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Rosa davurica is widely used to treat various kinds of diseases because of its high antioxidant, antiviral and anti-inflammatory activities. This use of plant-based materials as medicine is called phytomedicine and has been widely practiced since time immemorial. However, the pharmacological mechanism of R. davurica in skin photoaging is not yet fully understood. Therefore, this study was carried out to evaluate the recovery effects of R. davurica leaf extracts (RDE) in UVB-irradiated human skin keratinocytes (HaCaTs) and investigate whether RDE is a potential therapeutic agent against skin photoaging. The expression of aging-related markers including mitogen-activated protein kinases/activator protein 1 (MAPK/AP-1), nuclear factor-κB (NF-κB), and nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) was evaluated using Western blot analysis. The reactive oxygen species (ROS) was also used by FACS in HaCaTs. Findings indicated that RDE is efficient in scavenging free radicals and dose-dependently reducing ROS generation. Furthermore, RDE notably decreased UVB-induced matrix metalloproteinase-1 (MMP-1) expression through inhibition of MAPK/AP-1 and NF-κB signaling pathways as well as induced blocking of extracellular matrix (ECM) degradation in UVB-irradiated HaCaTs. In addition, RDE improved Nrf2/HO-1 signaling that increases oxidative defense capacity and enhances transforming growth factor-beta (TGF-β) signaling activation to promote procollagen type I synthesis, relieving UVB-induced skin cell damage. In conclusion, the protective effects of RDE on skin cellular components suggest that it has a high biological potential for skin protection from UVB-induced skin photoaging and is a good candidate for drug and cosmetic application. Graphical abstract

We assessed sex differences in amyloid- and tau-PET retention in 119 amyloid positive patients with mild cognitive impairment or Alzheimer’s disease (AD) dementia. Patients underwent 3T-MRI, (11)C-PIB amyloid-PET and (18)F-Flortaucipir tau-PET. Linear ordinary least squares regression models tested sex differences in Flortaucipir-PET SUVR in a summary temporal region of interest as well as global PIB-PET. No sex differences were observed in demographics, Clinical Dementia Rating Sum of Boxes (CDR-SoB), Mini-Mental State Exam (MMSE), raw episodic memory scores, or cortical thickness. Females had higher global PIB SUVR (η(p)(2)=.043, p=.025) and temporal Flortaucipir SUVR (η(p)(2)=.070, p=.004), adjusting for age and CDR-SoB. Sex differences in temporal Flortaucipir-PET remained significant when controlling additionally for PIB SUVR and APOE4 status (η(p)(2)=.055, p=.013), or when using partial volume-corrected data. No sex differences were present in areas of known Flortaucipir off-target binding. Overall, females demonstrated greater AD regional tau-PET burden than males despite clinical comparability. Further characterization of sex differences will provide insight into AD pathogenesis and support development of personalized therapeutic strategies.

A significant increase in genome instability is associated with the conformational shift of a guanine-run-containing DNA strand into the four-stranded G-quadruplex (G4) DNA. The mechanism underlying the recombination and genome rearrangements following the formation of G4 DNA in vivo has been difficult to elucidate but has become better clarified by the identification and functional characterization of several key G4 DNA-binding proteins. Mammalian nucleolin (NCL) is a highly specific G4 DNA-binding protein with a well-defined role in the transcriptional regulation of genes with associated G4 DNA-forming sequence motifs at their promoters. The consequence of the in vivo interaction between G4 DNA and nucleolin in respect to the genome instability has not been previously investigated. We show here that the yeast nucleolin Nsr1 is enriched at a G4 DNA-forming sequence in vivo and is a major factor in inducing the genome instability associated with the cotranscriptionally formed G4 DNA in the yeast genome. We also show that Nsr1 results in impeding replication past such a G4 DNA-forming sequence. The G4-associated genome instability and the G4 DNA-binding in vivo require the arginine-glycine-glycine (RGG) repeats located at the C-terminus of the Nsr1 protein. Nsr1 with the deletion of RGG domain supports normal cell growth and is sufficient for its pre-rRNA processing function. However, the truncation of the RGG domain of Nsr1 significantly weakens its interaction with G4 DNA in vivo and restores unhindered replication, overall resulting in a sharp reduction in the genome instability associated with a guanine-rich G4 DNA-forming sequence. Our data suggest that the interaction between Nsr1 with the intact RGG repeats and G4 DNA impairs genome stability by precluding the access of G4-resolving proteins and impeding replication.

