be conferred by a set of proteins localized to the endoplasmic reticulum, including a glucose-6-phosphate translocase, a G6Pase phosphohydrolase or catalytic subunit, and glucose and inorganic phosphate transporters in the endoplasmic reticulum membrane. In the current study, we used a recombinant adenovirus containing the cDNA encoding the G6Pase catalytic subunit (AdCMV-G6Pase) to evaluate the metabolic impact of overexpression of the enzyme in primary hepatocytes. We found that AdCMV-G6Pase-treated liver cells contain significantly less glycogen and Glu-6-P, but unchanged UDP-glucose levels, relative to control cells. Further, the glycogen synthase activity state was closely correlated with Glu-6-P levels over a wide range of glucose concentrations in both G6Pase-overexpressing and control cells. The reduction in glycogen synthesis in AdCMV-G6Pase-treated hepatocytes is therefore not a function of decreased substrate availability but rather occurs because of the regulatory effects of Glu-6-P on glycogen synthase activity. We also found that AdCMV-G6Pase-treated-cells had significantly lower rates of lactate production and [3-3H]glucose usage, coupled with enhanced rates of gluconeogenesis and Glu-6-P hydrolysis. We conclude that overexpression of the G6Pase catalytic subunit alone is sufficient to activate flux through the G6Pase system in liver cells. Further, hepatocytes treated with AdCMV-G6Pase exhibit a metabolic profile resembling that of liver cells from patients or animals with non-insulin-dependent diabetes mellitus, suggesting that dysregulation of the catalytic subunit of G6Pase could contribute to the etiology of the disease.     

Application of Fuzzy Moving Sliding Surface Approach for Container Cranes

International Journal of Control, Automation and Systems - In this paper, we consider the fuzzy moving sliding surface anti-sway control problem for container cranes. We first introduce the dynamic...     

From big smartphone data to worldwide research: The Mobile Data Challenge

This paper presents an overview of the Mobile Data Challenge (MDC), a large-scale research initiative aimed at generating innovations around smartphone-based research, as well as community-based evaluation of mobile data analysis methodologies. First, we review the Lausanne Data Collection Campaign (LDCC), an initiative to collect unique longitudinal smartphone dataset for the MDC. Then, we introduce the Open and Dedicated Tracks of the MDC, describe the specific datasets used in each of them, discuss the key design and implementation aspects introduced in order to generate privacy-preserving and scientifically relevant mobile data resources for wider use by the research community, and summarize the main research trends found among the 100+ challenge submissions. We finalize by discussing the main lessons learned from the participation of several hundred researchers worldwide in the MDC Tracks.     

Human interaction discovery in smartphone proximity networks

Since humans are fundamentally social beings and interact frequently with others in their daily life, understanding social context is of primary importance in building context-aware applications. In this paper, using smartphone Bluetooth as a proximity sensor to create social networks, we present a probabilistic approach to mine human interaction types in real life. Our analysis is conducted on Bluetooth data continuously sensed with smartphones for over one year from 40 individuals who are professionally or personally related. The results show that the model can automatically discover a variety of social contexts. We objectively validated our model by studying its predictive and retrieval performance.     

AH-64D main transmission accessory drive spur gear installation fault detections

The US Army has launched an aggressive program to implement condition based maintenance on its rotary wing assets. Condition Based Maintenance takes advantage of technology developments in the areas of machinery monitoring, signal processing and fault modeling to reduce the cost of ownership through improved maintenance procedures. Documenting the reduction in maintenance burden, cost savings and increased safety through early detection of helicopter faults is an important step in justifying the program. This paper describes a novel technique used to detect a serious fault in the accessory section of the AH-64D Apache main transmission. The technique determines if the primary or secondary clutch system is driving the aircraft accessories through a tachometer speed ratio. The method has identified three aircraft operating on the secondary system allowing Army maintenance crews to replace the affected transmissions and quickly restore the aircraft to operational status.     

