Analysis of Cerebrospinal Fluid Extracellular Vesicles by Proximity Extension Assay: A Comparative Study of Four Isolation Kits

There is a lack of reliable biomarkers for disorders of the central nervous system (CNS), and diagnostics still heavily rely on symptoms that are both subjective and difficult to quantify. The cerebrospinal fluid (CSF) is a promising source of biomarkers due to its close connection to the CNS. Extracellular vesicles are actively secreted by cells, and proteomic analysis of CSF extracellular vesicles (EVs) and their molecular composition likely reflects changes in the CNS to a higher extent compared with total CSF, especially in the case of neuroinflammation, which could increase blood–brain barrier permeability and cause an influx of plasma proteins into the CSF. We used proximity extension assay for proteomic analysis due to its high sensitivity. We believe that this methodology could be useful for de novo biomarker discovery for several CNS diseases. We compared four commercially available kits for EV isolation: MagCapture and ExoIntact (based on magnetic beads), EVSecond L70 (size-exclusion chromatography), and exoEasy (membrane affinity). The isolated EVs were characterized by nanoparticle tracking analysis, ELISA (CD63, CD81 and albumin), and proximity extension assay (PEA) using two different panels, each consisting of 92 markers. The exoEasy samples did not pass the built-in quality controls and were excluded from downstream analysis. The number of detectable proteins in the ExoIntact samples was considerably higher (~150% for the cardiovascular III panel and ~320% for the cell regulation panel) compared with other groups. ExoIntact also showed the highest intersample correlation with an average Pearson’s correlation coefficient of 0.991 compared with 0.985 and 0.927 for MagCapture and EVSecond, respectively. The median coefficient of variation was 5%, 8%, and 22% for ExoIntact, MagCapture, and EVSecond, respectively. Comparing total CSF and ExoIntact samples revealed 70 differentially expressed proteins in the cardiovascular III panel and 17 in the cell regulation panel. To our knowledge, this is the first time that CSF EVs were analyzed by PEA. In conclusion, analysis of CSF EVs by PEA is feasible, and different isolation kits give distinct results, with ExoIntact showing the highest number of identified proteins with the lowest variability.     

Very low threshold graded-indexseparate-confinement-heterostructure strained InGaAsPsingle-quantum-well lasers

A low threshold current density of ~100 A/cm² has been obtained at 1.55 μm using a graded-index separate-confinement-heterostructure strained InGaAsP single-quantum-well laser. The design of the laser structure is based on results calculated from the viewpoint of effective carrier injection into the well     

Stabilization of inter-area and/or oscillatory modes in large-scale power system by voltage impedance power system (VIPS) apparatus based on decentralized control scheme

New technologies such as power electronics have made it possible to change continuously the impedance of a power system not only to control power flow but also to enhance stability. A power system incorporating a variable impedance apparatus such as a variable series capacitor (VSrC) and high-speed phase shifter (HSPS) is called VIPS (Variable Impedance Power System) by the authors. This paper proposes a novel control method of VIPS apparatus such as VSrC and HSPS installed at an interconnecting point for stabilizing inter-area unstable and/or oscillatory modes. The proposed design method of the control system is a kind of hierarchical decentralized control method of a large-scale power system based on a Lyapunov function. Under the proposed control scheme, each subsystem can be stabilized independently by local controllers such as AVR, speed governor and PSS, and then the whole interconnected system can be stabilized by VIPS apparatus taking into account interactions between subsystems. The effectiveness and robustness of the VIPS apparatus control are shown by numerical examples with model systems including a large-scale power system.     

The relation between luminous properties and oxygen content inZnS:TbOF thin-film electroluminescent devices fabricated byradio-frequency magnetron sputtering method

The purpose of this paper is to study the relationship between the oxygen concentration and brightness degradation in ZnS:TbOF green thin-film electroluminescent (EL) devices. The characteristics including crystallinity, optical, and electrical properties were discussed. The brightness-voltage (B-V) measurement results shelved that with higher oxygen-content in ZnS:TbOF phosphor layer, lower brightness was measured. It was consistent with the poor crystallinity, worse photoluminescent intensity, and easier to get moisture in the oxygen-rich (O/Tb>1) phosphor film. Furthermore, deep level transient spectroscopy (DLTS) measurements identified that when the O/Tb ratio was greater than 1, the oxygen-related deep hole traps E_H1 and/or E_H2 could be detected in the ZnS:TbOF phosphor layer. These E _H1 and/or E_H2 traps were believed to be the main killers for the brightness of the device since they capture most of the holes from the generated electron-hole pairs. This evidence strongly supports that the modified energy transfer model is more dominant than direct impact excitation during the luminescent process     

Practical method for generation expansion planning based on dynamic programming

This paper presents an efficient method which provides the optimal generation mix and the optimal generation construction process. The approximation method in which the dynamic programming technique and gradient method are combined is applied to determine the optimal generation mix with hydropower generation technologies. The successive approximations dynamic programming (SADP) technique, which is very suitable for high-dimensional multistage decision process problems, is used for obtaining the optimal generation construction process. The effectiveness and feasibility of the developed technique are demonstrated on a practical power system model which has five types of generation technologies including a hydropower generation technology.     

