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This paper examines how to apply deep learning techniques to Mongolian bar exam questions. Several approaches that utilize eight different fine-tuned transformer models were demonstrated for recognizing textual inference in Mongolian bar exam questions. Among eight different models, the fine-tuned bert-base-multilingual-cased obtained the best accuracy of 0.7619. The fine-tuned bert-base-multilingual-cased was capable of recognizing “contradiction”, with a recall of 0.7857 and an F1 score of 0.7674; it recognized “entailment” with a precision of 0.7750, a recall of 0.7381, and an F1 score of 0.7561. Moreover, the fine-tuned bert-large-mongolian-uncased showed balanced performance in recognizing textual inference in Mongolian bar exam questions, thus achieving a precision of 0.7561, a recall of 0.7381, and an F1 score of 0.7470 for recognizing “contradiction”.

Abstract Hyperphosphatemia associated with chronic kidney disease (CKD) not only dysregulates mineral metabolism and bone diseases, but also strongly contributes to the progression of kidney disease itself. We have identified a novel drug for hyperphosphatemia, EOS789, that interacts with several sodium‐dependent phosphate transporters (NaPi‐IIb, PiT‐1, and PiT‐2) known to contribute to intestinal phosphate absorption. In this study, we investigated whether EOS789 could ameliorate kidney disease progression in glomerulonephritis rats. Anti‐glomerular basement membrane (GBM) nephritis was induced in rats by intravenously administering two types of anti‐rat GBM antibodies. We evaluated the effect of EOS789 administered in food admixture on hyperphosphatemia and kidney disease progression. In an anti‐GBM nephritis rats, which exhibit a significant increase in serum phosphate and a decline in renal function, EOS789 dose‐dependently improved hyperphosphatemia and EOS789 at 0.3% food admixture significantly ameliorated kidney dysfunction as shown in the decline of serum creatinine and BUN. Renal histopathology analysis showed that EOS789 significantly decreased crescent formation in glomeruli. To elucidate the mechanism underlying glomerular disease progression, human mesangial cells were used. High phosphate concentration in media significantly increased the expression of Collagen 1A1, 3A1, and αSMA mRNA in human mesangial cells and EOS789 dose‐dependently suppressed these fibrotic markers. These results indicate that EOS789 prevented glomerular crescent formation caused by mesangial fibrosis by ameliorating hyperphosphatemia. In conclusion, EOS789 would not only be useful against hyperphosphatemia but may also have the potential to relieve mesangial proliferative glomerulonephritis with crescent formation.

After producing triple (Gal, H-D and Sda)-KO pigs, hyperacute rejection appeared to no longer be a problem. However, the origin of xeno-rejection continues to be a controversial topic, including small amounts of antibodies and subsequent activation of the graft endothelium, the complement recognition system and the coagulation systems. The complement is activated via the classical pathway by non-Gal/H-D/Sda antigens and by ischemia-reperfusion injury (IRI), via the alternative pathway, especially on islets, and via the lectin pathway. The complement system therefore is still an important recognition and effector mechanism in xeno-rejection. All complement regulatory proteins (CRPs) regulate complement activation in different manners. Therefore, to effectively protect xenografts against xeno-rejection, it would appear reasonable to employ not only one but several CRPs including anti-complement drugs. The further assessment of antigens continues to be an important issue in the area of clinical xenotransplantation. The above conclusions suggest that the expression of sufficient levels of human CRPs on Triple-KO grafts is necessary. Moreover, multilateral inhibition on local complement activation in the graft, together with the control of signals between macrophages and lymphocytes is required.

Digital archives (DAs) usually store diverse expert-level materials. Nowadays, access to DAs is increasing for non-expert users, However, they might have difficulties formulating appropriate search queries to find the necessary information. In response to this problem, we propose a query log-based query recommendation algorithm that provides expert knowledge to non-expert users, thus supporting their information seeking in DAs. The use case considered is one where after users enter some general queries, they will be recommended semantically similar expert-level queries in the query logs. The proposed modified conditional restricted Boltzmann machines (M-CRBMs) are capable of utilizing the rich metadata in DAs, thereby alleviating the sparsity problem that conventional restricted Boltzmann machines (RBMs) will face. Additionally, compared with other CRBM models, we drop a large number of model weights. In the experiments, the M-CRBMs outperform the conventional RBMs when using appropriate metadata, and we find that the recommendation results are relevant to the metadata fields that are used in M-CRBMs. Through experiments on the Europeana dataset, we also demonstrate the versatility and scalability of our proposed model.

