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Aviation is a complicated transportation system, and safety is of paramount importance because aircraft failure often involves casualties. Prevention is clearly the best strategy for aviation transportation safety. Learning from past incident data to prevent potential accidents from happening has proved to be a successful approach. To prevent potential safety hazards and make effective prevention plans, aviation safety experts identify primary and contributing factors from incident reports. However, safety experts' review processes have become prohibitively expensive nowadays. The number of incident reports is increasing rapidly due to the acceleration of advances in information technologies and the growth of the commercial and private aviation transportation industries. Consequently, advanced text mining algorithms should be applied to help aviation safety experts facilitate the process of incident data extraction. This paper focuses on constructing deep-learning-based models to identify causal factors from incident reports. First, we prepare the data sets used for training, validation, and testing with approximately 200,000 qualified incident reports from the Aviation Safety Reporting System (ASRS). Then, we take an open-source natural language model, which is well trained with a large corpus of Wikipedia texts, as the baseline and fine-tune it with the texts in incident reports to make it more suited to our specific research task. Finally, we build and train an attention-based long short-term memory (LSTM) model to identify primary and contributing factors in each incident report. The solution we propose has multilabel capability and is automated and customizable, and it is more accurate and adaptable than traditional machine learning methods in extant research. This novel application of deep learning algorithms to the incident reporting system can efficiently improve aviation safety., Author(s): Tianxi Dong (corresponding author) [1]; Qiwei Yang [2]; Nima Ebadi [2]; Xin Robert Luo [3]; Paul Rad [4] 1. Introduction In the last two decades, we have witnessed rapidly [...]

Aviation is a complicated transportation system, and safety is of paramount importance because aircraft failure often involves casualties. Prevention is clearly the best strategy for aviation transportation safety. Learning from past incident data to prevent potential accidents from happening has proved to be a successful approach. To prevent potential safety hazards and make effective prevention plans, aviation safety experts identify primary and contributing factors from incident reports. However, safety experts' review processes have become prohibitively expensive nowadays. The number of incident reports is increasing rapidly due to the acceleration of advances in information technologies and the growth of the commercial and private aviation transportation industries. Consequently, advanced text mining algorithms should be applied to help aviation safety experts facilitate the process of incident data extraction. This paper focuses on constructing deep-learning-based models to identify causal factors from incident reports. First, we prepare the data sets used for training, validation, and testing with approximately 200,000 qualified incident reports from the Aviation Safety Reporting System (ASRS). Then, we take an open-source natural language model, which is well trained with a large corpus of Wikipedia texts, as the baseline and fine-tune it with the texts in incident reports to make it more suited to our specific research task. Finally, we build and train an attention-based long short-term memory (LSTM) model to identify primary and contributing factors in each incident report. The solution we propose has multilabel capability and is automated and customizable, and it is more accurate and adaptable than traditional machine learning methods in extant research. This novel application of deep learning algorithms to the incident reporting system can efficiently improve aviation safety., Author(s): Tianxi Dong (corresponding author) [1]; Qiwei Yang [2]; Nima Ebadi [2]; Xin Robert Luo [3]; Paul Rad [4] 1. Introduction In the last two decades, we have witnessed rapidly [...]

Biological properties of renal-specific oxidoreductase (RSOR), characteristics of its promoter, and underlying mechanisms regulating its expression in diabetes were analyzed. RSOR expression, normally confined to the renal cortex, was markedly increased and extended into the outer medullary tubules in db/db mice, a model of type 2 diabetes. Exposure of LLCPK cells to D-glucose resulted in a dose-dependent increase in RSOR expression and its enzymatic activity. The latter was related to one of the glycolytic enzymes, myo-inositol oxygenase. The increase in activity was in proportion to serum glucose concentration. The RSOR expression also increased in cells treated with various organic osmolytes, e.g., sorbitol, myoinositol, and glycerolphosphoryl-choline and [H.sub.2][O.sub.2]. Basal promoter activity was confined to -1,252 bp upstream of ATG, and it increased with the treatment of high glucose and osmolytes. EMSAs indicated an increased binding activity with osmotic-, carbohydrate-, and oxidant-response elements in cells treated with high glucose and was abolished by competitors. Supershifts, detected by anti-nuclear factor of activated T cells, and carbohydrate-response-element-binding protein established the binding specificity. Nuclear factor of activated T cells tonicity-enhancer-binding protein and carbohydrate-response-element-binding protein had increased nuclear expression in cells treated with high glucose. The activity of osmotic-response element exhibited a unique alternate binding pattern, as yet unreported in osmoregulatory genes. Data indicate that RSOR activity is modulated by diverse mechanisms, and it is endowed with dual properties to channel glucose intermediaries, characteristic of hepatic aldehyde reductases, and to maintain osmoregulation, a function of renal medullary genes, e.g., aldose reductase, in diabetes. diabetic nephropathy | hyperglycemia | osmoregulation