Faithful degradation of mRNAs is a critical step in gene expression, and eukaryotes share a major conserved mRNA decay pathway. In this major pathway, the two rate-determining steps in mRNA degradation are the initial gradual removal of the poly(A) tail, followed by removal of the cap structure. Removal of the cap structure is carried out by the decapping enzyme, containing the Dcp2 catalytic subunit. Although the mechanism and regulation of mRNA decay is well understood, the consequences of defects in mRNA degradation are less clear. Dcp2 has been reported as either essential or nonessential. Here, we clarify that Dcp2 is not absolutely required for spore germination and extremely slow growth, but in practical terms it is impossible to continuously culture dcp2∆ under laboratory conditions without suppressors arising. We show that null mutations in at least three different genes are each sufficient to restore growth to a dcp2∆, of which kap123∆ and tl(gag)g∆ appear the most specific. We show that kap123∆ and tl(gag)g∆ suppress dcp2 by mechanisms that are different from each other and from previously isolated dcp2 suppressors. The suppression mechanism for tL(GAG)G is determined by the unique GAG anticodon of this tRNA, and thus likely by translation of some CUC or CUU codons. Unlike previously reported suppressors of decapping defects, these suppressors do not detectably restore decapping or mRNA decay to normal rates, but instead allow survival while only modestly affecting RNA homeostasis. These results provide important new insight into the importance of decapping, resolve previously conflicting publications about the essentiality of DCP2, provide the first phenotype for a tl(gag)g mutant, and show that multiple distinct mechanisms can bypass Dcp2 requirement.

Introduction/PurposeSystemic lupus erythematosus (SLE) is a chronic auto-immune disease with a broad spectrum of clinical presentations, including heterogeneous and uncommon neuropsychiatric (NP) syndromes. Accurate diagnosis of neuropsychiatric SLE (NPSLE) is challenging due to lack of clinically useful biomarkers. Despite structural brain abnormalities on MRI in NPSLE being a common finding, a robust link between structural abnormalities and NPSLE has not been established, thus their contribution to the distinction between NPSLE patients and patients in which the NP symptoms are not primarily attributed to SLE is limited. Self-supervised contrastive learning algorithms do not require labels, and have been shown to be useful in classification tasks in rare diseases with limited number of datasets. The aim of our study was to apply self-supervised contrastive learning on T1-weighted images acquired from a well-defined cohort of SLE patients to distinguish between SLE patients with NP symptoms due to the disease (NPSLE) or and SLE patients with similar symptoms due to other causes (non-NPSLE).Subjects and Methods163 patients were included. We used 3T MRI T1-weighted images registered to the MNI152 template. The training set comprised 68 non-NPSLE and 34 NPSLE patients. During the training procedure, we applied random geometric transformations (cropping, left-right flipping and rotations) between iterations to enrich our data sets. Our ML pipeline consisted of convolutional base encoder and linear projector. To test the classification task, the projector was removed and one linear layer was measured. We trained the encoder and projector with the Normalized Temperature-scaled Cross Entropy Loss (NT-xent) loss function. We performed a Monte Carlo validation that consisted of 6 repeated random sub-samplings each using a random selection of a small group of samples from each group.ResultsIn the 6 trials described above, between 79% and 83% of the patients were correctly classified as NPSLE or non-NPSLE. For a qualitative evaluation of spatial distribution of the common features found in the NPSLE population, Gradient-weighted Class Activation Maps (Grad-CAM) were examined voxel-wise. Thresholded Grad-CAM maps show areas of common features identified for the NPSLE cohort, with no such communality found for the non-NPSLE group.Discussion/conclusionThe self-supervised contrastive learning model was effective in capturing diagnostic brain MRI features from a limited but well-defined cohort of SLE patients with NP symptoms. The interpretation of the Grad-CAM results is not straightforward, but points to involvement of the lateral and third ventricles, periventricular white matter and basal cisterns. We believe that the common features found in the NPSLE population in this study indicate a combination of tissue loss, local atrophy and to some extent that of periventricular white matter lesions, which are commonly found in NPSLE patients and appear hypointense on T1-weighted images.

