Critical role of TLR activation in viral replication, persistence, and pathogenicity of Theiler’s virus

Theiler’s murine encephalomyelitis virus (TMEV) establishes persistent viral infections in the central nervous system and induces chronic inflammatory demyelinating disease in susceptible mice. TMEV infects dendritic cells, macrophages, B cells, and glial cells. The state of TLR activation in the host plays a critical role in initial viral replication and persistence. The further activation of TLRs enhances viral replication and persistence, leading to the pathogenicity of TMEV-induced demyelinating disease. Various cytokines are produced via TLRs, and MDA-5 signals linked with NF-κB activation following TMEV infection. In turn, these signals further amplify TMEV replication and the persistence of virus-infected cells. The signals further elevate cytokine production, promoting the development of Th17 responses and preventing cellular apoptosis, which enables viral persistence. Excessive levels of cytokines, particularly IL-6 and IL-1β, facilitate the generation of pathogenic Th17 immune responses to viral antigens and autoantigens, leading to TMEV-induced demyelinating disease. These cytokines, together with TLR2 may prematurely generate functionally deficient CD25-FoxP3+ CD4+ T cells, which are subsequently converted to Th17 cells. Furthermore, IL-6 and IL-17 synergistically inhibit the apoptosis of virus-infected cells and the cytolytic function of CD8+ T lymphocytes, prolonging the survival of virus-infected cells. The inhibition of apoptosis leads to the persistent activation of NF-κB and TLRs, which continuously provides an environment of excessive cytokines and consequently promotes autoimmune responses. Persistent or repeated infections of other viruses such as COVID-19 may result in similar continuous TLR activation and cytokine production, leading to autoimmune diseases

Role of Dendritic Cells in Differential Susceptibility to Viral Demyelinating Disease

Although persistent viral diseases are a global health concern, the mechanisms of differential susceptibility to such infections among individuals are unknown. Here, we report that differential interactions between dendritic cells (DCs) and virus are critical in determining resistance versus susceptibility in the Theiler murine encephalomyelitis virus–induced demyelinating disease model of multiple sclerosis. This virus induces a chronic demyelinating disease in susceptible mice, whereas the virus is completely cleared in resistant strains of mice. DCs from susceptible mice are more permissive to viral infection, resulting in severe deficiencies in development, expansion, and function, in contrast to DCs from resistant mice. Although protective prior to viral infection, higher levels of type I interferons (IFNs) and IFN-γ produced by virus-infected DCs from susceptible mice further contribute to the differential inhibition of DC development and function. An increased DC number and/or acquired resistance of DCs to viral infection render susceptible mice resistant to viral persistence and disease progression. Thus, the differential permissiveness of DCs to infectious agents and its subsequent functional and developmental deficiencies determine the outcome of infection- associated diseases. Therefore, arming DCs against viral infection–induced functional decline may provide a useful intervention for chronic infection-associated diseases

Observation of First-Order Metal-Insulator Transition without Structural Phase Transition in VO_2

An abrupt first-order metal-insulator transition (MIT) without structural phase transition is first observed by current-voltage measurements and micro-Raman scattering experiments, when a DC electric field is applied to a Mott insulator VO_2 based two-terminal device. An abrupt current jump is measured at a critical electric field. The Raman-shift frequency and the bandwidth of the most predominant Raman-active A_g mode, excited by the electric field, do not change through the abrupt MIT, while, they, excited by temperature, pronouncedly soften and damp (structural MIT), respectively. This structural MIT is found to occur secondarily.Comment: 4 pages, 4 figure

Coulomb oscillations based on band-to-band tunneling in a degenerately doped silicon metal-oxide-semiconductor field-effect transistor

