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Several lines of evidence indicate the involvement of neuroinflammatory processes in the pathophysiology of schizophrenia (SCZ). Microglia are brain resident immune cells responding toward invading pathogens and injury-related products, and additionally, have a critical role in improving neurogenesis and synaptic functions. Hyperactivation of microglia in SCZ is one of the leading hypotheses for disease pathogenesis, but due to the lack of proper human cell models, the role of microglia in SCZ is not well studied. We used monozygotic twins discordant for SCZ and healthy individuals to generate human induced pluripotent stem cell-derived microglia to assess the transcriptional and functional differences in microglia between healthy controls, affected twins and unaffected twins. The microglia from affected twins had increased expression of several common inflammation-related genes, such as AIF1, HLA-DRA and IL1β compared to healthy individuals. Microglia from affected twins had also reduced response to IL1β treatment, but no significant differences in migration or phagocytotic activity. Ingenuity Pathway Analysis (IPA) showed abnormalities related to extracellular matrix signaling. RNA sequencing predicted downregulation of extracellular matrix structure constituent GO terms and hepatic fibrosis pathway activation that were shared by microglia of both affected and unaffected twins, but the upregulation of MHC class II receptors was observed only in affected twin microglia. Also, the microglia of affected twins had heterogeneous response to clozapine, minocycline, and sulforaphane treatments. Overall, despite the increased expression of inflammatory genes, we observed no clear functional signs of hyperactivation in microglia from patients with SCZ. We conclude that microglia of the patients with SCZ have genetic aberrations related to inflammation response and extracellular matrix without contributing to microglia hyperactivation.

Background/Purpose Sjogren's syndrome (SS) is an autoimmune disease and its conventional treatment has exhibited limited therapeutic efficacy. Traditional Chinese medicine has been demonstrated to ameliorate the sicca symptoms of SS by decreasing the level of TH1 and TH2 cytokines and increasing salivary flow rate. A newly designed traditional Chinese medicine, SS-1, showed improved efficacy in alleviating the dryness symptoms of SS patients in the National Taiwan SS cohort investigation. Here, we investigated the effect of SS-1 on T cell responses. Methods SS-1 was authenticated and its major compounds were verified by high-performance liquid chromatography. We examined the effects of SS-1 on the activation and TH1, TH2, and TH17 polarization of murine T cells. We also determined the level of TH1, TH2, and TH17 cytokine RNA in peripheral blood mononuclear cells of SS patients before and after SS-1 treatment. Results SS-1 treatment inhibits the activation and TH1, TH2, and IL-17A+IFNγ+ TH polarization of murine T cells. SS-1 treatment also significantly reduces IFN-γ, IL-4, and IL-13 expression, and moderately reduces IL-17A expression in peripheral blood mononuclear cells of SS patients. Conclusion Our results suggest that SS-1 inhibits T cell activation and diminishes TH1, TH2, and IL-17+IFN-γ+ TH responses in SS patients.

This Article suggests that the trust envisaged by a Northeast Asian lawyer is not like the trust a common lawyer would generally conceptualize, and that a structurally different species of trust has been reconstructed and reimagined in Northeast Asia. Trust law can be transplanted, yet some of its rules are too cumbersome to be accepted directly. This ultimately calls for modifications of some of the features of the common law trust, which happened in Northeast Asia when trust law was transplanted into Romano-Germanic civil law culture, culminating in a type of civil law trust. This Article explains how the doctrinal conflicts between the civil law tradition and the common law trust have been resolved by examining the transformations that took place in the course of the transplantation process and how these conflicts created a distinctive underlying structure of the trust in Northeast Asia. Many compromises and modifications were made to pare down conflicts arising from grafting the common law-based trust onto Romano-Germanic soil. However, adopting modified trusts unexpectedly led to the dilution of some of the traditional rules in the civil codes. These alterations and the ensuing discordance with some presently well-settled civil law theories are the core themes of this Article.

Previous studies have implicated several brain cell types in schizophrenia (SCZ), but the genetic impact of astrocytes is unknown. Considering their high complexity in humans, astrocytes are likely key determinants of neurodevelopmental diseases, such as SCZ. Human induced pluripotent stem cell (hiPSC)-derived astrocytes differentiated from five monozygotic twin pairs discordant for SCZ and five healthy subjects were studied for alterations related to high genetic risk and clinical manifestation of SCZ in astrocyte transcriptomics, neuron-astrocyte co-cultures, and in humanized mice. We found gene expression and signaling pathway alterations related to synaptic dysfunction, inflammation, and extracellular matrix components in SCZ astrocytes, and demyelination in SCZ astrocyte transplanted mice. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co-twins and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Differentially expressed transcriptomes and signaling pathways related to synaptic functions, inflammation, and especially collagen and glycoprotein 6 pathways indicate abnormal extracellular matrix composition in the brain as one of the key characteristics in the etiology of SCZ.

Human astrocytes are multifunctional brain cells and may contribute to the pathophysiology of schizophrenia (SCZ). We differentiated astrocytes from induced pluripotent stem cells of monozygotic twins discordant for SCZ, and found sex-specific gene expression and signaling pathway alterations related particularly to inflammation and synaptic functions. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co-twins, and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in demyelination, synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Altogether, our results show that astrocytes contribute to both familial risk and clinical manifestation of SCZ in a sex-specific manner.

