E-cadherin is often dysregulated in aggressive lung cancer, the mechanism of which cannot always be explained at the level of transcription. In 66 patients with lung cancer, immunohistochemical staining demonstrated that co-localization of E-cadherin and core fucose by Lens culinaris agglutinin was significantly less extensive in tumor than in nontumor tissue. Through gain and loss of fucosylation experiments in the giant lung carcinoma cell lines 95C and 95D, our results revealed that E-cadherin core fucosylation in 95C cells overexpressing α-1, 6-fucosyltransferase (Fut8) inhibited Fut8-95C cell migration, whereas knockdown of Fut8 in 95D cells enhanced migration of short-interfering RNA-targeting Fut8 (siFut8)-95D cells. The level of active Src (phosphorylated Src [Y416]) was significantly reduced in Fut8-95C cells, but elevated in siFut8-95D cells. In protein complexes immunoprecipitated from Fut8-95C cell lysates with anti-E-cadherin, less phosphorylated Src (Y416) and more β-catenin were observed, but immunoprecipitates from siFut8-95D cells, containing less core fucosylated E-cadherin, contained an elevated level of phospho-Src Y416. In Fut8-95C cells, phosphorylation of Akt (Y315, Y326) and GSK-3β (S9) was significantly reduced, but β-catenin (S37) phosphorylation was enhanced. Expression of N-cadherin and Snail1 was also reduced in Fut8-95C cells, but significantly increased in siFut8-95D cells. Intriguingly, when Src kinase activity was inhibited by treatment of cells with PP2 and SU6656, regulation of N-cadherin, Snail1 and cell migration by E-cadherin core fucosylation was abrogated in both Fut8-95C and siFut8-95D cells. Therefore, posttranslational modification of E-cadherin by less core fucosylation recruited and activated Src, and induced an epithelial-mesenchymal transition-like process in lung cancer cells.

Floods pose significant risk to riparian buildings as evidenced during many historical events. Although structural resilience to tsunami flooding is well studied in the literature, high-velocity and debris-laden floods in steep terrains are not considered adequately so far. Historical floods in steep terrains necessitate the need for flood vulnerability analysis of buildings. To this end, we report vulnerability of riparian-reinforced concrete buildings using forensic damage interpretations and empirical/analytical vulnerability analyses. Furthermore, we propose the concept and implications of functionality loss due to flooding in residential reinforced concrete (RC) buildings using empirical data. Fragility functions using inundation depth and momentum flux are presented for RC buildings considering a recent flooding event in Nepal. The results show that flow velocity and sediment load, rather than hydrostatic load, govern the damages in riparian RC buildings. However, at larger inundation depth, hydrostatic force alone may collapse some of the RC buildings.

No abstract

<p>Road construction in the Trans-Himalaya is always challenging task because of having fragile and rugged topography with the strong influence of monsoon. Three different road corridors namely Kaligandaki (Pokhara-Jomsoom-Zhongba), Trishuali (Kathamndu-Trishuli-Gyirong) and Bhotekoshi rivers (Kathmandu-Tatopani-Nyalam) cross the Himalaya with different geological discontinuities i.e. South Tibetan Detachment System (STDS), Main Central Thrust (MCT). The Himalayan range is acting a topographic barrier resulting different climate in the southern and northern part. These three roads are very strategic for the connectivity between Trans-Himalaya and midland. People have been living in these valleys for a long time. After the road construction, people have started to build houses along this road. However, people have are often forgetting the influence of these large scale mass movement that occurred in the past. Therefore, an attempt has been done to analyze these past events and their impacts. Preparation of engineering geological map, landslide inventories and investigation of large scale past mass movement have been done in detailed field investigations in 2018 and 2019 supported by remote sensing. Slope stability analysis has been done in different critical sections for the landslide hazard assessment. It is clearly seen that the road passes some of these large scale paleo-landslides and responsible for toe cutting. The road sections are critical in all three roads but more vulnerable in the southern slope of the Himalaya. The road between Beni to Larjung of the Kaligandaki has critical slope and susceptible for landslide occurrences. Therefore, proper mitigation measures have to be implemented for the stabilization of these mountain slope.</p>

Landslides are the most common natural hazards in Nepal especially in the mountainous terrain. The existing topographical scenario, complex geological settings followed by the heavy rainfall in monsoon has contributed to a large number of landslide events in the Kaski district. In this study, landslide susceptibility was modeled with the consideration of twelve conditioning factors to landslides like slope, aspect, elevation, Curvature, geology, land-use, soil type, precipitation, road proximity, drainage proximity, and thrust proximity. A Google-earth-based landslide inventory map of 637 landslide locations was prepared using data from Disinventar, reports, and satellite image interpretation and was randomly subdivided into a training set (70%) with 446 Points and a test set with 191 points (30%). The relationship among the landslides and the conditioning factors were statistically evaluated through the use of Modified Frequency ratio analysis. The results from the analysis gave the highest Prediction rate (PR) of 6.77 for elevation followed by PR of 66.45 for geology and PR of 6.38 for the landcover. The analysis was then validated by calculating the Area Under a Curve (AUC) and the prediction rate was found to be 68.87%. The developed landslide susceptibility map is helpful for the locals and authorities in planning and applying different intervention measures in the Kaski District.