486 research outputs found

    The Chronotope of the House (kuća) and the Discourses of Women in The Modernist Novels of Former Yugoslavia

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    The modernist literature of the former Yugoslavia inherited the legacy of realist literature in terms of "chronotope" and "subject," while also differing drastically from the legacy, conceptually speaking. This is most obviously revealed in psychological literary discourse about the low-ranking subjects of traditional society, particularly women. A typical example is the traditionally patriarchal space of the house (kuća), which typically functions as a negative motif of chronotope in the discourse about women and family by modernist writers of the former Yugoslavia

    Bayesian Belief Network Model Quantification Using Distribution-Based Node Probability and Experienced Data Updates for Software Reliability Assessment

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    Since digital instrumentation and control systems are expected to play an essential role in safety systems in nuclear power plants (NPPs), the need to incorporate software failures into NPP probabilistic risk assessment has arisen. Based on a Bayesian belief network (BBN) model developed to estimate the number of software faults considering the software development lifecycle, we performed a pilot study of software reliability quantification using the BBN model by aggregating different experts' opinions. In this paper, we suggest the distribution-based node probability table (D-NPT) development method which can efficiently represent diverse expert elicitation in the form of statistical distributions and provides mathematical quantification scheme. Besides, the handbook data on U.S. software development and V&V and testing results for two nuclear safety software were used for a Bayesian update of the D-NPTs in order to reduce the BBN parameter uncertainty due to experts' different background or levels of experience. To analyze the effect of diverse expert opinions on the BBN parameter uncertainties, the sensitivity studies were conducted by eliminating the significantly different NPT estimates among expert opinions. The proposed approach demonstrates a framework that can effectively and systematically integrate different kinds of available source information to quantify BBN NPTs for NPP software reliability assessment

    Patterned Si thin film electrodes for enhancing structural stability

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    A patterned film (electrode) with lozenge-shaped Si tiles could be successfully fabricated by masking with an expanded metal foil during film deposition. Its electrochemical properties and structural stability during the charge-discharge process were examined and compared with those of a continuous (conventional) film electrode. The patterned electrode exhibited a remarkably improved cycleability (75% capacity retention after 120 cycles) and an enhanced structural stability compared to the continuous electrode. The good electrochemical performance of the patterned electrode was attributed to the space between Si tiles that acted as a buffer against the volume change of the Si electrode

    Structural basis for arginine glycosylation of host substrates by bacterial effector proteins

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    The bacterial effector proteins SseK and NleB glycosylate host proteins on arginine residues, leading to reduced NF-κB-dependent responses to infection. Salmonella SseK1 and SseK2 are E. coli NleB1 orthologs that behave as NleB1-like GTs, although they differ in protein substrate specificity. Here we report that these enzymes are retaining glycosyltransferases composed of a helix-loop-helix (HLH) domain, a lid domain, and a catalytic domain. A conserved HEN motif (His-Glu-Asn) in the active site is important for enzyme catalysis and bacterial virulence. We observe differences between SseK1 and SseK2 in interactions with substrates and identify substrate residues that are critical for enzyme recognition. Long Molecular Dynamics simulations suggest that the HLH domain determines substrate specificity and the lid-domain regulates the opening of the active site. Overall, our data suggest a front-face SNi mechanism, explain differences in activities among these effectors, and have implications for future drug development against enteric pathogens

    Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis.

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    Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes' effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD

    Hypocapnia Attenuates, and Nitrous Oxide Disturbs the Cerebral Oximetric Response to the Rapid Introduction of Desflurane

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    The aim of this study was to develop a nonlinear mixed-effects model for the increase in cerebral oximetry (rSO2) during the rapid introduction of desflurane, and to determine the effect of hypocapnia and N2O on the model. Twelve American Society of Anesthesiologist physical status class 1 and 2 subjects were allocated randomly into an Air and N2O group. After inducing anesthesia, desflurane was then increased abruptly from 4.0 to 12.0%. The PETCO2, PETDESF and rSO2 were recorded at 12 predetermined periods for the following 10 min. The maximum increase in rSO2 reached +24-25% during normocapnia. The increase in rSO2 could be fitted to a four parameter logistic equation as a function of the logarithm of PETDESF. Hypocapnia reduced the maximum response of rSO2, shifted the EC50 to the right, and increased the slope in the Air group. N2O shifted the EC50 to the right, and reduced the slope leaving the maximum rSO2 unchanged. The N2O-effects disappeared during hypocapnia. The cerebrovascular reactivity of rSO2 to CO2 is still preserved during the rapid introduction of desflurane. N2O slows the response of rSO2. Hypocapnia overwhelms all the effects of N2O

    In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni

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    Several CRISPR-Cas9 orthologues have been used for genome editing. Here, we present the smallest Cas9 orthologue characterized to date, derived from Campylobacter jejuni (CjCas9), for efficient genome editing in vivo. After determining protospacer-adjacent motif (PAM) sequences and optimizing single-guide RNA (sgRNA) length, we package the CjCas9 gene, its sgRNA sequence, and a marker gene in an all-in-one adeno-associated virus (AAV) vector and produce the resulting virus at a high titer. CjCas9 is highly specific, cleaving only a limited number of sites in the human or mouse genome. CjCas9, delivered via AAV, induces targeted mutations at high frequencies in mouse muscle cells or retinal pigment epithelium (RPE) cells. Furthermore, CjCas9 targeted to the Vegfa or Hif1a gene in RPE cells reduces the size of laser-induced choroidal neovascularization, suggesting that in vivo genome editing with CjCas9 is a new option for the treatment of age-related macular degeneration.
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