Long-term exposure of the skin to solar radiation causes chronic inflammation and oxidative stress, which accelerates collagen degradation. This contributes to the formation of wrinkles and dark spots, skin fragility, and even skin cancer. In this study, Anemopsis californica (AC), a herb from North America that is well known for treating microorganism infection and promoting wound healing, was investigated for its photoprotective effects. The biological effects of AC were studied on two in vitro models, namely, lipopolysaccharide (LPS)-induced macrophages and ultraviolet B (UVB)-irradiated dermal fibroblasts, to characterize its underlying molecular mechanisms. The results showed that AC decreased the mRNA levels of inflammatory mediators in sensitized macrophages, including cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2). Moreover, AC alleviated UVB-induced photoaging in dermal fibroblasts by restoring procollagen synthesis. This resulted from the regulation of excessive reactive oxygen species (ROS) by AC, which was mediated by the activation of the antioxidative system nuclear factor erythroid 2-related factor 2 (NRF2). AC also alleviated oxidative stress and inflammatory responses by inhibiting the phosphorylation of mitogen-activated protein kinase (MAPK) and interfering with the nuclear translocation of the immune regulator nuclear factor of activated T-cells 1 (NFATc1). In conclusion, the protective effects of AC on skin cellular components suggested that it has the potential for use in the development of drugs and cosmetics that protect the skin from UVB-induced chronic inflammation and aging.

BackgroundMyasthenia gravis (MG) is an autoimmune, neuromuscular condition and patients with MG are vulnerable due to immunosuppressant use and disease manifestations of dyspnea and dysphagia during the coronavirus disease 2019 (COVID-19) pandemic.MethodsWe conducted a retrospective cohort study using the Optum® de-identified COVID-19 Electronic Health Record (EHR) dataset. Primary outcomes, such as hospitalization, ventilator use, intensive care unit (ICU) admission, and death in COVID-19 patients with MG, were compared with those of COVID-19 patients without MG: the subgroups of non-MG included those with rheumatoid arthritis (RA), systemic lupus (SLE), and multiple sclerosis (MS). We further analyzed factors affecting mortality, such as age, race/ethnicity, comorbidities, and MG treatments.ResultsAmong 421,086 individuals with COVID-19, there were 377 patients with MG, 7,362 patients with RA, 1,323 patients with SLE, 1,518 patients with MS, and 410,506 patients without MG. Patients with MG were older and had more comorbidities compared with non-MG patients and had the highest rates of hospitalization (38.5%), ICU admission (12.7%), ventilator use (3.7%), and mortality (10.6%) compared with all other groups. After adjusting for risk factors, patients with MG had increased risks for hospitalization and ICU compared with patients with non-MG and with RA but had risks similar to patients with SLE and with MS. The adjusted risk for ventilator use was similar across all groups, but the risk for mortality in patients with MG was lower compared with the SLE and MS groups. Among patients with MG, age over 75 years and dysphagia were predictors for increased COVID-19 mortality, but the recent MG treatment was not associated with COVID-19 mortality.ConclusionsCOVID-19 patients with MG are more likely to be admitted to the hospital and require ICU care. Older age and patients with dysphagia had an increased risk of mortality.

In this study, we propose dynamic model update methods for the adaptive classification model of text streams in a distributed learning environment. In particular, we present two model update strategies: (1) the entire model update and (2) the partial model update. The former aims to maximize the model accuracy by periodically rebuilding the model based on the accumulated datasets including recent datasets. Its learning time incrementally increases as the datasets increase, but we alleviate the learning overhead by the distributed learning of the model. The latter fine-tunes the model only with a limited number of recent datasets, noting that the data streams are dependent on a recent event. Therefore, it accelerates the learning speed while maintaining a certain level of accuracy. To verify the proposed update strategies, we extensively apply them to not only fully trainable language models based on CNN, RNN, and Bi-LSTM, but also a pre-trained embedding model based on BERT. Through extensive experiments using two real tweet streaming datasets, we show that the entire model update improves the classification accuracy of the pre-trained offline model; the partial model update also improves it, which shows comparable accuracy with the entire model update, while significantly increasing the learning speed. We also validate the scalability of the proposed distributed learning architecture by showing that the model learning and inference time decrease as the number of worker nodes increases.