Xenotransplantation is very attractive strategy for addressing the shortage of donors. While hyper acute rejection (HAR) caused by natural antibodies and complement has been well defined, this is not the case for innate cellular xenogeneic rejection. An increasing body of evidence suggests that innate cellular immune responses contribute to xenogeneic rejection. Various molecular incompatibilities between receptors and their ligands across different species typically have an impact on graft outcome. NK cells are activated by direct interaction as well as by antigen dependent cellular cytotoxicity (ADCC) mechanisms. Macrophages are activated through various mechanisms in xenogeneic conditions. Macrophages recognize CD47 as a “marker of self” through binding to SIRPα. A number of studies have shown that incompatibility of porcine CD47 against human SIRPα contributes to the rejection of xenogeneic target cells by macrophages. Neutrophils are an early responder cell that infiltrates xenogeneic grafts. It has also been reported that neutrophil extracellular traps (NETs) activate macrophages as damage-associated pattern molecules (DAMPs). In this review, we summarize recent insights into innate cellular xenogeneic rejection.

Background. Neutrophil-induced tissue damage contributes to the rejection in xenotransplantation. Therefore, suppressing neutrophil function could be effective in suppressing xenogeneic rejection. In a previous study, we demonstrated that the ectopic expression of human cluster of differentiation 31 (CD31) on porcine endothelial cells (PEC) significantly suppressed neutrophil-mediated cytotoxicity through the homophilic binding of CD31. Cluster of differentiation 177 (CD177) was recently reported to be a high-affinity heterophilic binding partner for CD31 on endothelial cells. Thus, we hypothesized that human CD177 on PEC might induce a stronger suppression in neutrophil-mediated cytotoxicity compared with CD31. In this study, the inhibitory function of human CD177 on PEC in neutrophil-mediated cytotoxicity was investigated. Methods. PEC were transfected with a cloning plasmid containing cDNA inserts that encoded for hCD177 and hCD31 genes. Neutrophil-induced cytotoxicity was evaluated by flow cytometry after coculturing with PEC or PEC/CD177 in the presence of phorbol 12-myristate 13-acetate. To elucidate the mechanisms responsible for hCD177-induced suppression, the phosphorylation of src homology region 2 domain containing phosphatase 1 was measured by immunoblot analysis. Results. Human CD177 on PEC induced a significant reduction in neutrophil-induced cytotoxicity. In addition, CD177 on PEC induced a significant increase in the phosphorylation of src homology region 2 domain-containing phosphatase 1 in neutrophils and suppressed NETosis. Conclusions. These findings suggest that human CD177 suppresses neutrophil-mediated cytotoxicity through the inhibition of NETosis.

In recent years, artworks have been increasingly digitized and built into databases, and such databases have become convenient tools for researchers. Researchers who retrieve artwork are not only researchers of humanities, but also researchers of materials science, physics, art, and so on. It may be difficult for researchers of various fields whose studies focus on the colors of artwork to find the required records in existing databases, that are color-based and only queried by the metadata. Besides, although some image retrieval engines can be used to retrieve artwork by text description, the existing image retrieval systems mainly retrieve the main colors of the images, and rare cases of color use are difficult to find. This makes it difficult for many researchers who focus on toning, colors, or pigments to use search engines for their own needs. To solve the two problems, we propose a cross-modal multi-task fine-tuning method based on CLIP (Contrastive Language-Image Pre-Training), which uses the human sensory characteristics of colors contained in the language space and the geometric characteristics of the sketches of a given artwork in order to gain better representations of that artwork piece. The experimental results show that the proposed retrieval framework is efficient for intuitively searching for rare colors, and that a small amount of data can improve the correspondence between text descriptions and color information.

Collector's seals provide important clues about the ownership of a book. They contain much information pertaining to the essential elements of ancient materials and also show the details of possession, its relation to the book, the identity of the collectors and their social status and wealth, amongst others. Asian collectors have typically used artistic ancient characters rather than modern ones to make their seals. In addition to the owner's name, several other words are used to express more profound meanings. A system that automatically recognizes these characters can help enthusiasts and professionals better understand the background information of these seals. However, there is a lack of training data and labelled images, as samples of some seals are scarce and most of them are degraded images. It is necessary to find new ways to make full use of such scarce data. While these data are available online, they do not contain information on the characters' position. The goal of this research is to assist in obtaining more labelled data through user interaction and provide retrieval tools that use only standard character typefaces extracted from font files. In this paper, a character segmentation method is proposed to predict the candidate characters' area without any labelled training data that contain character coordinate information. A retrieval-based recognition system that focuses on a single character is also proposed to support seal retrieval and matching. The experimental results demonstrate that the proposed character segmentation method performs well on Asian collector's seals, with 85% of the test data being correctly segmented.