DESIGN OF REDUCED‐ORDER FUNCTIONAL OBSERVERS FOR LINEAR SYSTEMS WITH UNKNOWN INPUTS

This brief paper presents new conditions for the existence and design of reduced‐order linear functional state observers for linear systems with unknown inputs. Systematic procedures for the synthesis of reduced‐order functional observers are given. Numerical examples are given to illustrate the attractiveness and simplicity of the new design procedures.     

Density-controllable growth of SnO2 nanowire junction-bridging across electrode for low-temperature NO2 gas detection

The junction-bridging structure of metal oxide nanowires (NWs) improves gas-sensing properties. In this study, an on-chip growth method was used to fabricate gas sensors, it easily and effectively controls NW junctions. SnO₂ NWs were synthesized by thermal evaporation at 800 °C with tin powder as the source. The density of the NW junctions was controlled by changing the mass of the source material. A source material with large mass yielded high-density NW junctions. With electrode spacing of 20 μm, NW junctions were formed from the source material of larger than 2 mg. Gas sensing results revealed that the junction sensors exhibited a good response to NO₂ gas at a concentration of 1–10 ppm. The sensors exhibited a good response to NO₂ gas at low temperature of up to 100 °C and short response–recovery time (~20 s). The sensors also had good selectivity to NO₂ gas. The response (R _gas /R _air) to 1 ppm NO₂ was as high as 22 at 100 °C, whereas the cross gas responses (R _air /R _gas) to 10 ppm CO, 10 ppm H₂S, 100 ppm C₂H₅OH, and 100 ppm NH₃ were negligible (1.1–1.3).     

Genetic Dissection of Light-Regulated Adventitious Root Induction in Arabidopsis thaliana Hypocotyls

Photomorphogenic responses of etiolated seedlings include the inhibition of hypocotyl elongation and opening of the apical hook. In addition, dark-grown seedlings respond to light by the formation of adventitious roots (AR) on the hypocotyl. How light signaling controls adventitious rooting is less well understood. Hereto, we analyzed adventitious rooting under different light conditions in wild type and photomorphogenesis mutants in Arabidopsis thaliana. Etiolation was not essential for AR formation but raised the competence to form AR under white and blue light. The blue light receptors CRY1 and PHOT1/PHOT2 are key elements contributing to the induction of AR formation in response to light. Furthermore, etiolation-controlled competence for AR formation depended on the COP9 signalosome, E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC (COP1), the COP1 interacting SUPPRESSOR OF PHYA-105 (SPA) kinase family members (SPA1,2 and 3) and Phytochrome-Interacting Factors (PIF). In contrast, ELONGATED HYPOCOTYL5 (HY5), suppressed AR formation. These findings provide a genetic framework that explains the high and low AR competence of Arabidopsis thaliana hypocotyls that were treated with dark, and light, respectively. We propose that light-induced auxin signal dissipation generates a transient auxin maximum that explains AR induction by a dark to light switch.     

Generalized Approach towards Secretion-Based Protein Production via Neutralization of Secretion-Preventing Cationic Substrate Residues

Many heterologous proteins can be secreted by bacterial ATP-binding cassette (ABC) transporters, provided that they are fused with the C-terminal signal sequence, but some proteins are not secretable even though they carry the right signal sequence. The invention of a method to secrete these non-secretable proteins would be valuable both for understanding the secretory physiology of ABC transporters and for industrial applications. Herein, we postulate that cationic “supercharged” regions within the target substrate protein block the secretion by ABC transporters. We also suggest that the secretion of such substrate proteins can be rescued by neutralizing those cationic supercharged regions via structure-preserving point mutageneses. Surface-protruding, non-structural cationic amino acids within the cationic supercharged regions were replaced by anionic or neutral hydrophilic amino acids, reducing the cationic charge density. The examples of rescued secretions we provide include the spike protein of SARS-CoV-2, glutathione-S-transferase, streptavidin, lipase, tyrosinase, cutinase, growth factors, etc. In summary, our study provides a method to predict the secretability and a tool to rescue the secretion by correcting the secretion-blocking regions, making a significant step in understanding the physiological properties of ABC transporter-dependent protein secretion and laying the foundation for the development of a secretion-based protein-producing platform.