Introduction: Cognitive impairment after concussion has been widely reported, but there is no reliable imaging biomarker that predicts the severity of cognitive decline post-concussion. This study tests the hypothesis that patients with a history of concussion and persistent cognitive impairment have fractional anisotropy (FA) and mean diffusivity (MD) values from diffusion tensor imaging (DTI) that are specifically associated with poor performance on the Montreal Cognitive Assessment (MoCA).Methods: Fifty-three subjects (19 females) with concussions and persistent cognitive symptoms had MR imaging and the MoCA. Imaging was analyzed by atlas-based, whole-brain DTI segmentation and FLAIR lesion segmentation. Then, we conducted a random forest-based recursive feature elimination (RFE) with 10-fold cross-validation on the entire dataset, and with partial correlation adjustment for age and lesion load.Results: RFE showed that 11 DTI variables were found to be important predictors of MoCA scores. Partial correlation analyses, corrected for age and lesion load, showed significant correlations between MoCA scores and right fronto-temporal regions: inferior temporal gyrus MD (r = −0.62, p = 0.00001), middle temporal gyrus MD (r = −0.54, p = 0.0001), angular gyrus MD (r = −0.48, p = 0.0008), and inferior frontal gyrus FA (r = 0.44, p = 0.002).Discussion: This is the first study to demonstrate a correlation between MoCA scores and DTI variables in patients with a history of concussion and persistent cognitive impairment. This kind of research will significantly increase our understanding of why certain persons have persistent cognitive changes after concussion which, in turn, may allow us to predict persistent impairment after concussion and suggest new interventions.

Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.

Na-ion solid-state electrolytes (Na-SSE) exhibit high potential for electrical energy storage owing to their high energy densities and low manufacturing cost. However, their mechanical properties critical to maintain structural stability at the interface are still insufficiently understood. In this study, a machine learning based regression model was developed for predicting the mechanical properties of Na-SSEs. As a training set, 12,361 materials were obtained from a well-known materials database (Materials Project) and were represented with their respective chemical and structural descriptors. The developed surrogate model exhibited a remarkable accuracy (R2 score) of 0.72 and 0.87, with a mean absolute error of 11.8 GPa and 15.3 GPa for the shear and bulk modulus, respectively. This model was then applied to predict the mechanical properties of 2,432 Na-SSEs, the properties of which have been validated with first principles calculations. Finally, the optimization process was performed to develop an ideal materials screening platform by adding the new minimized dataset, wherein the prediction uncertainty is reduced. We believe that the platform proposed in this study can accelerate the search for Na-SSEs with ideal mechanical properties at minimum cost., Comment: Submitted and Under Review

Many eukaryotes use RNA processing, including alternative splicing, to express multiple gene products from the same gene. The budding yeast Saccharomyces cerevisiae has been successfully used to study the mechanism of splicing and the splicing machinery, but alternative splicing in yeast is relatively rare and has not been extensively studied. Alternative splicing of SKI7/HBS1 is widely conserved, but yeast and a few other eukaryotes have replaced this one alternatively spliced gene with a pair of duplicated, unspliced genes as part of a whole genome doubling (WGD). We show that other examples of alternative splicing known to have functional consequences are widely conserved within Saccharomycotina. A common mechanism by which alternative splicing has disappeared is by replacement of an alternatively spliced gene with duplicate unspliced genes. This loss of alternative splicing does not always take place soon after duplication, but can take place after sufficient time has elapsed for speciation. Saccharomycetaceae that diverged before WGD use alternative splicing more frequently than S. cerevisiae, suggesting that WGD is a major reason for infrequent alternative splicing in yeast. We anticipate that WGDs in other lineages may have had the same effect. Having observed that two functionally distinct splice-isoforms are often replaced by duplicated genes allowed us to reverse the reasoning. We thereby identify several splice isoforms that are likely to produce two functionally distinct proteins because we find them replaced by duplicated genes in related species. We also identify some alternative splicing events that are not conserved in closely related species and unlikely to produce functionally distinct proteins.