Sjögren's syndrome (SS) is an autoimmune disease and its conventional treatment has exhibited limited therapeutic efficacy. Traditional Chinese medicine has been demonstrated to ameliorate the sicca symptoms of SS by decreasing the level of TSS-1 was authenticated and its major compounds were verified by high-performance liquid chromatography. We examined the effects of SS-1 on the activation and TSS-1 treatment inhibits the activation and TOur results suggest that SS-1 inhibits T cell activation and diminishes T

X-ray diffraction was used to study the optoelectronic characteristics of Ga-doped TiZnO (GTZO) thin film and revealed increased crystallinity with annealing temperatures ranging from as-grown to 450 °C. The low thin film resistivity of 6.1 × 10(-4) Ω cm and the average high optical transmittance of 93% in the wavelength range between 350 and 800 nm make GTZO an alternative candidate for application in organic light-emitting diodes (OLEDs). Both GTZO and indium-tin-oxide (ITO) anodes are employed for the successful fabrication of blue, green, and red phosphorescent OLEDs. The similar device electrical characteristics observed could be interpreted as evidence of the effectiveness of doping Ga in TiZnO. The simplified tri-layer blue, green, and red phosphorescent OLEDs demonstrated high performance with respective maximum efficiencies of 19.0%, 14.5%, and 9.1%, representing an improvement over ITO-based OLEDs. Furthermore, the OLEDs with the GTZO anode exhibited superior performance at higher current densities, demonstrating high potential for OLED display and lighting applications.

Acanthamoeba, human pathogens and natural hosts of pathogenic bacteria, may be accurately detected and quantified by real-time PCR if Acanthamoeba DNA are properly extracted and PCR inhibitors are effectively eliminated. However, the optimization of DNA extraction methods has not been reported for Acanthamoeba. This study compared the effectiveness of two DNA extraction/purification methods (FastDNA® Spin Kit for soil and Wizard® SV genomic DNA Purification System) by using trophozoites and cysts of Acanthamoeba castellanii and water and biofilm samples of cooling towers. DNA of A. castellanii extracted with the FastDNA® Kit and quantified by TaqMan PCR resulted in a lower variation (CV of Ct

The purpose of this work is to scrutinize the legal structure of trusts in Taiwan, Japan and South Korea. The so-called infrastructure of the private law of them is rooted in the Roman-Germanic basis, which adopts dichotomous system in respect of the private law dealing with property: the law of property and that of obligation. However, the adoption of the trust has caused some problems. Though controversial, the contract-based view seems to be the majority thesis in the East Asian civil jurisdictions, yet the property-based view dominates the common law world nowadays. However, being influenced by common law, the property-approach is also asserted in the aforementioned jurisdictions. It should be noted there has been another approach normally adopted by some civil jurisdictions and mixed jurisdictions, i.e. the doctrine of separate patrimony. The East Asian civi jurisdictions’ approach is somehow at a crossroads. Being a legal system where nomenclature matters, the issue of taxonomic classification can hardly be ignored. We must find a way out from the crossroads, either perfect or not. It is to this task to which the present work is devoted.

Code-profiling is the process of determining the types of codes found in a given heterogeneous task. Once this information is available, it is desirable to know how many processors are needed for each of the code types. In this paper, we propose two methods for estimating the minimum number of processors required for each of these code types. The first method involves making use of task compatibility graphs. We show that a task compatibility graph can be generated by analyzing certain compatible relations between task module pairs of a given task flow graph. We define the resource (processor) minimization problem therefore to be equivalent to finding the minimal number of cliques that cover the task compatibility graph, or to finding the minimal number of colors that color the vertices of its complement graph, called task conflict graph. We solve this problem using a greedy approach in O(|V|log|V||E|) time, where |V| and |E| are the number of vertices and edges of the task compatibility graph. We further show that for three special types of task compatibility graphs, optimal solution can be obtained in polynomial time. The second method studied in this paper uses the Cluster-M methodology for estimating the minimum number of processors. Examples are shown to compare the estimated results obtained using different techniques.

We study the heterogeneous use of two programming paradigms for heterogeneous computing called Cluster-M and HAsC. Both paradigms can efficiently support heterogeneous networks by preserving a level of abstraction which does not include any architecture mapping details. Furthermore, they are both machine independent and hence are scalable. Unlike almost all existing heterogeneous orchestration tools which are MIMD based, HAsC is based on the fundamental concepts of SIMD associative computing. HAsC models a heterogeneous network as a coarse grained associative computer and is designed to optimize the execution of problems with large ratios of computations to instructions. Ease of programming and execution speed, not the utilization of idle resources are the primary goals of HAsC. On the other hand, Cluster-M is a generic technique that can be applied to both coarse grained as well as fine grained networks. Cluster-M provides an environment for porting various tasks onto the machines in a heterogeneous suite such that resource utilization is maximized and the overall execution time is minimized. We illustrate how these two paradigms can be used together to provide an efficient medium for heterogeneous programming. Finally, their scalability is discussed. >

The blood–brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer’s disease and Parkinson’s disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area.