Abstract Background Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase extensively implicated in diseases such as cancer, atherosclerosis and fibrosis. Multiple preclinical studies, performed using either a gene deletion or a gene silencing approaches, have shown this receptor being a major driver target of fibrosis and glomerulosclerosis. Methods The present study investigated the role and relevance of DDR1 in human crescentic glomerulonephritis (GN). Detailed DDR1 expression was first characterized in detail in human GN biopsies using a novel selective anti-DDR1 antibody using immunohistochemistry. Subsequently the protective role of DDR1 was investigated using a highly selective, novel, small molecule inhibitor in a nephrotoxic serum (NTS) GN model in a prophylactic regime and in the NEP25 GN mouse model using a therapeutic intervention regime. Results DDR1 expression was shown to be mainly limited to renal epithelium. In humans, DDR1 is highly induced in injured podocytes, in bridging cells expressing both parietal epithelial cell (PEC) and podocyte markers and in a subset of PECs forming the cellular crescents in human GN. Pharmacological inhibition of DDR1 in NTS improved both renal function and histological parameters. These results, obtained using a prophylactic regime, were confirmed in the NEP25 GN mouse model using a therapeutic intervention regime. Gene expression analysis of NTS showed that pharmacological blockade of DDR1 specifically reverted fibrotic and inflammatory gene networks and modulated expression of the glomerular cell gene signature, further validating DDR1 as a major mediator of cell fate in podocytes and PECs. Conclusions Together, these results suggest that DDR1 inhibition might be an attractive and promising pharmacological intervention for the treatment of GN, predominantly by targeting the renal epithelium.

This paper introduces a framework for retrieving low-resource font typeface databases by handwritten input. A new deep learning model structure based on metric learning is proposed to extract the features of a character typeface and predict the category of handwrittten input queries. Rather than using sufficient training data, we aim to utilize ancient character font typefaces with only one sample per category. Our research aims to achieve decent retrieval performances over more than 600 categories of handwritten characters automatically. We consider utilizing generic handcrafted features to train a model to help the voting classifier make the final prediction. The proposed method is implemented on the ‘Shirakawa font oracle bone script’ dataset as an isolated ancient-character-recognition system based on free ordering and connective strokes. We evaluate the proposed model on several standard character and symbol datasets. The experimental results showed that the proposed method provides good performance in extracting the features of symbols or characters’ font images necessary to perform further retrieval tasks. The demo system has been released, and it requires only one sample for each character to predict the user input. The extracted features have a better effect in finding the highest-ranked relevant item in retrieval tasks and can also be utilized in various technical frameworks for ancient character recognition and can be applied to educational application development.

Induced pluripotent stem cells (iPSCs) can serve as a source of cardiomyocytes (CMs) to treat end-stage heart failure; however, transplantation of genetically dissimilar iPSCs even within species (allogeneic) can induce immune rejection. We hypothesized that this might be limited by matching the major histocompatibility complex (MHC) antigens between the donor and the recipient. We therefore transplanted fluorescence-labeled (GFP) iPSC-CMs donated from a macaque with homozygous MHC haplotypes into the subcutaneous tissue and hearts of macaques having heterozygous MHC haplotypes (MHC-matched; group I) or without identical MHC alleles (group II) in conjunction with immune suppression. Group I displayed a higher GFP intensity and less immune-cell infiltration in the graft than group II. However, MHC-matched transplantation with single or no immune-suppressive drugs still induced a substantial host immune response to the graft. Thus, the immunogenicity of allogeneic iPSC-CMs was reduced by MHC-matched transplantation although a requirement for appropriate immune suppression was retained for successful engraftment.

BackgroundThe association of complement with the progression of acute T cell mediated rejection (ATCMR) is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs) in acute T-cell mediated rejection using rat and human renal allografts.MethodsWe prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR) and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP) by immunohistochemical staining in human renal grafts and their clinical course.ResultsqRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry), was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.ConclusionsWe conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.

Cell surface glycans vary widely, depending on cell properties. We hypothesized that glycan expression on induced pluripotent stem cells (iPSCs) might change during cardiomyogenic differentiation toward the myocardial phenotype. N-glycans were isolated from iPSCs, iPSC-derived cardiomyocytes (iPSC-CM), and original C57BL/6 mouse myocardium (Heart). Their structures were analyzed by a mapping technique based on HPLC elution times and MALDI-TOF/MS spectra. Sixty-eight different N-glycans were isolated; the structures of 60 of these N-glycans were identified. The quantity of high-mannose type (immature) N-glycans on the iPSCs decreased with cardiomyogenic differentiation, but did not reach the low levels observed in the heart. We observed a similar reduction in neutral N-glycans and an increase in fucosylated or sialyl N-glycans. Some structural differences were detected between iPSC-CM and Heart. No N-glycolyl neuraminic acid (NeuGc) structures were detected in iPSC-CM, whereas the heart contained numerous NeuGc structures, corresponding to the expression of cytidine monophosphate-N-acetylneuraminic acid hydroxylase. Furthermore, several glycans containing Galα1-6 Gal, rarely identified in the other cells, were detected in the iPSC-CM. The expression of N-glycan on murine iPSCs changed toward the myocardial phenotype during cardiomyogenic differentiation, leaving the structural differences of NeuGc content or Galα1-6 Gal structures. Further studies will be warranted to reveal the meaning of the difference of N-glycans between the iPSC-CM and the myocardium.