Faithful degradation of mRNAs is a critical step in gene expression, and eukaryotes share a major conserved mRNA decay pathway. In this major pathway, the two rate determining steps in mRNA degradation are the initial gradual removal of the poly(A) tail, followed by removal of the cap structure. Removal of the cap structure is carried out by the decapping enzyme, containing the Dcp2 catalytic subunit. While the mechanism and regulation of mRNA decay is well-understood, the consequences of defects in mRNA degradation are less clear. Dcp2 has been reported as either essential or nonessential. Here we clarify that Dcp2 is essential for continuous growth and use experimental evolution to identify suppressors of this essentiality. We show that null mutations in at least three different are each sufficient to restore viability to adcp2Δ, of whichkap123Δ andtl(gag)gΔ appear the most specific. Unlike previously reported suppressors of decapping defects, these suppressor do not restore decapping or mRNA decay to normal rates, but instead allow survival while only modestly affecting transcriptome homeostasis. These effects are not limited to mRNAs, but extend to ncRNAs including snoRNAs and XUTs. These results provide important new insight into the importance of decapping and resolves previously conflicting publications about the essentiality ofDCP2.

Background: Obesity has emerged as a global public health challenge associated with increased risk of hyperlipidemia and hypertension. It contributes to high sympathetic activity and increased catecholamine levels. The hypothalamic melanocortin system is known to regulate the energy homeostasis. The role of melanocortin 4 receptor (MC4R) has been demonstrated pharmacologically and in animal studies, which showed that severe obesity in MC4R knockout mice was caused by increased food intake and decreased energy consumption. Over 70 multiple different mis- -sense and nonsense mutations in hMC4R have been found at a high frequency of 2-8% in severe early onset or hereditary obesity. The single amino acid variation (D90N) located in the second transmembrane domain (TM2) of MC4R results in accelerated growth and childhood onset obesity. Interestingly, the functional characterization of D90N hMC4R mutant TM2 (m-hMC4R-TM2) revealed normal cell surface expression and binding with agonist similar to the hMC4R wild-type TM2 (wt-hMC4R-TM2) but loss of signal transduction mediated via Gs/adenylyl cyclase activation. It is essential to delineate the three-dimensional structure of MC4Rs in order to elucidate their functional aspects. Objective: In this study, we demonstrate the optimized expression and isolation of wt/m-hMC4R-TM2 proteins under different chemical cleavage reaction times and purification procedures via SDS precipitation. The solid-state NMR spectroscopy was carried out to study the structure of wt/m-hMC4R- TM2 protein in the anisotropic phospholipid bicelles. Methods: The KSI-wt/m-hMC4R-TM2 fusion proteins developed in cell culture with LB medium. In order to isolate the expressed fusion protein from the cell, ultrasonication, Ni-NTA affinity chromatography, dialysis, and lyophilization techniques were used. Then, to obtain a protein with higher purity and higher yield, the CNBr chemical cleavage time was subdivided into 30 minutes, 1 h, 2 h, 3 h, and 4 h. Purification process was performed using FPLC, and 100 mM KCl and dialysis were used to remove the SDS. CD spectrometer, MALDI-TOF, solution-state NMR, and solid-state NMR were used to confirmed purity and structure of the wt/m-hMC4R-TM2. Results: The precipitation method was used to remove the SDS bound to proteins as KCl-SDS. We optimized the 2 h cleavage reaction times for both wt-hMC4R-TM2 and m-hMC4R-TM2 depending on the purity based on mass spectra and 1H-15N HSQC spectra and the yield after final purification. The 1D 1H-15N CP (Cross polarization) solid-state NMR spectra suggest that the wt/m-hMC4R- TM2 undergo rotational diffusion around a perpendicular axis along the bilayer normal. Conclusion: We expressed wt/m-hMC4R-TM2 in E.coli and optimized the isolation and purification process, especially CNBr chemical cleavage time. The efficiency of KCl-SDS precipitation was confirmed via MALDI-TOF MS and the pure proteins obtained using this method were characterized by CD spectroscopy and solution-state NMR. The results of 1H-15N HSQC spectra in solution- state NMR also show the probability for structural studies. The 1D 1H-15N CP solid-state NMR spectra indicate that most of the residues in both the wt/m-hMC4R-TM2 peptides are integrated into the membrane.