One of the hallmarks of mammalian nephrogenesis includes a mesenchymal-epithelial transition that is accomplished by intercalation of the ureteric bud, an epithelium-lined tubelike structure, into an undifferentiated mesenchyme, and the latter then undergoes an inductive transformation and differentiates into an epithelial phenotype. At the same time, the differentiating mesenchyme reciprocates by inducing branching morphogenesis of the ureteric bud, which forms a treelike structure with dichotomous iterations. These reciprocal inductive interactions lead to the development of a functioning nephron unit made up of a glomerulus and proximal and distal tubules. The inductive interactions and differentiation events are modulated by a number of transcription factors, protooncogenes, and growth factors and their receptors, which regulate the expression of target morphogenetic modulators including the ECM, integrin receptors, and cell adhesion molecules. These target macromolecules exhibit spatiotemporal and stage-specific developmental regulation in the metanephros. The ECM molecules expressed at the epithelial-mesenchymal interface are perhaps the most relevant and conducive to the paracrine-juxtacrine interactions in a scenario where the ligand is expressed in the mesenchyme while the receptor is located in the ureteric bud epithelium or vice versa. In addition, expression of the target ECM macromolecules is regulated by matrix metalloproteinases and their inhibitors to generate a concentration gradient at the interface to further propel epithelial-mesenchymal interactions so that nephrogenesis can proceed seamlessly. In this review, we discuss and update our current understanding of the role of the ECM and related macromolecules with respect to metanephric development. renal development; integrins; metalloproteinases

Renal-specific oxidoreductase (RSOR), an enzyme relevant to diabetic nephropathy, is exclusively expressed in renal tubules. Studies were initiated to determine whether, like other tubule-specific proteins, it selectively modulates tubulogenesis. Northern blot analyses revealed a ~1.5-kb transcript, and RSOR expression was detectable in mice embryonic kidneys at day 13, gradually increased by day 17, and extended into neo- and postnatal periods. RSOR mRNA and protein expression was confined to proximal tubules, commencing at gestational day 17 and increasing subsequently, but remained absent in glomeruli and medulla. Treatment with RSOR antisense oligodeoxynucleotide resulted in a dose-dependent dysmorphogenesis of metanephric explants harvested at gestational day 13. The explants were smaller and had expanded mesenchyme, and the population of tubules was markedly decreased. The glomeruli were unaffected, as assessed by mRNA expression of glomerular epithelial protein 1 and reactivity with wheat germ agglutinin. Antisense treatment led to a selective reduction of RSOR mRNA. Immunoprecipitation also indicated a selective translational blockade of RSOR. These findings suggest that RSOR is developmentally regulated, exhibits a distinct spatiotemporal distribution, and probably plays a role in tubulogenesis. nephrogenesis; diabetes mellitus

The importance of extracellular matrix (ECM), its receptors and cell adhesion molecules (CAMs) in nephrogenesis in mammals was explored. Previous studies indicate that the basement membrane of the ECM evokes a paracrine effect resulting in the facilitation of the interactions between the ureteric bud and the blastema which lead to the epithelial conversion of the mesenchyme and the formation of the metanephros. On the other hand, CAMs may be involved in increased adhesiveness of cells which lead to the formation of condensates around ureteric bud branches during development.

Author(s): Catherine M. Shachaf [1]; Andrew M. Kopelman [1]; Constadina Arvanitis [1]; Ãsa Karlsson [1]; Shelly Beer [1]; Stefanie Mandl [2]; Michael H. Bachmann [2]; Alexander D. Borowsky [3]; Boris [...]