The Coulomb oscillations based on band-to-band tunneling through a valence band in silicon metal-oxide-semiconductor field-effect-transistors were discussed. It was found that the formation of tunnel barries and a quantum dot in a single-electron transistor structure originated from two p+ - p+ tunnel junctions and a p+ -doped channel with mesoscopic dimension, respectively. At liquid nitrogen temperature, the Coulomb-blockade oscillations with multiple peaks were also observed. Analysis shows that the single-electron charging effect based on band-to-band tunneling was confirmed using the electrical and thermal characterization of the quantum dots.open2

Effective colloidal processing for densification before SPS

In conventional dry processing, fine particles tend to agglomerate spontaneously due to Van der Waals attractive forces. Since the agglomeration of particles forms large residual pores in green bodies, elevated temperatures are necessary for densification. Colloidal processing is a very effective technique for controlling the pore size distribution in green compacts before sintering. The green compacts having small residual pores with a narrow size distribution is expected to enhance the densification at low sintering temperature during SPS. We already reported that colloidal processing for controlling the packing structure in green compact is effective for densification in SPS in the case of SiC. A commercially available SiC (6H) powder with the average particle size of 0.55 mm was used as the starting materials. When using the dry processing for consolidation, the density of the sample sintered by SPS in a vacuum atmosphere at 1950°C was 92% of the theoretical value. Aqueous suspensions with dispersed particles were prepared by adjusting pH and consolidated by slip casting to prepare the dense green compacts. The relative density of SiC prepared by SPS was increased with increasing temperature and reached more than 97% at 1950°C as shown in Fig. 1. In this presentation, this processing was applied to fabrication of transparent alumina. Commercially available Al2O3 powder with the average particle size of 0.4 mm was used as the starting materials. Suspensions with 30 vol% solid were consolidated by slip casting. The green compacts before sintering were further densified by cold isostatic pressing at 392 MPa for 10 min and calcined at 500°C for 1 h in air in order to burn off the dispersant. Final sintering was carried out at 1150°C under a uniaxial pressure of 100 MPa using an SPS. After rapid heating to 600°C, the temperature was raised from 600°C to 1150°C using a heating rate of 5°C/min. After holding samples at the sintering temperature for 10 min and then subsequently annealing them at 1000°C for 10 min, we obtained a sintered disk with a diameter of 25 mm and a thickness of 2 mm. Fig. 2(a) shows the photograph of the sample from the green compact prepared by slip casting, Fig2(b) is the sample densified by SPS from the as-received powder directly. The transparency of the sample prepared by slip casting is clearer than that of the sample by SPS from the as-received powder directly. Please click Additional Files below to see the full abstract

Analysis of Platforms and Functions of Mobile-Based Personal Health Record Systems

ObjectivesLittle is known about the platforms and functionalities of mobile-based personal health record (PHR) applications. The objective of this study was to investigate these two features of PHR systems.MethodsThe unit of analysis was general hospitals with more than 100 beds. This study was based on a PHR survey conducted from May 1 to June 30, 2020 and the National Health Insurance administrative data as of March 31, 2020. The study considered the platform, Android and iPhone operation system (iOS), and types of functionalities of PHR systems. Among the 316 target hospitals, 103 hospitals had adopted PHR systems. A logistic regression analysis was used.ResultsThis study found that 103 hospitals had adopted mobile-based PHR systems for their patients. Sixty-four hospitals (62.1%) were adopting both Android and iOS, but 36 (35.0%) and 3 (2.9%) hospitals were adopting Android only or iOS only, respectively. The PHR systems of hospitals adopting both platforms were more likely to have functions for viewing prescriptions, clinical diagnostic test results, and upcoming appointment status compared to those adopting a single platform (p \u3c 0.001). The number of beds (odds ratio [OR] = 1.004; confidence interval [CI], 1.001–1.007; p = 0.0029) and the number of computed tomography systems (CTs) per 100 beds (OR = 6.350; CI, 1.006–40.084; p = 0.0493) were significantly associated with the adoption of both platforms.ConclusionsMore than 60% of hospitals had adopted both Android and iOS platforms for their patients in Korea. Hospitals adopting both platforms had additional functionalities and significant association with the number of beds and CTs