Naturally derived antibacterial peptides exhibit excellent pharmacological action without the risk of resistance, suggesting a potential role as biologicals. Lactophoricin-I (LPcin-I), found in the proteose peptone component-3 (PP3, lactophorin) of bovine milk, is known to exhibit antibiotic activity against Gram-positive and Gram-negative bacteria. Accordingly, we derived a new antibacterial peptide and investigated its structure–function relationship. This study was initiated by designing antibacterial peptide analogs with better antibacterial activity, less cytotoxicity, and shorter amino acid sequences based on LPcin-I. The structural properties of antibacterial peptide analogs were investigated via spectroscopic analysis, and the antibacterial activity was confirmed by measurement of the minimal inhibitory concentration (MIC). The structure and mechanism of the antibacterial peptide analog in the cell membrane were also studied via solution-state nuclear magnetic resonance (NMR) and solid-state NMR spectroscopy. Through 15N one-dimensional and two-dimensional NMR experiments and 31P NMR experiments, we suggest the 3D morphology and antibacterial mechanism in the phospholipid bilayer of the LPcin analog. This study is expected to establish a system for the development of novel antibacterial peptides and to establish a theoretical basis for research into antibiotic substitutes.

Crataegus laevigata belongs to the family Rosaceae, which has been widely investigated for pharmacological effects on the circulatory and digestive systems. However, there is limited understanding about its anti-oxidative stress and anti-inflammatory effects on skin. In this study, 70% ethanol C. laevigata berry extract (CLE) was investigated on lipopolysaccharide (LPS)-stimulated keratinocytes. The LPS-induced overproduction of reactive oxygen species (ROS) was suppressed by the treatment with CLE. In response to ROS induction, the overexpression of inflammatory regulating signaling molecules including mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB), and nuclear factor of activated T-cells (NFAT) were reduced in CLE-treated human keratinocytes. Consequently, CLE significantly suppressed the mRNA levels of pro-inflammatory chemokines and interleukins in LPS-stimulated cells. Our results indicated that CLE has protective effects against LPS-induced injury in an in vitro model and is a potential alternative agent for inflammatory treatment.

Antimicrobial peptides (AMPs) are effective alternatives to conventional antibiotics. They protect the host from the constant invasion of a broad range of infectious microorganisms. AMPs have been at the forefront of the response to multidrug-resistant microbial strains and appear to be ideal drug candidates. Lactophoricin (LPcin), naturally produced from bovine milk, is a typical cationic antimicrobial peptide. Three analog peptides, including LPcin-YK5, LPcin-YK8, and LPcin-YK11, with enhanced antimicrobial activity compared to the wild-type LPcin, were designed and expressed in our laboratory. We investigated the structure and antimicrobial mechanisms of action of the three novel antimicrobial peptide analogs derived from LPcin using solution NMR and solid-state NMR spectroscopy in membrane environments. Our results revealed that the three LPcin analogs exhibited helical structures with different tilt angles on the phospholipid membrane surface. We proposed three-dimensional conformations and antibacterial mechanisms of action of the three peptide analogs in the phospholipid bilayers using two-dimensional solid-state separated local field NMR experiments.

Accurate identification of prognostic biomarkers is an important yet challenging goal in bioinformatics. Many bioinformatics approaches have been proposed for this purpose, but there is still room for improvement. In this paper, we propose a novel machine learning-based method for more accurate identification of prognostic biomarker genes and use them for prediction of cancer prognosis. The proposed method specifies the candidate prognostic gene module by graph learning using the generative adversarial networks (GANs) model, and scores genes using a PageRank algorithm. We applied the proposed method to multiple-omics data that included copy number, gene expression, DNA methylation, and somatic mutation data for five cancer types. The proposed method showed better prediction accuracy than did existing methods. We identified many prognostic genes and their roles in their biological pathways. We also showed that the genes identified from different omics data were complementary, which led to improved accuracy in prediction using multi-omics data.