Determination of three dimensional in situ stress from core discing based on analysis of principal tensile stress

To determine all of the components of in situ stress from core discing, both the directions and magnitudes of the principal in situ stresses must be determined for a disc of a given thickness. In this study, we analyzed the direction and magnitude of tensile stress below an HQ core stub for 11 core lengths using stress conditions under which core discing is likely to occur. First, based on an analysis of the direction of tensile stress below the core stub, we propose a method for determining directions of in situ stress from the height distribution at the periphery of the end surface of a disc. This method can be used with a disc of any thickness. Next, based on an analysis of the magnitude of tensile stress in the central part of a core, we propose a linear criterion for core discing, which can be applied to a core of any length. This criterion was in good agreement with an empirical formula obtained previously in laboratory experiments. By combining information on the direction of in situ stress and the linear criterion for core discing, we propose a method for determining all of the components of in situ stress from core discing under the assumption that vertical stress is given by the overburden stress. Finally, these methods were applied to discs obtained from a field where hydraulic fracturing was performed to measure horizontal stresses. The results showed that the azimuths of the principal stresses estimated from core discing were consistent with those of the principal horizontal stresses determined by hydraulic fracturing and that while the magnitudes of the principal horizontal stresses estimated from core discing showed a large scatter, they were similar to those determined by hydraulic fracturing.     

Cytomegalovirus disease accompanied by severe hypoproteinemia in a patient with adult T-cell leukemia-lymphoma

A 62-year-old Japanese man complained of fever, general fatigue, anorexia and watery diarrhea during remission of adult T-cell leukemia-lymphoma. Laboratory examinations showed severe hypoproteinemia (2.9 g/dl). However, neither intestinal lesions associated with ATL nor findings suggesting protein losing gastroenteropathy were observed. Cytomegalovirus (CMV) antigen detection assay using peripheral blood leukocytes revealed that he had an active CMV infection with hemophagocytic syndrome. Treatment with ganciclovir and methylprednisolone led to an improvement of hypoproteinemia. CMV disease and associated hemophagocytic syndrome should be considered as a cause of hypoproteinemia in an immunocompromised host.     

Damage tolerance of glass mat/epoxy laminates hybridized with flexible resin under static and impact loading

This study deals with the impact property and damage tolerance of matrix hybrid composite laminates with different laminate constitution. The matrix hybrid composite laminates consisted of the laminae with a conventional epoxy resin and the laminae with a flexible epoxy resin modified from the conventional resin to avoid the interlaminar delamination. The impact energy absorption ratio greatly depended on the matrix resin placed at the impact face. The energy absorption was almost constant if the conventional resin was placed at the impact surface layer, while it increased exponentially with the increasing fraction of the flexible resin if the flexible resin was placed at the impact face. The impact energy was absorbed by the damage development and propagation in the laminate with conventional resin laminae as the impacted face, while it was absorbed by both the recoverable deformation of the flexible resin and the damage propagation in the laminate with flexible resin laminae as the impacted face.     

Synthesis and applications of fluoroalkyl end-capped cooligomers having fullerene and mixed fullerenes in the main chain

Fluoroalkanoyl peroxides reacted with FULLERENES [fullerene (C₆₀) and commercially available fullerenes (Nanom Mix^TR and Nanom Black^TR)] and radical polymerizable comonomers such as acrylic acid, N,N-dimethylacrylamide, N-(1,1-dimethyl-3-oxobutyl)acrylamide, and acryloylmorpholine to afford fluoroalkyl end-capped cooligomers having FULLERENES in the main chain under very mild conditions. Fluoroalkyl end-capped Nanom Mix and Nanom Black cooligomers thus obtained were found to exhibit a similar solubility to that of the corresponding fluoroalkyl end-capped cooligomers having fullerene in the main chain. These fluorinated FULLERENES cooligomers were found to form the nanometer size-controlled self-assembled cooligomeric aggregates in aqueous solutions. These fluoroalkyl end-capped FULLERENES cooligomers were more effective for solubilizing fullerene, Nanom Mix and Nanom Black into water, compared to those of the corresponding fluoroalkyl end-capped homooligomers having no FULLERENES in the main chain. Fluoroalkyl end-capped fullerene- and Nanom Mix-acrylic acid cooligomers were found to exhibit fluorescence spectra related to fullerene and Nanom Mix in cooligomers, respectively, in aqueous solutions. Additionally, these fluorinated fullerene- and Nanom Mix-acrylic acid cooligomers were able to increase chemiluminescence intensity related to luminol, effectively, compared to the corresponding fluorinated acrylic acid homooligomers.