A Heuristic Approach for Shortest Path Problem With Rectilinear Obstacles.

This dissertation presents new heuristic search algorithms, the Guided Minimum Detour (GMD) algorithm and the Line-by-Line Guided Minimum Detour (LGMD) algorithm for searching rectilinear (L\sb1) shortest paths in the presence of rectilinear obstacles. The GMD algorithm combines the best features of maze-running algorithms and line-search algorithms. The LGMD algorithm is a modification of the GMD algorithm that improves on efficiency using line-by-line extensions. Our GMD and LGMD algorithms always find a rectilinear shortest path using the guided A\sp* search method without constructing a connection graph that contains a shortest path. The GMD algorithm and the LGMD algorithm can be implemented in $O(m + (e + N$)loge) and $O((e + N$)loge) time, respectively, and $O(e + N$) space, where m is the total number of searched nodes, e is the number of boundary sides of obstacles, and N is the total number of searched line segments. We consider the problem of finding a shortest path in terms of the number of bends and the combined length and bends

Development of Web GIS-Based VFSMOD System with Three Modules for Effective Vegetative Filter Strip Design

In recent years, Non-Point Source Pollution has been rising as a significant environmental issue. The sediment-laden water problem is causing serious impacts on river ecosystems not only in South Korea but also in most countries. The vegetative filter strip (VFS) has been thought to be one of the most effective methods to reduce the transport of sediment to down-gradient area. However, the effective width of the VFS first needs to be determined before VFS installation in the field. To provide an easy-to-use interface with a scientific VFS modeling engine, the Web GIS-based VFSMOD system was developed in this study. The Web GIS-based VFSMOD uses the UH and VFSM executable programs from the VFSMOD-w model as core engines to simulate rainfall-runoff and sediment trapping. To provide soil information for a point of interest, the Google Map interface to the MapServer soil database system was developed using the Google Map API, Javascript, Perl/CGI, and Oracle DB programming. Three modules of the Web GIS-based VFSMOD system were developed for various VFS designs under single storm, multiple storm, and long-term period scenarios. These modules in the Web GIS-based VFSMOD system were applied to the study watershed in South Korea and these were proven as efficient tools for the VFS design for various purposes

Development of Web GIS-Based VFSMOD System with Three Modules for Effective Vegetative Filter Strip Design

In recent years, Non-Point Source Pollution has been rising as a significant environmental issue. The sediment-laden water problem is causing serious impacts on river ecosystems not only in South Korea but also in most countries. The vegetative filter strip (VFS) has been thought to be one of the most effective methods to reduce the transport of sediment to down-gradient area. However, the effective width of the VFS first needs to be determined before VFS installation in the field. To provide an easy-to-use interface with a scientific VFS modeling engine, the Web GIS-based VFSMOD system was developed in this study. The Web GIS-based VFSMOD uses the UH and VFSM executable programs from the VFSMOD-w model as core engines to simulate rainfall-runoff and sediment trapping. To provide soil information for a point of interest, the Google Map interface to the MapServer soil database system was developed using the Google Map API, Javascript, Perl/CGI, and Oracle DB programming. Three modules of the Web GIS-based VFSMOD system were developed for various VFS designs under single storm, multiple storm, and long-term period scenarios. These modules in the Web GIS-based VFSMOD system were applied to the study watershed in South Korea and these were proven as efficient tools for the VFS design for various purposes

Mutations in DDX58, which Encodes RIG-I, Cause Atypical Singleton-Merten Syndrome

Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies

Mutations in DDX58, which Encodes RIG-I, Cause Atypical Singleton-Merten Syndrome

Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.GLu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373A1a) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.X116452Ysciescopu

Determination of Malignant and Invasive Predictors in Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Suggested Scoring Formula

Prediction of malignancy or invasiveness of branch duct type intraductal papillary mucinous neoplasm (Br-IPMN) is difficult, and proper treatment strategy has not been well established. The authors investigated the characteristics of Br-IPMN and explored its malignancy or invasiveness predicting factors to suggest a scoring formula for predicting pathologic results. From 1994 to 2008, 237 patients who were diagnosed as Br-IPMN at 11 tertiary referral centers in Korea were retrospectively reviewed. The patients' mean age was 63.1 ± 9.2 yr. One hundred ninty-eight (83.5%) patients had nonmalignant IPMN (81 adenoma, 117 borderline atypia), and 39 (16.5%) had malignant IPMN (13 carcinoma in situ, 26 invasive carcinoma). Cyst size and mural nodule were malignancy determining factors by multivariate analysis. Elevated CEA, cyst size and mural nodule were factors determining invasiveness by multivariate analysis. Using the regression coefficient for significant predictors on multivariate analysis, we constructed a malignancy-predicting scoring formula: 22.4 (mural nodule [0 or 1]) + 0.5 (cyst size [mm]). In invasive IPMN, the formula was expressed as invasiveness-predicting score = 36.6 (mural nodule [0 or 1]) + 32.2 (elevated serum CEA [0 or 1]) + 0.6 (cyst size [mm]). Here we present a scoring formula for prediction of malignancy or invasiveness of Br-IPMN which can be used to determine a proper treatment strategy

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field