Eukaryotes maintain fidelity of gene expression by preferential degradation of aberrant mRNAs that arise by errors in RNA processing reactions. In Saccharomyces cerevisiae, Ski7 plays an important role in this mRNA quality control by mediating mRNA degradation by the RNA exosome. Ski7 was initially thought to be restricted to Saccharomyces cerevisiae and close relatives because the SKI7 gene and its paralog HBS1 arose by whole genome duplication (WGD) in a recent ancestor. We have recently shown that the preduplication gene was alternatively spliced and that Ski7 function predates WGD. Here, we use transcriptome analysis of diverse eukaryotes to show that diverse eukaryotes use alternative splicing of SKI7/HBS1 to encode two proteins. Although alternative splicing affects the same intrinsically disordered region of the protein, the pattern of splice site usage varies. This alternative splicing event arose in an early eukaryote that is a common ancestor of plants, animals, and fungi. Remarkably, through changes in alternative splicing and gene duplication, the Ski7 protein has diversified such that different species express one of four distinct Ski7-like proteins. We also show experimentally that the Saccharomyces cerevisiae SKI7 gene has undergone multiple changes that are incompatible with the Hbs1 function and may also have undergone additional changes to optimize mRNA quality control. The combination of transcriptome analysis in diverse eukaryotes and genetic analysis in yeast clarifies the mechanism by which a Ski7-like protein is expressed across eukaryotes and provides a unique view of changes in alternative splicing patterns of one gene over long evolutionary time.

This paper is the result of a research conducted for "Knowledge Resource Development by Excavation and preservation and DB Establishment of Traditional Home Remedy", a part of Korean Medicine knowledge infrastructure establishment and Korean Medicine therapy development project executed by Korea Institute of Oriental Medicine. This paper is a part of the plans to standardize Korean acupuncture and moxibustion and surgical techniques in order to make new techniques derived from Korean traditional medicine patentable, as presented in the Nagoya Protocol. By first reviewing traditional text sources and classifying them into index literature and index techniques, we can see a mutual relationship between these two categories. Based on current research papers, this study has established a total of 121 pieces of index literature as well as extracted 64 types of index techniques in acupuncture and surgery technique. Both index literature and index technique have been concurrently visualized in this paper in the "Korean Acupuncture & Moxibustion Technique and Surgical Manipulation Base Map".

CoFe2O4@MnFe2O4, with a mixed core-shell structure was fabricated by a high temperature thermal decomposition. From the Rietveld refinement, these nanoparticles were found to be cubic spinel with space group Fd-3m and with a Bragg factor (R B ) and a structure factor (R F ) less than 5%. The size and the shape of the nanoparticles were examined with high-resolution transmission electron microscopy (HR-TEM). The values of the magnetization (M S ) and the coercivity (H C ) of these nanoparticles at room temperature were 78.95 emu/g and 21.2 mT, respectively. The effect of hyperthermia, measured with a magneTherm device showed that the self-heating temperature of the nanoparticles could reach 133 °C. To determine the applicability of nanoparticles in hyperthermia therapy, we evaluated the in-vitro cell viability of nanoparticles. Based on the probability distribution of cations, we determined the Mossbauer spectra at 4.2 K with two sets of six lines under various applied fields parallel to the direction of the γ-rays. To separate the A and the B sites, we also obtained the Mossbauer spectra of the nanoparticles under high external field up to 5 T at 4.2 K. From the detailed analysis of the Mossbauer spectra, the spin canting angles and the anisotropy energies at the A and the B sites were determined.