Yang, Qiwei, Yufeng Tian, Jun Wada, Naoki Kashihara, Elisabeth Wallner, Darryl Peterson, and Yashpal S. Kanwar. Expression characteristics and relevance of sodium glucose cotransporter-1 in mammalian renal tubulogenesis. Am J Physiol Renal Physiol 279: F765-F777, 2000.--Expression and role of sodium glucose cotransporter (SGLT-1) in tubulogenesis were investigated during renal development. A mouse SGLT-1 cDNA was cloned, and it had substantial homology with human and rat forms. Four mRNA transcripts were detected, which differed in size from other species. SGLT-1 transcripts were detected at day 13 of gestation, and their expression increased during later stages extending into the postnatal period. A high mRNA and protein expression of SGLT-1 was seen in tubular segments of the inner cortex and outer medulla at day 16, and it was developmentally regulated. Treatment with SGLT-1 antisense selectively decreased the population of tubules in the metanephric explants. Expression of glomerular mRNA and WGA binding were unchanged. SGLT-1 activity, as measured by [[sup.14]C]methyl-[Alpha]-D-glucopyranoside uptake, increased during gestation in the tubular segments where it is expressed. Glucose uptake was inhibited by the treatment with SGLT-1 antisense and D-galactose. The data suggest that SGLT-1 exhibits a restricted spatiotemporal expression with functional activity confined to the corresponding tubular segments, and it selectively maintains renal tubulogenesis during development. renal development

Aldose reductase (ALR2), a NADPH-dependent aldo-keto reductase (AKR), is widely distributed in mammalian tissues and has been implicated in complications of diabetes, including diabetic nephropathy. To identify a renal-specific reductase belonging to the AKR family, representational difference analyses of cDNA from diabetic mouse kidney were performed. A full-length cDNA with an ORF of 855 nt and yielding a [approximately equals] 1.5-kb mRNA transcript was isolated from a mouse kidney library. Human and rat homologues also were isolated, and they had [approximately equals] 91% and [approximately equals] 97% amino acid identity with mouse protein. In vitro translation of the cDNA yielded a protein product of [approximately equals] 33 kDa. Northern and Western blot analyses, using the cDNA and antirecombinant protein antibody, revealed its expression exclusively confined to the kidney. Like ALR2, the expression was up-regulated in diabetic kidneys. Its mRNA and protein expression was restricted to renal proximal tubules. The gene neither codistributed with Tamm-Horsfall protein nor aquaporin-2. The deduced protein sequence revealed an AKR-3 motif located near the N terminus, unlike the other AKR family members where it is confined to the C terminus. Fluorescence quenching and reactive blue agarose chromatography studies revealed that it binds to NADPH with high affinity ([K.sub.dNADPH] = 66.9 [+ or -] 2.3 nM). This binding domain is a tetrapeptide (Met-Ala-Lys-Ser) located within the AKR-3 motif that is similar to the other AKR members. The identified protein is designated as RSOR because it is renal-specific with properties of an oxido-reductase, and like ALR2 it may be relevant in the renal complications of diabetes mellitus. diabetes mellitus | diabetic nephropathy

Kanwar, Yashpal S., Kosuke Ota, Qiwei Yang, Jun Wada, Naoki Kashihara, Yufeng Tian, and Elisabeth I. Wallner. Role of membrane-type matrix metalloproteinase 1 (MT-1-MMP), MMP-2, and its inhibitor in nephrogenesis. Am. J. Physiol. 277 (Renal Physiol. 46): F934-F947, 1999.--Extracellular matrix (ECM) proteins, their integrin receptors, and matrix metalloproteinases (MMPs), the ECMdegrading enzymes, are believed to be involved in various biological processes, including embryogenesis. In the present study, we investigated the role of membrane type MMP, MT-1-MMP, an activator pro-MMP-2, in metanephric development. Also, its relationship with MMP-2 and its inhibitor, TIMP-2, was studied. Since mRNAs of MT-1-MMP and MMP-2 are respectively expressed in the ureteric bud epithelia and mesenchyme, they are ideally suited for juxtacrine/paracrine interactions during renal development. Northern blot analyses revealed a single -4.5-kb mRNA transcript of MT-1-MMP, and its expression was developmentally regulated. Inclusion of MT-1-MMP antisense oligodeoxynucleotide (ODN) in the culture media induced dysmorphogenetic changes in the embryonic metanephros. MMP-2 antisense ODN also induced similar changes, but they were relatively less; on the other hand TIMP-2 antisense ODN induced a mild increase in the size of explants. Concomitant exposure of MT-1-MMP and MMP-2 antisense ODNs induced profound alterations in the metanephroi. Treatment of TIMP-2 antisense ODN to metanephroi exposed to MT-1-MMP/MMP-2 antisense notably restored the morphology of the explants. Specificity of the MT-1-MMP antisense ODN was reflected in the selective decrease in its mRNA and protein expression. The MT-1-MMP antisense ODN also resulted in a failure in the activation of pro-MMP-2 to MMP-2. These findings suggest that the trimacromolecular complex of MT-1-MMP:MMP-2:TIMP-2 modulates the organogenesis of the metanephros, conceivably by mediating paracrine/juxtacrine epithelial:mesenchymal interactions. membrane-type matrix metalloproteinase-1; matrix metalloproteinase-2; embryonic development