Dislocation defects in GaN epilayers grown on Si substrates were investigated using cathodoluminescence (CL) and atomic force microscopy (AFM). The dislocation densities of the films were deduced from two-dimensional CL image measurements and ranged from 1 × 10 cm−2 to 5 × 10 cm−2. These values are larger than those reported for GaN epilayers grown on sapphire substrates. The surface morphology and dislocations in the GaN epilayers were investigated by using AFM. From a comparative study of the CL and the AFM measurements, the GaN epilayers with lower dislocation densities are seen to have good surface morphologies with smaller densities of surface defects.

introduction: While the development of genomic sequencing methods has greatly improved the efficiency of collecting sequence data, experimental methods to obtain structure information have been lagging significantly. In order to elucidate protein structures, researchers have developed computational structural modeling techniques such as homology modeling and fold recognition (threading). The general consensus is that homology modeling is a superior approach with templates of high sequence similarity to the desired target (>30%), whereas threading is better suited for lower (

In this paper, we propose a novel subthreshold current method using the optical current-voltage (I-V) curve for interface-state extraction. The new method is simpler and more accurate than the conventional interface-state extraction methods in MOSFETs. Based on the photonic highfrequency capacitance-voltage response of MOS capacitors and the conventional subthreshold current method, an improved characterization method is reported for the analysis of interface-states in MOS systems. An optical source with a photonic energy Eph = 0.943 eV (wavelength = 1314.5 nm) is employed for optical subthreshold current characterization of interface-states distributed in the photo-responsive energy-band. By using the optical subthreshold current and dark subthreshold current, we obtained a U-shaped distribution for the interface-trap density (Dit) in N-type and P-type MOSFETs.

In order to understand the behavior of nonylphenol (NP) in Han River, water, suspended particle and sediment samples were analyzed during summer, autumn and winter. Concentrations of nonylphenol in water ranged from 23.2 to 187.6 ng/l, in suspended particle from 6.8 to 190.8 ng/l and in sediment from 25.4 to 932.0 ng/g dry wt. An increasing trend in the concentration is noticed in all matrices along down the river. In case of water and suspended particle, concentrations were higher in warmer season than in colder season. Percentage of nonylphenol in the suspended particle phase decreased from 67% to 28% with decreasing temperature in water. A reasonable correlation (R2=0.63) was obtained for water and suspended particle. The partition coefficient Log Kp is 4.8. No seasonal variation of the concentration in sediment is noticed in this study.

Nonylphenols were determined from the water, suspended particle, and sediment samples taken from the Lake Shihwa in Korea and its surrounding creeks flowing through municipal and industrial areas, and into the lake. The nonylphenols were detected at the concentration ranges of 0.0-41.3 microg/l, 0.0-116.6 and 0.3-31.7 mg/kg in water, suspended particle and sediment samples respectively. The contamination levels of nonylphenols were increased along the down stream. Considerably high levels of nonylphenols were found at the industrial area compared to the municipal area. No remarkable differences were found between the isomer patterns of nonylphenols for the sample matrices of each sampling site, i.e. water, suspended solids and sediment. Strong correlations between water and sediment with 10(5.2) of the mean partition coefficient (Koc ) were observed. These indicate that most of nonylphenols came from industrial wastewater at high level. It is thought that the water quality of the Lake Shihwa is affected greatly by industrial environments surrounding.

Environmentally important phthalic esters have been analyzed by GC-MS in terms of individual phthalic esters or total phthalic esters directly or after derivatization. Derivatization improves the chromatographic characteristics of the highly polar phthalic esters. This study focused on the GC-MS determination of the total phthalic esters and the individual phthalic esters simultaneously. The phthalic esters were hydrolyzed to phthalate and corresponding alcohols in 1 M NaOH solution at 90 °C for 30 min followed by extraction with ethyl acetate after acidifcation. The phthalic acid and alcohols were simultaneously silyl derivatized using bis(trimethylsilyl)trifluoroacetamide (BSTFA) to their corresponding silyl ester and ethers in the mixture of 60% acetone and 40% ethyl acetate at room temperature within 30 min. Because of the high reactivity of BSTFA with the phthalic acid and alcohols effective silyl derivatization was possible simultaneously. GC-MS analysis of the silyl derivatives of phthalic acid and alcohols was performed. The total phthalic ester content was estimated from the analytical result of phthalic silyl ester, while the individual phthalic ester was quantified from the analytical results of alcoholic silyl ethers. This technique was applied to spiked tab water and real seawater samples from the Lake Shihwa in Korea. The results were checked against the results from the direct GC-MS analysis of the phthalic esters and reasonable recoveries with high sensitivity were achieved. The recoveries were higher than 75% with low relative standard deviation (below 10%).