Tubulointerstitial nephritis antigen (TIN-ag) is an extracellular matrix protein and is expressed in the renal tubular basement membranes. Its role in metanephric development was investigated. TIN-ag cDNA, isolated from the newborn mouse library, had an ORF of 1,425 nucleotides, a putative signal sequence, and an ATP/GTP-binding site. The translated sequence had [approximately equals] 80% identity with rabbit TIN-ag. Among various tissues, TIN-ag mRNA was primarily expressed in the newborn kidney. In the embryonic metanephros, TIN-ag expression was confined to the distal convolution or pole of the S-shaped body, the segment of the nascent nephron that is the progenitor of renal tubules. Treatment with TIN-ag antisense oligodeoxynucleotide induced dysmorphogenesis of the embryonic metanephroi, malformation of the S-shaped body, and a decrease in the tubular population, whereas the glomeruli were unaffected. Treatment also led to a decrease of TIN-Ag mRNA, de novo synthesis of TIN-ag protein, and its antibody reactivity. The mRNA expression of glomerular epithelial protein 1 (a marker for renal podocytes), anti-heparan-sulfate-proteoglycan antibody reactivity, and wheat germ agglutinin lectin staining of the metanephros were unaffected. The anti-TIN-ag antibody treatment also caused deformation of the S-shaped body and a reduction in the tubular population, whereas the glomeruli were unchanged. The data suggest that the TIN-ag, unlike other basement membrane proteins, selectively regulates tubulogenesis, whereas giomerulogenesis is largely unaffected.

Fibrillin-2 is an extracellular matrix protein. It is associated with elastic fibers in several tissues and is believed to serve as a ligand for [Alpha]v[Beta]3 integrin, the latter being a known morphogen. In this study, the role of fibrillin-2 in lung development was investigated. Also, rat fibrillin-2 cDNA was isolated and sequenced and its spatiotemporal expression determined. It had [approximately]88% homology with human fibrillin-2 and had [Ca.sup.2+] binding epidermal growth factor-like domains, transforming growth factor-[Beta] binding protein motifs, and two RGD binding sites. Northern blot analysis revealed an [approximately]10-kb transcript, and fibrillin-2 expression was developmentally regulated, and it paralleled that of tropoelastin. At day 13 of gestation, fibrillin-2 was expressed in the mesenchyme and at the epithelial:mesenchymal interface. From day 13 to 19 of gestation, its expression intensified and was confined around the tracheobronchial airways, while it lessened during the postnatal period. Immunoprecipitation revealed an [approximately]350-kDa band by SDS-PAGE. Treatment with fibrillin-2 antisense oligodeoxynucleotide induced dysmorphogenesis of the lung explants. They were smaller and had rudimentary lung bud branches, collapsed conducting airways, and loose expanded mesenchyme. Concomitantly, fibrillin-2 mRNA, antibody reactivity in the explants, and fibrillin-2-specific radioincorporation were reduced. Anti-[Alpha]v and -laminin antibody reactivity and their respective incorporated specific radioactivities were unaltered. These data indicate that fibrillin-2 modulates organogenesis of the lung in the context of epithelial:mesenchymal interactions. Conceivably, the collapse of the conducting airways may also be related to the perturbed biology of the fibrillin-2 interacting protein, i.e., elastin, the latter being critical for the normal biophysiology of the lungs. Key Words: fibrillin; cDNA cloning; extracellular matrix; lung development.

Experiments were undertaken to determine the function of fibrillin-1 in rat kidney development through the use of the metanephric culture. Fibrillin-1 is contained in the extracellular matrix and is believed to be a protein with multiple calcium binding epidermal growth factor-like (cbEGF) domains. Results revealed that fibrillin-1 served as a ligand for an integrin receptor that influenced the interactions between the paracrine epithelial and the mesenchyme. Fibrillin also regulated kidney vascularization.